A Cobalt Mediated Nitrene Transfer aza-Wittig Cascade Reaction To Access 1,3,4-Oxadiazole Scaffolds.

A cobalt(II) mediated three-component synthesis of 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imines using sulfonyl azides, N-isocyaniminotriphenylphosphorane (NIITP), and carboxylic acids has been developed. This one-pot tandem reaction starts with a nitrene transfer to NIITP, followed by addition of the carboxylic acid to the in situ formed carbodiimide and subsequent intramolecular aza-Wittig reaction. Both the steric constraints of carboxylic acid and the stoichiometry of the employed cobalt salt determine the selectivity toward the two products, i.e. 5-substituted-N-sulfonyl-1,3,4-oxadiazol-2(3H)-imine versus 5-substituted-4-tosyl-2,4-dihydro-3H-1,2,4-triazol-3-one.

Enantioselective Total Synthesis of (-)-Limaspermidine and (-)-Kopsinine by a Nitroaryl Transfer Cascade Strategy.

We report an intramolecular conjugate addition/Truce-Smiles/E1cb cascade of 2-nitrobenzenesulfonamide-functionalized cyclohexenones as a new entry to the core scaffold of monoterpene indole alkaloids. The method was applied to the asymmetric total synthesis of (-)-limaspermidine, (-)-kopsinilam, and (-)-kopsinine, as well as the framework of the kopsifoline alkaloids, thus highlighting its complementarity to existing approaches involving the use of indole-based starting materials or the interrupted Fischer indole synthesis. Furthermore, we show that the cascade tolerates various substituents on the nitroarene, opening the way to other natural products as well as non-natural analogues.