Stereodefined Access to Lactams via Olefin Difunctionalization: Iridium Nitrenoids as a Motif of LUMO-Controlled Dipoles

Reported herein is a general platform
of a stereodefined access
to γ-lactams via Cp*Ir-catalyzed olefin difunctionalization,
where in situ generated Ir-nitrenoid is utilized as a key motif of
1,3-dipoles to enable amido transfer in a syn-selective
manner. Computational studies suggested that the stereodefined process
can be attributed to the proposed working mode of concerted [3 + 2]
cyclization. Frontier molecular orbital (FMO) analysis implied that
a low-lying lowest unoccupied molecular orbital (LUMO) of the Ir-imido
fragment engages in the olefin interaction. Mechanistic understanding
on the nitrene transfer process led us to develop mild catalytic protocols
of stereoselective difunctionalization of alkenyl dioxazolones to
furnish α-(haloalkyl)- or (oxyalkyl)­lactam products which are
of high synthetic and medicinal utility. Product stereochemistry (threo and erythro) was found to be designated
by the olefin geometry (E/Z) of
substrates.