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Synfacts 2006(2): 0122-0122  
DOI: 10.1055/s-2005-924826
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Regioselective Lithiation of (S)-Nicotine

Contributor(s): Victor Snieckus, Robert Engqvist
F. C. Février, E. D. Smith, D. L. Comins*
North Carolina State University, Raleigh, USA
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Publication History

Publication Date:
23 January 2006 (online)

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Significance

Regioselective C-6 or C-2 substitution of (S)-nicotine was accomplished via lithiation using n-BuLi/LiDMAE or LiTMP, respectively. Although the first reaction proceeds in variable yields as a function of the electrophile used, the latter provides consistently excellent yields. C-6 regioselectivity is presumably dictated by the coordination of the bulky LIDMAE complex away from the more hindered C-2 position. The use of LIDMAE on C-2 lithiations of pyridines has been previously reported by Fort et al. (J. Org. Chem. 2002, 67, 234-237).