New oxy-dihydrofuran annulation methodology

Abstract

This work describes mechanistic studies concerning the addition of the dienolate derived from ethyl 2-bromocrotonate 11 to enones and aldehydes to yield vinylcyc1opropanes 12 and 13, and vinyloxiranes 14 respectively. The conditions that affect the generation of the lithium dienolate 16 from croton ate 11 and the dienolate composition have been investigated. The possibility of asymmetric induction using chiral auxiliaries located either at the ester site or at the r- position of 11 was addressed.

A new oxydihydrofuran annulation methodology was developed following the above investigation. The addition of the lithium dienolate generated from ethyl 2-bromo-4-[(tert-butyldimethylsilyl)oxy]-butenoate 105 to aldehydes provided vinyloxiranes of type 127 as single isomers. Vinyloxirane 127 was thermally rearranged to give dihydrofuran 141 as mixture of stereoisomers. Alternatively, 127 was converted to dihyrofuran via a new low temperature rearrangement. This rearrangement proceeded stereoselectively under mild conditions to give a single isomer of dihydrofuran 141 in good to excellent yields. Thus, the addition of the dienolate derived from 105 to aldehydes and the subsequent low temperature rearrangement of the vinyloxirane intermediate constitute a versatile new [2+3] dihydrofuran annulation.