Base-Mediated Intramolecular Aryne-Ene Cyclization

Significance

Reported is the intramolecular aryne-ene reaction of benzylic ethers and amines bearing aromatic directed metalation groups (DMG, 1). Reaction optimization demonstrated the importance of both reaction mixture concentration (0.024 M) and base choice (LDA) in the suppression of the competing [2,3]-Wittig rearrangement of 1. Olefin substitution was also investigated demonstrating that alkenes bearing ­oxygen (4) and aryl (5) functionality were well tolerated. In addition, both cyclic (6) and homoallylic alkenes (7) proved acceptable substrates. Mechanistic studies demonstrated the necessity of a trans-olefin geometry for product formation, an observation further supported by deuteration experiments.