General stereoretentive preparation of chiral secondary mixed alkylmagnesium reagents and their use for enantioselective electrophilic aminations

Abstract

A general preparation of enantiomerically and diastereomerically enriched secondary alkylmagnesium reagents was reported as well as their use for performing highly stereoselective transition-metal free electrophilic aminations leading to α-chiral amines in up to 97% ee. Thus, the reaction of t-BuLi (2.2 equiv.) with a mixture of chiral secondary alkyl iodides and the commercially available magnesium reagent Me3SiCH2MgCl in a 2 : 1 mixture of pentane and diethyl ether at up to −50 °C provided optically enriched secondary mixed alkylmagnesium species of the type alkyl(Me)CHMgCH2SiMe3 with high retention of configuration (up to 99% ee). The resulting enantiomerically enriched dialkylmagnesium reagents were trapped with electrophiles such as non-enolizable ketones, aldehydes, acid chlorides, isocyanates, chlorophosphines and O-benzoyl hydroxylamines providing α-chiral tertiary alcohols, ketones, amides, phosphines and tertiary amines in up to 89% yield (over three reaction steps) and up to 99% ee.

Graphical abstract: General stereoretentive preparation of chiral secondary mixed alkylmagnesium reagents and their use for enantioselective electrophilic aminations

Supplementary files

Article information

Article type
Edge Article
Submitted
24 Sep 2021
Accepted
18 Oct 2021
First published
19 Oct 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021, Advance Article

General stereoretentive preparation of chiral secondary mixed alkylmagnesium reagents and their use for enantioselective electrophilic aminations

A. Kremsmair, H. R. Wilke, M. M. Simon, Q. Schmidt, K. Karaghiosoff and P. Knochel, Chem. Sci., 2021, Advance Article , DOI: 10.1039/D1SC05315A

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