Rhodium-Catalyzed Regio-, Diastereo-, and Enantioselective [2+2+2] Cycloaddition of 1,6-Enynes with Acrylamides

Transition-metal-catalyzed intermolecular [2+2+2] cycloadditions of a,w-diynes or enynes with unsaturated compounds are valuable methods for the synthesis of complex bicyclic molecules in a single step.[1] For example, the transitionmetal- catalyzed [2+2+2] cycloaddition of 1,6-enynes with alkynes enables the facile preparation of densely substituted annulated cyclohexadienes.[2] In 2005, the groups of Evans and Shibata developed asymmetric variants of this reaction that furnish annulated cyclohexadienes with one stereogenic center by using cationic rhodium(I)/chiral bisphosphine complexes as catalysts (Scheme 1).[3, 4] Additionally, it has been reported that the cationic rhodium(I)/chiral bisphosphine complexes catalyze the asymmetric [2+2+2] cycloaddition of 1,6-diynes with electron-deficient alkenes, to also afford annulated cyclohexadienes with one stereogenic center (Scheme 1).[5] However, the transition-metal-catalyzed [2+2+2] cycloadditions involving two alkene units have been largely limited to the intramolecular reactions of dienynes.[6] Only two examples of the transition-metalcatalyzed intermolecular [2+2+2] cycloaddition involving two alkene units have been reported to date.[7, 8] In 1999, Montgomery and co-workers reported the nickel-catalyzed [2+2+2] cycloaddition of 1,6-enynes with enones.[7] In 2010, Ogoshi et al. reported the nickel-catalyzed [2+2+2] cycloaddition of two enones with alkynes.[8] However, these reactions are limited to enone derivatives and their asymmetric variants have not been realized (Scheme 1). On the other hand, our research group has demonstrated that acrylamide derivatives are highly reactive substrates in cationic rhodium(I)/bisphosphine-catalyzed carbon-carbon bond-forming reactions.[9] Herein, we have achieved the unprecedented catalytic asymmetric [2+2+2] cycloaddition of 1,6-enynes with alkenes by using acrylamides as alkenes and a cationic rhodium(I)/(R)-H8-binap complex as the catalyst. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.