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. 2017 Jun 1:8:15547.
doi: 10.1038/ncomms15547.

Broad-spectrum kinetic resolution of alcohols enabled by Cu-H-catalysed dehydrogenative coupling with hydrosilanes

Xichang Dong  1 , Andreas Weickgenannt  1 , Martin Oestreich  1
Affiliations

Broad-spectrum kinetic resolution of alcohols enabled by Cu-H-catalysed dehydrogenative coupling with hydrosilanes

Xichang Dong et al. Nat Commun. .

Abstract

The enantioselective silylation of racemic alcohols, where one enantiomer reacts faster than the other, is an alternative approach to established enzymatic and non-enzymatic acylation techniques. The existing art is either limited to structurally biased alcohols or requires elaborate catalysts. Simple substrates, such as benzylic and allylic alcohols, with no coordinating functionality in the proximity of the hydroxy group have been challenging in these kinetic resolutions. We report here the identification of a broadly applicable chiral catalyst for the enantioselective dehydrogenative coupling of alcohols and hydrosilanes with both the chiral ligand and the hydrosilane being commercially available. The efficiency of kinetic resolutions is characterized by the selectivity factor, that is, the ratio of the reaction rates of the fast-reacting over the slow-reacting enantiomer. The selectivity factors achieved with the new method are good for acyclic benzylic alcohols (≤170) and high for synthetically usefully cyclic benzylic (≤40.1) and allylic alcohols (≤159).

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Kinetic resolution of alcohols through silylation.
(a) General equation and known strategies. (b) Representative substrate and reported catalysts. s, selectivity factor.
Figure 2
Figure 2. Catalytic asymmetric Si–O coupling for kinetic resolution of alcohols.
(a) Catalytic cycle of Cu–H catalysis. (b) Silicon-stereogenic hydrosilane and typical donor-functionalized substrate. (c) Enantioselectivity-determining transition states in the various approaches.
Figure 3
Figure 3. Kinetic resolution of benzylic alcohols and an example of a pair of diastereomeric cyclohexanols.
(a) General equation. (b) Acyclic benzylic alcohols. (c) Cyclic benzylic alcohols. (d) Diastereomeric 2-phenylcyclohexan-1-ols.
Figure 4
Figure 4. Kinetic resolution of representative allylic alcohols and an example of an aliphatic secondary alcohol.
(a) General equation. (b) Selected allylic alcohols (Ar=4-anisyl). (c) Cyclic systems with exo- and endocyclic double bonds. (d) 1-Cyclohexylethan-1-ol.
See this image and copyright information in PMC

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