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

Kremsmair, Alexander; Wilke, Henrik R.; Simon, Matthias M.; Schmidt, Quirin; Karaghiosoff, Konstantin and Knochel, Paul (2021): General stereoretentive preparation of chiral secondary mixed alkylmagnesium reagents and their use for enantioselective electrophilic aminations. In: Chemical Science, Vol. 13, No. 1: pp. 44-49

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 alpha-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 degrees 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 alpha-chiral tertiary alcohols, ketones, amides, phosphines and tertiary amines in up to 89% yield (over three reaction steps) and up to 99% ee.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2041-6520
• Language: English