Synthesis of -Quaternary Centers at the α-Positions of Cyclohexanones via Copper(I)-Catalyzed Claisen Rearrangement: The Substituent Effect from the Opposing α-Quaternary Center on Diastereoselectivity.

We report the synthesis of -quaternary centers at the α-positions of cyclohexanones. In this chemistry, ionization of an α-hydroxy allyl vinyl ether with Cu(MeCN)4BF4 catalyst at room temperature formed an allyloxy allyl cation that was captured by indole in a regioselective manner to create an α-quaternary center. Upon heating, the Claisen rearrangement occurred to produce a second quaternary center at the opposing α'-position, thereby furnishing the targeted -quaternary center motif. Studies in this article examined the alkyl substituents at the α-carbon and their effect on diastereoselectivity of the Claisen rearrangement. Interestingly, the copper catalyst enhanced the delivery of the allyl group with respect to the indole versus the background diastereoselectivity of the uncatalyzed reaction.