Enantioselective alpha-arylation of benzylamines using chiral lithium amides Rajendra Kumar Mallick, Rakesh K Saunthwal, Jonathan Clayden University of Bristol, UK Chiral lithium amides offer a simple, practical and transition-metal free way to obtain chiral α,α- diarylbenzylamines, which are very valuable building blocks for products of pharmaceutical or agrochemical interest. Chiral lithium amides can be used to enantioselectively deprotonate an appropriately hindered urea derivative of a benzylamine, although much stronger chiral organolithium bases, namely sec-BuLi in combination with sparteine, are normally used for asymmetric benzylic deprotonations. The initial deprotonation can be followed by an anionic N to C aryl migration in the case of N-aryl urea benzylamines leading to α-arylation in good yields and enantiomeric excess up to >99%. Next, N-urea α,α-diaryl benzylamines employed in acid condition to access the N-Methyl α,α-diaryl benzylamines via stereospecific azatropic shift. Finally, we have achieved the Levocetirizine intermediate by using this methodology.
References 1. C(sp3)-Arylation by Conformationally Accelerated Intramolecular Nucleophilic Aromatic Substitution (SNA); Steven M. Wales, Rakesh K. Saunthwal and Jonathan Clayden; Acc. Chem. Res. 2022 , 55 , 1731–1747.
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