9248
Conversion of (R)-nornicotine 7 to (R)-nicotine 1 was carried out using either a one- or a
two-step procedure. Addition of an excess of LiHMDS to (R)-nornicotine 7, followed by
trapping with MeI gave (R)-nicotine 1 with a good yield (77%). Alternatively, the N-ethylcarba-
mate, prepared from 7, was reduced by an excess of LiAlH4 to give (R)-nicotine 7 in 92% overall
yield for the two steps. (R)-nicotine 1 was finally checked by an analysis on chiral HPLC and
was found to have an ee of 92–93%, representing a slight drop of ee (less than 2%) relative to
the chiral alcohol 5.23
In summary, a short and efficient synthesis of the unnatural (R)-enantiomer of nicotine 1 (ee
92–93%) has been achieved in only four steps, with an overall yield of 51% (or in six steps with
an overall yield of 65%). The natural (S)-enantiomer of nicotine could be prepared identically
by replacing (−)-Ipc2BCl with (+)-Ipc2BCl. Extension of this straightforward approach to the
preparation of (S) and (R) analogues is currently underway in our laboratories.
Acknowledgements
We thank the Conseil Ge´ne´ral de Loire Atlantique for financial support (grant for S.G.). The
authors are indebted to Drs Bertrand Carboni and Franc¸ois Carreaux (Universite´ de Rennes,
UMR-CNRS 6510) for helpful discussions and reprints. Thanks are also due to Mr Gilbert
Nourrisson and Dr Errol Blart for technical assistance.
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