Pergamon Tetrahedron Letters, Vol. 38, No. 32, pp. 5631-5634, 1997 © 1997 ElsevierScienceLtd All rights reserved.Printed in Great Britain 0040-4039/97 $17.00 + 0.00 PII: S0040-4039(97)01267-7 High Pressure Induced Mukaiyama Type Aidol Reaction of bis Trimethylsilyl Ketene Acetals Moncef Bellassoued, *a Emmanuelle Reboul, a Franfoise Dumas *b sc Univefsit6 de Paris VI,/.aboramire de Synthtas O~maa~alliqee associd au CNRS, Tour 45; 4, place Jussieu, 75252 Paris Cedex 05, FRANCE b: Cealre d'Etades Phamutceutiques, Universit~ de Paris Sad, ~ de Synth~ Oqcmique, asscci6 au CNRS, 5¢ne J.-B. Ci6nlelit.92296 ChAleamy-Mala&y Cedex. FRANCE Abstract." The Makaiyama type aldel reaction of his trimcthylsilyl ketene acetals 3 was investigated under high pressure conditions. Silyl aldois $ were oblained with a syn stereoselectivity, signifa?antly correlated upon the stedc bulk of R substitnent. In the case of unsaturated bis trimethylsilyl ketene acelal 4, a pressuredependance of the regioselectivity was observed, the desiredlinearadducts g being formed at lower pressure. © 1997 Elsevier Science Ltd. The Mukaiyama aldol reaction of silyl enol ethers I and silyl ketene acetals 2 is recognized as an important reaction in modem synthetic chemistry, normally carried out in the presence of acids or bases as catalyst) The success of this procedure hinges on the fact that the reactions are carried out in such a way that the newly formed aldol is trapped as a neutral silyl compound and is thus protected from wasteful side reactions, particularly from dissociation into the free carbonyl components which could in turn undergo non selective condensation. One of us has established that his trimethylsilyl ketene acetals 3 reacted efficiently and stereoseleetively under these conditions. 2a OTMS OTMS OTMS ° 0 1 2 3 In connection with our work on the total synthesis of refinoids, 3 we were interested in the high pressure induced aldol condensation of bis silyl ketene acetals 4, allowing a rapid assembly of the polyene units of these biomolccules. R R R OTMS Ar~-~,~tY , Ar-CHO + ~OTMS Y = COOTMS, COOH 4 R = H, alkyl Indeed, Yamamoto 4 reported the high pressure activation of such reaction, using silyl enol ethers 1. Three imlxaxant points were observed: (1) the reaction proceeds without catalyst even at room temperature; (2)the a FAX: 01 44 27 30 67 b E-mail: francoise.dumas@cep.u-psud.fr 5631