Iridium-Catalyzed Enantioconvergent Borrowing Hydrogen Annulation of Racemic 1,4-Diols with Amines

J Am Chem Soc. 2023 Mar 8;145(9):5007-5016. doi: 10.1021/jacs.2c09958. Epub 2023 Feb 21.

Abstract

We present an enantioconvergent access to chiral N-heterocycles directly from simple racemic diols and primary amines, through a highly economical borrowing hydrogen annulation. The identification of a chiral amine-derived iridacycle catalyst was the key for achieving high efficiency and enantioselectivity in the one-step construction of two C-N bonds. This catalytic method enabled a rapid access to a wide range of diversely substituted enantioenriched pyrrolidines including key precursors to valuable drugs such as aticaprant and MSC 2530818.