Synthesis and Stereoselective Lithiation of Enantiopure 2‐(1‐Aminoalkyl)aziridine–Borane Complexes

Abstract

Two alternative methodologies can be used to obtain enantiopure aziridine–borane complexes 2: successive treatment of 2‐(1‐aminoalkyl)aziridines 1 with BF3⋅Et2O and LiAlH4 or by direct reaction with BH3⋅THF (see scheme, Bn=benzyl). The complexes 2 can be deuterated or silylated highly stereoselectively at C3 by reaction with sBuLi and subsequent treatment with D2O or ClSiMe3, respectively.

BH3-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines

“…Focusing on the deprotonation of simple N -alkyl-substituted aziridines, Vedejs reported the lithiation of a simple unsubstituted aziridine by using BH 3 activation, a procedure originally developed by Kessar to promote the α-metalation of tertiary amines. A stereochemical analysis of the reaction was consistent with a dominant aziridine lithiation syn to the BH 3 group . Starting from this evidence, and conscious that N -alkyl-2-phenylaziridines undergo exclusive ortho -lithiation, we decided to investigate the lithiation of the corresponding BH 3 complexes lacking the nitrogen lone pair availability.…”

“…By comparison of 1 H NMR spectra of 1a and 4a , the syn relationship between the phenyl group and the deuterium on the β-carbon was established. By assuming that the reaction at the lithiated carbon occurs with retention of configuration, this finding strongly suggests that metalation occurred exclusively syn to the BH 3 moiety as reported for other aziridino−borane complexes …”

An Experimental and Computational Study of Stereoselectivity and Reactivity in Lewis Acid Promoted Lithiation-Substitution of Tertiary Amines

“…The Lewis acid promoted lithiation−electrophile reaction sequence (1-2-3-4) has emerged as a powerful methodology for forming new bonds at weakly acidic α-C−H centers of tertiary amines and phosphines (Scheme-1). − Regarding its stereochemical course, Vedjes has inferred that BH 3 complexed aziridines get lithiated syn to the boranato group under conditions of kinetic control, and subsequent reaction with electrophile is retentive , while BH 3 complexed phospholanes afford nearly equal proportions of syn and anti substitution products .…”

Selective Ring-Opening of Nonactivated Amino Aziridines by Thiols and Unusual Nucleophilic Substitution of a Dibenzylamino Group

“…Formation of compounds 2 and 3 may be explained by assuming that, in the first step of the reaction, selective coordination of the Lewis acid with the aziridine nitrogen takes place. This selective coordination of the Lewis acid with the aziridine nitrogen instead of the dibenzylamino group can be justified on steric grounds and has been proved by isolation of the corresponding aziridine−borane complex after treatment of compounds 1 with BF 3 ·OEt 2 and subsequent reduction with LiAlH 4 . Presumably, the activated aziridine−Lewis acid complex 5 receives anchimeric assistance from the dibenzylamino group, affording aziridinium salt 6 .…”