jo202652f_si_003.pdf (1.13 MB)
Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (N-Sulfinyl Imines)
journal contribution
posted on 2012-03-02, 00:00 authored by Franklin A. Davis, Narendra V. Gaddiraju, Naresh Theddu, Joshua R. Hummel, Sandeep K. Kondaveeti, Michael J. ZdillaThe first examples of cocaine analogues having substituents
(methyl,
ethyl, n-propyl, n-pentyl, and phenyl)
at the C-1 position of the cocaine tropane skeleton were prepared
by heating sulfinimine-derived α,β-unsaturated pyrrolidine
nitrones. In the presence of the Lewis acid Al(OtBu)3 the nitrones undergo an intramolecular [3
+ 2] cycloaddition to give tricyclic isoxazolidines that were transformed
in three steps to the cocaine analogues. In the absence of the Lewis
acid, lactams were formed resulting from rearrangement of the nitrone
to an oxaziridine. A novel Pd- and base-promoted rearrangement of
methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines
was discovered.