Enantioselective total synthesis of the indole alkaloid 16-episilicine.
The first total synthesis of (-)-16-episilicine has been completed from a phenylglycinol-derived bicyclic lactam, the key steps being stereoselective conjugate addition and alkylation reactions, and a ring-closing metathesis.
Gold-catalyzed cycloisomerizations of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols to 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols.
A method to prepare 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols by gold(I)-catalyzed cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols with N-iodosuccinimide (NIS) is reported. The reactions were shown to be operationally simplistic and proceed efficiently for a wide variety of substrates, affording the corresponding products in good to excellent yields (70-99%). The mechanism is suggested to involve activation of the alkyne moiety of the substrate by the gold(I) catalyst. This triggers intramolecular addition of the tethered aniline moiety to give a vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct. Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the 1H-indole-2-carbaldehyde.
Synthesis of enantiomerically pure cis-2,4-disubstituted piperidines: extension of chiral homoenolate alkylations toward the preparation of nitrogen heterocycles
Abstract Enantiomerically pure cis -2,4-disubstituted piperidines were synthesized from chiral thiolactam 2 in six steps via a highly diastereoselective homoenolate alkylation which set the stereochemistry at the C4 carbon. In addition, two cleavage methods were used to cleave the lactam to the desired piperidines with a high level of diastereoselection at the newly created C2 stereocenter.