Intramolecular nucleophilic addition of phenolate to unactivated double and triple bonds. Relative reactivity, regiospecificity, stereochemistry, and mechanism

Abstract

The intramolecular nucleophilic addition of phenolate oxygen to the unactivated triple bond of a series of terminal acetylenes (11) is a two-step process, involving rate-determining formation of a vinyl carbanion. Reaction is almost 10⁴ times faster than the cyclisation of the corresponding alkene (a factor already reduced by the change in mechanism). The cyclisation of the corresponding methyl acetylene (18) is over 10³ times slower, and is general acid-catalysed, presumably because the methyl-substituted vinyl carbanion is a prohibitively high-energy species. It is clear that the much greater reactivity of alkynes, compared with the alkenes, towards nucleophilic attack is primarily a transition-state property, reflecting the greater stability of the sp²(compared with sp³)-hybridised carbanions produced. Antiperiplanar addition is probably involved in all these reactions. There is little difference in intrinsic reactivity between 5-exo, 6-exo, and 6-endo-trig olefin cyclisations, but a stronger preference for the 5-exo over the 6-endo-dig mode for the acetylene reaction.