TETRAHEDRON LETTERS Pergamon Tetrahedron Letters 40 (1999) 871-874 Copper (I) mediated Highly Diastereoselective Conjugate Addition of Grignard Reagents to functionalised 6-membered ring cycloalkenols. Synthesis of cyclohexanes derivatives substituted on three contiguous atoms. Val~ry Dambrina, Monique Villi~ras a, Jacques Lebretona, Lo'ic Toupetb, Hassen Amric and Jean Villi~rasa*. aLaboratoire de Synth~se Organique, UMR CNRS 6513, Facult6 des Sciences et des Techniques, 2 rue de la Houssini~re, BP 92208 - F44322 Nantes Cedex 03-France. Fax 02 51 12 54 12. bGroupe Mati~re Condens6e et Mat6riaux, URA CNRS 804, Universit6 de Rennes 1, Campus de Beaulieu, F-35042 Rennes, France. CLaboratoire de Chimie Organique, Facult6 des Sciences, Campus Universitaire, 1060 Tunis. Received 21 October 1998; accepted 24 November 1998 Key words : Conjugate Addition ; Michael reactions ; Copper catalysed Grignard reactions ; 2-Silyloxycyclohexene carboxylates; ketene acetals ; 2-Hydroxycyclohexane carboxylates ; Diastereoselectivity. Abstract : Copper catalysed conjugate addition of Grignard reagents to 2-silyloxycyclohexene carboxylates in the presence of an excess chlorotrimethylsilane, leads diastereoselectively to related (anti) (Z) silylketene acetals. Subsequent hydrolysis and desilylation afford 2-hydroxycyclohexane carboxylates in high yields and diastereoselectivities. © 1999 Published by Elsevier Science Ltd. All rights reserved. Conjugate addition of organocopper reagents and related Copper (I) mediated addition of Grignard reagents has proven to be highly effective in promoting C-C bonds formation for many yearsL The ability of such species to realise the 13-alkylation of a,13-unsaturated carbonyl derivatives in a stereoselective way has also been extensively used as a key-step in numerous natural products syntheses and has been widely reviewed 2. We have previously described 3 the conjugate addition of magnesium organocuprates (3.5 eq.) to acyclic alkenols 1, affording 1,4-adducts in high yields without any protection of the alcohol moiety (Scheme 1). f OH i) 3.5 R2CuMgX THF / - 40 °C OH 'N ~" Yield = 66-89 % CO2Et ii) NH4CI / H20 R CO2Et 1 R = Me, n-Bu, kPr, t-Bu, H2C=CH, Ph Scheme 1. Nevertheless, such a method could not be applied to 5-membered and 6-membered ring analogues without exclusive formation 4 of the SN2' reaction type by-products 3 (Scheme 2) probably formed via an addition / 13-elimination process. E-mail : villiera@chimie.univ-nantes.fr 0040-4039/99/$ - see front matter © 1999 Published by Elsevier Science Ltd. All rights reserved. PII: S0040-4039(98)02543-X