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. 2010 Jul 7;132(26):8810-2.
doi: 10.1021/ja103631u.

An enantioselective Claisen rearrangement catalyzed by N-heterocyclic carbenes

Juthanat Kaeobamrung  1 , Jessada Mahatthananchai, Pinguan Zheng, Jeffrey W Bode
Affiliations

An enantioselective Claisen rearrangement catalyzed by N-heterocyclic carbenes

Juthanat Kaeobamrung et al. J Am Chem Soc. .

Abstract

In the presence of a chiral azolium salt (10 mol %), enols and ynals undergo a highly enantioselective annulation reaction to form enantiomerically enriched dihydropyranones via an N-heterocyclic carbene catalyzed variant of the Claisen rearrangement. Unlike other azolium-catalyzed reactions, this process requires no added base to generate the putative NHC-catalyst, and our investigations demonstrate that the counterion of the azolium salt plays a key role in the formation of the catalytically active species. Detailed kinetic studies eliminate a potential 1,4-addition as the mechanistic pathway; the observed rate law and activation parameters are consistent with a Claisen rearrangement as the rate-limiting step. This catalytic system was applied to the synthesis of enantioenriched kojic acid derivatives, a reaction of demonstrated synthetic utility for which other methods for catalytic enantioselective Claisen rearrangements have not provided a satisfactory solution.

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Figures

Figure 1
Figure 1
Possible mechanistic pathways for NHC-catalyzed annulation.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Azolium-catalyzed annulations of ynals via Claisen rearrangements.
See this image and copyright information in PMC

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