Enantioselective Inverse Electron Demand (3 + 2) Cycloaddition of Palladium-Oxyallyl Enabled by a Hydrogen-Bond-Donating Ligand

Cycloaddition reactions between oxyallyl
cations and alkenes are
important transformations for the construction of ring systems. Although
(4 + 3) cycloaddition reactions of oxyallyl cations are well-developed,
(3 + 2) cycloadditions remain rare, and an asymmetric version has
not yet been developed. Moreover, because oxyallyl cations are highly
electrophilic, only electron-rich olefins can be used as cycloaddition
partners. We herein report a method for enantioselective (3 + 2) cycloaddition
reactions between palladium-oxyallyl species and electron-deficient
nitroalkenes. This transformation was enabled by a rationally designed
hydrogen-bond-donating ligand (FeUrPhos) and proceeded via an inverse
electron demand pathway. Using this method, we could assemble cyclopentanones
with up to three contiguous stereocenters with high enantioselectivity
and good to excellent diastereoselectivity.