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3744 Chem. Soc. Rev., 2011, 40, 37443763 This journal is c The Royal Society of Chemistry 2011

Cite this: Chem. Soc. Rev., 2011, 40, 37443763

BINEPINES: chiral binaphthalene-core monophosphepine ligands

for multipurpose asymmetric catalysis

Serafino Gladiali,*a Elisabetta Alberico,b Kathrin Jungec and Matthias Beller*c

Received 2nd November 2010

DOI: 10.1039/c0cs00164c

The atropisomeric structure of 4,5-dihydro-3H-dinaphtho[2,1-c;10,20-e]phosphepine is the common

axially chiral scaffold of a library of monophosphine ligands nicknamed BINEPINES that have

shown a quite remarkable stereoselection efficiency in a broad variety of enantioselective reactions

involving the formation of new CH or CC or CX bonds. In this critical review the properties

and scope of this type of chiral ligands are illustrated (70 references).

Introduction

The last decade has witnessed the enormous success of

chiral monodentate phosphorus ligands in several metal- and

organo-catalyzed enantioselective reactions. The renaissance

of this class of chiral inducers has turned around the established

belief that only bidentate diphosphines could be the ligands of

choice for asymmetric catalysis. The breakthrough in the

field was achieved in 2000 when almost simultaneously three

independent groups pointed out the exceptional stereoselective

ability displayed in Rh-catalyzed asymmetric hydrogenation

of a-acyldehydroamino acid derivatives by the phosphor-

amidites 1,1 phosphites 22 and phosphonites 33 of binaphthol

(Fig. 1). Given the presence of polar Pheteroatom bonds

(heteroatom = O; N), these compounds are ligands of comparably

higher p-acidity than tertiary trialkyl or triaryl phosphines.

a Dipartimento di Chimica, Universita` di Sassari, via Vienna 2,07100 Sassari, Italy. E-mail: [email protected];Fax: +39 079 229559; Tel: +39 079 229546

b Istituto di Chimica Biomolecolare, CNR, trav. La Crucca 3,07040, Italy

c Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock,Albert-Einstein-Strae 29a, Rostock 18059, Germany.E-mail: [email protected]; Fax: +49 381 1281 51113;Tel: +49 381 1281 113

Serafino Gladiali

Prof. Serafino Gladiali was born

in Milano. He accomplished

his studies in Industrial

Chemistry at the University

of Milano where he received

the laurea in Industrial

Chemistry in 1968. After gaining

four years of experience in

industrial research on steroid

chemistry, in 1972 he moved to

the University of Sassari,

where he is full Professor of

Industrial Organic Chemistryat the Faculty of Sciences. His

main research interests are

centred on asymmetric homo-

geneous catalysis and ligand design. Stereoselective synthesis of

optically active organic compounds, mainly nitrogen hetero-

cycles and atropisomeric phosphorus and sulfur derivatives, is

a further subject of his research. He has co-authored over

250 papers, patents and communications covering the areas of

enantioselective hydroformylation and hydrogen transfer reduction;

synthesis and applications to asymmetric catalysis of chiral hetero-

cycles with pyridine nitrogen donors; preparation and catalytic

applications of atropisomeric phosphorus and sulfur donor ligands;

catalysis for energy production.

Elisabetta Alberico

Elisabetta Alberico obtained her

degree in Chemistry (Laurea)

from the University of Sassari

in 1993. From 1993 to 1996

she worked at the University

of Sassari in Prof. Gladialis

group and for the National

Research Council as research

assistant in the field of

asymmetric homogeneous cata-

lysis. After spending ten months

at the University of Ottawa in

1998 in the group of Prof.Howard Alper, she moved to

the Rheinisch-Westfalische

Technische Hochschule where

she obtained her PhD under the supervision of Prof. Albrecht

Salzer. Since 2001 she has held a permanent position as researcher

at the Institute of Biomolecular Chemistry of the National

Research Council in Sassari. Her research interests are in the

fields of organometallic chemistry, asymmetric homogeneous

catalysis and application of catalytic methods to the synthesis of

molecules endowed with biological activity.

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This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 37443763 3745

BINEPINES 5 are monodentate phosphines which retainthe basic structural features of these monodentate binaphthalene-

core ligands, i.e. a seven-membered phosphepine ring embedded

in a C2-symmetrical environment with an endocyclic P-donor

atom and a stereogenic axis as the unique chiral element, but

possess a P-donor of comparably higher electron density

(Scheme 1). This feature is expected to display a positive

effect in several catalytic processes like the hydrogenation of

enamides by Rhphosphine complexes where the turn-over

limiting step of the catalytic cycle is the oxidative addition of

hydrogen.4

Like the other chiral monophosphines, BINEPINES have

several advantages over the bidentate counterparts: they are

readily accessible from rather inexpensive starting materialsvia synthetic routes which enable the easy introduction of

structural diversity; they are amenable to combinatorialscreening of catalysts;5 they allow the design of catalysts built

up on metal complexes containing an unpaired number

of chiral ligands. The higher lability of monophosphines as

compared to chelating bidentate diphosphines may influence

the dissociation equilibria in favor of unsaturated species.

While this may have contrasting effects on the catalytic

process, an increase of the rate is anticipated in the case where

vacation of a coordination site is required in an early step of

the catalytic cycle. The main drawback in the use of mono-

phosphines as chiral ligands follows from the higher number

of regioisomers that, depending on the geometry of the complex,

can be obtained when two or more ligands are complexed to

the metal. The presence of a mixture of catalysts is normallydetrimental for the selectivity of the reaction.

Fig. 1 Selection of chiral monodentate biaryl phosphoramidites 1,

phosphites 2 and phosphonites 3 for asymmetric hydrogenations.Scheme 1 First synthesis ofBINEPINES 5 according to Gladiali et al.

Kathrin Junge

Dr Kathrin Junge, born in

1967 in northern Germany,

received her PhD degree in

Chemistry from the University

of Rostock in 1997 (Prof.

E. Popowski Laboratory).

After a postdoctoral position

in the Max-Planck group of

Prof. U. Rosenthal she joined

the group of Prof. M. Beller in2000. Since 2008 she is group

leader for homogeneous redox

catalysis at LIKAT. She has

been involved for years on

catalysis and has developed

efficient hydrogenations for

ketoesters and other carbonyl compounds. Moreover, new chiral

ligands based on the binaphthophosphepine structure were developed

by her. Her current main interest is the development of environ-

mentally benign and efficient catalytic reactions based on cheap

nonprecious metals.

Matthias Beller

Matthias Beller, born in 1962,

studied chemistry at the

University of Gottingen,

Germany, where he completed

his PhD thesis in 1989 in the

group of Prof. Tietze. As a

recipient of a Liebig scholar-

ship, he then spent one year in

the group of Prof. Sharpless at

the MIT. From 1991 to 1995,Beller was an employee of

Hoechst AG in Frankfurt, where

he directed the Homogeneous

Catalysis project in the

companys central research

unit. In 1996 he moved to the

Technical University of Munchen as Professor for Inorganic

Chemistry. In 1998, he relocated to the University of Rostock to

head the Institute for Organic Catalysis. Since 2006 Matthias

Beller is director of the newly formed Leibniz-Institute for

Catalysis. His scientific work has been published in around

450 original publications and review articles. In addition, ca.

100 patent applications have been filed.

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Synthesis and structure of BINEPINES

Synthesis

The first preparation of a 4,5-dihydro-3H-dinaphtho-

[2,1-c;10,20-e]phosphepine derivative 5 (BINEPINE) was reported

in 1994 (Scheme 1).6 A nickel-catalyzed Kumada coupling

of 1-bromo-2-methylnaphthalene with its Grignard reagent7

gave racemic 2,2

0

-dimethylbinaphthyl 4 which was selectivelydouble-lithiated on the methyl groups and subsequently

quenched with phenyldichlorophosphine to yield racemic

P-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;10,20-e]phosphepine 5a.

Resolution of the enantiomers was carried out by fractional

crystallization of the diastereomeric complexes with (+)-

di-m-chloro-bis[(S)-N,N-dimethyl-a-phenylethylamine-2C,-N]-

dipalladium 6.8 Finally, the enantiopure monodentate

phosphine 5a (PhBINEPINE) was liberated by reacting the

single diastereomeric complex with bidentate phosphines

(e.g. DPPE). Some years later the group of Stelzer reported

the synthesis of the secondary phosphepine 5 (R = H) (Scheme 2)

in good yields.9

Both these approaches were however unpractical withrespect to up-scaling due to the expensive auxiliaries and low

overall yields. A more convenient two step pathway starting

from enantiomerically pure 2,20-binaphthol (498% ee) was

established later when enantiopure 2,20-binaphthol became

commercially available on large scale.10,11 This material

can be efficiently converted into enantiopure 2,2 0-dimethyl-

binaphthyl 4 in more than 90% overall yield via a two step

sequence involving a Kumada coupling of the intermediate

ditriflate (Scheme 2).12,13 Two different methodologies were

developed for the conversion of 4 into 5. In the first procedure

double metallation of 2,20-dimethylbinaphthyl 4 with n-butyl-

lithium in the presence of TMEDA (N,N,N0,N0-tetramethyl-

ethylenediamine) followed by quenching with commercially

available dichlorophosphines gave ligands 5a (P-phenyl) and

5b (P-tert-butyl) in 6083% yield, which were both synthesised

on a scale greater than 10 g.10

In the second procedure the dilithiated 2,20-dimethyl-

binaphthyl 4 was quenched with diethylaminodichlorophosphine

to produce the amino BINEPINE 814 which, upon treatment

with gaseous HCl, was converted into the chloro BINEPINE9

in 80% yield. By coupling with various Grignard or lithium

reagents the chlorophosphine provides a broad selection of

ligands 5. The limited number of commercially available

dichlorophosphines and the large diversity of Grignard

reagents make the access through 4-chloro-4,5-dihydro-

3H-dinaphtho[2,1-c;1

0

,2

0

-e]phosphepine 9 the route of choicefor a library of ligands 5.11 Very recently, Wild and co-workers

have added one more member to the ligand family 5. The

2-(methoxymethyl)phenyl derivative 5t was exploited in the

enantioselective synthesis of arsenium and bis(arsenium)

salts.15

Scheme 2 Synthetic approach to 4,5-dihydro-3H-dinaphtho[2,1- c;10,20-e]phosphepines developed by Beller et al.

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A synthetic approach to monodentate BINEPINESanalogous

to the one devised by Beller et al. was reported at the same time

by the group of Zhang (Scheme 3).

13

The t-Bu derivative 5b wasexploited in the preparation of the bidentate ligand with the

phosphepine motif 1113 which adds to the bis-phosphepine

ligands 1016 and 1217 previously reported by the same group.

Structural diversity in the BINEPINElibrary can be generated

in different ways and nowadays a vast array of derivatives has

been reported. While the group of Beller has focused on the

variation of substituents on the P-centre, Widhalm et al. have

managed to introduce one or two substituents on the benzylic

carbons a- to the phosphorus (Scheme 4).18 The introduction

of new stereocentres in the proximity of the P-donor was

deemed to improve the transfer of chiral information. The

sulfide 13, prepared from 5a, was deprotonated with n-butyl-

lithium and then quenched with suitable electrophiles to provide

monosubstituted ligands. Monosubstitution at the benzylic

carbon destroys the C2-symmetry of the supporting scaffold

and generates, at the same time, two new stereogenic centres,at C and at P. The monoalkylated products 14 (Scheme 4) are

obtained as a mixture of two diastereoisomers with a relative

syn (Sax,S,SP)-14 or anti (Sax,S,RP)-14 arrangement of the

substituents on C and P. The latter stereochemistry is favoured

in all cases. Dialkylation of the phosphepine sulfide (S)-13 is

better achieved by a step-wise protocol involving two sequential

deprotonationalkylation reactions with the same alkylating

agent. t-BuLi is necessary in order to place the second

substituent on C(5). This step proceeds with complete diastereo-

selectivity providing the trans protected phosphepine

(Sax,S,S)-16 as the exclusive reaction product and restoring

the original C2-symmetry of the supporting scaffold. Ligands

15 and 17 are accessible also from the relevant phosphine

Scheme 3 Synthesis of 4,5-dihydro-3H-dinaphtho[2,1-c;10,20-e]phosphepines by a protocol established by Zhang et al.

Scheme 4 Synthesis ofa- and a,a0-substituted 4,5-dihydro-3H-dinaphtho[2,1-c;10,20-e]phosphepines.

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oxide following a similar deprotonation/alkylation protocol

followed by deoxygenation.19 The observed stereochemistry

was identical and again only one diastereomer is formed.

Dimethoxydibenzophosphepine (R)-23 is the unique example

of phosphepine where a diaryl template other than binaphthalene

has been used for the installation of the phosphepine ring

(Scheme 5). The enantiopure (R)-configured product is readily

accessible from the phenol 18 through the bisphenol 20 which

has been resolved with the aid of menthyl chlorocarbonate.20

Structural and electronic properties of BINEPINE derivatives

The 1H- and 13C-NMR spectra of PhBINEPINE 5a

(Scheme 1) show the non-equivalence of the methylene and

the naphthyl groups of the 1,1 0-binaphthyl-2,20-bis(methylene)

backbone. Accordingly, the diastereotopic CH2 groups show

in the 13C{1H} NMR spectrum two doublets with different

PC coupling constants. In the 1H-NMR spectrum, the

diastereotopic hydrogens of the CH2 groups give rise to four

sets of partially overlapping double doublets arising from

geminal 1H,1H and from 31P,1H couplings. The 31P{1H} NMR

spectra of ligands 5 show a single peak whose chemical shift

depends on the nature of the R substituent on the phosphorus

and varies within the range ofd 3 to +28 ppm.

These spectral data, which are common to ligands 5,

indicate that no atropisomerization of the dinaphthyl frame-

work occurs at room temperature and that the seven membered

phosphepine ring is locked in a single conformation which

does not undergo any significant dynamic process. A noticeable

feature of BINEPINES is that the phosphorus atom is not a

stereogenic centre since it is located on the C2-symmetry axis

of the dinaphthyl substituent. As a consequence, if pyramidal

inversion at phosphorus had to occur, which however is

not the case, this should not affect the chirality of the molecule

which is determined exclusively by the atropisomeric dinaphthyl

framework.

When the C2-symmetry of the dinaphthyl backbone is lost,

as it occurs upon introduction of one substituent at the

benzylic position (ligands 15ae, Scheme 4), the phosphorus

becomes a stereogenic centre. In ligands 17ae (Scheme 4),

where the two substituents R1 and R2 are identical and have a

mutual trans arrangement, the C2-symmetry of the binaphthyl

template is restored and the phosphorus is no longer stereogenic.

X-Ray structures have been obtained for ligands 5H R = H,9

(S)-5c and (S)-5k (Fig. 2),11 rac-14b and rac-16b (Fig. 3).18

Common features of the BINEPINE ligands resulting

from the comparison of these structures are the distorted skew-

boat conformation of the seven-membered phosphepine ring

containing the phosphorus atom and the large dihedral angle

(Table 1) existing between the average planes of the naphthalene

rings.

These torsional angles lie in the range 651701 for BINEPINES5,

lower values being associated to the presence of aryl substituents

at the P-centre. Since the amplitude of this angle is almost

unchanged in the relevant P-oxide (compare entries 3 and 4,

Table 1), it can be confidently assumed that the torsional angle

Scheme 5 Synthesis of diphenyl templated phosphepines.

Fig. 2 Crystal structures of (S)-5c (left hand side) and (S)-5k

(right hand side). For ligand 5c, only one of the two symmetry-

independent molecules of the asymmetric unit is depicted. H-atoms

are omitted for clarity.

Fig. 3 Crystal structures600 dpi in TIF format)??4 of rac-16b

(left hand side) and rac-14b (right hand side). In both cases, structures

having S configuration at the benzylic carbons are depicted. H-atoms

are omitted for clarity.

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of the parent ligand PhBINEPINE 5a should be very close to

that of the relevant P-oxide (631). Unlike the case ofP-oxides,

the introduction of sulfur in place of oxygen induces a signifi-

cant increase of the dihedral angle (compare entries 6 and 7,

Table 1) as to span over 711 in rac-14b and in rac-16b. In both

these last ligands the methyl substituents at the benzyliccarbons hold a pseudo-axial position.

A few transition metal complexes containing PhBINEPINE5a

have been isolated and characterized. Cationic [Rh(nbd)(5a)2]+X

derivatives, where nbd is norbornadiene and X is a non-

coordinating anion (CF3SO3; BF4

; PF6; SbF6; BaRF

)

show in solution a NMR pattern consistent with the presence

of two units of P-ligand coordinated to the metal and an

overall C2-symmetry of the complex.21 The same structural

features can be extracted from the NMR spectra of neutral

dichloro and cationic ditriflate Pt-complexes synthesized

by reacting Pt(cod)Cl2 (cod = 1,5-cycloctadiene) with two

equivalents of 5a followed by treatment of the dichloro

derivative with aqueous silver triflate.22

Crystals suitable for X-ray analysis have been obtained for two

metal complexes containing just one unit of (S)-PhBINEPINE

5a: the cyclopalladated complex with the (R)-phenethylamine

derivative 246 and the cycloplatinated complex 25a23 (Fig. 4).

The measure of the dihedral angle of the BINEPINE is

reported only for the cyclopalladated complex 24 and is very

close to that of the corresponding phosphepine oxide (compare

entries 5 and 9, Table 1). From this it follows that the binding of

a metal at the P-centre has only minor consequences on the

atropisomeric conformation of the ligand.

Tolmans cone angle y of PhBINEPINE as extracted from

the crystal structure of (S,R)-24 spans some 1511, slightly

larger than that of triphenylphosphine (1451

).24

The electron density at the P-donor of a range ofBINEPINES

has been evaluated by means of the 1JP,Se of the corresponding

selenides, prepared in situ by heating the phosphepine derivative

and selenium in CDCl3.25 This method is among the most

reliable ones for assessing the donating ability of the phosphorus

donors, smaller coupling constants corresponding to a higher

electron density at the phosphorus and vice versa.26

Fromthe data of Table 2 it is apparent that the electronic effect

of the substituents on the phenyl ring is effectively transmitted

to the P-donor of aryl substituted BINEPINES and that the

dimethoxydibenzophosphepine23 (1JP,Se = 725 Hz) is slightly

more basic than PhBINEPINE5a (1JP,Se = 728 Hz).3 For the

sake of comparison, the 1JP,Se of a typical phosphoramidite

such as Monophos (1; R1 = R2 = Me), a ligand much more

p-acidic than any BINEPINE 5, is as high as 971.1 Hz

(Table 2; entry 9).

Formation of CH bonds

Hydrogenation of CQC double bonds. Hydrogenation of

CQC double bonds is the benchmark reaction for assessing

the efficiency of a chiral ligand. Driven by the success of mono-

dentate phosphorus ligands based on the binaphthyl backbone

(Fig. 1), the ligand tool box 5 was assessed in the asymmetric

catalytic hydrogenation of a variety of substrates. A first set

of experiments was dedicated to the rhodium-catalyzed

asymmetric hydrogenation of a-aminoacid precursors.10,11

Here, methyl-(Z)-a-acetamidocinnamate 26 and methyl-

a-acetamidoacrylate 27 were chosen as model substrates

(Scheme 6). High enantioselectivities (up to 93% ee) and

activities (TOF 10006000 h1) were achieved in toluene and

in ethyl acetate with 26 as the substrate.11 The use of sodium

dodecyl sulfate (SDS) as an additive frequently led to improved

enantioselectivities (up to 95% ee in the case of 5a) for the

reaction in toluene.10 This result is rather unexpected because

aromatic hydrocarbons are known to induce the formation of

coordinatively saturated Rh-complexes which are less reactive

towards hydrogen.27 A negative effect on the kinetics of the

hydrogenation is the expected consequence and this may have

an unfavorable impact also on the stereoselectivity. In the

present case, however, the decrease in the reaction rate is

counterbalanced by a definite increase of the stereoselectivity.

The same happens in the hydrogenation in ethyl acetate when

the ligand to metal ratio is increased from 2 : 1 to 4 : 1.10 Both

these results are most probably related to the stabilization of

Table 1 Dihedral angles of BINEPINE derivatives

Entry Compound Torsion angle Reference

1 5H 67.6(5)1 92 5k 70.21(5)1 113 5c 65.11(10)1a 11

66.20(9)14 5c-oxide 65.05(7)1

a 1966.86(6)1

5 5a-oxide 63.01(7)1 196 17b-oxide 67.39(4)1 197 16b 71.361 188 14b 71.431 189 24 63.81 6

a The two values refer to the two symmetry independent molecules

present in the asymmetric unit.

Fig. 4 Crystal structures of cyclometalated Pd (24) and Pt (25a)

complexes with (S)-5a. H-atoms are omitted for clarity.

Table 2 31P-NMR chemical shifts for selected BINEPINES and1JP,Se coupling constants of the corresponding selenides measured inCDCl3 at room temperature

Entry Ligand d (31P)/ppm 1JP,Se/Hz

1 5d 2.3 711.42 5r 4.3 711.43 5c 5.7a 721.84 5l 7.8a 723.1

5 23 1.7 725.06 5a 7.8 728.37 5n 8.2a 739.98 5h 5.1a 761.79 1 148.7 971.1

a Values measured in CD2Cl2.

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the resting state of the catalyst and to the consequent decrease

in the rate of its decomposition.27

The best enantioselectivities were obtained with aryl substituted

BINEPINES, while alkyl derivatives led, in most cases, to

enantiomeric excesses lower than 50%. In the case of asymmetric

hydrogenation of methyl a-acetamidocinnamate 26 a detailed

study of various ligands with substituted aryl groups at the

phosphorus demonstrated no significant change in enantio-

selectivity, when electron-donating or electron-withdrawing

functionalities were situated in the para-position. Analogous

substitution in the ortho-position caused a decrease in the

enantioselectivity. The substituents on the P-phenyl group

display a significant influence on the activity of the catalyst

which is increased by electron donating substituents such as

p-OMe and reduced by electron-withdrawing ones such as p-F

and p-CF3. While the majority of the catalysts gave lower enantio-

selectivities in the reduction of methyl a-acetamidoacrylate 27

as compared with methyl a-acetamidocinnamate 26, in the

case of the best ligand, (S)-5o, the ee was practically the same

(9495%). With both substrates, ligand (S)-5o gives also rise

to the catalyst with the highest activity. As a general trend, with

BINEPINES 5 the handedness of the reaction is opposite

(the inducing ligand and the reaction product have opposite

configurations). The sole exception to this behavior has been

noticed in the reduction of 27 with t-BuBINEPINE 5b,

where the inducing ligand and the product have the same

configurations.

With C-substituted BINEPINES, the best results in the

reduction of a-acetamidocinnamic acid 28 (91% ee) and its

methyl ester 26 (73% ee) are achieved with ligands (Sax

,S,S)-

17b and (Sax,S,S)-17d respectively (Scheme 7).18 Interestingly,

with all these ligands the handedness of the reaction is reversed

as compared to the corresponding unsubstituted BINEPINES

5, indicating that axial- and central chiralities are mismatched

and that stereoselection is steered by the configuration of the

stereogenic centres rather than by that of the stereogenic axis.

The hydrogenation ofb-aminoacid precursors is attracting

increasing interest because the resulting products are useful

building blocks for various novel biologically active compounds.28

While investigating the application of ligand class 5 in the

rhodium-catalyzed asymmetric hydrogenation ofb-dehydroamino

acids derivatives, the necessity of different reaction conditions

for the E- and Z-isomers became soon apparent (Scheme 8).29

A good enantioselectivity (79% ee (R)) was obtained for

the reduction of (E)-methyl-3-acetamido butenoate E-29 in

2-propanol at 2.5 bar hydrogen pressure, while higher pressures(50 bar) and ethanol as the solvent turned out to be beneficial

for the Z-isomer Z-29 (92% ee (S)). Notably, a chiral switch in

the product configuration was noticed depending on the geometry

of the double bond, which had been scarcely reported before.30

Furthermore, a higher reaction rate was monitored for the

Z-isomer compared to the E-isomer, in spite of the opposite

behavior reported for most other catalysts.31

With Z-29 the highest enantioselectivity was reached with

ligand 5a while the tert-butyl-substituted derivative 5b was

completely inactive. Surprisingly, ligand 5b gave a good enantio-

selectivity in the hydrogenation ofE-29. Several b-dehydroamino

acids derivatives have been screened and in the best case 94%

ee was attained when the methyl ester of Z-29 was replacedby the ethyl ester. From the observation of a non-linear

dependence of the stereoselectivity of the reduction on the

enantiopurity of the used BINEPINES, it was inferred that

2 equiv. of ligand per metal were present in the active catalyst.32

This circumstance gave the chance for a combinatorial screening

of catalysts. Unfortunately no positive effect was observed upon

combining 5a with different achiral phosphorus ligands.29

Scheme 6 Asymmetric hydrogenation of 26 and 27 in the presence of

BINEPINE ligands 5.

Scheme 7 Hydrogenation of acetamidocinnamic acid 28 and its

methyl ester 26 catalyzed by Rh-complexes of PhBINEPINE 5a

and a,a0-disubstituted PhBINEPINES 17b and 17d.

Scheme 8 Hydrogenation ofE-29 and Z-29 with different BINEPINES5.

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The mechanistic details of the hydrogenation ofb-aminoacid

precursors are still to be clarified. This does not allow us to

draw any sound conclusion from the results obtained in the

RhBINEPINE catalyzed hydrogenation.

In the asymmetric hydrogenation of dimethyl itaconate 31

with BINEPINES 5 the best results (enantioselectivities up to

88% ee) were obtained in dichloromethane (Scheme 9).11

The hydrogenation of itaconic, acetamidocinnamic and

acetamidoacrylic acids and of the relevant methyl esters

proceeds at a fast rate and with a high ee, up 96%, even in

the presence of dimethoxydibenzophosphepine (R)-23 as the

chiral inducer. In this case dichloromethane is the solvent of

choice and a preformed cationic Rh-complex containing two

units of the ligand (R)-23 has been used as the catalyst.20

PhBINEPINE (S)-5a and related BINEPINES were

applied to the rhodium-catalyzed reduction of enamides, an

atom economic and straightforward route for the synthesis of

chiral amines (Scheme 10).33

As a general trend, with these substrates aryl-substituted

phosphepines are much better suited chiral inducers than the

alkyl-substituted ones and, among them, (S)-5a is the most

efficient. Electron-rich substrates such as 33 were hydrogenated

in somewhat higher enantioselectivity compared to N-(1-phenyl-

vinyl)acetamide, the opposite behaviour being observed with

electron-poor substrates. Under optimized conditions an

enantioselectivity as high as 93% has been obtained in the

reduction of N-(1-phenylvinyl)acetamide 32 (Scheme 10) with

ligand (S)-5a. This is the highest stereoselectivity obtained up

to now with monodentate phosphine ligands in this reaction.

The enantioselective reduction of enol carbamates offers an

alternative approach for the preparation of chiral benzylic

alcohols.19 Pioneering work in this field has been reported by

Feringa and co-workers who have obtained enantioselectivities

up to 98% ee with rhodium-catalysts containing monodentate

phosphoramidites (MonoPhos-family).34 Utilizing compound

34 as a model substrate, various reaction parameters were

investigated in detail and enantioselectivities up to 96% ee

were achieved with a catalyst made up in situ from

[Rh(cod)2]+BF4

and ligand 5a (Scheme 11).19 Notably, the

catalyst gave a similar enantioselectivity (9496% ee) over the

entire temperature range 1090 1C.

The influence of a,a0-substitution in the ligand was also

explored in a comparative study. Ligand (Sax,S,S)-17b was the

best chiral inducer for some enolcarbamates and caused in

most cases a switch of configuration compared to the parent

ligand 5a.19

Transfer hydrogenation of CQX bonds. Phenyl BINEPINE

5a is an excellent chiral inducer in the hydrogen transfer

reduction of the CQC double bond of a,b-unsaturated acid

derivatives, a reaction which had no other precedent for the

use of chiral monodentate P-donors. In the presence of preformed

and well-defined cationic [Rh(nbd)(5a)2]+X complexes

(X = non-coordinating anion) a range of a,b-unsaturated

acids and esters have been selectively reduced to the corres-

ponding saturated products using formic acid as the hydrogen

donor (Scheme 12).21 While with most substrates the stereo-

selectivities were moderate, an excellent enantioselectivity

(97% ee), definitely higher than that obtained in the reduction

with hydrogen, was attained in the reduction of itaconic acid

35 where 5a outperformed by far all the other monodentate

P-donors screened. Notably, while the corresponding a-methyl

monoester (R1 = H; R2 = Me) was quantitatively reduced

to the saturated derivative of the same configuration with

respectable ee (81%), under the same conditions the dimethyl 31

and the b-methyl monoester (R1 = Me; R2 = H) gave modest

yields of the opposite enantiomer in low ees (13% and 28%,

respectively). This chiral switch stresses the role played in the

catalytic process by the free b-COOH group in the substrate.

This structural feature not only dictates the configuration of

the reduction product, but is as well needed for high conversions

and stereoselectivities to be obtained.

We may speculate that the b-COOH can be involved in the

intramolecular oxidative addition to the metal centre facilitating

the formation of the first Rh(III)-intermediate of the catalytic

cycle. Replacement of the carboxylato ligand at the metal

centre by formate anion provides the conditions for carbon

dioxide extrusion, leading to a Rh(III)dihydride. Such a species

Scheme 9 Asymmetric hydrogenation of dimethyl itaconate 31 in the

presence of BINEPINE ligands 5.

Scheme 10 Asymmetric hydrogenation of N-acyl enamides.

Scheme 11 Hydrogenation of enolcarbamate 34 in the presence ofBINEPINE 5a.

Scheme 12 Transfer hydrogenation of itaconic acid derivatives.

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has been proposed as the intermediate in the highly enantio-

selective asymmetric hydrogenation of itaconic acid by chiral

Rhdiphosphine complexes.35

Ligands 5 in association with chiral pyridinebisimidazoline

ligands have been used in the Ru-catalyzed hydrogen transfer

reduction of ketones yielding enantioselectivities up to 95% ee

(Scheme 13).36 The role of the P-ligand in this reaction,

however, is of scarce significance since the ees obtained in

the presence of5 are equal or sometimes even lower than those

observed when the chiral pyridinebisimidazolines are associated

with triphenylphosphine. In the same reaction stereoselectivities

lower than 30% were obtained using a catalyst prepared in situ

from [Ru(cod)(methallyl)2] and PhBINEPINE 5a.

Hydroboration of CQC bonds. The rhodium-catalyzed hydro-

boration of styrene with catechol borane proceeds smoothly

with ligands 5a, 15, and 17 affording predominately the branched

product (Scheme 14).18 The stereoselectivities are rather modest

with a top value of 42% ee obtained with ligand 17b. A switch of

the product configuration may occur depending on the nature of

the substituents on the benzylic carbons of the phosphepine ring.

This may be indicative of a mismatched combination of the

stereogenic elements present in the ligands.

Hydrogenation of CQO bonds. The asymmetric hydrogenation

of carbonyl groups provides a straightforward route to chiral

alcohols and a number of Ru- or Rh-complexes modified with

chiral bidentate phosphine have been successfully employed in

the reduction of ketones. The first successful application of mono-

dentate phosphines to the catalytic asymmetric hydrogenation

ofb-ketoesters was described in 2004 when it was shown that

BINEPINES 5 in combination with [Ru(cod)(methallyl)2]

complexes give rise in situ to a catalytic system capable of hydro-

genating b-ketoesters 36 in a high stereoselectivity of up to 95%

(Scheme 15) even at fairly high temperatures (100120 1C).37

Interestingly, other monodentate ligands of excellence in hydro-

genation such as phosphites, phosphonites and phosphoramidites

were much less efficient than BINEPINES5 in this reaction.

When the enantioselective hydrogenation of b-ketoesters

was run in a homogeneous solution made up of ionic liquids

(IL) and methanol,38 the reaction rate was higher than in pure

ILs but the enantioselectivity was lower than that observed in

plain methanol.39 These differences have been attributed to the

concurrent formation of ketal and hemiketal that is suppressed

to a significant extent in the mixed system IL/methanol.

Nature and performance of the catalysts heavily depend on

the structure of the cationic part of IL.38 With bis(trifluoro-

methylsulfonyl)-imide anions [NTf2] hydroxyalkylammonium

salts display the best catalytic activity and the induction

time for the generation of the active species is short. In these

systems the enantioselectivities were found to be in the same

range as for pure methanol (9096% ee).

Very recently it has been reported that the asymmetric

hydrogenation of CQO double bonds can be efficiently performed

in the presence of a Cu-catalyst generated in situ from

Cu(OAc)2 and 5.40 A wide array of aryl- and alkyl-substituted

ketones including cyclic and heterocyclic ones were success-

fully hydrogenated with enantioselectivities of up to 89% eeunder optimized reaction conditions (50 bar H2, 1030 1C,

i-PrOH, KO-t-Bu) (Scheme 16). A base is essential for the

formation of an active copper catalyst, presumably a hydridic

species. Although the model reaction is run with a base in

i-PrOH, the transfer hydrogenation pathway is not operating

since without hydrogen no reaction at all is observed.

The same catalytic system is effective also in the hydrosilyl-

ation of ketones where slightly higher enantiomeric excesses

have been reported (next section).

Hydrosilylation of CQO bonds. Although asymmetric

hydrogenation shows excellent enantioselectivities and yields

for a wide range of ketones, high pressure and temperatures

Scheme 13 Transfer hydrogenation of acetophenone in the presence

of Pybim ligand and ligand 5a.

Scheme 14 Asymmetric hydroboration of styrene with catechol

borane.

Scheme 15 Ruthenium-catalyzed hydrogenation of b-ketoesters in

the presence of p-anisylBINEPINE 5c.

Scheme 16 Copper-catalyzed enantioselective hydrogenation of

ketones with BINEPINE 5n.

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and special equipment are often required. Asymmetric hydro-

silylation offers an attractive alternative due to smooth reac-

tion conditions and easy to handle starting materials. Various

copper-based catalysts have been investigated for the asymmetric

hydrosilylation of carbonyl compounds, but there was no report

on the use of copper complexes with chiral monodentate

phosphorus ligands until 2010 when the first copper-catalyzed

asymmetric hydrosilylation of carbonyl compounds using

monodentate BINEPINE ligands 5 has been described(Scheme 17).41

These CuBINEPINE catalysts have been successfully used

in the hydrosilylation of a broad range of carbonyl compounds

including aryl alkyl, cyclic, heterocyclic and aliphatic ketones.

The reaction proceeds under mild conditions without any

base providing, after desilylation with tetrabutylammonium

fluoride (TBAF), the expected carbinols in high yields and

enantioselectivities (up to 96% ee).

Formation of CC bonds

Addressing the stereochemistry in the formation of CC bonds

is frequently the most challenging task to be faced in the synthesisof an organic product of medium complexity. Asymmetric

transition metal catalysis provides one of the most powerful

instruments for driving the reaction towards the desired stereo-

isomer. Due to the huge number of CC bond-forming reactions,

chiral ligands of broad general scope are extremely helpful in

sorting out the best synthetic strategy and the sequence of CC

bonds to be formed.

Hydroformylation

The Rh-catalyzed hydroformylation of styrene was the first

asymmetric catalytic reaction where PhBINEPINE 5a was

screened as a chiral inducer.6 The catalyst, prepared in situ

from [Rh(CO)2(acac)] and 5a, displayed a good activity and

the reaction proceeded at a satisfactory rate even at tempera-

tures as low as 30 1C. Under standard conditions (benzene;

substrate/P/Rh, 500: 4 : 1, CO/H2, 1 : 1, 50 bars) the reaction

was completely chemoselective towards aldehydes and afforded

a 64% conversion in 3 h. The branched isomer accounted for

95% of the aldehydic product, but the enantioselectivity was

very poor, 20% ee.6

Several years later, a systematic screening of the potential of

BINEPINES in Rh-catalyzed asymmetric hydroformylation

of styrene was undertaken and the influence of the structure of

the substituent at the P-centre on catalytic activity and

selectivity of the reaction was investigated in some detail

(Scheme 18).25

This study confirmed that Rh/BINEPINE complexes

are quite active catalysts for this reaction and that they

show a pronounced preference towards the branched isomer

(8596%). The enantiomeric purity of 2-phenylpropanal improved

substantially from the first report (48% ee obtained with the

phosphepine 5r) but was still far away from an acceptable

threshold so as to make the process a viable tool for the

enantioselective synthesis of arylpropionic acids.25

Allylic alkylation of 1,3-diphenylallyl esters

The asymmetric allylic alkylation of 1,3-diphenylallyl esters by

dimethylmalonate anions has been performed in the presence

of palladium/BINEPINE complexes prepared in situ from

[Pd(allyl)Cl]2 and the appropriate ligand (Scheme 19).42

The outcome of the reaction is strongly affected by the solvent,

the base, the ligand and the temperature. In this reaction aryl

substituted BINEPINES are by far better chiral inducers than

the P-alkyl derivatives which leads to low stereoselectivities.

By proper choice of the reaction conditions and of the substi-

tuent on the phosphorus, stereoselectivities up to 92% have

been achieved in the alkylation of 1,3-diphenylprop-2-enyl-

1-acetate using the p-anisyl substituted ligand 5d, while phenyl

BINEPINE 5a ranked the second in efficiency (86% ee)

among the ligands tested. Similar enantioselectivities have

been recorded with 1,3-diphenylprop-2-enyl-1-carbonate as

the substrate. These results are among the best ones recorded

in this reaction with a monodentate P-donor.

Allylation of aldehydes by p-allyl Pd-complexes

(umpolung of reactivity)

The first ever documented example of catalytic asymmetric

aldehyde allylation by umpolung of a p-allyl palladium complex

Scheme 17 Copper-catalyzed enantioselective hydrosilylation of

ketones using PhBINEPINE 5a.

Scheme 18 Rhodium-catalyzed asymmetric hydroformylation of

styrene using ligands 5a and 5r.

Scheme 19 Allylic alkylation of 1,3-diphenylallyl esters catalyzed by

PdBINEPINE complexes.

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was accomplished in 2004 when it was demonstrated that upon

addition of an excess of diethylzinc, an electrophilic Pdallyl

complex undergoes transmetallation and is turned into

a nucleophilic metalallyl species, supposedly an allyl zinc

reagent, which can then deliver the allyl fragment to a

carbonyl electrophile.43 Preliminary evidence suggests that

transmetallation involves the transfer of an ethyl group from

zinc to palladium and that elimination of diethylpalladium

eventually occurs. The structure of the nucleophilic reagent

and its binding to the chiral ligand, however, have not been

determined. The net result is the addition of an allyl fragment

to the aldehyde group with formation of a homoallylic alcohol

(Scheme 20).

Remarkably chiral bidentate phosphines are not well suited

ligands for this catalysis as they fail to produce optically

active products. When the reaction of benzaldehyde with

cinnamyl acetate is performed in the presence of a catalytic

amount of [Pd(allyl)Cl]2 and 5a at 30 1C, the allylation

reaction is completely diastereoselective and affords only the

anti homoallylic alcohol in 77% yield and in 70% enantio-

selectivity. Even if this value can be hardly considered in

the range of excellence, this ee was by far the best one scored

in an extensive screening where some twenty different chiral

monodentate phosphorus donors were compared as chiral

inducers.

Addition of organoaluminium reagents to aldehydes

The 1,2-addition of AlMe3 or its air-stable analogue DABCO

(AlMe3) to aldehydes proceeds with high stereoselectivity in

the presence of Ni-complexes containing chiral P-donors. In

this catalysis monodentate phosphines enable the enantio-

selective preparation of secondary alcohols in high ee, whereas

chelating diphosphines afford very low enantioselectivities.

44

The complex prepared in situ by addition of a suitable

amount of phosphoramidite 1 to Ni(acaca)2 is the catalyst of

choice for this transformation: on a range of aromatic and a

few aliphatic aldehydes it enables high turnover numbers and

frequencies even at 25 1C with stereoselections in between

85% and 94%. Cinnamaldehyde, however, turned out to be a

poor substrate for the phosphoramidite complex, possibly due

to competition in CQC vs. CQO p-bonding to the metal

centre. In this case the BINEPINE ligand 5a was by far more

efficient, affording the relevant methyl carbinol in a gratifying80% ee (Scheme 21).

SuzukiMiyaura coupling of aryl boronic acids

PhBINEPINE 5a and its 3-mono- and 3,5-disubstituted

congeners (Sax,S,RP)-15b and (Sax,S,S)-17b respectively, have

been tested in the palladium-mediated SuzukiMiyaura coupling

of 1-iodo-2-methoxynaphthalene with o-tolyl boronic acid.18 A

good yield of the expected biaryl derivative (76%) was obtained

with ligand 17b (Scheme 22), but the stereoselectivities were

poor, lower than 20% ee whichever the ligand employed.

Conjugate addition

The Rh-complex [RhCl(Sax,S,Sp)-15f]2 containing the phosphepine

alkene ligand 15fhas proved to be an efficient chiral ligand for

the Rh-promoted conjugate addition of aryl boronic acids to

cyclohex-2-enone (Scheme 23).45

A range of aryl boronic acids, with either electron-rich

or electron-poor aryl substituents, were used and in all cases

the reactions proceeded in fair to good yields (6478%) and

excellent enantioselectivities (9298% ee). These results compare

favourably with the previous ones which have been obtained

with different chiral diolefin or phosphanealkene ligands. The

high efficiency displayed by the catalytic system supports the

view that, despite the comparably high degree of conformational

freedom of the ligand, the catalytic active species is quite robust

and endowed with an efficient chiral bias.

The conjugate addition to open chain a,b-unsaturated

ketones or to nitroolefins can be performed under completely

different conditions using copperphosphepine complexes as

catalysts and alkylzinc as a nucleophile.46a This reaction gives

good yields, but the enantioselectivities are not exceptional

and by far lower than those obtained with the analog

phosphoramidite-based catalysts.46b The best ee was obtained

with 5a as the ligand and was not higher than 74% (Scheme 24).

Scheme 20 Enantioselective catalytic allylation of aldehydes by

umpolung ofp-allyl palladium complexes.

Scheme 21 Ni-catalyzed 1,2-addition of AlMe3 to cinnamaldehyde.

Scheme 22 SuzukiMiyaura coupling catalyzed by palladiumBINE-

PINE complexes.

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Platinum catalyzed cycloisomerization and tandem

cycloisomerizationoxyaddition or hydroarylation

of 1,6-enynes

Noble metal complexes are able to promote the cycloisomeri-

zation of 1,6-enynes via a sequential multi-step reaction path

proceeding through a cyclopropylcarbene intermediate that, in

suitable conditions, may terminate in a bicyclic derivative

featuring a cyclopropane ring (Scheme 25). While in apolar

solvents and in the absence of nucleophiles, this species is the

terminal product, when the reaction is run in the presence of a

nucleophilic species, either a reactant or a solvent, ring

opening of the cyclopropane and reorganization of the

multiple bonds take place in such a way as to lead to the

incorporation of a unit of the nucleophile in the final product

(Scheme 25).

If the metal catalyst promoting this transformation is

capable of driving the reaction cascade with high selectivity

and in an enantioselective manner, the synthetic utility of such

atom-economic sequence of events is immediately apparent for

the preparation of cyclic compounds of significant molecular

complexity. Platinum complexes with P-donors are quite

active and chemoselective catalysts for this transformation

both in the presence and in the absence of nucleophiles. This

gives the choice to terminate the transformation at the stage of

the bicyclocyclopropane derivative or to push it further until

incorporation of the nucleophile occurs.

In a first paper on this topic, PhBINEPINE 5a was shown

to outperform by far any other mono- or bidentate chiral

inducer of the pool of P-donors screened for this process in the

Pt-catalyzed tandem cycloisomerizationoxyaddition, providing

the corresponding oxy-cycloadduct in high chemical yield

and in up to 85% ee (Scheme 26: i).47 In this reaction the

BINEPINEPt catalyst shows a remarkable substrate tolerance

Scheme 23 Rh-catalyzed conjugate addition of aryl boronic acids to

cyclohex-2-enone.

Scheme 24 Cu-catalyzed conjugate addition of diethylzinc totrans-chalcone.

Scheme 25 Platinum catalyzed cycloisomerization of 1,6-enynes: reaction

path.

Scheme 26 Platinum catalyzed cycloisomerization and tandem-

cycloisomerization of 1,6-enynes.

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and a range of diverse functionalities can be admitted in the

starting 1,6-enynes without compromising the outcome of the

reaction to a major extent. The specificity of PhBINEPINE5a

in this process is unique and, more important, is not limited to

this single case. More recent work has shown that very high

enantioselectivities, up to 96% ee, can be obtained when the

cycloisomerization is performed in the presence of electron rich

arenes or heterocycles such as indoles. In this case the final

product arises from a tandem cycloadditonhydroarylation

involving an electrophilic aromatic substitution as the terminal

step of the sequence (Scheme 26: ii).48 In this study evidence has

been provided that the Pt-catalyst might contain three P-donors

in the coordination sphere of the metal and that in principle one

equivalent of BINEPINE might suffice to enable high stereo-

selectivities to be obtained. This assumption is corroborated

by a report by Marinetti et al. who have performed the

Pt-catalyzed cycloisomerization of 1,6-enynes in apolar solvent

(toluene) using a preformed cyclometalated carbenePt

complex 25 containing one unit of PhBINEPINE 5a as

the sole chiral fragment.23 Under these conditions the reaction

stops at the stage of the bicyclic cyclopropane derivative

(Scheme 26: iii) that can be isolated in good chemical yields

and excellent enantioselectivity, up to 97% (absolute configuration

was not assigned).

Asymmetric platinum-catalyzed BayerVilliger oxidation

of cycloalkanones: regiodivergent kinetic resolution

of cyclobutanones

The ability of platinum complexes with chiral diphosphines to

catalyze the enantioselective BayerVilliger oxidation of ketones

with moderate to high stereoselectivities is well documented in

the literature.49 Monodentate phosphines are much less efficient

chiral inducers than the bidentate chelating counterparts whenused in the BV oxidation of achiral ketones. With tert-butyl-

cyclohexanone, for instance, the ee obtained with the preformed

bis-aquo cationic Pt-complex containing PhBINEPINE5a is as

low as 16% to be compared with 92% ee of the relevant BINAP

complex (Scheme 27).22

In the BV oxidation of unsymmetrical ketones two parallel

reaction paths are available for the substrate which lead either to

the normal or to the abnormal lactone (NL and AL,

respectively). In the presence of Pt-chiral phosphine catalysts,

chiral racemic substrates are expected to undergo kinetic resolu-

tion and rate differentiation may be convergent or divergent,

meaning that the same enantiomer of the substrate might react at

a faster rate in both the competitive reactions leading to NL andto AL (regioconvergent process) or vice versa (regiodivergent

process). In the case of Pt/5a complexes, the BV oxidation of two

racemic cyclobutanones does proceed through a regiodivergent

process, thus enabling very high stereoselectivities for both the

lactones to be attained. Notably, in this transformation mono-

dentate P-donors are better suited than bidentate derivatives and

PhBINEPINE5a is better than phosphoramidite 1 (Scheme 28).

Organocatalysis

The use of monophosphines as chiral organocatalysts has

become more and more frequent in recent years and the

subject has been recently reviewed.50

Scheme 27 Pt-catalyzed BayerVilliger oxidation of achiral ketones.

Scheme 28 Regiodivergent kinetic resolution in BayerVilliger oxidation of chiral racemic cyclobutanones catalyzed by Pt/PhBINEPINE

complexes.

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Cycloaddition reactions of activated allenes and alkynes

[3+2] cycloaddition. Phosphines are able to catalyze the

[3+2] cycloaddition of activated alkynes and allenes to suitable

dipolarophiles such as b-substituted a,b-unsaturated enones

and N-tosylimines. The reaction involves addition of the

phosphorus nucleophile to the central carbon atom of the

allene moiety or to the b-carbon of the alkyne as the key step,

followed by reaction of the resulting zwitterionic intermediate I(Scheme 29) with an electron-deficient unsaturated substrate.

The products of the annulation are, respectively, cyclo-

pentenes and 3-pyrrolines which, due to the presence of the

double bond, are prone to further, often highly stereoselective,

derivatization. Two regioisomers A and B are possible, which

arise from a Michael-type addition of the phosphine-adduct I

to the electrophilic partner through its g or a carbon respectively

(Scheme 29).

Synthesis of carbocycles. t-BuBINEPINE 5b catalyzes the

asymmetric [3+2] cycloaddition of ethyl-2,3-butadienoate

with a wide array ofb-substituted a,b-unsaturated enones to

give substituted cyclopentenes (Scheme 30).

51

These products are generated in good ee (7590%) from both

electron-rich and electron-poor chalcone derivatives. In line

with the known reactivity of allenes towards nucleophiles, with

electron rich-substrates (entries 3 and 5, Table 3) the reac-

tion is less efficient and two equivalents of allenes instead of

1.2 are required for the reaction to proceed. The prevailing

regioisomer A shows the opposite regioselectivity compared to

b-unsubstituted a,b-unsaturated enones for which the

prevailing regioisomer is B.51 This protocol can be applied to

trisubstituted olefins thus generating adjacent quaternary and

tertiary stereocentres.

t-BuBINEPINE 5b is as well efficient when 2-aryl-1,1-dicyanoethylenes are used as substrates.52 The corresponding

cyclopentenes are obtained as single regioisomers in high yield

and with over 70% enantioselectivity in most cases (Scheme 31).

Best substrates are olefins with heteroaromatic substituents: with-

in this class, 95% ee was scored when 1,1-dicyano-2(2-N-methyl-

indolyl)ethene was reacted with ethyl-2,3-butadienoate at 0 1C.52

Allenylphosphonates represent another class of substrates

suitable for the construction of carbocycles through t-Bu

BINEPINE5b promoted [3+2] cycloadditon witha,b-unsaturated

esters (Scheme 32).53 Even if the lower reactivity of allenyl-

phosphonates compared to allenic esters requires the application

of more drastic conditions, the expected products are obtained

with very good selectivity and in moderate yield.

53

Synthesis of heterocycles. When arylimines bearing electron-

withdrawing N-substituents are used in place of activated

olefines, the phosphine promoted [3+2] cycloaddition gives

access to functionalized 3-pyrrolines (Scheme 33). In this

process Ph and t-BuBINEPINES5a and 5b were by far more

effective in terms of conversion rates and enantioselectivities

than any other mono- or bidentate chiral inducer of the pool

of P-donors screened.54

The preferred regioisomer arises from electrophilic addition

of the imine to the a-position of the zwitterionic phosphonium

intermediate followed by cyclisation.55 By proper combination

Scheme 29 Reaction pathway of [3+2] cycloaddition promoted by

phosphine catalysts.

Scheme 30 t-BuBINEPINE 5b catalyzed asymmetric [3+2] annula-

tion of ethyl-2,3-butadienoate with b-substituted a,b-unsaturated enones.

Table 3 Selected results obtained in the t-Bu-BINEPINE 5b catalyzedasymmetric [3+2] annulation of ethyl-2,3-butadienoate with b-substituteda,b-unsaturated enones (see Scheme 30)

Entry R R0 Yielda (%) eeb (%) A : Bc

1 C6H5 C6H5 64 88 13 : 12 C6H5 4-ClC6H5 76 82 7 : 13 C6H5 4-OMeC6H5 54 88 42 0 :14 C6H5 2-Thienyl 74 90 6 : 1

5 C5H11 C6H5 39 75 42 0 :1a Yield of isolated A and B. b Enantiomeric excess of A. c Absolute

configuration of B not assigned.

Scheme 31 Asymmetric [3+2] cycloaddition of allenes with dicyano-

ethylenes (absolute configuration of product not assigned).

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of allenic ester, aryl-substituted tosylimines and BINEPINE,

3-pyrrolines can be obtained with ee up to 86%. The best ees

are obtained when the aryl substituent on the imine is either a

phenyl or an electron-rich aryl. High levels of asymmetric

induction (7392% ee), but at the expenses of reactivity, are

obtained by applying t-BuBINEPINE nucleophilic catalyst

5b to the cycloaddition of N-diphenylphosphino (DPP)

arylimines and 2-butynoates. The DPP protecting group offers

the advantage of being more easily removed than the Ts group

from the reaction product.56

3-Pyrrolines can be prepared also from allenylphosphonates

under t-BuBINEPINE catalysis 5b but with modest results

(2545% yield, 5768% ee).53

Synthesis of spirocyclic compounds. Electron-poor allenes

participate in the phosphine-catalyzed [3+2] cycloaddition

with 4-substituted 2,6-bis(benzylidene)cycloesanone 39 to

afford spirocyclic compounds. Upon reaction with an alkyl

allenoate in the presence of either (S,S)-FerroPHANE 41 or

t-BuBINEPINE (S)-5b, the substrate undergoes desymmetri-

zation providing the product 40 via a regio-, diastereo- and

enantioselective process (Scheme 34).57

The product 40 results from the formation of a new CC

bond at the b-olefinic carbon of the substrate and is obtained

as a mixture of two diastereomers. The stereoselectivity obtained

with BINEPINE (S)-5b compares well with those obtained with

FerroPHANE. The latter one, however, is a more efficient

catalyst and promotes higher yields (compare entries 3 and 4,

Table 4) probably in consequence of a higher electron-donating

ability and nucleophilicity.

As evinced from the X-ray structure, the major diastereomer

of 40a comes from the addition of the allenoate syn to the

R2 substituent. Likely, the latter group rests in the equatorial

position of the most stable conformer of the substrate and the

syn approach of the nucleophile minimizes steric interactions

with the axial H-substituent. This might explain the improved

enantioselectivities observed with FerroPHANE when increasing

the steric bulk of the R2 group from Me-, to i-Pr to t-Bu.

The phosphine-mediated [3+2] cycloaddition of alkyl

2,3-butadienoate to 3-alkylideneindolin-2-ones 42 is a valuable

procedure for the highly enantioselective synthesis of 3-spiro-

cyclopentane-2-oxindoles 43 (Scheme 35). This scaffold is

found in several natural alkaloid derivatives and bioactive

compounds.58

The stereochemistry of the quaternary carbon at position

3 is the main synthetic challenge in this reaction and the

Scheme 32 [3+2] cycloaddition of allenylphosphonates with

a,b-unsaturated esters.

Scheme 33 Asymmetric [3+2] cycloaddition of N-tosyl arylimines

with unsaturated esters.

Scheme 34 Synthesis of spirocyclic compound 40 via asymmetric

[3+2] cycloaddition of enones 39.

Table 4 Results obtained in the synthesis of spirocyclic compound 40via asymmetric [3+2] cycloaddition of enones 39 (see Scheme 34)

Entry Cat. Product R1 R2 Yield (%) dr eea (%)

1 (S)-5 b 40 a Et Me 75 85 : 15 822 (S)-5 b 40 b t-Bu Me 20 80 : 20 86

3 (S)-5 b 40 c Et t-Bu 50 495 : 5 924 (S,S)-4 1 40 c Et t-Bu 98 495 : 5 92

a The two catalysts display the same sense of chiral induction.

Scheme 35 Synthesis of spirocyclic compounds 43 via asymmetric

[3+2] cycloaddition of 3-alkylideneindolin-2-ones 42.

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BINEPINE (S)-5b stood out as the most effective catalyst

among all the other chiral P-donors screened in this task. The

low yields obtained with some of the substrates (entries 3, 8, 10,

Table 5) could be improved by the use of FerroPHANE

although at the expense of the enantioselectivity. From the

X-ray absolute configuration of product 43b it is established

that the substrate double bond retains the E-geometry during

the cycloaddition.

[4+2] cycloadditions

Heterocycles. BINEPINE 5b is an effective nucleophilic

catalyst for the synthesis of functionalized piperidine derivatives

through the Kwon [4+2] cycloaddition59 of imines with 2-allyl

substituted 2,3-butadienoate (Scheme 36).60 A range of aryl

imines with either electron-rich (Table 6, entry 2), electron-

poor (Table 6, entries 3 and 4) or ortho-substituted aromatic

groups have been successfully reacted (Table 6, entry 4).

Heteroaryl imines are also suitable substrates for this reac-

tion (Table 6, entries 6 and 7). The desired heterocycles

are obtained in good yield with excellent enantio- and

diastereoselectivity.

[2+2] cycloadditions. t-BuBINEPINE5b has been tested in

the catalytic asymmetric cycloaddition of phenyl ethyl

ketene to dimethyl azodicarboxylate and nitrosobenzene to

generate aza-b-lactams61 and 1,2-oxazetidin-3-ones62 respectively

(Scheme 37). The BINEPINE ligand is able to catalyze this

reaction, but in both cases the product is almost racemic. The

catalyst of choice for this process turned out to be a planar-chiral

ferrocene-based 4-dimethylaminopyridine derivative.

Additions of nucleophiles to the c-position of activated

alkynes and allenes. Phosphines can catalyze the addition of

some carbon, nitrogen and oxygen nucleophiles to the g-position

of 2-butynoates and 2,3-butadienoates.63 On suitable substrates

the formation of the new bond may generate a new stereogenic

centre (Scheme 38). The synthetic utility of these processes may

be impaired by the competitive phosphine-catalyzed isomeri-

zation of the substrates to the corresponding dienones.

C-Nucleophiles. Formation of CC bonds has been achieved

using nitromethane and 1,3-dicarbonyl compounds as C-based

nucleophiles.

Table 5 Selected results obtained in the synthesis of spirocycliccompounds 43 via asymmetric [3+2] cycloaddition of 3-alkylideneindolin-2-ones 42: variations of the olefin substituent R1 (see Scheme 35)

Entry Product R1 Yield (%) 43/44 43 ee (%)

1 43a C6H5 95 49 5 :5 4992 43b 1-naphthyl 98 49 5 :5 499a

3 43c 4-C6H4C6H4 20 (61) 90 : 10 99 (92)4 43d 4-CF3C6H4 62 85 : 15 99

5 43e 4-ClC6H4 80 92 : 8 4996 43f 3-BrC6H4 82 85 : 15 4997 43g 4-MeC6H4 99 88 : 12 4998 43h 2-Furyl 25 (80) 76 : 24 97 (90)9 43i 2-Quinolyl 75 90 : 10 9710 43l CRCC5H11 38 (56) 74 : 26 97 (86)

Values within parentheses refer to the use of FerroPHANE 41 under

otherwise identical reaction conditions.a (1S,5R) configuration according

to X-ray data.

Table 6 Selected results obtained in the t-Bu-BINEPINE 5bpromoted Kwon [4+2] annulation of imines with 2-allyl substituted2,3-butadienoate: scope with respect to the imines (see Scheme 36)

Entry Ar Yielda (%) cis : trans eeb (%)

1 C6H5 93 91 : 9 982 3-MeC6H4 98 93 : 7 983 4-ClC6H4 99 91 : 9 964 2-(NO2)C6H4 98 96 : 4 685 2-Naphthyl 96 93 : 7 996 2-Furyl 98 87 : 13 977 3-Pyridyl 76 91 : 9 97

a Isolated yields. b The ee-value is for the cis diastereomer.

Scheme 36 t-BuBINEPINE 5b promoted Kwon [4+2] annulation

of imines with 2-allyl substituted 2,3-butadienoate.

Scheme 37 Phosphepine catalyzed cycloaddition of phenyl ethyl

ketene to dimethyl azodicarboxylate and nitrosobenzene.

Scheme 38 BINEPINE-catalyzed addition of nucleophiles to theg-position of activated alkynes and allenes.

Scheme 39 Asymmetric g-addition of a nitromethane to allenes catalyzed

by chiral BINEPINES.

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In the addition of nitromethane to a variety of racemic

electron-poor allenes (Scheme 39), the amine-substituted

BINEPINE 8 afforded the best results in terms of enantio-

selectivity among several bis- and monophosphines tested as

catalysts.64 The reactions proceed with good to excellent yields

and stereoselectivities (7397%) under mild conditions. Several

functional groups in the R substituent of the allenamides are

tolerated and in all cases only the E isomer of the product

is observed. Since no kinetic resolution of the starting racemic

allene has been noticed in the course of the reaction, the

stereochemical bias is determined by enantioface selection.

PhBINEPINE5a turned out to be the catalyst of choice for the

asymmetric g-addition of malonate esters to g-substituted 2,3-

allenoate (Scheme 40) and 2,3-allenamides (Weinreb allenamides)

where very high yields (6598%) and enantioselectivities (8595%)

have been achieved.65

The formation of the CC bond is compatible with the

presence of diverse functional groups in the substrate such as

alkynes, halides, ethers, acetals, esters and alkenes (Table 7).

At variance with other phosphine catalyzed enantioselective

g-addition reactions, in this process kinetic resolution of the

allene is observed. From mechanistic investigations a reaction

path where addition of the phosphine catalyst to the substrate

is the turnover-limiting step can be proposed (Scheme 41).

O-Nucleophiles. Chiral tetrahydrofurans and tetrahydropyrans

are accessible from a variety of substrates possessing a hydroxy-

2-alkynoate motif through phosphine-catalyzed intramolecular

g-addition (Scheme 42).66

Substituents a, b or g to the hydroxygroup are tolerated in the reaction thus allowing for structural

diversity. In this transformation, t-Bu and PhBINEPINES

(S)-5b and (S)-5a are ranked the best effective ligands immediately

after the spirophosphocin (S)-45 among a range of mono- and

bisphosphines.

BINEPINE-promoted intramolecular Michael addition

Monophosphines have been exploited by Fu et al. as nucleo-

philic catalysts in the synthesis of diquinanes 50 from properly

functionalized alicyclic substrates through a double-cyclization

process (Scheme 43).67

Following a reactivity manifold discovered by Tomita,68

the synthesis is triggered by the conjugated addition of the

phosphine to the ynone subunit of the substrate to give inter-

mediate 46 (Scheme 43), which by cross-tautomerization turns

into the zwitterionic enolate 47. The latter undergoes intra-

molecular Michael addition to the unsaturated ester subunit to

generate the first ring as in 48. A second intramolecular

addition affords intermediate 49 and eventually, after catalyst

release, the desired diquinane 50. In optimal conditions and

using PBu3 as nucleophile, the products are obtained with

very high diastereoselectivity (dr 4 20: 1). By applying

t-BuBINEPINE 5b, a moderate but encouraging enantio-

selectivity, 60% ee, could be achieved.67 This is the sole

Scheme 40 PhBINEPINE 5a promoted asymmetric g-addition of

malonate esters to g-substituted 2,3-allenoate.

Table 7 Selected results obtained in the Ph-BINEPINE 5a promotedasymmetric g-addition of malonate esters to g-substituted 2,3-allenoate(see Scheme 40)

Entry R1 Yielda (%) ee (%)

1 Me 94 94

2 88 92

3 (CH2)3Cl 91 934 (CH2)4TLPS 78 875 (CH2)4OBn 78 90

6 71 94

7 (CH2)3CO2Me 77 94

8 71 86

a Yield of purified products. Only the E product is observed.

Scheme 41 Possible mechanism for the phosphine catalyzed asymmetric

g-addition of malonate ester to an activated allene.

Scheme 42 Asymmetric g-addition of an oxygenated nucleophile

catalyzed by chiral monophosphines.

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example of the enantioselective version of this reaction which

provides for the elaboration of fused-ring systems featuring

three vicinal stereocentres and one double bond.

Desymmetrization ofmeso-diols. PhBINEPINE5a has been

tested as organocatalyst in the enantiotoposelective mono-

acylation of cis-1,2-cyclohexane-diol and meso-hydrobenzoin

(Scheme 44).

In this transformation BINEPINE5a was a poor inducer and

much less efficient than (2S,5S)-dimethyl-1-phenyl-phospholane

(S,S)-51, which in this reaction gave the best conversion (up to

84%) and selectivity (up to 81% ee), outperforming the chiral

bidentate phosphines used in the screening test.69

Asymmetric phase-transfer catalysts. Quaternary tetraalkyl-

phosphonium salts 52 and 53, prepared by alkylation of the

corresponding phosphepines with butyl bromide, have been

used as phase transfer catalysts to mediate the asymmetricamination of cyclic b-keto esters and b-diketones with di-tert-

butyl azodicarboxylate (Scheme 45). Under optimized conditions,

the expected products have been obtained in quantitative yields

and ee ranging from 73 to 95%.70

Chiral auxiliary. The BINEPINE 5t has been exploited as

the chiral auxiliary to assist the generation of a stereogenic

arsenic centre in the chiral tertiary arsine 54 (Scheme 46).15

The key step in this preparation is the irreversible nucleophilic

addition of n-butyllithium to the corresponding diastereo-

meric phosphepine-stabilized methylphenylarsenium hexafluoro-

phosphate salts (Scheme 46). When the reaction is carried out

Scheme 43 Enantioselective phosphepine-promoted synthesis of

diquinanes 50.

Scheme 44 Enantiotopo-differentiating acylation ofmeso-diolspromoted

by monodentate phosphines.

Scheme 45 Asymmetric phase transfer catalyzed amination of

b-ketoesters.

Scheme 46 BINEPINE-assisted enantioselective synthesis of

As-stereogenic trisubstituted arsine.

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at 95 1C in dichloromethane, the chiral arsine 54 is obtained

with 70% enantioselectivity. The 2-methoxymethyl substituent

in 5t is crucial for a good selectivity to be achieved as with

PhBINEPINE 5a the diastereoselectivity in the complex

formation is only 16%.

Conclusions and outlook

More than fifteen years have passed since the first preparation

of PhBINEPINE 5a was reported in the literature. From that

first report, this fairly simple P-ligand has tremendously

expanded its fields of application which at present comprise

a wide variety of asymmetric reactions covering metal catalyzed,

organocatalyzed, phase transfer catalyzed and stoichiometric

asymmetric processes. The versatility displayed by the parent

ligand is further supported by the size and the diversity of the

library of BINEPINE derivatives built up in recent times and

that is still growing. The number of different asymmetric

processes where BINEPINES have demonstrated their

stereorecognitive efficiency is pretty wide and for this reason

BINEPINE can be considered a multipurpose chiral ligand.

Based on previous results, specific fields of transition metal

catalyzed reactions where the use of BINEPINES can be

recommended are the Rh-catalyzed hydrogenation and transfer

hydrogenation of CC double bond; the Pt-catalyzed cyclo-

addition of 1,6-enynes and the BayerVilliger oxidation of

strained ketones; the Pd-catalyzed allylation of aldehydes by

umpolung of reactivity. Due to the peculiar electronic properties

of these ligands which are characterized by a fairly high electron

density at the P-donor in these reactions BINEPINES are

expected to perform at the highest level of efficiency.

The second area where BINEPINES can be recommended

for their versatility and their efficiency in chiral recognition is

in organocatalysis. Their use as chiral catalysts has led to veryhigh yields/stereoselectivities in several cases, particularly in a

variety of [3+2] and [4+2] cycloaddition reactions, both in

the intra- and inter-molecular fashion. There is little doubt

that these good performances are strictly related to the basicity

of the P-centre that substantially increases the nucleophilicity

of BINEPINES as compared to other monodentate P-donors

derived from binaphthol 1, 2 and 3. We can reasonably expect

that good results will be achieved by the application of these

chiral ligands in similar reactions.

Acknowledgements

EA acknowledges financial support from the Regione Autonomadella Sardegna, L.R. 7 Agosto 2007, n. 7.

Notes and references

1 A. J. Minnaard, B. L. Feringa, L. Lefort and J. G. de Vries, Acc.Chem. Res., 2007, 40, 12671277.

2 M. T. Reetz, G. Mehler, A. Meiswinkel and T. Sell, TetrahedronLett., 2002, 43, 79417493.

3 C. Claver, E. Fernandez, A. Gillon, K. Heslop, D. J. Hyett,A. Martorell, A. G. Orpen and P. G. Pringle, Chem. Commun.,2000, 961962.

4 I. D. Gridnev and T. Imamoto, Chem. Commun., 2009,74477464.

5 M. T. Reetz, Angew. Chem., Int. Ed., 2008, 47, 25562588.

6 S. Gladiali, A. Dore, D. Fabbri, O. De Lucchi and M. Manassero,Tetrahedron: Asymmetry, 1994, 5, 511514.

7 N. Maigrot and J.-P. Mazaleyrat, Synthesis, 1985, 317319.8 K. Tani, L. D. Brown, J. Ahmed, J. A. Ibers, M. Yokota,

A. Nakamura and S. Otsuka, J. Am. Chem. Soc., 1977, 99,78767886.

9 F. Bitterer, O. Herd, M. Ku hnel, O. Stelzer, N. Weferling,W. S. Sheldrick, J. Hahn, S. Nagel and N. Ro sch, Inorg. Chem.,1998, 37, 64086417.

10 K. Junge, G. Oehme, A. Monsees, T. Riermeier, U. Dingerdissenand M. Beller, Tetrahedron Lett., 2002, 43, 49774980.

11 K. Junge, B. Hagemann, S. Enthaler, A. Spannenberg,M. Michalik, G. Oehme, A. Monsees, T. Riermeier andM. Beller, Tetrahedron: Asymmetry, 2004, 15, 26212631.

12 D. Cai, J. F. Payack, D. R. Bender, D. L. Hughes, T. R. Verhoevenand P. J. Reider, Org. Synth., 1999, 76, 611.

13 W. Tang, W. Wang, Y. Chi and X. Zhang, Angew. Chem., Int. Ed.,2003, 42, 35063509.

14 K. Junge, G. Oehme, A. Monsees, T. Riermeier, U. Dingerdissenand M. Beller, J. Organomet. Chem., 2003, 675, 9196.

15 M. L. Coote, E. H. Krenske, K. A. Porter, M. L. Weir,A. C. Willis, X. Zhou and S. B. Wild, Organometallics, 2008, 27,50995107.

16 D. Xiao, Z. Zhang and X. Zhang, Org. Lett., 1999, 1, 16791681.17 D. Xiao and X. Zhang, Angew. Chem., Int. Ed., 2001, 40, 34253428.18 P. Kasa k, K. Mereiter and M. Widhalm, Tetrahedron: Asymmetry,

2005, 16, 34163426.19 S. Enthaler, G. Erre, K. Junge, D. Michalik, A. Spannenberg,

F. Marras, S. Gladiali and M. Beller, Tetrahedron: Asymmetry,2007, 18, 12881298.

20 E. Alberico, S. Karandikar and S. Gladiali, ChemCatChem, 2010,2, 13951398.

21 E. Alberico, I. Nieddu, R. Taras and S. Gladiali, Helv. Chim. Acta,2006, 89, 17161729.

22 A. Caverzan, G. Bianchini, P. Sgarbossa, L. Lefort, S. Gladiali,A. Scarso and G. Strukul, Chem.Eur. J., 2009, 15, 79307939.

23 D. Brissy, M. Skander, H. Jullien, P. Retailleau and A. Marinetti,Org. Lett., 2009, 11, 21372139.

24 C. A. Tolman, Chem. Rev., 1977, 77, 313348.25 G. Erre, S. Enthaler, K. Junge, S. Gladiali and M. Beller, J. Mol.

Catal. A: Chem., 2008, 280, 148155.26 (a) D. A. Allen and B. F. Taylor, J. Chem. Soc., Dalton Trans.,

1982, 5154; (b) J. Holz, O. Zayas, H. Jiao, W. Baumann,

A. Spannenberg, A. Monsees, T. H. Riermeier, J. Almena,R. Kadyrov and A. Bo rner, Chem.Eur. J., 2006, 12, 50015013.

27 D. Heller, H.-J. Drexler, A. Spannenberg, B. Heller, J. You andW. Baumann, Angew. Chem., Int. Ed., 2002, 41, 777780.

28 E. Juaristi and V. Soloshonok, Enantioselective Synthesis ofb-amino acids, 2nd edn, Wiley-Interscience, New Jersey, 2005.

29 S. Enthaler, G. Erre, K. Junge, J. Holz, A. Bo rner, E. Alberico,I. Nieddu, S. Gladiali and M. Beller, Org. Process Res. Dev., 2007,11, 568577.

30 X.-P. Hu and Z. Zheng, Org. Lett., 2005, 7, 419422.31 H.-J. Drexler, J. You, S. Zhang, C. Fischer, W. Baumann,

A. Spannenberg and D. Heller, Org. Process Res. Dev., 2003, 7,355361.

32 T. Satyanarayana, S. Abraham and H. B. Kagan, Angew. Chem.,Int. Ed., 2009, 48, 456494.

33 S. Enthaler, B. Hagemann, K. Junge, G. Erre and M. Beller, Eur.

J. Org. Chem., 2006, 29122917.34 L. Panella, B. L. Feringa, J. G. de Vries and A. J. Minnaard, Org.Lett., 2005, 7, 41774180.

35 (a) W. C. Christopfel and B. D. Vineyard, J. Am. Chem. Soc., 1979,101, 44064408; (b) S. Lange and W. J. Leitner, J. Chem. Soc.,Dalton Trans., 2002, 752758.

36 S. Enthaler, B. Hagemann, S. Bhor, G. Anilkumar, M. K. Tse,B. Bitterlich, K. Junge, G. Erre and M. Beller, Adv. Synth. Catal.,2007, 349, 853860.

37 B. Hagemann, K. Junge, S. Enthaler, M. Michalik, T. Riermeier,A. Monsees and M. Beller, Adv. Synth. Catal., 2005, 347,19781986.

38 E. O chsner, K. Schneiders, K. Junge, M. Beller and P. Wasserscheid,Appl. Catal., A, 2009, 364, 814.

39 E. O chsner, B. Etzold, K. Junge, M. Beller and P. Wasserscheid,Adv. Synth. Catal., 2009, 351, 235245.

View Online


20/20

40 K. Junge, B. Wendt, D. Addis, S. Zhou, S. Das, S. Fleischer andM. Beller, Chem.Eur. J., 2011, 17, 101105.

41 K. Junge, B. Wendt, D. Addis, S. Zhou, S. Das and M. Beller,Chem.Eur. J., 2010, 16, 6873.

42 E. Alberico, S. Gladiali, R. Taras, K. Junge and M. Beller,Tetrahedron: Asymmetry, 2010, 21, 1406.

43 G. Zanoni, S. Gladiali, A. Marchetti, P. Piccinini, I. Tredici andG. Vidari, Angew. Chem., Int. Ed., 2004, 43, 846849.

44 K. Biswas, A. Chapron, T. Cooper, P. K. Fraser, A. Novak,O. Prieto and S. Woodward, Pure Appl. Chem., 2006, 78, 511518.

45 P. Kasa k, V. B. Mereiter and M. Arion, Tetrahedron: Asymmetry,2006, 17, 30843090.

46 (a) A. Alexakis, private communication to S. G; (b) M. VuagnouxdAugustin, S. Kehrli and A. Alexakis, Synlett, 2007, 20572060.

47 L. Charruault, V. Michelet, R. Taras, S. Gladiali and J.-P. Genet,Chem. Commun., 2004, 850851.

48 P. Y. Toullec, C.-M. Chao, Q. Chen, S. Gladiali, J.-P. Genet andV. Michelet, Adv. Synth. Catal., 2008, 250, 24012408.

49 A. Gusso, C. Baccin, F. Pinna and G. Strukul, Organometallics,1994, 13, 34423451.

50 A. Marinetti and A. Voituriez, Synlett, 2010, 174194.51 J. E. Wilson and G. C. Fu, Angew. Chem., Int. Ed., 2006, 45,

14261429.52 M. Schuler, A. Voituriez and A. Marinetti, Tetrahedron: Asymmetry,

2010, 21, 15691573.53 A. Panossian, N. Fleury-Bre geot and A. Marinetti, Eur. J. Org.

Chem., 2008, 38263833.54 N. N. Fleury-Bre geot, L. Jean, P. Retailleau and A. Marinetti,

Tetrahedron, 2007, 63, 1192011927.55 Z. Xu and X. Lu, J. Org. Chem., 1998, 63, 50315041.

56 N. Pinto, N. Fleury-Bre geot and A. Marinetti, Eur. J. Org. Chem.,2009, 146151.

57 N. Pinto, P. Retailleau, A. Voituriez and A. Marinetti, Chem.Commun., 2011, 47, 10151017.

58 A. Voituriez, N. Pinto, M. Neel, P. Retailleau and A. Marinetti,Chem.Eur. J., 2010, 16, 1254112544.

59 X.-F. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc., 2003, 125,47164717.

60 R. P. Wurz and G. C. Fu, J. Am. Chem. Soc., 2005, 127,1223412235.

61 J. M. Berlin and G. C. Fu, Angew. Chem., Int. Ed., 2008, 47,70487050.

62 M. Dochnahl and G. C. Fu, Angew. Chem., Int. Ed., 2009, 48,23912393.

63 This kind of reactivity was described for the first time byTrost: B. M. Li and C.-J. Li, J. Am. Chem. Soc., 1994, 116,31673168.

64 S. W. Smith and G. C. Fu, J. Am. Chem. Soc., 2009, 131,1423114233.

65 R. Sinisi, J. Sun and G. C. Fu, Proc. Natl. Acad. Sci. U. S. A., 2010,107, 2065220654.

66 Y. K. Chung and G. C. Fu, Angew. Chem., Int. Ed., 2009, 48,22252227.

67 J. E. Wilson, J. Sun and G. C. Fu, Angew. Chem., Int. Ed., 2010,49, 161163.

68 H. Kuroda, I. Tomita and T. Endo, Org. Lett., 2003, 5, 129131.

69 E. Vedejs, O. Daugulis and S. T. Diver, J. Org. Chem., 1996, 61,430431.

70 R. He, X. Wang, T. Hashimoto and K. Maruoka, Angew. Chem.,Int. Ed., 2008, 47, 94669468.

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