Substituted Diarylmethylamines by Stereospecific Intramolecular Electrophilic Arylation of Lithiated Ureas

Link: JACS ASAP

Jonathan Clayden,* Jérémy Dufour, Damian M. Grainger, and Madeleine Helliwell

School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom

This is a neat and remarkable methodology for the synthesis of diarylmethylamines. The reaction starts with N-aryl-N'-methylaryl-urea. Upon treatment with sec-BuLi, the bezylic position is deprotonated. This benzylic lithium then adds across the urea carbonyl to the ipso-position of the other aryl group on the other nitrogen. The complex formed then rearranges to give the aryl-migrated product, ie 3. This product can serve as a precursor to diarylmethylamine 4 upon reduction or hydrolysis.

The reaction was found to be stereosepcific, that is the configuration of the benzylic position in the SM is retained in the product. The reaction was found to be widely applicable regardless of electronic character of the aryl ring being transferred.

And as mentioned above, the reaction is stereospecific. In case of chiral SM, the configuration of the stereogenic center is retained. This is summarized in the table below.

The stereospecificity of the reaction was further demonstrated in the synthesis of chiral 7.

The reaction was found to be intramolecular as proven by the absence of cross-over products in a cross-over experiment. The intermediate of the reaction was found to be 9 as proven by the isolations of 10o and 10p upon exposure of the intermediates to dry air, thus fully proving the mechanism of the reaction. In this reaction, DMPU was added to help promote the dearomatization reaction for the formation of intermediate 9 (both DMPU and HMPA are known to promote such reaction).

This is a neat reaction which can provide a ready access to racemic or enantio-enriched diarylmethylamines.