Enones enone-alkyne reductive cyclization

Reaction conditions amenable to nickel-catalyzed reductive cyclization of alkynyl enones were ineffective in the intermolecular variant In the course of developing catalytic [3 -l- 2] cycloadditions of alkynes and enals [24], it was discovered that by simply using an enone instead of an enal electrophile, catalytic intermolecular reductive coupling could be achieved in a Ni(COD)2/Bu3P catalyst system using EtsB as a reducing agent in a MeOH/THF (8 1) solvent system (Scheme 8.5) [25). 

In contrast, the mercurial enones (89) (obtained by specific solvomercuration of the corresponding pendant terminal olefins) are isolated, and on treatment with sodium trimethoxyborohydride are reductively cyclized to (90). Alkynes... 

In the hopes of accessing similar molecules that would contain C-6 functionalization, our group explored the cycloisomerization of such alkyne hemiketals as 152.70 Compound 152 was prepared by addition of ethynyltrimethylsilane to 5-0-terf-butyl-diphenylsilyl-2,3-0-isopropylidene-D-ribonolactone (151), followed by desilylation (25% over two steps). Trie thy lamine-mediated cycloisomerization71 provided an oxepinone, compound 153, in 41% yield. 1,2-Reduction of the enone functionality followed by acetylation under standard conditions provided 154 in 56% yield over two steps as a 3 1 ratio of diasteromers (the favored diastereomer is shown in Scheme 24). A small group of oxepines were prepared by this method. Variability in the yield of the cyclization step, which was moderate at best, has prevented this route from being applied more generally for the preparation of oxepines. 

Whereas the preceding processes involving ring openings of cyclopropanes provide useful [3+2] entries to cyclopentanes, the use of simpler substrates in [3+2] cycloadditions is made possible by the development of reductive cycloaddition pathways. Such reactions were initially developed in the context of stoichiometric processes, where metallacycles were prepared by oxidative cyclizations of enones and alkynes, followed by either protonation or alkylation of the nickel 0-enolate functionality. Catalytic protocols involving various intramolecular combinations of 7t-systems include formal [3+2] reductive cycloadditions of bis-enones to form bicyclooctanols (Scheme 3-33), of enones with unsaturated acyl oxazolidinones to form triquinane derivatives, and of enals with alkynes to form bicyclooctenols. ... 

The formal 2 -l- 2-cycloaddition of enones bearing a bulky substituent group at the P-position with alkynes, in the presence of [Ni(cod)2l and tricyclohexylphosphine, yielded substituted cyclobutenes. The mechanism is thought to involve an oxidative cyclization of an enone with the alkyne to give a > -oxyallylnickel intermediate that is converted to the cyclobutene by reductive elimination. ... 

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