Pergamon Tetrahedron Letters 41 (2000) 1227–1230 TETRAHEDRON LETTERS Coupling of chiral 1-bromo-1,2-dienes with zinc-based cuprates: a new procedure for the regio and stereoselective synthesis of functionalized acetylenic compounds Anna Maria Caporusso, * Sara Filippi, Federica Barontini and Piero Salvadori Centro di Studio del CNR per le Macromolecole Stereordinate ed Otticamente Attive, Dipartimento di Chimica e Chimica, Industriale dell’Università di Pisa, Via Risorgimento 35, 56126 Pisa, Italy Received 12 October 1999; accepted 3 December 1999 Abstract Zinc alkylcyanocuprates (Knochel reagents) are found to be active in the cross-coupling reaction with allenic bromides affording acetylenic products with a high regio and stereoselective 1,3-anti substitution. The coupling process, which has been successfully extended to functionalized cuprates, can also be performed with alkylzinc chlorides in the presence of catalytic amounts of cuprous salts. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: coupling reactions; copper; copper compounds; allenes; alkynes. Few simple organic molecules are the object of more interest than acetylenes for molecular engineering work in organic and organometallic chemistry. 1 In particular, optically active 1-alkynes are often essential as versatile building blocks for the construction of more complex chiral molecules. 2 In previous papers 3–6 we discussed utilization of enantioenriched 3-substituted and 3,3-disubstituted 1-bromo-1,2-dienes 1 as precursors of chiral 1-alkynes 2, characterized by a tertiary or a quaternary stereogenic center in the α-position to the triple bond, via a cross-coupling reaction with bromocuprates (RCuBr)MgBr . LiBr, obtained in THF from equimolar amounts of Grignard reagents and LiCuBr 2 . The reaction proceeds in a highly 1,3-anti stereoselective fashion, but the regioselectivity appears to be sensitive to steric interactions at the reaction sites, the bulk of the R substituents in the copper species being the dominant factor. The acetylenic compounds 2 can be obtained in good yields (70–98%) independent of the structure of the allenic bromide only employing phenyl 3 or n-alkyl bromocuprates; 6 when tertiary, secondary or α-branched primary copper reagents are used, the competitive formation of allenic derivatives 3 can be favoured (Table 1). 6 We report here new results that emphasize the dramatic improvement of our coupling methodology when cuprates based on organozinc derivatives are used. * Corresponding author. 0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)02249-2 tetl 16177