Enantioselective Rhodium-Catalyzed Allylic Addition of Pyrazoles to Terminal 1,3-Enynes

Round and round – From 1,3-Enynes to Allenes and beyond. Enynes and pyrazoles are prevalent structural motifs in both natural products and pharmaceuticals. Consequently, methods for the selective functionalization of enynes, as well as the enantioselective incorporation of pyrazoles, are of significant interest. Allylation reactions are very important for target-oriented synthesis since the allyl group provides a versatile platform for all kinds of further transformation. Herein, we report the development of a rhodium-catalyzed allylic addition of pyrazoles to terminal 1,3-enynes, enabled by a rhodium/(R)-Xyl-BINAP catalytic system. The transformation proceeds through a 2-fold catalytic process involving an allene intermediate and delivers the 1,4-diamination products in high yields (up to 94%), with exclusive (Z)-diastereoselectivity and high enantiomeric ratios (up to 99:1 er), and broad functional group tolerance. The present method demonstrates the extension of our group’s established rhodium-catalyzed allylic addition of (pro)nucleophiles to allenes and alkynes towards a twofold allylic functionalization of 1,3-enynes.