Studies on the Enantioselective Kinugasa Reaction: Efficient Synthesis of β-Lactams Catalyzed by N-PINAP/CuX Complexes

Abstract

Catalytic enantioselective Kinugasa reactions between acyclic and, for the first time, cyclic nitrones and terminal alkynes are described herein. A catalytic amount of the readily available PINAP/CuX complexes, generated in situ, efficiently catalyzed the Kinugasa reactions, leading to a series of β-lactams with good enantioselectivities and moderate diastereoselectivities and yields. A broad range of nitrones and terminal alkynes, including the seldom reported alkyl-substituted alkynes, were tolerated under the reaction conditions. Further investigations proved that the PINAP/CuX catalytic system enabled the synthesis of monobactams on the gram scale (without loss of stereoselectivity and yield) and also both enantiomers by the appropriate choice of readily available atropisomeric N-PINAP ligands.

Asymmetric Kinugasa reactions between acyclic and, for the first time, cyclic nitrones and terminal alkynes afforded synthetically useful β-lactams in moderate-to-good yields (up to 70 %) and diastereo- and enantioselectivities. Exchanging CuI for CuOTf or Cu(OTf)₂ allowed β-lactams to be obtained with the opposite configuration at the C-4 stereogenic center by using the same chiral ligand.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1pPXkGc
via IFTTT