Stereoselective Synthesis of 4-Alkyl- or 4-Aryl-3-ethoxycarbonyl-2-halo-1,3-dienes from the Reaction of Allenols Having Ethoxycarbonyl Group with Indium Trihalide

Abstract

Ref. 4 Because Diels-Alder reaction represents an extremely versatile tool in organic synthesis, reactions leading to 1,3-diene formation are often key steps in a wide range of organic processes. Especially, 2-halo-1,3-dienes are very important compounds due to the further functionalization of vinyl halide after or before Diels-Alder reaction. A few methods have been developed for the synthesis of 2-halo-1,3-dienes. Backvall et al. described stereoconvergent synthesis of (Z,E)-2-bromo-1, 3-dienes from Pd(II)-catalyzed SN2' reactions of α-allenic acetates. Ma et al. reported SN2'-type addition-elimination reactions of 1-aryl-2,3-allenols with LiX to provide 2-halo1,3-dienes and stereoselective addition-elimination reactions of 3-(methoxycarbonyl)-1,2-allen-4-ols with MX (M: Na, Li, K. X: Cl, Br, I). In addition, Cho et al. developed indium trihalide-mediated SN2' reaction of alkylor aryl-substituted allenols, producing 2-halo-1,3-dienes. Recently, we developed not only the efficient synthetic method of a variety of allenols having ethoxycarbonyl group but also Diels-Alder reaction of 2-azetidinone having 1,3-butadien-2-yl and 1,2,4,5-hexatetraen-3-yl group. During the course of our research program aimed at finding new indium-mediated organic reactions, we became interested in the stereoselective synthesis of 2-halo-1, 3-dienes from allenols having an ethoxycarbonyl group. Herein, we report a stereoselective synthetic method of 3-ethoxycarbonyl-2-halo-1,3-dienes from the reaction of α-hydroxyalkyl allenic esters possessing ethoxycarbonyl group with indium trihalide (Scheme 1). First, reaction of α-hydroxyalkyl allenic esters with a variety of Lewis acids were examined (Table 1). α-Hydroxyalkyl allenic esters were regioselectively obtained from the reaction of various aldehydes with organoindium reagent generated in situ from indium and ethyl 4-bromobutynoate in the presence of LiI in DMF (eq. 1).