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. 2018 Mar;29(4):433-439.
doi: 10.1055/s-0036-1590951. Epub 2017 Nov 13.

Investigating the Enantiodetermining Step of a Chiral Lewis Base Catalyzed Bromocycloetherification of Privileged Alkenes

Dietrich Böse  1 , Scott E Denmark  1
Affiliations

Investigating the Enantiodetermining Step of a Chiral Lewis Base Catalyzed Bromocycloetherification of Privileged Alkenes

Dietrich Böse et al. Synlett. 2018 Mar.

Abstract

The development of catalytic, enantioselective halofunctionalizations of unactivated alkenes has made significant progress in recent years. However, the identification of generally applicable catalysts for wide range of substrates has yet to be realized. A detailed understanding of the reaction mechanism is essential to guide the formulation of a truly general catalyst. Herein, we present our investigations on the enantiodetermining step of a Lewis base catalyzed bromocycloetherification that provides important insights and design criteria.

Keywords: Lewis base; alkenes; bromiranium ions; bromocycloetherification; halofunctionalization; selenophosphoramides.

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Figures

Scheme 1
Scheme 1
Lewis base catalyzed bromolactonization via bromiranium ion formation
Scheme 2
Scheme 2
Chiral tetrahydrothiophene 8 catalyzed enantioselective bromocyclization of 1,3-diols and racemic bromocycloetherification of simple olefinic alcohol 10a using N-bromosuccinimide (NBS) and chloroacetic acid
Scheme 3
Scheme 3
Proposed mechanistic pathways for an enantioselective bromocycloetherification desymmetrization of olefinic 1,3-diols with a enantiotopic group differentiating hypobromite ii formation as the stereodetermining step (pathway A) and an enantioselective bromiranium ion iii formation as the stereodetermining step (pathway B).
Scheme 4
Scheme 4
Mechanistic probe reaction set up to investigate the enantio determining step of the Lewis base catalyzed bromocycloetherification
Scheme 5
Scheme 5
Mechanistic analysis for an enantioselective bromocycloetherification with stereodetermining bromiranium ion formation (pathway B)
Scheme 6
Scheme 6
Enantioselective bromocycloetherification of gem-dimethyl-containing olefinic alcohols
Scheme 7
Scheme 7
Mechanistic rationale for a suppressed olefin-to-olefin isomerization through a stabilization of the intermediate bromiranium ion by a Lewis base catalyst with an additional coordination side in the catalyst’s structure
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