Chiral-at-Iron Catalyst for Highly Enantioselective and Diastereoselective Hetero-Diels-Alder Reaction

Abstract

This study demonstrates that chiral-at-iron complexes, in which all coordinated ligands are achiral and the overall chirality the consequence of a stereogenic iron center, are capable of catalyzing asymmetric transformations with very high enantioselectivities. The catalyst is based on a previously reported design (J. Am. Chem. Soc. 2017, 139, 4322), in which iron(II) is surrounded by two configurationally inert achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbenes in a C2-symmetric fashion and complemented by two labile acetonitriles. By replacing mesityl with more bulky 2,6-diisopropylphenyl substituents at the NHC ligands, the steric hindrance at the catalytic site was increased, thereby providing a markedly improved asymmetric induction. The new chiral-at-iron catalyst was applied to the inverse electron demand hetero-Diels-Alder reaction between β,γ-unsaturated α-ketoester and enol ethers provide 3,4-dihydro-2H-pyrans in high yields with excellent diastereoselectivities (up to 99 : 1 dr) and excellent enantioselectivities (up to 98 % ee). Other electron rich dienophiles are also suitable as demonstrated for a reaction with a vinyl azide.