Control of skeletal connectivity in indium promoted reactions: 1,2-additions and cope rearrangements en route to lactol formation.

Indium promoted coupling reactions between propargyl aldehydes (3) and allyl halides under aqueous and organic conditions are reported. Coupling reactions under aqueous conditions occur via 1,2-addition with excellent yields to afford 4-hydroxy-1-ene-5-ynes (8). Coupling reactions under organic conditions also add in a 1,2-fashion, but the initial products can be induced to undergo oxy-Cope rearrangements giving 2,5-hexadienals (9). Oxy-Cope rearrangement of 8 followed by a secondary addition step under highly basic conditions leads to lactol formation (10) in good to excellent yields. This paper reveals the versatility and control of product formation which may be attained when working with propargyl aldehyde (3) and allyl halide systems under indium promoted coupling conditions.