1 research outputs found
Concerted Enantioselective [2+2] Cycloaddition Reaction of Imines Mediated by a Magnesium Catalyst
Enantioselective [2 + 2] cyclization between an imine
and a carbon–carbon
double bond is a versatile strategy to build chiral azetidines. However,
α-branched allenoates have never been successfully applied in
[2 + 2] cyclization reactions with imines, as they always undergo
Kwon’s [4 + 2] annulation in previous catalytic methods. Herein,
a simple in situ generated magnesium catalyst was employed to successfully
achieve the enantioselective [2 + 2] cyclization reaction of DPP-imines
and α-branched allenoates for the first time. Insightful experiments
including KIE experiments, controlled experiments, Hammett plot analysis,
and 31P NMR studies of initial intermediates indicate that
the current [2 + 2] cyclization of imine most likely involves an asynchronous
concerted transition state. Further mechanistic investigations by
combining kinetic studies, ESI experiments, 31P NMR studies
of coordination complexes, and controlled experiments on reaction
rates under different catalyst loading amounts provided the coordination
details for this [2 + 2] cyclization reaction between DPP-imines and
α-branched allenoates. This new approach was applied to the
synthesis of various chiral aza-heterocycles, including the enantioselective
synthesis of the key intermediate of a lipid-lowering agent Ezetimibe