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. 2020 Dec 4;22(23):9269-9275.
doi: 10.1021/acs.orglett.0c03495. Epub 2020 Nov 18.

Diastereo-, Enantio-, and anti- Selective Formation of Secondary Alcohol and Quaternary Carbon Stereocenters by Cu-Catalyzed Additions of B-Substituted Allyl Nucleophiles to Carbonyls

Emilie Wheatley  1 , Joseph M Zanghi  1 , Simon J Meek  1
Affiliations

Diastereo-, Enantio-, and anti- Selective Formation of Secondary Alcohol and Quaternary Carbon Stereocenters by Cu-Catalyzed Additions of B-Substituted Allyl Nucleophiles to Carbonyls

Emilie Wheatley et al. Org Lett. .

Abstract

A general method for the synthesis of secondary homoallylic alcohols containing α-quaternary carbon stereogenic centers in high diastereo- and enantioselectivity (up to >20:1 dr and >99:1 er) is disclosed. Transformations employ readily accessible aldehydes, allylic diboronates, and a chiral copper catalyst and proceed by γ-addition of in situ generated enantioenriched boron-stabilized allylic copper nucleophiles. The catalytic protocol is general for a wide variety of aldehydes as well as a variety of 1,1-allylic diboronic esters. Hammett studies disclose that diastereoselectivity of the reaction is correlated to the electronic nature of the aldehyde, with dr increasing as aldehydes become more electron poor.

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Conflict of interest statement

Authors declare no competing financial interests.

Figures

Scheme 1.
Scheme 1.
Catalytic Enantioselective Additions to Aldehydes with γ,γ-Disubstituted Allyl Reagents
Scheme 2.
Scheme 2.
Aldehyde Scopea aReactions performed under N2 atmosphere. 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. b1.0 mmol scale.
Scheme 3.
Scheme 3.
1,1-Allylic Diboron Scopea aSee Scheme 2. See the SI for details.
Scheme 4.
Scheme 4.
Mechanism Experimentsa aSee the SI for details.
Scheme 5.
Scheme 5.
Proposed Catalytic Cycle and Stereochemical Model
Scheme 6.
Scheme 6.
Synthetic Utilitya aSee the SI for details.
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