Efficient Synthesis of Isoquinoline Derivatives through Sequential Cyclization–Deoxygenation Reaction of 2-Alkynylbenzaldoximes

We describe a novel, simple, robust, and efficient cyclization/deoxygenation approach for the synthesis of functionalized isoquinoline derivatives. Over the course of continued studies on o-alkynylbenzaldoxime cyclization reactions, the formation of cyclic nitrones through 6-endo-dig cyclization was achieved using silver triflate or bromine as an electrophile, and subsequently, the deoxygenation process was carried out in the presence of CS2 in good to high yields.

Blue-light-promoted radical C–H azolation of cyclic nitrones enabled by Selectfluor®

The use of Selectfluor® enables the cross-dehydrogenative coupling of model cyclic aldonitrones, 2H-imidazole 1-oxides, with NH-containing azoles, the process being accelerated by blue light irradiation.

Efficient Synthesis of O-tert-Propargylic Oximes via Nicholas Reaction

A synthetic protocol to access O-tert-propargylic oximes derived from tertiary propargylic alcohols was established via Nicholas reaction. Thus, BF3·OEt2-mediated reaction between the dicobalt hexacarbonyl complex of tert-propargylic alcohols and p-nitrobenzaldoxime followed by decomplexation with cerium(IV) ammonium nitrate afforded the corresponding O-tert-propargylic oximes in good to high yields. The obtained O-tert-propargylic oximes were effectively converted into heterocycles, such as four-membered cyclic nitrones, oxazepines, and isoxazolines, by using π-Lewis acidic catalysts.

Enantioselective Synthesis of Cyclic Nitrones and Oxime Ethers by Chemoselective Allylic Alkylation of Oximes

The enantio- and chemoselective iridium-catalyzed <i>N</i>- and<i> O</i>-allylation of oximes is described for the first time. Kinetic resolution in an intramolecular setting provides access to cyclic nitrones, oxime ethers and enantioenriched aliphatic allylic alcohols. Salient features of this transformation are its ability to employ <i>E</i>/<i>Z</i>-isomeric mixtures of oxime starting materials convergently, high functional group tolerance, and divergent <i>N</i>- or <i>O</i>-allylation by choice of the reaction conditions. The implementation of <i>N</i>-allylation/1,3-dipolar cycloaddition reaction cascades furnish tricyclic isoxazolidines in highly enantio- and diastereoselective fashion. Expansion of this approach to the selective allylation of hydrazones allows enantioselective preparation of azomethine imines. The synthetic utility of the approach is demonstrated by the efficient, formal syntheses of glycoprotein GP IIb‐IIIa receptor antagonist (–)-roxifiban and marine natural product (+)-halichlorine.

Enantioselective Synthesis of Cyclic Nitrones and Oxime Ethers by Chemoselective Allylic Alkylation of Oximes

The enantio- and chemoselective iridium-catalyzed <i>N</i>- and<i> O</i>-allylation of oximes is described for the first time. Kinetic resolution in an intramolecular setting provides access to cyclic nitrones, oxime ethers and enantioenriched aliphatic allylic alcohols. Salient features of this transformation are its ability to employ <i>E</i>/<i>Z</i>-isomeric mixtures of oxime starting materials convergently, high functional group tolerance, and divergent <i>N</i>- or <i>O</i>-allylation by choice of the reaction conditions. The implementation of <i>N</i>-allylation/1,3-dipolar cycloaddition reaction cascades furnish tricyclic isoxazolidines in highly enantio- and diastereoselective fashion. Expansion of this approach to the selective allylation of hydrazones allows enantioselective preparation of azomethine imines. The synthetic utility of the approach is demonstrated by the efficient, formal syntheses of glycoprotein GP IIb‐IIIa receptor antagonist (–)-roxifiban and marine natural product (+)-halichlorine.