TETRAHEDRON LETTERS Tetrahedron Letters 43 (2002) 9649–9652 Pergamon An unprecedented outcome of the lithium–ammonia reduction of enones: the formation of cyclopropanols Franc ¸oise Dumas, a Cyrille Thominiaux, a Christine Miet, a Jean d’Angelo, a, * Didier Desmae ¨le, a Mohammed Nour, b Christian Cave ´, b Georges Morgant c and Marie-Elise Tran Huu-Dau d a Unite ´ de Chimie Organique associe ´e au CNRS, Universite ´ Paris -Sud, Centre d’Etudes Pharmaceutiques, 5 rue J.-B. Cle ´ment, 92296 Cha ˆtenay -Malabry, France b Unite ´ de Mole ´cules d’Inte ´re ˆt Biologique, UFR Pharmacie, BP 87900, 21079 Dijon, France c Laboratoire de Cristallochimie Bioinorganique, Universite ´ Paris -Sud, Faculte ´ de Pharmacie, 5 rue J.-B. Cle ´ment, 92296 Cha ˆtenay -Malabry, France d Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France Received 14 October 2002; revised 16 October 2002; accepted 21 October 2002 Abstract—An unusual process takes place during the lithium–ammonia reduction of a variety of cyclic enones bearing an ester group in the -position, furnishing cyclopropanols. The reason for this unprecedented outcome has been attributed to the through-space stabilization of a developing cyclopropyl radical by interaction with the neighboring ester substituent. © 2002 Elsevier Science Ltd. All rights reserved. The lithium–ammonia (L–A) reduction of ,-ethylenic ketones, disclosed by Birch in the early 1950s, has been from the outset recognized as a potent tool in the field of synthetic organic chemistry, leading to its rapid expansion, as evidenced by the abundant documenta- tion devoted to the subject. Perhaps the most attractive feature of this reaction is its remarkable stereochemical outcome. In this respect, in 1964, in a seminal series of structural studies, Stork unraveled the stereochemistry of L–A reduction of a variety of enones that have had considerable impact upon the direction of subsequent synthetic efforts in the area. 1 Of particular significance was the observation that the stereochemical course of L–A reduction of octalones 1, furnishing the trans - fused decalones 3, is determined by the transient angu- lar carbanions 2, adopting the conformation of lowest energy prior to protonation (Scheme 1). 2 In this communication, we report that an unprece- dented process occurs during the L–A reduction of octalone 5, affording the fused cyclopropanol 6. Since it appeared that this unusual outcome might be due to the fact that an angular carbomethoxy group is present in starting material 5, the L–A reductions of related - enones 7 and 9, both bearing in the -position an ester group at a quaternary carbon center, were also exam- ined. In fact these reductions paralleled completely the conversion [56], giving cyclopropanols 8 and 10, respectively, a result in accord with our expectation. In recent synthetic endeavors directed towards the elab- oration of decalin-based scaffolds, 3 the L–A reduction of (±)-octalone 5, prepared by allylic oxidation 4 of alkene 4, 5 was investigated. Much to our surprise, when the reduction of 5 was conducted with 7 equiv. of Li in Scheme 1. Keywords : cyclopropanation; enones; reduction; radical and radical reactions; molecular modeling/mechanics. * Corresponding author. Fax: +33 (01) 46 83 57 52; e-mail: jean.dangelo@cep.u-psud.fr 0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(02)02382-1