On the reactivity of i-propylidenetriphenylphosphorane with some α, β-unsaturated esters, -amides and acyl chlorides

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TerrahedronLenerr..Vol. 34. No. 16. PP.2691-2694.1993 RintcdinCre.atBritain

On the Reactivity of LPropylidenetriphenylphosphorane with some a, j34Jnsaturated Esters, -Amides and Acyl Chlorides Alain Krief * and Philippe Dubois 1 Department of chemistry,Facultk Univasitaires Notre-Dame de la Paix. 61 w de BNX~&S, B-5000. Namur (Belgium).

AbstrcKt:IsopmpyIidcnehipbeny~

aIIowa tbc cyclopropanation ofa$-unsahlrated-Yl

in&&g ~&unsaturated cstms.-Iretones,-amidesand -acid~hlk&~. me&y1 chamates

and cinnamoyl ChlCli&S leading t0 CyCbpowl

concomitant

kCtOlM

has btcn

compounds

IIXIZ~~OII OII the carbony

&roup

of

obsavtd.

In the course of a work directed towaxds the synthesis of chrysantbemic e~ters,t-~ we had the occasion to react 1 isopropylidenetriphenylphosphorane

1, generated from the corresponding phosphonium iodide and n-

BuLi, with methyl cmtonate 3p. -hexenoate 2b and -cinnamate k used as models. Whereas the former derivative did not produce a definite product, probably due to a competing enolisation

reaction, the second led

chemoselectively to the corresponding methyl gemdimethyl cyclopropane carboxylate 7b in modemte yield and the later sqrisingly

delivered a mixture of the expected methyl cyclopropane carboxylate 7c beside substantial

amounts of (2,2-dimethyl-3-phenyl)cyclopropyl isopropyl ketone & (Schemes 1.2 entries 3,4). This type of reactivity seems to be general for those u&unsaturated methyl esters bearing an aryl group at the B-site since we observed similar results from the o-methoxy phenyl substituted cinnamate zd (Scheme 2 entries 5)

AI=~WX’~

Al=ph ho-McOPh

26

8C

Ed ’

Scheme 1 These ketones might arise from the wtion

of isopropylidenetriphenylphosphorane

1 (i) on the carbonyl

group Of methyl cinnamates k, 2d prior to their cyclopropanation or (ii) on the carbonyl group of methyl 2-aryl2691

2692

3.%dimethylcylopropane carboxylates 7c, ‘Id just after the cyclopropanation has taken place. We have ruled out the second alternative since we found that isopropyUenetriphenylphosphorane methyl 2-phenyl-3,3dimethyl

1 does not react furtber with

carboxylate 7ceven under forced conditions.

The ester 7c rcquircd for this control experiment cannot be obtained directly from the corresponding methyl cinnamate

kand

the phosphonium

ylide 1 since we have been unable to separate it, by distillation

or

chromatography on Si@, from the cyclopropyl ketone &concomitantly produced. We have however found that this ester can be chemoselectively

produced. after touts-esterification,

from the same ylide and isopropyl

cinnamate 2s whose carbonyl group is mom hit&red than the previous one’s (Scheme 2, entry 6). These results led us to investigate the m&on of isopropylidenetriphenylphosphorane 1 with 4-methyl-lphenyl-penten3-one 3c (Scheme 2, entry 7),a u,~unsaturated N,Ndimethyl amides 4 including the cinnamoyl amide d (Scheme 2, entries g-13). and cinnamoyl chlorides SCand 51 (Scheme 2, entries 14, 15). whose electrophilicity as well as stetic hindrance around the carbonyl group differ from those of the esters described above.

ii 1

Scheme 2

bhy

x

R

Exp&Lnentstm (tquiv.)

Startill8 mateXial

loMe

Me

2oMe R 3 OMe Ph 4 OMe Ph 5 OMe o-Me0Ph 6 OiA Ph I i-R Ph 8 NM9 Me 9 NMe2 R

ta

1 (1.1). THF. -78“C. lh. 2OT, l.Sh

2b

1 (IA), ‘I-I-IF.-78T. Sh, 2OT, 3.5h

Yield % in 7-10 (X)

tracea,7a (OMe) 46%. 7b (OMe)

2c

l(l.1).

THF, 0°C. lh, 2OT. 3.5h

31%. 7c (OMe.): 7%. 8c (i-R)

tc

l(l.3).

THF. 0°C. lh. UPC, 5h

45%. 7c (OIvIc); 21%. 8c (i-R)

2d

l(1.3).

THP, 0°C. lh, 20°C. 12h

33%. 7d (OMe); 12%. 8d (i-R)

2e

l(1.3).

THF, Ooc, lh. 2ooC. 2.4h

70%. 7e(O-i-R)

3c

l(1.2).

T?IP, 0°C. lh. 20°C, 2h

67%. 8c (i-R)

4s

l(l.1).

THF, Ooc, Ih. 20°C, 4h

0%. 9a (NMe2)

THF. 20°C, 6.Sh

4b

l(l.2).

R

4b

l(2). ‘lMP, 2ooC. lh, 7O”C, 3h

Ph

4c

l(1.3).

THP, OOC,lh. 20°C. 3.5h

38%. 9~ (NMe2)

Ph

4c

l(1.3).

THP, 0°C. lh, UPC. 48h

48%.9c(NMg)

20%. 9b (NMez)

10

NMe2

11

NMe2

12

NMez

13

NM9

Ph

4c

l(2.4).

THP. 0°C. lh. 2O“C.4h

14

Cl

Ph

SC

l(2.4).

TI-IP, OT, lh, 20°C. 4h

30%. & ji-R); 63%. 1Oc (C(hie)2+PPh3), I _

15

Cl

pNO2-Ph

Sf

l(2.4).

THF, OT. lh, 20°C. 4h

46%. 81 (i-R); 46%. 101 (C(Me)2+PPh3), I

60%, 9b -2)

67%,9c(NMg)

_

The ketone k reacted efficiently (Scheme 2, entry 7) whereas the amides 4 proved, as expected, much less reactive and required quite drastic conditions for successful cyclopropanation (Scheme 2, entries 9-13). Both

reactions were completely chemoselective leading to an analytically pure authentic sample of (2.2-dimethyL3phenyl)cyclopropyl isopropyl ketone k (Scheme 2, entries 7) and to the cyclopropane carboxamides 9b and k (Scheme 2, entries l&13) in reasonably good yields. Again the crotonic acid derivative 4a did not deliver the corresponding cyclopmpane derivative (Scheme 2, entry 8 compare to entry 1). The case of cinnamoyl chlorides k and Sf (Scheme 2. entries 14 and 15) requited further comments since these compounds do not lead to 2,2dimethyl-3-aryl

cyclopropane carboxylic acid chlorides nor to the

corresponding acids (by hydrolysis) but provided instead a readily separable mixtum of the (2.2dimethyL3phenyl)cyclopropyl

isopropyl

ketones

8c and 81and of (2,2-dimethyl-3-phenyl)cyclopropyl

2-(2-

triphenylphosphino)propyl ketones 1Ocand lof which are expected to be their direct precursors. Treatment of the phosphonium salt ltk with lithium methylate (1.5 equiv.. MeOH, 20°C. 48h). the by-product expected to be formed concomitantly

to (2.2~dimethyl-3-phenyl)cyclopropyl

reaction of isopropylideneniphenylphosphorane

2-(2-triphenylphosphino)pmpyl

ketone 10con

with methyl cinnamate, led to the formation of (2,2dimethyl-3-

phenyl)cyclopropyl isopropyl ketone k suppotting thus the mechanism suggested in the Schm

To our knowledge they are only few reports dealing with the tea&on of phosphonium chlorides or carboxamides and even fewer involve their a$-unsaturated

3.

ylides with acid

analogues.9 The reaction we have

mported on methyl &namate does not seem to be pmcedented.2-7st3 In fact if reactions of phosphonium ylides ‘on the carbonyl group of carboxylic esters or acid chlorides have been from time to time reported? they all deal with ylides bearing at least one hydrogen on the carbanionic center and the resulting bketo phosphonium salts, which possess particularly acidic hydrogens suffer from a metallation reaction rather than from the reaction reported here. Work is now in progress in order to use this novel reaction for the regioselective synthesis of highly substituted enolates.

2694

REFERENCESAND NOTES. Dubois P. Memoire de hence. d@rtement

de chimie, Facultis N.D. de la Paix. 1987, Juin.

Devos. M.J.; Hevesi. L.; Bayet, P.; K&f, A. Tetruhedron Len. 1976.3911. Devos. M.J.; Denis. J.N.; Krief, A. TetrahedronL&t. 1978. 1847. Dwos, M.J.; Krief, A. TetrahedronL.ett.1983, 103. Krief, A.; Dumont, W.; Pasau. P. TetrahedronL&t., l!B& 29. lM9. Kricf, A.; Dumont, W.; Pasau. P.; Lecomte. Ph. Tetrahedron, 1989.45.3039. fief, 8

A.; Surlercaux, D.; Dumont, W.; Paw,

P.; Lecomte, Ph. Pure andApp1. Chem.. 1988,62. 1311.

Proceeding of the XVII IUPAC Conference on NaturalProducts,New Dehli, India, l!ElO. For a reaction involving a phosphonium ylide and an cc&unsaturated ketone: (a) Freeman. J.P. J. Org. Chem. 1966,3I. 538 (b) Krief, A.; Lccomtc. P. Accompanyingpaper.

9

Johnson, A.W. Yiid Chemistry,organic chemistry a series of monographs, 1966, Vo17.

10

Bestmann, H. J.; Seng. F. Angew. Chem. Int. Ed. 1962.1, 116.

11

Grkxo, P.; Finkelhor. R. S. Tetrahedron L&t. 1972.3781.

12

Gritxo. P.; Finkelhor. R. S. Tetrahedron titt. 1974,527.

13

Dauben, G.W.; Kozikowski, A. P. Tetrahedron ht.

(Received in UK 8 February 1993)

1973.3711.