Regioselective Hydroaminoalkylation with Silylated Alkenes for β-Amino Acid Synthesis

Catalyst and substrate steric and electronic features that influence regioselectivity in hydroaminoalkylation were leveraged to develop a synthetic approach for the selective synthesis of β-amino acids. An in situ generated tantalum-ureate catalyst was used to prepare 18 γ-silylated amines in up to 93% yield from internal silylated alkenes. β-Amino silane regioisomer production was rarely observed, making this work one of the few examples of highly regioselective hydroaminoalkylation with unsymmetric internal alkenes. These γ-amino silanes were converted to γ-amino alcohols with a modified Tamao-Fleming oxidation strategy followed by two additional steps to prepare β-amino acids, including a key fragment of the anticancer drug candidate Ipatasertib.