Issue in Honor of Prof. Arlette Solladie-Cavallo ARKIVOC 2008 (viii) 42-49 ISSN 1551-7012 Page 42 © ARKAT USA, Inc. Stereoselective conjugate addition of organolithium reagents to unprotected 4-hydroxy-2-cyclopentenones Gabriela de la Herrán, Joaquín Plumet, Amaya Segura, Araceli Silverio, and Aurelio G. Csákÿ* Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, 28040-Madrid, Spain E-mail: csaky@quim.ucm.es Dedicated to Professor Arlette Solladié-Cavallo on occasion of her 70th birthday Abstract The stereoselective conjugate addition reaction of organolithium reagents to unprotected 4- hydroxycyclopentenones is reported. The OH group on the substrate is transformed into the corresponding magnesium alkoxide, which has been used to control the regioselectivity of the organolithium addition. Following this procedure, the conjugate addition reaction was obtained instead of the products of direct addition to the carbonyl group usually found in other organolithium additions to similar starting materials. Additionally, the OH group controls the cis- stereochemistry of the final products. Both aspects, regio- and stereoselectivity, can be understood by means of a chelation-controlled addition. Keywords: Cyclopentenones, organolithium reagents, conjugate addition Introduction 4-Hydroxy-2-cyclopentenones and their O-silyl derivatives 1 constitute valuable synthetic intermediates. In particular, their regio- and stereocontrolled transformation into the 4,5- disubstituted 3-hydroxycyclopentanones 2 is a cornerstone in the synthetic approach to prostaglandins and related bioactive compounds. 1 Thus, additions of dialkylcuprates or Grignard reagents in the presence of copper(I) salts to compounds 1 take place in a 1,4-anti fashion with respect to the bulky O-silyl substituent (Scheme 1). Electrophilic capture of the intermediate enolates affords cyclopentanones 2 with a 3,4-trans-4,5-trans stereochemistry in a three- component coupling. Similar findings have been reported for the reaction of O-silyl protected 2- substituted 4-hydroxy-2-cyclopentenones 3 with organocopper reagents. On the other hand, a highly regio- and stereoselective method for the conjugate addition to unprotected 2-substituted 4-hydroxy-2-cyclopentenones 4 has been reported making use of