Journal of Kolecukr Cutatysis, 11 (1981) 119 - 12i 0 E2sevier Sequoia CT_.&, Lausanne - Printed in the Netherlands

119

CATALYTIC ASYMMETREC SYNTHESIS OF CYCLOPRGPANE CARBOXYLATES: LIGAND-REAGENT ENTER_4CI’fONS LN DEAZOACETATE REACT-EONS CATALYSED BY COPPER (11) SPECIES BEARING SUGAR-SCHEFF BASE LIGANDS

DAVID HOLLAND, DALE A. LAFDLEZR

ImpetiZ Chemical Industries Ltd.. Corpomte Laboratory, The Heath. Runcorr?. Cheshire (Gt. Britain)

2nd DAVID J. MILNER

Imperial 6kemfcaZ Industries Ltd., Plant Protection Products Section. Process TecknoZcgy Department, Organics Division, BZackZey, hianckester (Gt. Britairr)

The concept that ligand-reagent interactions might be useful in asym- metric catalysis has been used in designing copper (II) czMy.sti bearing Schiff base ligands derived from naturally occurring sugars. In reactions of etinyl diazoacetate w-itn certt halogerm o!efins, these catalysts have af- forded precursors of photostable pyrethroids rich in the insecticidaJly im- portant LR cyclopropane isomers. Ln one case the cyclopropane cuboxylate product contained 58% of the insecticidally most desirable ck-LR isomer. Less than 15% of this isomer is present in an equihbrium mixture of the carboxylates. The most stereoselective catalysts give the cyclopropane car- boxylates in low yields, about 1070, based on ethyldiazoacetate used.

Introduction

-4 new class of photostable pyrethroid insecticides has been devised by Elliott et al. [l, 21 and extended by Huff [3] _ The readily prepared olefins (E) and (F) (Scheme 1) [4,5] reactwTth ethyl diazoacetate TV eeld cyclo- propane carboxylates which are direct precursors of the new insecticides (J)_

The diazoacetate addition step gives a mixture of four isomeric cycio- propane carboxy2ateq and these isomers are conveniently described [S] as the LR and IS forms, each of which has two geometric isomer% (ck and trarrs). The configuration about the cyclopropane carbon atom (C-I), bearing the carboethoxy group, is crucial for insecticidal activity; both IR isomers are active, the cis being more active than the tram, &de both ‘_S farms are inactive.

Asy-mmetic and geometric control during formation of the cyclopro- pane ring by means of chira.I catalysts, an attractive commercial target, is the

474 -== ~ +Y I

\

(F) (Cl1

(a) X = Y = Cl; (b) X = Cl, Y = CF3, R = CHrCsH40Pb-m or CH(CM)Cs&OPb-m

Schene 1

subject of this paper. Catalyst design was based on the assumption that cyclopropanation ‘Gxvolved a metal-carbene intermediate and that enant.& selectivity might result from a polar interaction between the carbene and a suitable chiral ligand.

Experimental

Chiral F chiff bases were prepared by treatment of either s-&cyMdehyde (Sj z Ijyrzdtie-2carboxakehydc (P) with one of the foEking amino-sugar derivatives (Fig. 1): metinyl 4,6~-benzylidene-2-amino-2~eqxy-a-D-gIuco- pyranoside (I) [a, 81; methyl 4,6+-benzylidene-2-amamino-2+Teo~y~-D-altro- pyranoside (II) (9] ; methyl-2-amino-2~e~~xy_8-D-glucopyMnoside (HI) [IO] and methyl 4,6~-benzylidene-2-amino-Z-deoxy-cr-D-aIlopyranosidc (IT) ET].

Copper (II) complexes of the Scbiff bases were prep& by three methods, A, B and C. which each gave mononuclear corcpiexes having ttio Schiff base ligands per copper ion.

Methods A and B have been described prev=o%!-f [Il. 121. En method C, a solution of Schifi base in methanol was treated with a methanol&z sus- pension of copper (II) bk(salicylaIdehyde). Reparative, an&&icaI and physi- cal details for the catalysb will be described elsewhere [X3] _

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(I) (II)

err) (IV)

Fig. 1. Aminosugar derivatives used in preparing chiral Schiff bases.

Reaction procedure Typically, the catalyst (0.4 mg atom copper) was added to a solution of

‘ihe olefin (60 mmol) in 2 solvent (IO ml) and the mixture was brought te the desired reaction temperature. The reaction ve.ssel and an attached gas burette were flushed with nitrogen and then the system was closed. To the stirred reaction mixture there was added, at a cons’kutt rate, a solution cf ethyl diazoacetate (15 mmol) and olefin (SO mmol) in sokent (IO ml). Suitable solvents inchied 1,2ifichioroethane and toluene. The rate of addi- tion of ethyl diazoacetzte, which was about 0.8 mmol h-' , corresponded to the rate of nitrogen evolution_

Product arz.cysis The amounts of cyclopropane carboxylates fcrmed and the ck/trclns

ratios were determined by GLC (FID) using a 3 m column of 3% silicone OV17 at 13c “C and a 2 m column of 5% carbowax 20M at 120 %. Follow- ing removal of sokznt at the pump, the distribution of the four stereo- isomers was detemined as follows.

(Ha, was isolated by column chromatography on alumina (type HI). Unreacted (Ea) was s-ashed from the column by elution tith pekoIeum ether (40 - 60”) and the (Ha) recovered by elution with diethyl ether. The major byproducts, diethyl fumarate and diethy maieate, remained on the column. The (Ha) was hydroIys&d with ethanok sodium hydroxide and the resuking free .rcid was con-derted into the acid chloride with thiorql chIoride. Reaction of the c-de pro&ct with d-o&an-2-I tEen gave a mixture of four isomers which was analysed by GLC on a 5 m column of 5% LAG2RaG. at

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130 “C. The reliability of the method was demonstrated with (Ha) samples having known ratios of isomers.

This method was unsuitable for anrdysis of (Gb) sampks because the unrmacted (Fb) could not be removed by column chromatography and it

interfered with the hydrolysis. Instead, the residud carhoxylai-e was treated with an equimolar quarztity of tetra-n-butyl titanate and a hunckedfofd excess of d-octan-Z-01 at 150 “C for 3 h. The resulting d-2actvl esters were analysed by GLC. The reliability of this analytical method ~25 confirmed by experiments with (Gb) mixtures of known isomeric composition. The tans- esterification was unaffected by the presence of the chira! copper catalysts both in their initial form and after reaction with ethyl diazoacetate.

The results are shown in ‘Tables 1 and 2.

TABLE ‘1

Catalyzed reactions of (Ea) with ethyl diazoacetate

Catalyst

A.minosugar Aldehyde

Reaction Yield (Ha) isomers

Method of temperature (Ha)= cis IR

preparation W) cis IS frans 1R trans 1s

(W (P) A 53 22 21 19 25 35

(II) (S) C 50 44 20 22 27 3L

$11) w A 50 49 19 L7 34 30

(W 6) C 50 44 22 18 29 31

(IV) (S) B 50 17 24 20 29 27

VW (SI C 50 43 25 18 32 25

eYield = moles cyclopropane carbo~yk~te formed

x 100 rnok nitrogen evolved

I23

TABLE 2

Catiysed reactions of (Fb) with ethyl diazoacetate

Catalyst Reaction Yield a (Gb) isomers

_4mi~O5Ug~ AIdehyde Method of temperature (Gb) ck ZR

preparation WI cis 1s trams 1R trams 1s

(TV) (S) C 80 13 41 17 20 22

(fW (PI A 80 8 58 22.5 23.5

6

(I) 6% B 80 25 30 21 25 24

(1) 69 C 80 lC 33 25 P8

. 24

‘Yield = moles cyclopropane carboxylate formed

x 100 moles nitrogen evolved

Homogeneous copper catalysed reactions of diazoacetates wrth olefims have been claimed to involve metal-carbeno intermediates [X4] . Studies of- asymmetric catalysis can test this claim and may reveal details of the reaction mechanism.

As an aid in designing catalysts, an intermediate metal-cubene, in which carboethoxy carbene wes deemed to donate to the d, orbital of an otherwise approximately planarcoordinated metal atom, was assumed [15] _ Subsequent z-apprcach [IS] of the ofefin was taken to Lead, in a rate limiting step, to the cycIopro$ane. This model has also been proposed for cobalt (IQ catalysts by Ogata [I?] and by Nakamura [IS] _ Nakamura

pointed out that -there was probabiy a low barrier to rotation about the metal-carbene bond, thus giving two preferred conformers in which the car- bene, the meti and a tins paur of coordinating atoms were coplanar. The configuration of the cyclopropane formed wouIc1 depend on which side of the carbene was approached by the olefin (Scheme 2)_

Scheme 2. The envisaged formation of (i) 1R and (ii) 1S cyclopropane carhor;yhte_ The olefk approaches from stove the plane of the paper.

Fig. 2. Chira! copper(H) Schiff complexes.

Aratani and coworkers [I 2, 191 havo used ch&l PrJpper (II) Schiff complexes (Fig. 2(a)) derive6 Porn amino-acids to catalyse the reactions of diazoacetates with 2,5dime: lylhexa-2,4ili?ne_ Chrysanthemic esters were formed with high optical yields but these observaticns <a.rz not easy to inter- pret mechanistically. The presence of a h.vdroxyl group vicinal to the Schiff 11ase nitrogen may have been important. S;~cturally similar cat&y&-s lacking

this feature (Fig. 2(b)) have shown c~nly low opt&J selectivity 1143 _ Alter- natively, the greater selectivity zchieyed by Aratani’s catalysts may have res .;llted from the steric bulk near the chiral centre prosided by the Tao aromatic groups R.

Presumably, the Schif+c bases ir? Aratani’s 1: 1 copper:Schiff base com- plexes acted as tridentate ligands (Fig. 2(c)) 112, 191 . TAe enhanced selec- tivity may then have resulted from the extra rigidi* o;_’ these species. How- ever, Aratani found that 1:2 copper:Schiff base complexes, direct anaIogues of the relatively unsetective catalysts (Fig. 2(b)) and un!ikeEy precztrsors of complexes with trident&e ligands, were &so highly selective catalysts.

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Fig. 3. Pro+xsed intennedkte showing binclrance by the glycosidic methyl grcup to orefin approach from above the plane of the paper.

These observations prompt the possibility that a suitably positioned pokz group may be able to participate in secondary balding during cyclo- propanation. The ikporknce of secondary interactions, between &and and substrate, in enhancing optical yieids during catalytic olefin hydrogenation has been reported [20 - 221. Polar interactions between ligand and reagent may also prove to be useM in asymmetric catalysis.

Thus, a hydrogen bond might result in one strongly preferred confonna- tion of a metal-carbene intermediafe. A suitably positioned substitzzent on the ligvld might then lead to the approach of an oIe!Zn preferentially on one side of the carbene, so affording a cyclopropane enantioselectively. This idea has been tested by using stericafly uncrowded copper (IT) Schiff base com- plexes derived from 2-amin9 glycosides. To provide the proposed hydrogen bond, the ligands had a free hydroxyl group at C-3 of the sugar. To reduce the chance of the Schiff bases acting as *dentate Iigands (cf. Fig. 2(c)) I:1 copper: Schiff base complexes were used.

Previous work with (Ea) gave much lower optical yields than those ob- tied in analogous reactions with 2,5dirnethylhexa-2,4diene 1233 _ With catalysts bearing ligands derived from amino-sugars, (Ea) also reacted with only low enantioselectivity (Table I). Certain trends are discernible, how- ever_ Thus, the direction of optical induction depended primarily on the con- figuration at the sugar carbon carrying the nitrogen atom; formation of the insecticidaily desiraiile IR cyclopropane carboxylates was favoured by the gluco<onfiguration at C-2 of the sugar ligand. This selectivity agree with pr&ictions derived from the reaction model outlined above. Comparison of ca@lysts made from (III] arid (IV) suggests that the degree of optical tiduc_- tion depends on the configtiration at atom C-l and C-3 of the scrgar.

Mole& models of the proposed copper-carbene intermediate, with the suggested hydrogen bead indicate maximum IGndrance to that approach of olefirr leading to IS cyclopropane carboxylate when the heteroatoms at C-I, C-2 a?d C-3 of the 2-aminogtycoside Lie on the same side of the nominal piane of the giycosidk ring (Fig. 3). This arrangement is present-in the Q-

alloside derivative (IV) and catalysts mad& from (IV) were significantiy more selectise t,han those derived from the other amino-sugars +Rsted.

126

Ciene (Eb) was largely unreactive towards ethyl diazoacetate but mono- me (Fb) yieldea (Gb). With the copper (II) complex of Schiff base (IV)-(S), greater enantioselectivity was observed from (Fb) than from (Ea). The higher optical yields observed with (Fb) and 2,5_dimethylhexa-2,4&ene. as com- lIared with (Ea), may illustrate the need ^3r relatively electron rich olefins in e.lantioselective cyclopropanations.

The high selectivitizs obt‘ained using catalysts incorporating the (r- alloside moiety (IV) provide strong evidence both for a copper-carbene intermediate and for the proposed ligand-reagent interaction. It would be of interest to test the theory further by means of catalysts in which the hyL”roxy1 group on C-3 of (IV) was replaced by a group, such as methoxy or metb iyl, unable to hydrogen bond with carboethoxy carbene.

The preferred cr-alloside (IV) required a lengthy synthesis [7] _ The next best amino-sugar derivative tested (I) was readily prepared frcm natural D- giucosamine but it was inarkedly less effective than (IV) (Table 2). The ob- servation that hish enantioselectivity was accompanied by slow reaction, and by low yields of cyclopropane based on nitrogen evolved, further limits the use of the catalysts in synthesis. Moreover, reaction of diazozcetate with the ligand’s free :?ydroxyl group might be expectid to limit the lifetime of cata- lyst. selectiv.ty .

The magnitude of enantioseiection during cyclopropanation was gener- ally much greater with the cis than with the tians isomers. It is not clear why this should be, but a similar effect has been noted before [24, 251 _ Con- versely, Aratani et al. [26] obtained higher optical yields OK trarzs rather than cis chrysar;themates using diazoacetic esters prepared &om bulky alto- hols. This difference may reflecb the greater importznce of steric repu!sion in Aratani’s work and of polar effects in this study. More surprising is the indication (Tables 1 and 2) that the direction of optical induction at C-l of the cyclopropane may be different for the cis than for the @zrrs isomers. This effect is only slight with the amino-sugar catalysts, but it is quite pro- nounced with other catalysts, which will be reported on later.

The high selectivity observed to the insecticidally preferable but ther- modynamically less stable &s-isomer of (Gb), particularly with the copper (II) complex of (IV)-(P), I& striking. Equilibrium for (Gb) is thought to lie near to cidtrans = 25f75.

The idea of ligand-reagent interactions has led to the design of cycio- propanation catalysts displaying the intended enantioselectivity. The concept may prove useful when applied to other reactions, such as epoxidation.

_ catalysed in soiution by transition metal species.

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