Jackson Kelvin E, Mortimer Claire L, Odell Barbara, McKenna Jeffrey M, Claridge Timothy D W, Paton Robert S, Hodgson David M
Department of Chemistry, Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford OX1 3TA, U.K.
Novartis Institutes for BioMedical Research , Wimblehurst Road, Horsham, West Sussex RH12 5AB, U.K.
J Org Chem. 2015 Oct 16;80(20):9838-46. doi: 10.1021/acs.joc.5b01804. Epub 2015 Sep 24.
(1)H NMR and computational analyses provide insight into the regiodivergent (α- and α'-) lithiation-electrophile trapping of N-thiopivaloyl- and N-(tert-butoxythiocarbonyl)-α-alkylazetidines. The magnitudes of the rotation barriers in these azetidines indicate that rotamer interconversions do not occur at the temperature and on the time scale of the lithiations. The NMR and computational studies support the origin of regioselectivity as being thiocarbonyl-directed lithiation from the lowest energy amide-like rotameric forms (cis for N-thiopivaloyl and trans for N-tert-butoxythiocarbonyl).
