Enantioselective Synthesis of 2,2-Disubstituted Tetrahydrofurans: Palladium-Catalyzed [3+2] Cycloadditions of Trimethylenemethane with Ketones


  • We thank the NSF (CHE-1145236) and the NIH (GM 033049) for their generous support of our programs. Additional financial support was provided by the W. S. Johnson Graduate Fellowship (D.A.B.). Palladium salts were a generous gift from Johnson Matthey. We thank Dr. Allen Oliver at the University of Notre Dame for X-ray crystal analyses.


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O rings: An approach to the title compounds has been developed utilizing a cycloaddition of trimethylenemethane with aryl ketones. The products are formed in up to a 96 % yield with 95 % ee. The reaction is catalyzed by palladium in the presence of L1, which possesses a stereogenic phosphorus atom, and only a single epimer at the phosphorus atom yields the active catalyst. Cp=cyclopentadiene, TMS=trimethylsilyl.