Abstract
AbstractAn oxidative NHC‐catalyzed kinetic resolution (KR) of racemic mixtures is presented. The developed reaction furnishes tricyclic dihydropyranones with three contiguous stereocenters in excellent dia‐ and enantioselectivity, with good‐to‐moderate yields. Mechanistic studies indicate that the rate‐determining step of the reaction is the formation of the Breslow intermediate, while the selectivity determining step occurs later in the mechanism. The presented methodology enables rapid synthesis of complex structures in a single step.
Highlights
An oxidative N-heterocyclic carbenes (NHCs)-catalyzed kinetic resolution (KR) of racemic mixtures is presented
A prerequisite for a successful dynamic kinetic resolutions (DKRs) is that the rate of racemization of the substrate is significantly higher than the rate of reaction for the slow reacting isomer
We present a method for the asymmetric synthesis of chroman-substituted dihydropyranones with three contiguous stereocenters by an NHC-catalyzed KR (Scheme 1C)
Summary
An oxidative NHC-catalyzed kinetic resolution (KR) of racemic mixtures is presented. We present a method for the asymmetric synthesis of chroman-substituted dihydropyranones with three contiguous stereocenters by an NHC-catalyzed KR (Scheme 1C). With 1,3-dicarbonyls (Scheme 2), as first reported by Studer and co-workers.[16] Chromane is a privileged scaffold in medicinal chemistry,[17] and several drugs and bioactive natural products contain a tricyclic chromane core as found in 2, for instance nabilone,[18] tetrahydrocannabinol[19] and the ohioensins.[20] α,βDisubstituted enals are known to give dihydropyranones in poor diastereoselectivity,[16] which inspired Xu et al to design a new NHC-catalyst that displayed moderate to good diastereoselectivity.[21] Biju and co-workers have shown that coumarins are an excellent substrate for the synthesis of tricyclic dihydropyranones.[22] there are no reports on the effect of cyclic enals or the presence of an existing stereocenter in the annulation.
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