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. 2014 Mar 24;53(13):3387-91.
doi: 10.1002/anie.201309982. Epub 2014 Feb 24.

Enantioselective synthesis of boron-substituted quaternary carbon stereogenic centers through NHC-catalyzed conjugate additions of (pinacolato)boron units to enones

Suttipol Radomkit  1 , Amir H Hoveyda
Affiliations

Enantioselective synthesis of boron-substituted quaternary carbon stereogenic centers through NHC-catalyzed conjugate additions of (pinacolato)boron units to enones

Suttipol Radomkit et al. Angew Chem Int Ed Engl. .

Abstract

The first examples of Lewis base catalyzed enantioselective boryl conjugate additions (BCAs) that generate products containing boron-substituted quaternary carbon stereogenic centers are disclosed. Reactions are performed in the presence of 1.0-5.0 mol% of a readily accessible chiral accessible N-heterocyclic carbene (NHC) and commercially available bis(pinacolato)diboron; cyclic or linear α,β-unsaturated ketones can be used and rigorous exclusion of air or moisture is not necessary. The desired products are obtained in 63-95% yield and 91:9 to >99:1 enantiomeric ratio (e.r.). The special utility of the NHC-catalyzed approach is demonstrated in the context of an enantioselective synthesis of natural product antifungal (-)-crassinervic acid.

Keywords: N-heterocyclic carbenes; boron; conjugate additions; enantioselective synthesis; organic synthesis.

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Figures

Scheme 1
Scheme 1
Comparison of Cu-catalyzed and Cu-free enantioselective boron conjugate addition (BCA). B(pin) = (pinacolato)boron.
Scheme 2
Scheme 2
β-Boryl cyclohexenones can be accessed efficiently and enantioselectively. For general conditions see Table 1. [a] Proto-deboration byproduct formed (ca. 30%); 63% is the yield of pure 4h.
Scheme 3
Scheme 3
NHC-catalyzed BCA reactions can be performed with five- or seven- and eight-membered enones.
Scheme 4
Scheme 4
Efficient and highly enantioselective NHC-catalyzed BCA reactions of acyclic enones. [a] Performed at 35 °C.
Scheme 5
Scheme 5
Subjection of an enantiomerically enriched BCA product to common bleach at room temperature affords the ketone aldol product or the derived β-hydroxy-acid (e.s. = product enantiomeric excess/substrate enantiomeric excess x 100).
See this image and copyright information in PMC

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