Three-Carbon Homologation of Diorganozincs with Lithiated Acetylenic Epoxides Aure ́ lien Denichoux, Laurent Debien, Mathieu Cyklinsky, Malika Kaci, Fabrice Chemla,* Franck Ferreira,* and Alejandro Pe ́ rez-Luna Institut Parisien de Chimie Mole ́ culaire, Institut de Chimie Molé culaire (FR 2769), UPMC-Univ Paris 6, UMR CNRS 7201, Case 183, 4 place Jussieu, F-75252 Paris Cedex 05, France * S Supporting Information ABSTRACT: Reaction of dialkylzincs with lithiated acetylenic epoxides is described to give zincates that undergo a 1,2- metallate rearrangement by an anti-S N 2′ pathway. This rearrangement occurs with the transfer of an alkyl or a silyl group affording allenylzinc intermediates. Allenic and/or homopropargylic alcohols are obtained upon hydrolysis. Quenching the reaction mixture with aldehydes or ketones is shown to give access to 2-alkynyl-1,3-diols in a stereoselective manner. ■ INTRODUCTION Allenylmetals are versatile reagents intensively used in organic synthesis. 1 The preparation of allenylmetals (with boron, copper, tin, indium, or zinc as the metal) through the direct S N 2′ substitution reaction of metallic reagents to propargylic substrates bearing a leaving group at the propargylic position is well-documented (Scheme 1, path A). 2 Conversely, little is known on the alternate preparation of allenylmetals by the 1,2- metallate rearrangement of alkynylogous carbenoids of type 1. 3 The overall process leading to allenylmetals 2 involves the initial formation of 1 through metalation at the acetylenic terminus and the subsequent 1,2-migration of the R 3 substituent with displacement of the leaving group through an S N 2′ pathway (Scheme 1, path B). In seminal works, this approach was successfully applied to the preparation of allenylborons from propargylic chlorides, 4 acetates, 4d,5 acetals, 6 or mesylates. 4d An enantioenriched allenylboron could be obtained with a good level of selectivity from an enantiopure chiral propargylic mesylate as the result of the stereoselective transfer of a dimethylphenylsilyl group through an anti-S N 2′ mechanism (Scheme 2). 4d Allenyl aluminums 4c and zirconiums 7 have been analogously obtained from propargylic chlorides, mesylates, or tosylates. Moreover, allenylzincs 3 have been generated by the three- carbon homologation of lithium triorganozincates, a process that involves the intermediate formation of alkynylogous zinco- carbenoids undergoing a 1,2-migration (Scheme 3). 8 Allenylzincs 3 are particularly interesting and have been reacted with several electrophiles to provide allenes 4 (via an S E 2 pathway) 7a or homopropargylic 5 7b as well as propargylic alcohols 6 7c (via an S E 2′ pathway). A related reaction involving an acetylenic epoxide and lithium tributylzincate was described by Marshall in 1994 (Scheme 4). 9,10 However, unlike propargylic mesylates, in this case, the reaction was evidenced to proceed to some extent (ca. 25%) by direct S N 2′ displacement, thus without intermediate formation of an alkynylogous zinco-carbenoid. Deuterated allenic alcohol 8 was indeed obtained (through an S E 2 process) upon quenching of the allenylzinc intermediate 7 with D 2 O with only ca. 75% D-incorporation. Despite this promising preliminary result, no other example of the use of acetylenic epoxides for three-carbon homologation of organozinc reagents has been reported to date. We thus Special Issue: Robert Ireland Memorial Issue Received: September 28, 2012 Published: December 4, 2012 Scheme 1. Three-Carbon Homologation with Propargylic Substrates Scheme 2. Preparation of an Enantioeneriched Allenylboron Article pubs.acs.org/joc © 2012 American Chemical Society 134 dx.doi.org/10.1021/jo302128n | J. Org. Chem. 2013, 78, 134−145