α-Oxo-Ketenimines from Isocyanides and α-Haloketones: Synthesis and Divergent Reactivity.

The palladium-catalyzed reaction of α-haloketones with isocyanides afforded α-oxo-ketenimines through ß-hydride elimination of the ß-oxo-imidoyl palladium intermediates. Reaction of these relatively stable α-oxo-ketenimines with nucleophiles such as hydrazines, hydrazoic acid, amines, and Grignard reagent afforded pyrazoles, tetrazole, ß-keto amidines, and enaminone, respectively, with high chemoselectivity. Whereas amines attack exclusively on the ketenimine functions, the formal [3+2] cycloaddition between N-monosubstituted hydrazines and α-oxo-ketenimines was initiated by nucleophilic addition to the carbonyl group.

Total Synthesis of (+)-Lophirone H and Its Pentamethyl Ether Utilizing an Oxonium-Prins Cyclization.

The first total synthesis of (+)-lophirone H (1) and its pentamethyl ether 29, featuring an oxonium-Prins cyclization/benzylic cation trapping reaction, is described.

Ketenimines from Isocyanides and Allyl Carbonates: Palladium-Catalyzed Synthesis of ß,γ-Unsaturated Amides and Tetrazoles.

The reaction of allyl ethyl carbonates with isocyanides in the presence of a catalytic amount of Pd(OAc)2 provided ketenimines through ß-hydride elimination of the allyl imidoylpalladium intermediates. The insertion of the isocyanide into the π-allyl Pd complex proceeded via an unusual η1 -allyl Pd species. The resulting ketenimines were hydrolyzed to ß,γ-unsaturated carboxamides during purification by flash column chromatography on silica gel or converted in situ into 1,5-disubstituted tetrazoles by [3+2] cycloaddition with hydrazoic acid or trimethylsilyl azide.

Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine.

Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles through a formal reductive C(sp(2) )-H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From ß,ß-disubstituted o-nitrostyrenes, 2,3-disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine.