Nickel-Catalyzed Three-Component Cycloadditions of Enoates, Alkynes, and Aldehydes.

ABSTRACT: A method for the three-component cycloaddition of enoates, alkynes, and aldehydes has been developed. Building upon previous work by this group in which stoichiometrically generated metallacycles undergo alkylation, we report a catalytic, alkylative [3 + 2] cycloaddition. From simple starting materials, structurally complex cyclopentenones may be rapidly assembled. Computational investigation of the mechanism (?B97X-D3/cc-pVTZ//?B97X/6-31G(d)) identified three energetically feasible pathways. Based on the relative rates of ketene formation compared to isomerization to a seven-membered metallacycle, the most likely mechanism has been determined to occur "ketene-first", with carbocyclization prior to aldol addition. Deuterium labeling studies suggest that formation of the seven-membered metallacycle becomes possible when an ?-substituted enoate is used. This observed change in selectivity is due to the increased difficulty of phenoxide elimination with the inclusion of additional steric bulk of the ?-substituent. The net transformation results in a [3 + 2] cycloaddition accompanied by an alkylation of the enoate substituent.

SUBMITTER: Jenkins AD 

PROVIDER: S-EPMC7167596 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature