Construction of a quaternary stereogenic center by asymmetric hydroformylation: a straightforward method to prepare chiral α-quaternary amino acids

The construction of chiral quaternary carbon stereocenters has been a long-standing challenge in organic chemistry. Particularly, alpha-quaternary amino acids that are of high importance in biochemistry still lack a straightforward synthetic method. We here reported a hydroformylation approach to access chiral quaternary stereogenic centers, which has been a long-standing challenge in transition metal catalysis. alpha,beta-Unsaturated carboxylic acid derivatives undergo hydroformylation with a rhodium catalyst to generate an alpha-quaternary stereocenter under mild conditions. By using this method, a variety of chiral alpha-quaternary amino acids could be synthesized with satisfactory enantioselectivity. In-depth investigation revealed that the regioselectivity is dramatically influenced by the electronic properties of the substituents attached to the target C=C bond. By applying NMR and DFT analyses, the chiral environment of a rhodium/Yanphos complex was depicted, based on which a substrate-catalyst interaction model was proposed.