Synthesis of seven-membered lactones via nickel- and zinc-catalyzed highly regio- and stereoselective cyclization of 2-iodobenzyl alcohols with propiolates

A new class of substituted seven-membered lactones 3 were conveniently synthesized via cylization of o-iodobenzyl alcohol 1 (o-IC6H4CH2OH) with various propiolates 2 (RC≡CCOOMe) in the presence of Ni(dppe)Br2 and Zn powder in acetonitrile at 80 °C. The catalytic reaction is highly regio- and stereoselective affording seven-membered lactones in moderate to good yields. This methodology can be successfully extended to various substituted o-iodobenzyl alcohols. An intermediate 7 was obtained from the reaction of 1a with methyl 2-octynoate (2a) in the presence of Ni(dppe)Br2 and Zn at room temperature. A mechanism involving an unusual E/Z isomerization of the carbon-carbon double bond of 7 prior to lactone formation is proposed to account for the catalytic reaction. Copyright © 2002 American Chemical Society.