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. 2020 May 25;59(22):8451-8455.
doi: 10.1002/anie.202000675. Epub 2020 Mar 24.

Cu-Catalyzed Diastereo- and Enantioselective Reactions of γ,γ-Disubstituted Allyldiboron Compounds with Ketones

Joseph M Zanghi  1 , Simon J Meek  1
Affiliations

Cu-Catalyzed Diastereo- and Enantioselective Reactions of γ,γ-Disubstituted Allyldiboron Compounds with Ketones

Joseph M Zanghi et al. Angew Chem Int Ed Engl. .

Abstract

A catalytic diastereo- and enantioselective method for the preparation of complex tertiary homoallylic alcohols containing a vicinal quaternary carbon stereogenic center and a versatile alkenylboronic ester is disclosed. Transformations are promoted by 5 mol % of a readily available copper catalyst bearing a bulky monodentate phosphoramidite ligand, which is essential for attaining both high dr and er. Reactions proceed with a wide variety of ketones and allylic 1,1-diboronate reagents, which enables the efficient preparation of diverse array of molecular scaffolds.

Keywords: 1,1-allyldiboron compounds; asymmetric catalysis; copper; ketones; quaternary carbon centers.

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Figures

Scheme 1.
Scheme 1.
Catalytic Diastereo- and Enantioselective γ,γ-Disubstituted Allylic Nucleophile Additions to Ketones. B(pin) = (pinacolato)boron.
Scheme 2.
Scheme 2.
Investigation of Chiral Cu Complexes. Reactions performed under N2 atmosphere. Yield and diastereomeric ratios (dr) determined by analysis of 1H NMR spectra of crude reactions with hexamethyldisiloxane as internal standard. Enantiomeric ratios (er) determined by HPLC analysis. See SI for details.
Scheme 3.
Scheme 3.
Diastereo- and Enantioselective Cu-Catalyzed Synthesis of Homoallyl Alcohols and Quaternary Carbon Stereocenters by Allylic Nucleophile Additions to Aryl, Heteroaryl, Alkenyl, Alkynyl, and Alkyl Ketones. Reactions performed under N2 atmosphere on 0.05 mmol scale with 1.0 equiv of ketone, 1.2 equiv. of 5, in 0.350 ml of THF. Yields of purified products after SiO2 chromatography. Experiments were run in duplicate. Diastereomeric ratios (dr) determined by analysis of 1H NMR spectra of purified products. Enantiomeric ratios (er) determined by HPLC or SFC analysis. [a] Reactions run at −50 °C. [b] 2.0 equivalents of CD3OD used in place of CH3OH. See SI for details.
Scheme 4.
Scheme 4.
Variation of Allyl 1,1-Diboronate Scope. Reactions performed under N2 atmosphere on 0.05 mmol scale with 1.0 equiv of ketone, 1.2 equiv. of 2, in 0.350 ml of THF. Yields of purified products after SiO2 chromatography. Experiments were run in duplicate. Diastereomeric ratios (dr) determined by analysis of 1H NMR spectra of purified products. Enantiomeric ratios (er) determined by HPLC or SFC analysis. See the SI for details.
Scheme 5.
Scheme 5.
X-Ray Structure of 6q. See SI for details.
Scheme 6.
Scheme 6.
Synthetic Utility of Alkenyl Boronate Products. See SI for details.
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