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number 124

Contribution

Fascination of metallosalen complexes:

Diverse catalytic performances and high asymmetry-inducing ability

Tsutomu Katsuki

Department of Chemistry, Faculty of Science, Graduate School, Kyushu University

Introduction

Studies on asymmetric reactions using optically activemetallosalen complexes as catalyst have recently beenrapidly increasing. This is attributable to the facts thatvarious derivatives of salen complexes can be easilysynthesized and they exhibit distinctive catalyticperformances. During a recent two-decade period,various metallosalen complexes have been introduced andconspicuous development has been made in thechemistry of “metallosalen complex.” This paper reportson the basic structural features and catalytic performancesof metallosalen complexes, as well as recent developmentsin asymmetric reactions using them as catalyst, focusingon the author’s studies.

1. Synthesis of metallosalen complexes and theirstructural features

Salen ligand [N,N'-bis(salicylidene)ethylenediamine] andits derivatives can be synthesized by the dehydrationcondensation reaction of salicyl aldehydes and ethylene-diamine derivatives. The formation of metallosalencomplex (1) can be achieved by simply mixing the ligandwith a metal ion after its conversion to the corresponding

phenoxide ion derivative or under basic conditions (Scheme1). Most metal ions can form salen complexes, with theexception of alkali, alkaline-earth and some of therare-earth metals. Of these complexes, trivalent chromium,cobalt, and manganese complexes that are widely usedas catalyst are synthesized by aerobic or chemicaloxidation of the corresponding divalent complexes. Sincesynthetic methods for the various 3-substituted or 3,5-disubstituted salicyl aldehydes and for optically activediamines have already been established (some of whichare commercially available), a variety of salen complexeswith different central metals are now easily available.

The important structural features of salen complexes arethe existence therein of an ethylene unit located adjacentto a metal ion and that of the large space between the 3-and 3'- positions. These features allow the reaction fieldaround the metal ion, to be tailored to fit with specificreactions through the introduction of suitable substituentsat the ethylene and the 3- and 3'-positions. Another impor-tant feature of salen complexes is the structural-flexibilitythat is provided by the existence of the ethylene unit. Mostof the salen complexes have an octahedral structure, andin many cases the salen ligand coordinates tetravalentlywith the central ion on the same plane (trans-isomer, 2).Namely, four of the coordinating atoms (N, N, O, O) of theligand occupy equatorial positions and the other ligands(X, Y) bind at the apical positions (Figure 1 ). 1)

OH

N N

HO

R1R1

*= stereogenic center

OH

O

R2 R2

H2N NH2

HO

O+ +

R1 R1

* *

-2H2O

R2 R2

R1= bulky and/or chiral substituent

O

N N

O

R1R1

M

3 3'

R2 R2

MXn

X5 5'

35

* *

1

* *

Scheme 1.

3

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Figure 1.

MN

O

N

O

X

Y

NNM OO

stepped conformation

NNM OO

umbrella conformation

N NMO O

enantiomericX and Y= achiral

X X

diastereomericX or Y= chiral

R

R

R

chiral metallosalen complex(R H)

A B (= ent-A)

A B A B

R

Y Y

2achiral metallosalen complex

(R= H)

C

Although salen ligands coordinate tetravalently on asingle plane, this does not mean that the ligands adoptplanar structures. A five-ring chelate constituted fromethylene diamine and a central ion can adopt a half-chairconformation, an envelope conformation or a slightly dis-torted form of one of these. Consequently, salen complexesadopt a conformation that is either stepped (A and B ), anumbrella (C) or a slightly distorted form of either.1) Thestepped conformation is chiral, but the umbrella is achiral.The substituents introduced at the ethylene unit occupythe stable pseudo-equatorial position and they are gaucheto each other. Thus, the stepped conformation (A) hassome advantage over the conformation (B) in which thesubstituents occupy the pseudo-axial position or theumbrella conformation (C) with an eclipsed relationshipbetween both substituents. This means that the introduc-tion of the substituents not only creates asymmetry at theethylene site, but also makes the salen skeleton chiral.2)

An achiral complex with no substituent (R = H) generallyexists as an equilibrium mixture of two enantiomers [A andB (= ent-A)]. However, if an apical ligand (X or Y) is chiral,the enantiomers (A and B ) become diastereomeric, andtherefore the equilibrium tends towards one or other of theisomers. By leveraging this phenomenon, asymmetricsynthesis using an achiral complex as the catalyst becomespossible.3) In fact, when using achiral manganese(salen)complex (3) as the catalyst in the presence of chiralbipyridine-N,N'-oxide (4), the epoxidation proceeds in ahighly enantioselective manner (Scheme 2 ).4) Thesestudies were the first examples of asymmetric synthesisusing a conformationally controlled achiral metal complexas catalyst. Similar attempts were widely undertakenafterwards.5)

Another major feature of salen complexes is the exist-ence of coordination isomers. As stated above, many ofthe salen ligands primarily adopt a planar-tetravalentcoordination, however, they can adopt cis-coordinationwhere one oxygen atom on the salen ligand shifts to theapical position, when a bidentate additive (X-Y) coordinat-ing with the metal ion is added (Figure 2 ).6) Salencomplexes of metal ions of second and third series suchas Zr, Ru, Hf, etc. sometimes adopt cis-β coordination with-out the existence of a bidentate ligand. Unlike planartetravalent complexes, these cis-β complexes are chiral atthe first coordination sphere of the complex, and thereforepossess a significant advantage in terms of the construc-tion of an asymmetric field. More specifically, a cis-βcomplex can exist as the ∆ or Λ isomer with an enantio-meric relationship in which the central metal ion is chiral.The chirality of this central metal atom is generally deter-mined by asymmetry of the diamine portion. If the designof a ligand that can utilize this feature of a cis-β complexproves to be possible, then the design of a catalytic agentwith higher asymmetry-inducing ability is expected tobecome a reality. In particular, it is believed that a cis-βcomplex could provide an effective reaction field forsubstrates that can take a bidentate coordination or inter-molecular reactions between substrates with a coordinat-ing functional moiety. Although salen complexes are ableto take a conformation in which two oxygen moleculescoordinate at apical positions (cis-α isomer), they arenormally unstable and there are almost no reports on theirapplication to chiral catalytic reactions, and their chemistryis not dealt with in this paper.

Scheme 2.

O2N

AcNH

O O2N

AcNH

O

O

N

O

N

O

Mn+

PF6

t-But-Bu

t-Bu t-BuN+N+

-OO-

CH2Cl2, -20 °C

3 (4 mol%)

82% ee, 65%

43

4 (5 mol%)

PhIO

*

Figure 2.

MN

XO

N

Y

O

MN

X O

N

Y

O

(∆) (Λ)

enantiomeric

cis-β isomer

MN

X Y

N

O

O

cis-α isomer

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2. Asymmetric atom transfer reactions usingsquare planar salen complexes

By reacting with appropriate precursors, the squareplanar salen complexes afford oxenoid, nitrenoid orcarbenoid intermediates that undergo addition reactions toolefins or hetero-atoms or insertion reactions to C-H bonds.

from the diamine side to avoid the 3,5-substituents,11) thisargument does not agree with the results reported lateron.2b) tert-Butyl group is often used as bulky 3 and 3'-sub-stituents, and this leads to favorable results in asymmetricepoxidation. However, in atom-transfer reactions other thanepoxidation, the results are not always favorable.

O MNON

X

P-G=YO MN

ON

X

GP

H

S

PGH

PG

S

G-P

G=O: P= non, Y= IPhG=N: P= R, Y= IPh or N2

G=C: P= R and H, Y= N2

Scheme 3.

For effective and highly-stereoselective atomic transfersto be performed, the following requirements need to befulfilled: i) the selection of central metal atoms that aresuitable for the the oxenoid, nitrenoid or carbenoid forma-tion and ii) the appropriate design of salen ligands that takeinto account the structures of the intermediates. Fujitaet al. reported the asymmetric oxidation of sulfides usingoptically active vanadium(salen) complex (5) as catalyst in1986.7) In 1990, Jacobsen et al.8) and the present authorset al.9) independently reported on asymmetric epoxidationusing manganese complexes (68), 79)), which revealed theusefulness of salen ligands bearing bulky constituents atthe 3-position (Scheme 4 ). These reports led to the initia-tion of active studies on asymmetric oxidation usingmetallosalen complexes. The stereoselectivity of thereactions (taking epoxidation for example) are dependenton the direction from which the oxenoid species (oxospecies in Scheme 3, G = O, P = none) are approached bythe substrate and the orientation of the substrate duringthis process. In other words, high-stereoselectivity can beachieved during the reaction by controlling the direction ofapproach and the orientation. Although controversy stillexists regarding the exact mechanism for controlling thedirection of approach and the orientation, in this report theauthor describes his own hypothesis, which is based onexperimental results. As mentioned earlier in this report, itwas assumed that oxo compounds could adopt the steppedconformation as suggested by the experimental results ofasymmetric epoxidation using achiral salen complexes.3,4)

This assumption is supported by the calculated results.10)

In the case where bulky substituents (R1) exist at the 3,3'-positions, olefins approach the oxo compound along theN-M bond axis near to the downward-bent benzene ring,thereby directing the bulkier substituent (RL) away from thebulky 3- or 3'-substituents (R1) (Figure 3 ).2) The alterna-tive approach pathway along the N-M bond axis is consid-ered to be less effective due to a repulsive interaction withthe upward-bent benzene ring. With a bulky substituent(R2) at the 5-position (complex 811)), an approach from thedirection of the upwardly-bent benzene ring becomes evenless effective, and thus the enantioselectivity of the reac-tions improves (Scheme 4 ).11) Although Jacobsen et al.(who introduced compound (8)) claim that olefins approach

Figure 3.

The authors expected that if the 3,3'-substituents wereconfigured closer to the oxo bond, the orientation of theolefins could be more stringently regulated, resulting inimproved enantioselectivity. Therefore, we constructed anew salen complex (9) bearing 2-phenylnaphthyl groupsas 3,3'-substituents instead of tert-butyl groups.12a) In thiscomplex, the 2-phenyl groups on the naphthyl ring facetoward the oxo-bond, which are then configured in thedesired space. This was later confirmed by X-raystructural analysis.13) Epoxidation using complex (9)provided significantly improved enantioselectivity, asexpected. In the epoxidation of cis-2-substituent and 3-substituent olefins, high enantioselectivity (greater than90% ee) is generally achieved.12) Enantioselectivityduring epoxidation is affected by the characteristics of theapical ligands, and 4-phenylpyridine N-oxide (4-PPNO) isusually added in the reaction (Scheme 4 ). However, dueto the facts that manganese complexes adopt a relativelylittle-stepped conformation and the reactions proceed viaradical intermediates, good selectivity cannot be achievedduring the epoxidation of trans-2-substituent olefins orterminal olefins.12b)

N NO

MnO

R1R1

R2

R2

L

R3R3

O Rs

RL

3'3

5

5'

Rs

RL

Scheme 4.

Recently, we discovered that ruthenium(salen) complex(10) served as an efficient catalyst for the epoxidation ofolefins, and high-enantioselectivity was achieved, irrespec-tive of the substitution pattern of the olefins (Scheme 5 ).14)

Complex (10) adopted a distorted stepped conformation,

N

O

N

O

M

X

R1 R1

R3R3

5: M= V=O, R1= t-Bu, R2= H, R3,R3= -(CH2)4-, X= non

6: M= Mn+, R1= t-Bu, R2= H, R3= Ph, X= PF6-

7: M= Mn+, R1= CH(Et)Ph, R2= H, R3= Ph, X= PF6-

R2 R2

8: M= Mn, R1,R2= t-Bu, R3,R3= -(CH2)4-, X= Cl

O

NMn

N

OPhPh

(R)

(S)ArAr

OAc

9: Ar= 3,5-(CH3)2C6H4

PhI=O or NaClOO

Mn(salen)

6: 78% ee, 72%8: 86% ee, 67%9: 96% ee, 61%

4-PPNO

4-PPNO= 4-phenylpyridine N-oxide

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so trans-di-substituted or tetra-substituted olefins couldapproach the oxo species.15) These reactions arestereospecific, so cis-epoxides can be obtained from cis-olefins and trans-epoxides from trans-olefins. It is note-worthy that photo-radiation activates complex (10) toexhibit catalytic performance for asymmetric epoxidation.In short, complex (10) is coordinatively-saturated andcatalytically inactive; however, photo-irradiation promotesthe dissociation of the nitrosyl groups and makes itcoordinatively-unsaturated and catalytically active.

substituent on the nitrogen atom, and its orientation has agreat influence on the asymmetric environment of thereaction site. This affects on the orientation of the approach-ing substrates. Therefore, rapid application of complex (11)that is a good catalyst for hydroxylation, to aziridinationcannot lead to sufficient selectivity. However, complex (12)designed by taking into consideration that the orientationof the p-toluenesulfonyl group can achieve high-enantioselectivity in the aziridination of styrene and itsderivatives (Scheme 7 ).17)

Scheme 5.

The oxenoid species (oxo species) catalyze both theepoxidation and hydroxylation of C-H bonds. However,since the appropriate structures of the manganesecomplexes and the reaction conditions used in both reac-tions are different from each other, it was assumed that themechanism for asymmetric induction in both reactions isdifferent. R,R-type complex (11) rather than R,S-type isappropriate to desymmetrization of meso-tetrahydrofuranvia C-H oxidation and the reaction obtains a high-selectivity of 90% ee.16) Unlike the epoxidation reaction,the addition of 4-PPNO results in decreased selectivity.

PhPh

TMPO= tetramethylpyrazine N,N'-dioxide

O

**

82% ee

10, hν, TMPO

r.t.

DCPO= 2,6-dichloropyridine N-oxide

PhPh

O87% ee

O

NRu

N

OPhPh

(R)

(S)

Cl

NO

10

10, hν, DCPO

r.t.

O

N

Ru

N

OCl O

N

Ru

N

OCl O

N

Ru

N

OCl

-NO

hν

NO DCPO Oepoxidation

10

TMPOor

Scheme 6.

Nitrenoids are active species that possess the sameelectronic structure as oxenoids. However, they have a

O

NMn+

N

OPhPh

(R)

(R)

O O

OH

11 (2 mol%), PhIO

-30 °C, C6H5Cl

89% ee

O O

OH

11 (2 mol%), PhIO

-30 °C, C6H5Cl

90% ee

H

H

H

H

PF6

11

Ph Ph

N N

Me Me

O OMn+

12

Ar 12, CH3C6H4SO2N=IPh

rt, 4-PPNO

Ar

NTs

Ar= Ph: 94% ee, 76%Ar= p-ClC6H4: 86% ee, 70%

AcO

Scheme 7.

Recently, Che et al. reported that salen rutheniumcomplexes (13) can effectively catalyze nitrogen transferreactions. Although the yield needs to be improved,significant selectivity in the amination of enols has beenachieved (Scheme 8 ).18) However, since N-(p-toluene-sulfonyl)iminophenyliodinane was used as the nitreneprecursor in these reactions, iodobenzene was generatedas a by-product as the reaction progressed, and atom-economy of the reaction is inefficient. Use of a more atom-efficient precursor is required.

Scheme 8.

The atom economy of nitrene precursors should besignificantly improved if toluenesulfonyl azide could beused, instead of the corresponding phenyliodinanederivative. Jacobsen et al. have reported that Cu-diiminecomplexes catalyze aziridination with TsN3 as the precur-sor. However, the enantioselectivity that was obtained wasinsufficient, besides that UV irradiation was required for

13a (11 mol%)

PhI=NTs, CH2Cl2, r.t.

RuN N

O O

Bu-t t-Bu

83% ee, 68%

NTs*

*

L

LR R

13a: R= NO2, 13b: R= Br

13b (11 mol%)

OSiMe3 O

NHTs

97% ee, 17%

*PhI=NTs, CH2Cl2, r.t.

L= PPh3

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the decomposition of the azide.19) The authors et al. havediscovered that ruthenium(salen) complex (14), which bearsa CO ligand at the apical position, promotes the decompo-sition of azide at room temperature in the presence ofsulfide groups and affords the corresponding sulfimides ina highly enantioselective manner (Scheme 9 ). In additionto N-arylsulfonylazide,20) a carbamoylazide that possessesa bulky and electron-withdrawing alkyl group can be usedas the precursor.21) The aziridination of styrene deriva-tives can also be performed with high-enantioselectivity byusing TsN3 (Scheme 10 ) .22)

Scheme 11.

Diazo-compounds are widely used as precursors forasymmetric cyclopropanation via carbenoid intermediates.Inspired by the epoch-making Aratani’s achievement,various excellent methods for asymmetric cyclopropanationusing copper, rhodium and ruthenium catalysts have beenreported. Most of these reactions are trans-selective.24, 25)

The authors also discovered that cobalt(III)(salen)complex (16) can serve as the catalyst for highly trans-and highly enantio-selective cyclopropanation using a diazoester (Scheme 12 ). Interestingly, the electronic effect ofthe 5-substituent (Y) and the trans-effect of the apical ligand(X) exert a favorable effect on the enantioselectivity of thereaction. On the other hand, since the presence of the3,3'-substituents vitiates the catalysis, it is very likely thatolefins approach the carbenoid intermediate along theO-Co bond axis (Scheme 12 ). 26)

Scheme 9.

O

N N

O

Ru

Ph Ph

PhS

CH3

PhS

CH3

NTs

CO

TsN3

14

14 (2 mol %)

MS 4A, CH2Cl2, r.t.

+

98% ee, 99%

+

PhS

CH3

PhS

CH3

NR

Cl3CC(CH3)OCON3

14 (2 mol %)

MS 4A, CH2Cl2, r.t.

+

95% ee, 93%

+

R= COOC(CH3)2CCl3

Scheme 10.

In a similar way to the oxenoid species, nitrenoidspecies can be inserted into active C-H bonds at benzylicor allylic positions. C-H amination and aziridination canoccur competitively, when the substrates are olefins.However, amination becomes the dominant reaction if acatalyst bearing an electron-withdrawing groups is usedas the catalyst. The use of the suitably brominatedmanganese(sa len) complex (15 ) rea l ized h ighenantioselectivity of 89% ee in C-H amination (Scheme11).23) However, there is a room for improvement in theatom economy, because N-sulfonyliminoiodinane has beenused as the precursor.

Ph 14, TsN3

MS 4A, CH2Cl2, r.t.

Ph

NTs 87% ee, 71%

14, TsN3

MS 4A, CH2Cl2, r.t. NTs 95% ee, 85%

Ph Ph

14, TsN3

MS 4A, CH2Cl2, r.t.

NTs

*

*

92% ee, 25%

Mn+N N

O O

NHTs

Br

BrBr

BrPF6

15, PhI=NTs

MS 4Å, -40 °C, CH2Cl2

15

*

NHTs

77% ee, 67%

89% ee, 71%

15, PhI=NTs

MS 4Å, -40 °C, CH2Cl2

Scheme 12.

On the contrary, ruthenium(salen) complex (17)catalyzes cyclopropanation under photo-irradiation, despitethe existence of substituents at the 3,3'-positions. Thisreaction exhibits high cis-selectivity and high enantio-selectivity (Scheme 13 ).27) This is the first example in whichhigh cis-selectivity was observed in the cyclopropanationof a simple olefin. As described in the chapter on

Ph + N2CHCO2-t-Bu16

CH2Cl2, r.t.

CO2-t-Bu

Ph +

CO2-t-Bu

Ph

trans cis

trans : cis

X= I, Y= t-Bu: 75% ee (95 : 5)

X= Br, Y= t-Bu: 83% ee (94 : 6) 42% ee

X= Br, Y= MeO: 93% ee (96 : 4) 91% ee

O

N N

OCo

X

Ph Ph

Y Y

16

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epoxidation, the ruthenium(salen) complex adopts adistorted-stepped conformation and a large inter-atomicspace exists between the substituents at the 3,3'-positions.The orientation of the olefin passing through the space canbe contro l led, resul t ing in h igh- c is se lect iv i ty.Cobalt(II)(salen) complex (18) bearing the same ligand alsoexhibit a similar catalytic action. Although both 17 and 18show high-cis enantioselectivity, the senses of asymmetricinduction for 18 and 17 are opposite to each other.28) Thissuggests that olefins approach 18 and 17 along differentaccess routes. In reactions using the cobalt(II) complex(18), as with the cobalt(III) complex (16), the substituentsat the 3,3'-positions is considered to hamper the approachof the olefin along the O-Co bond axis. This means thatthe olefin approaches along the N-Co bond axis in thereaction with 18. This direction of approach is impossiblewhen using 16, but the reason for this difference insubstrate-approach is still unclear. On the other hand, thefollowing results support the notion that different accessroutes are used by 18 and 17. When derivatives of 17 and18 (without any chirality at the diamine site) are used ascatalysts for cyclopropanation, the derivative of 17 showssimilar enantioselectivity to 17 but the derivative of 18 doesnot exhibit any enantioselectivity.28b) Furthermore,complex (18) also shows high cis- and high enantio-selectivity even in reactions using commercially-availableethyl diazoacetate as a precursor of carbene.

Intramolecular cyclopropanation of alkenyl diazoacetateis catalyzed with high enantioselectivity by complex 19, amodified complex of 18, while intramolecular cyclo-propanation of alkenyl diazo ketone by using complex 17as catalyst (Scheme 14 ). 29)

As described so far, the stereochemistry of oxenoid,nitrenoid and carbenoid transfer reactions can be highlycontrolled by using properly-designed salen complexes ofsquare planar coordination.

3. Asymmetrical synthesis using cis -β salen

complexes

As described in Section 1, most of the metallosalencomplexes adopt the square planar structure (trans-configuration). However, if a bidentate ligand such asoxalate ions or acetylacetone is coordinated, they will trans-form to the cis-β structure. The cis-β salen complexes showvarious features that cannot be obtained in the squareplanar structure, in addition to the feature whereby thecentral metal is chiral. Some salen complexes (includingtitanium salen complexes) form dimers via µ-oxo bonds(Figure 4 ). In the µ-oxo trans-complexes, the two apicalligands (L1, L2) are distant and the intramolecular reaction

Scheme 13.

+Ph Ph

CO2-R

+ Ph

CO2R

N2CHCO2R

17, R= t-Bu: 2% ee (7 : 93) 98% ee (hν)

N

O

N

O

Ru

PhPh

NO

Cl

17

catalyst

N

O

N

O

Co

PhPh

18

18, R= t-Bu: -% ee (2 : 98) -98% ee (NMI)18, R= Et: -% ee (1 : 99) -99% ee (NMI)

: proposed approach of olefinNMI= N-methylimidazole

O

NCo

N

OMeMe

19

R1= Ph, R2, R3 =H: 97% ee, 67%

O

O

CHN2

R1 R2

OR2

R1

H

R3

O

R1= Ph, R2= Me, R3 =H: 90% ee, 70%

R3

19 (5 mol %)

N-methylimidazoleTHF, r.t.

OH

R3

R217 (5 mol%), hν

THF (5 ml), r.t., 16 h R1

R2R1

R3

CHN2

O R1= Ph, R2, R3 =H: 94% ee, 78%

R1= (CH3)2C=CH(CH2)2, R2= Me, R3 =H: 90% ee, 70%

Scheme 14.

8

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between them is impossible. However, when the ligandsadopt the cis-β structure, the ligands are equatoriallycoordinated and the intramolecular reaction becomespossible. Furthermore, as shown in Figure 2, the cis-βcomplexes are expected to provide excellent reaction sitesfor reactions using bidentate substrates or reagents (X-Y).

trimethylsilyl cyanide, one of the two µ-oxo bond incomplex 20 is cleaved and a µ-oxo complex bearing thealdehyde and the cyanide is generated. Each salen ligandthen adopts the cis-β structure, so the aldehyde andcyanide can take part in an intramolecular reaction. Sinceboth the substrate and agent are coordinated to theoptically active Ti-ions, the reaction progresses with high-enantioselectivity.

Taking into consideration the facts that alkoxideexchange on titanium ion is rapid and that peroxo-hydrogen is a bidentate ligand, the authors assumed thatthe di-µ-oxo complex would be converted into a cis-β peroxoTi complex (21) (Scheme 16 ). In 21, the peroxo-portion isfixed in asymmetric space; therefore, asymmetric oxida-tion using 21 attracted some attention. After the Ticomplex (22) was converted to the corresponding di-µ-oxocomplex (23), subsequent treatment with urea•hydrogenperoxide adduct gave the peroxo-complex that was usedfor various sulfoxidation reactions. It was found that notonly alkyl aryl sulfides, but also dialkyl sulfides and dithianescan be oxidized with high enantioselectivity (Scheme 17 ).31)

In the following study, it was revealed that 21 cannot beobtained directly from the di-µ-oxo complex, but is actuallygenerated via the trans-complex (Scheme 16 ).31b)

MN

O

N

OM

N

O

N

O

MN

O

N

O

O

MO

N

N

O

O

µ-oxo-trans µ-oxo-cis

L1

L1

L2

L2

Figure 4.

In order to exploit the characteristics of cis-β-µ-oxocomplexes, Belokon’ et al. reported highly-enantioselectivetrimethylsilyl cyanation.30) When a Ti salen complex istreated with water in the presence of an amine, it affordsthe di-µ-oxo complex (20), which bears the salen ligandsof cis-β geometry. Upon treatment with aldehyde and

Ti

O

O

N OO

N

Ti

O

NO

NTiN NO O

Cl

Cl

H2O N

OH

N

HO

Bu-t

t-Bu

t-Bu

Bu-t

N N

OH HO

NEt3

Me3SiCN PhCHOTiN

ONNC

O

O

TiOO

NO

N H

Ph

+

CNO

TiN NO O

NC

TiN NO O

NC

O

TiN NO O

NC

TiN NO O

OMe3SiCN

PhNC

NC Ph

OSiMe3

RCHO + Me3SiCN CNR

OSiMe3

R= Ph: 86% ee, R=4-MeOC6H4: 84% ee

20

20

20

Scheme 15.

Ti

O

O

N O

O

N

Ti

O

N

O

N

di-µ-oxo Ti(salen)

21

TiN N

O O

O

O

H2O2

MeOH-d4

MeOH-d4

TiN NO O

OCD3

OCD3

MeOH-d4

H2O2

trans-Ti(salen) complex

Scheme 16.

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O

RL Rs

HOOR

RL Rs

O O

ORH

O RsRL

O

Criegee intermediate

B:

O

RL Rs

OR

O

H :B:

. .

>

O

RL Rs

O

HB:

:

. .

RO

SPh Me urea•H2O2

23S

Ph Me

O

98%ee, 78%

n-C8H17S

Men-C8H17

SMe

O

*

92% ee, 70%

O

N

Ti

N

OPhPh

Cl

Cl

22(R,R)-Ti(salen) 22H2O, NEt3

CH2Cl2, r.t.di-µ-oxo Ti(salen) 23

MeOH, 0 °C, 24h

23 (2 mol%) , UHP (1.0 eq)S S

R

S S

R

* O

99% ee, 91%R= Ph

99% ee, 93%R= Bn

trans /cis

>99 : 1

94 : 6

urea•H2O2

23

Scheme 17.

The Baeyer-Villiger reaction is the most convenientmethod of transforming carbonyl compounds into esters orlactones (Scheme 18 ).

Scheme 18.

The reaction proceeds through the migration of theCriegee intermediate. It is essential for the migration thatthe alkyl group is anti-periplanar to the O-O bond forstereoelectronic reason (σ-σ* interaction). In general, moreramiform alkyl group shows higher nucleophilicity and themore ramiform group (RL) migrates in preference to theless ramiform one (Rs), if the conformation of the O-O bondis not regulated. Therefore, if the conformation is controlledsomehow, it was expected that the less nucleophilic Rsgroup could migrate preferentially. Such examples areknown in enzymatic reactions, and a similar reaction hasbeen reported in the case of asymmetric Baeyer-Villigerreaction,33) although the mechanism is unclear.34) There-fore, if the conformation of the intermediate could be con-trolled by using a catalyst, the catalyst was expected toshow high selectivity comparable to that observed in enzy-matic reactions.

The Criegee intermediate (R = H) that is obtained withhydrogen peroxide as an oxidant is considered to be abidentate ligand; therefore it is expected to form chelatecompounds with cis-β complexes. By properly controllingthe chelate conformation, the stereochemistry of theBaeyer-Villiger reaction could also be controlled. Basedon this idea, the catalytic performances of the trans-cobalt

complex (24) and the cis-β complex 25 were compared.Although both the complexes showed catalytic activity, theformer did not show any enantioselectivity at all; however,the latter showed moderate selectivity (Scheme 19 ) .35,36)

Scheme 19.

Then, we attempted to control the stereochemistry ofthe Baeyer-Villiger reaction by using a catalyst that,despite its original trans-conformation, can form a cis-βchelate upon the coordination of the Criegee intermediatein the reaction. As the result, the reaction using the salenzirconium complex (26) was found to show good selectiv-ity of more than 80% ee (Scheme 20 ).37) More interest-ingly, an investigation of the reactions using racemicketones as the starting materials revealed that the toposselectivity induced by the catalyst was beyond the regularmigratory aptitude of Baeyer-Villiger reactions; oneenantiomer gave a normal-lactone, which was generated

N N

O O

Co

t-Bu Bu-t

t-BuBu-t

SbF6

N N

O O

Co

F F

FF

SbF6

Ph Ocatalyst, H2O2

CH2Cl2, r.t. OPh

O

24

25

24: 20%, 0% ee25: 30%, 57% ee25: 72%, 77% ee (EtOH, -20 °C)

10

number 124

by methine carbon migration, and the other enantiomeryielded an abnormal-lactone generated by methylenecarbon migration (Scheme 21 ).38) This topos selectivity iscomparable to that of enzymatic reaction.

4. Applications to aerobic oxidation

As described in the preceding sections, salen manga-nese and ruthenium complexes are excellent asymmetricoxidation catalysts. However, each reaction requiresstoichiometric chemical oxidants. From the viewpoints ofatom economics and environmental friendliness, thedevelopment of an efficient method for the use of molecu-lar oxygen (particularly air) has been keenly sought.Recently, the authors discovered that salen rutheniumcomplexes are excellent catalysts for aerobic oxidation.

Under irradiation with visible light, ruthenium complex(27) and a racemic secondary alcohol were stirred in air,resulting in the kinetic resolution of the alcohol (Scheme22). The relative reaction rate was 11 − 20. This was thefirst example of oxidative kinetic resolution using oxygen.39)

Although the reaction mechanism is not clear, it wasconsidered to proceed in such a way that the rutheniumion coordinated by an alcohol undergoes single-electronoxidation, generating an alkoxy radical, since opticallyactive binaphthol is obtained from 2-naphthol under thesame conditions (Scheme 23 ). However, it is unclear atthe moment how the single-electron transfer accompaniesproton shift.

N N

O O

Ph Ph

Zr

Y

Y

26

UHP= urea•H2O2R= C6H5: 87% ee, 68%

R= p-MeOC6H4: 84% ee, 43%

R= n-C8H17: 81% ee, 63%

OR

26 (5 mol%), UHP

CH2Cl2, r.t.

94% ee, 99%

O

OO

O

O

R

26 (5 mol%), UHP

CH2Cl2, r.t.

H H

Y= PhO

O

O26, UHP, ClC6H5 r.t.(racemic)

fast isomer

slow isomer

O

OO

O

+

normal lactone ent-abnormal lactone40 : 1

(matching pair)

O

OO

O

+

ent-normal lactone abnormal lactone1 : 35(mis-matching pair)

RuN N

O OPhPh

Cl

NO

Ph

OH

27

27, air, hν, r.t.Ph

OH

Ph

O

+kS/kR= 20

65% conversion >99.5% ee

OH

OH

OH

(X 2)

*

65% ee

N N

RuIII

OO

OH

RR

Cl

N N

RuIV

OO

OP

RR

Cl

N N

RuIII

OO

OH

RR

Cl

N N

RuIII

OO

OP

RR

Cl

O2

H2O2

27hν, –NO

R2C=O

R2CHOH

•O2Hor

•O2–

hν

R2CHOH

•O2Hor

•O2–

P= H or non

Scheme 20.

Scheme 21.

Scheme 22.

Scheme 23.

11

number 124

With the thought in mind that oxidation proceeds via thecoordination of an alcohol to ruthenium, it was expectedthat if the diamine portion near to the ions could be madebulkier, then the primary alcohol and the secondaryalcohol would be oxidized individually. In fact, the use ofcomplex (28) (which is derived from 1,2-tetramethylethylenediamine) as a catalyst oxidized the primary alcohol selec-tively (Scheme 24 ).41) In the case of diol, the terminalalcohol is selectively oxidized resulting in lactole.42) Noexcess oxidation to carboxylic acid or lactone was observedin either reaction.

Therefore, by using an optically active ruthenium salencomplex as catalyst, it was expected that the oxidation ofmeso-diol would generate optically active lactol. The asym-metric oxidation of meso-diols has been widely examined,but enzymatic or chemical methods afford optically activelactones as the product. As a result of extensive examina-tion, when complex (29), which has hydroxyl group at theapical position, was used in the oxidation of meso-1,2-di(hydroxymethyl)cyclohexane, enantioselectivity of 80%ee was observed (Scheme 25 ).43) Recently, the scope ofthis oxidation and its mechanism have been examined indetail.

In conclusion

In addition to the catalytic activities described here, themetallosalen complexes show various asymmetric catalyticactivities, including Lewis acid catalysis. Not all of thesecan be described here due to limitations of space. Wewould ask you to refer to reviews45) for further information.

The results presented in this article were achieved dueto the enthusiasm and careful observations made by thosewho are listed in the references as co-workers. I wouldlike to extend my sincere appreciation to all of them.

Appreciation is also due for the financial support grantedby the Ministry of Education, Culture, Sports, Science andTechnology and by CREST, Japan Science and Technol-ogy Agency.

References

1) M. Calligaris, G. Nardin, L. Randaccio, Coord. Chem. Rev.,7, 385 (1972).

2) a) T. Katsuki, Adv. Synth. Catal., 344, 131 (2002); b) T. Kuroki,T. Katsuki, Chem. Lett., 5, 337 (1995).

3) a) T. Hashihayata, Y. Ito, T. Katsuki, Synlett, 1996, 1079; b) T.Hashihayata, Y. Ito, T. Katsuki, Tetrahedron, 53, 9541 (1997).

4) K. Miura, T. Katsuki, Synlett, 1999, 783.5) P. J. Walsh, A. E. Lurain, J. Balsells, Chem. Rev., 103, 3297

(2003).6) a) M. M. Ali, Rev. Inorg. Chem., 16, 315 (1996); b) T. Katsuki,

Chem. Soc. Rev., in press.7) K. Nakajima, M. Kojima, J. Fujita, Chem. Lett., 1986, 1483.8) W. Zhang, J. L. Loebach, S. R. Wilson, E. N. Jacobsen, J.

Am. Chem. Soc., 112, 2801 (1990).9) R. Irie, K. Noda, Y. Ito, N. Matsumoto, T. Katsuki,

Tetrahedron Lett., 31, 7345 (1990).10) a) T. Strassner, K. N. Houk, Org. Lett., 1, 1, 419 (1999); b) H.

Jacobsen, L. Cavallo, Chem. Eur. J., 7, 800 (2001); c) J.El-Bahraoui, O. Wiest, D. Feichtinger, D. A. Plattner, Angew.Chem. Int. Ed. Engl., 40, 2073 (2001).

11) E. N. Jacobsen, W. Zhang, L. C. Muci, J. R. Ecker, L. Deng,J. Am. Chem. Soc., 113, 7063 (1991).

12) a) H. Sasaki, R. Irie, T. Hamada, K. Suzuki, T. Katsuki,Tetrahedron, 50, 11827 (1994); b) T. Katsuki, J. Mol. Cat. A,113, 87 (1996).

13) T. Hashihayata, T. Punniyamurthy, R. Irie, T. Katsuki, M. Akita,Y. Moro-oka, Tetrahedron, 55, 14599 (1999).

14) a) T. Takeda, R. Irie, Y. Shinoda, T. Katsuki, Synlett, 1999,1157; b) K. Nakata, T. Takeda, J. Mihara, T. Hamada, R. Irie,T. Katsuki, Chem. Eur. J., 7, 3776 (2001).

15) T. Takeda, R. Irie, T. Katsuki, Synlett, 1999, 1166.16) A. Miyafuji T. Katsuki, Tetrahedron, 54, 10339 (1998).

OHn O

n OH

n= 1: 81%n= 2: 95%

OH

28, air, hν

ether

OH

OH28, hν, air

d6-benzene, r.t., 12 h

O

O Hquantitative

0%

+

N

O

N

O

Ru

28

Bu-tt-Bu Cl

Bu-t t-Bu

NO

RuN N

O OArAr

OH

NO

29

Ar= p-C6H5C6H4

MeMeOH

OH

29, air, hν

CHCl3, r.t.O

OH

80% ee, 80%

Scheme 24.

Scheme 25.

12

number 124

(Received February, 2006)

TCI’s Metallosalen Complexes

17) H. Nishikori, T. Katsuki, Tetrahedron Lett., 37, 9245 (1996).18) J.-L. Liang, X.-Q. Yu, C.-M. Che, Chem. Commun., 2002, 124.19) Z. Li, R. W. Quan, E. N. Jacobsen, J. Am. Chem. Soc., 117,

5889 (1995).20) M. Murakami, T. Uchida, T. Katsuki, Tetrahedron Lett., 42,

7071 (2001).21) Y. Tamura, T. Uchida, T. Katsuki, Tetrahedron Lett., 44, 3301

(2003).22) K. Omura, M. Murakami, T. Uchida, R. Irie, T. Katsuki, Chem.

Lett., 32, 354 (2003).23) Y. Kohmura, T. Katsuki, Tetrahedron Lett., 42, 3339 (2001).24) a) T. Aratani, Pure & Appl. Chem., 57, 1839 (1985); b) M. P.

Doyle, M. N. Protopopova, Tetrahedron, 54, 7919 (1998); c)H. Nishiyama, H. Matsumoto, S.-B. Park, K. Itoh, J. Am. Chem.Soc., 116, 2223 (1994); d) T. Katsuki, in “ComprehensiveCoordination Chemistry II,” ed. by J. McCleverty, ElsevierScience Ltd., Oxford (2003), Vol. 9, Chapter 9.4, p 207.

25) Aratani et al. reported on the good cis- and enantio-selectiv-ity observed during cyclopropanation of 5,5,5-trichloro-2-methlpene-2-ene (Ref. 24a)

26) T. Fukuda, T. Katsuki, Tetrahedron, 53, 7201 (1997).27) a) T. Uchida, R. Irie, T. Katsuki, Synlett, 1999, 1163; b) T.

Uchida, R. Irie, T. Katsuki, Tetrahedron, 56, 3501 (2000).28) a) T. Niimi, T. Uchida, R. Irie, T. Katsuki, Tetrahedron Lett.,

41, 3647 (2000); b) T. Niimi, T. Uchida, R. Irie, T. Katsuki,Adv. Synth.Catal., 343, 79 (2001).

29) a) T. Uchida, B. Saha, T. Katsuki, Tetrahedron Lett., 42, 2521(2001); b) B. Saha, T. Uchida, T. Katsuki, Tetrahedron:Asymmetry, 14, 823 (2003).

30) a) Y. Belokon’, S. Caveda-Cepas, B. Green, N. Ikonnikov, V.Khrustalev, V. Larichev, M. Moskalenko, M. North, C. Orizu,V. Tararov, M. Tasinazzo, G. Timofeeva, L. Yashkina, J. Am.Chem. Soc., 121, 3968 (1999); b) Y. Belokon’, B. Green, N.Ikonnikov, V. Larichev, B. Lokshin, M. Moskalenko, M. North,C. Orizu, A. Peregudov, G. Timofeeva, Eur. J. Org. Chem.,2000, 2655.

31) a) B. Saito, T. Katsuki, Tetrahedron Lett., 42, 3873 (2001); b)B. Saito, T. Katsuki, Tetrahedron Lett., 42, 8333 (2001); c) T.Tanaka, B. Saito, T. Katsuki, Tetrahedron Lett., 43, 3259(2002).

32) G. R. Krow, Org. React., 43, 251 (1993).33) C. Bolm, O. Beckmann, in “Comprehensive Asymmetric Ca-

talysis,” eds. by E. N. Jacobsen, A. Pfaltz, H. Yamamoto,Springer, Berlin (1999), Vol. II, 803.

34) C. Bolm, G. Schlingloff, Chem. Commun., 1995, 1247.35) T. Uchida, T. Katsuki, Tetrahedron Lett., 42, 6911 (2001).36) Seebach attempted to achieve stereocontrol of the Baeyer-

Villiger reaction based on control of the conformation of theCriegee intermediate at the same time of the author’sexperiment. See M. Aoli, D. Seebach, Helv. Chim. Acta, 84,187 (2001).

37) A. Watanabe, T. Uchida, K. Ito, T. Katsuki, Tetrahedron Lett.,43, 4481 (2002).

38) A. Watanabe, T. Uchida, R. Irie, T. Katsuki, Proc. Natl. Acad.Sci. USA, 101, 5737 (2004).

39) K. Masutani, T. Uchida, R. Irie, T. Katsuki, Tetrahedron Lett.,41, 5119 (2000).

40) R. Irie, K. Masutani, T. Katsuki, Synlett, 2000, 1433.41) A. Miyata, M. Murakami, R. Irie, T. Katsuki, Tetrahedron Lett.,

42, 7067 (2001).42) A. Miyata, M. Furukawa, R. Irie, T. Katsuki, Tetrahedron Lett.,

43, 3481 (2002).43) a) H. Shimizu, K. Nakata, T. Katsuki, Chem. Lett., 2002, 1080;

b) H. Shimizu, T. Katsuki, Chem. Lett., 32, 480 (2003).44) H. Shimizu, S. Onitsuka, H. Egami, T. Katsuki, J. Am. Chem.

Soc. 127, 5396 (2005).45) a) E. N. Jacobsen, Acc. Chem. Res., 33, 421 (2000); b) E. N.

Jacobsen, M. H. Wu, in “Comprehensive Asymmetric Cataly-sis,” eds. by E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Springer,Berlin (1999), Vol. III, 1309.

Introduction of the authors

Tsutomu Katsuki : Professor of Organic Chemistry, Department of Chemistry, Faculty of Science, Graduate School,Kyushu University

Tsutomu Katsuki obtained his M.S. Degree from Kyushu University in 1971 and served as a research associate atKyushu University. He then became a post-doctoral fellow with Professor K.B. Sharpless at Stanford University and atMassachusetts Institute of Technology. He has held the post of Professor at Kyushu University since 1989. He has heldhis current position since 2000. He was awarded the Inoue Science Award in 1996, the Synthetic Organic ChemistryAward in 1998 and the Molecular Chirality Award and the Japanese Society of Chemical Association Award in 2001.

[Specialties] Asymmetric catalysis, synthetic reactions and the synthesis of natural organic compounds.

(1S,2S)-N,N'-Bis[(R)-2-hydroxy-2'-phenyl-1,1'-binaphthyl-3-ylmethylene]-1,2-diphenylethylenediaminatoManganese(III) Acetate 100mg [B2409]

Chloronitrosyl[N,N'-bis(3,5-di-tert-butylsalicylidene)-1,1,2,2-tetramethylethylenediaminato]ruthenium(IV)

100mg [C1944]

AcOO

N N

OMn

PhPh

Ph Ph ORu

N

tBu

tBu

N

O tBu

tBu

Me MeMeMe

Cl

NO

13

number 124

USEFUL SYNTHETIC METHOD for LACTONES

T1593 4-Trifluoromethylbenzoic Anhydride (1) 10g

M1439 2-Methyl-6-nitrobenzoic Anhydride (2) 5g 1g

Recently, Shiina et al. have been reported a new condensation method using dehydrating condensingagents 1 and 2. In the presence of 1 or 2, carboxylic acids react with nearly equimolar amounts of alcoholsor amines to obtain corresponding carboxylic esters or amides in high yields.

1 and 2 perform effectively under Lewis acidic conditions and basic conditions, respectively. There-fore, a wide variety of substrates can be used by choosing 1 and 2.

OH OBn

OH

O

Hf(OTf)4 (20 mol%)

O

O O

F3C CF3

O

O

HO

Cephalosporolide D

H2, Pd/C

98%

O

O

BnO1 (1.1 eq.)

for Acidic Condition

MeCN, reflux (Y. 67%)

TBDPSO OH

OH OBn OO

O

BnO

HOTBDPS

2 (1.3 eq.)

DMAP (6.0 eq.), toluene,r.t., 13 h (Y. 84%)

O

O

HO

H

O OH

Octalactin B

O

O O NO2NO2

Me Mefor Basic Condition

This method also applies to intramolecular reactions. For example, 1 and 2 have been used the synthesisof the lactone moieties of cephalosporolide D and octalactin B, respectively.

1 and 2 are easy to handle, and condensation reactions using these reagents in this simple procedurehave obtained desired products in high yields. 1 and 2 are quite effective as dehydrating condensing agentsin the synthesis of carboxylic esters and amides, especially, when synthesizing lactones and lactams.

References1) Condensation reaction by using 4-trifluoromethylbenzoic anhydride

a) I. Shiina, S. Miyoshi, M. Miyashita, T. Mukaiyama, Chem. Lett., 1994, 515.b) I. Shiina, M. Miyashita, M. Nagai, T. Mukaiyama, Heterocyles, 40, 141 (1995).c) I. Shiina, H. Fujisawa, T. Ishii, Y. Fukuda, Heterocycles, 52, 1105 (2000).d) I. Shiina, Tetrahedron, 60, 1587 (2004).

2) Condensation reaction by using 2-methyl-6-nitrobenzoic anhydridea) I. Shiina, R. Ibuka, M. Kubota, Chem. Lett., 2002, 286.b) J. Tian, N. Yamagiwa, S. Matsunaga, M. Shibasaki, Org. Lett., 5, 3021 (2003).c) I. Shiina, H. Oshiumi, M. Hashizume, Y. Yamai, R. Ibuka, Tetrahedron Lett., 45, 543, (2004).d) I. Shiina, Tetrahedron, 60, 4729 (2004).e) I. Shiina, M. Kubota, H. Oshiumi, M. Hashizume, J. Org. Chem., 69, 1822 (2004).f) I. Shiina, M. Hashizume, Y. Yamai, H. Oshiumi, T. Shimazaki, Y. Takasuna, R. Ibuka, Chem. Eur. J., 11, 6601 (2005).g) Tokyo Kasei Kogyo Co., Ltd, JP Patent 2003-335731.

ReviewI. Shiina, Yuki Gosei Kagaku kyokaishi (J. Synth. Org. Chem., Jpn), 63, 2 (2005).

14

number 124

TNBS & CHLORANIL TEST KIT

To conduct the solid phase synthesis, as simple methods TNBS and Chloranil Test are used to detect freeamino group on the resin after reaction. Using TNBS Test, the primary amino group can be detected, whileChloranil Test can detect the presence of both primary and secondary amino groups. This method is muchsafe and simple detection method of free amino group compared to Kaiser Test which requires toxic sub-stance, potassium cyanide fall under the Poisonous and Deleterious Substances Control Law in Japan.

T2024 TNBS Test Kit [for Detection of Primary Amines] 1kit Picrylsulfonic Acid (ca. 1% in DMF) 10ml x 1 N,N-Diisopropylethylamine (ca. 10% in DMF) 10ml x 1

C1771 Chloranil Test Kit [for Detection of Primary and Secondary Amines] 1kit Chloranil (ca. 2% in DMF) 10ml x 1 Acetaldehyde (ca. 2% in DMF) 10ml x 1

P1447 Picrylsulfonic Acid (ca. 1% in DMF) 10mlD2937 N,N-Diisopropylethylamine (ca. 10% in DMF) 10mlC1770 Chloranil (ca. 2% in DMF) 10mlA1640 Acetaldehyde (ca. 2% in DMF) 10ml

MONODENTATE OPTICALLY ACTIVE PHOSPHINE LIGAND

D2774 (R)-(+)-2-Diphenylphosphino-2'-methoxy-1,1'-binaphthyl (1a)1g 100mg

D2775 (S)-(-)-2-Diphenylphosphino-2'-methoxy-1,1'-binaphthyl (1b)1g 100mg

The optically active monodentate phosphine ligand 1, developed by Hayashi et al., forms opticallyactive metal complex catalysts with transition metals.1) In particular, palladium complexes of 1 are used forthe highly regioselective and highly enantioselective hydrosilylation of olefins. The obtained hydrosilylationproducts 2 are readily transformed into the secondary alcohols 3 by the Tamao oxidation.2) This use of 1 hasfrequently been utilized as a procedure to obtain optically active alcohols from prochiral olefins. Forexample, optically active exo-norbornanol, which is an important raw material for making a variety ofbioactive compounds, can be obtained from norbornene in highyield.3)

References1) Review

T. Hayashi, Acc. Chem. Res., 33, 354 (2000).2) Asymmetric hydrosilylation of 1-alkenes with Pd-MOP catalysts

Y. Uozumi, T. Hayashi, J. Am. Chem. Soc., 113, 9887 (1991).3) Asymmetric functionalization of bicyclic olefins catalyzed by Pd-MOP

Y. Uozumi, S-Y. Lee, T. Hayashi, Tetrahedron Lett., 33, 7185 (1992).

R HSiCl3

H2O2

Entry Yield of 2(%)a %ee of 3

aIsolated yield of 2bIsolated yield(overall from 1-alkene) of 3

Yield of 3 (%)b

1a , [PdCl(π-C3H5)]2

2 3

OMePPh2

R

SiCl3

R

OH n-C4H9n-C6H13n-C10H21

R

123

919790

707075

949595

15

number 124

TLC STAINS

GC and HPLC are commonly used as methods for highly sensitive separation analysis. Novel detectionmethods and high resolution columns have been developed, thereby highly-sensitive and highly-selectiveseparation analysis is now routinely performed. Furthermore, the substances that are being analyzed are ofa wide variety, ranging from such things as trace biological constituents to trace environmental pollutants.GC and HPLC are playing important roles in the advancement of today’s microanalytical technology.

Thin-layer chromatography (TLC) is also an important analytical tool, being used to confirm the progressof reaction, and for evaluation of HPLC separation conditions. Furthermore, the Japanese Pharmacopoeia(JP) has established that the identification tests by TLC must be conducted for many of the naturalmedicine, such as Scutellaria Root, Phellodendron Bark and Rhubarb, etc. As mentioned, TLC is still animportant method of simple separation analysis, which widely used in the many fields.

The Rf-value is a very important piece of data that is provided by TLC. When TLC developmentconditions are same, the Rf-value is characteristic for a substance. Therefore, the Rf-values are often usedfor identification of substances. Additionally, selective detection of compounds is possible by choosingthe appropriate TLC stains. For example, after development of the TLC plate, if one seeks to identify acompound containing an amino group, the TLC plate is treated with ninhydrin solution which stain onlythose compounds with an amino group. There are many types of TLC stains reported and used. To obtainaccurate results, it is important to select the appropriate TLC stains.

The below table indicates typical TLC stains and the corresponding functional groups. Each of themis prepared so that can be used straight away after the TLC development.

Prepared TLC Stains

Prod. #

Detection reagents for TLC, are also available as spray solutions, such as ninhydrin spray solution.Please refer to our catalog.

Prod. Name Treatment Targent Compounds Unit size

A1674p-Anisaldehyde, Ethanol Solution (contains Acetic Acid, H2SO4)

HeatVersatile-type, effective with almostall functional groups, esp. nucleo-philic ones such as phenols, sugars

500ml

P1484 Phosphomolybdic Acid, Ethanol Solution (PMA) Heat Versatile-type, effective with almost

all functional groups 500ml

P1483Potassium Permanganate Solution (contains K2CO3, NaOH)

−−Versatile-type, effective with oxidiz-able functional groups, multiple-bond, alcohols, amines, sulfides,mercaptans

500ml

N0719 Ninhydrin, Ethanol Solution (contains Acetic Acid)

HeatAmines, amino acids, Boc protectedamino groups after deprotectionwhile on the TLC plate

500ml

D29682,4-Dinitrophenylhydrazine, Ethanol Solution (contains H2SO4)

Heat Aldehydes, ketones 500ml

B2401Bromocresol Green (BCG), Ethanol Solution (contains NaOH)

−−Compounds with acidic functionalgroups, carboxylic acids, sulfonicacids, etc.

500ml

C1794Ceric Ammonium Molybdate Solution (CAM) (contains H2SO4)

Heat Effective with almost all functionalgroups 500ml

V0080 Vanillin, Ethanol Solution (contains H2SO4)

Heat Alcohols, phenols 500ml