Asymmetric homoaldol reactions with cyclohex-2-enyl N,N-diisopropylcarbamate:: Kinetic resolution, elucidation of the stereochemical course and applications in the synthesis of hexahydroisobenzofuran-4-(1H)-ones

Enantio-enriched cyclohex-2-enyl N,N-diisopropylcarbamate (5) is stereospecifically deprotonated by sec-butyllithium/(-)-sparteine (9) to form the configurationally stable lithium complex 7.9. A kinetic resolution of rac-5 by n-butyllithium/(-)-sparteine (9) yielded (R)-5 with up to 99% ee. Electrophilic substitution with tin electrophiles proceeds in a anti-S-E' fashion as shown by chemical correlations. The synthesized allylstannanes 10 undergo a highly stereospecific TiCl4-mediated homoaldol reaction with various aldehydes, yielding syn-configured homoaldol products 12. These were transferred into all-cis-configured hexahydroisobenzofuran-4(1H)-ones 22 by BF3 center dot OEt2-mediated reactions with aldehydes. The configurations of several products were determined by X-ray structure analysis. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).