Enantioselective synthesis of cocaine C-1 analogues using sulfinimines (N-sulfinyl imines).
The 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(O(t)Bu)(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.
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA. fdavis@temple.edu
Franklin A
FA
Davis
Narendra V
NV
Gaddiraju
Naresh
N
Theddu
Joshua R
JR
Hummel
Sandeep K
SK
Kondaveeti
Michael J
MJ
Zdilla
D003042:Cocaine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry*
D007097:Imines; D013452:Sulfonium Compounds; C522016:sulfinimine; D003042:Cocaine