Asymmetric Synthesis of Chiral Sulfimides through the O-Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles.

Chiral sulfimides, the aza-analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen-selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K2 CO3 , and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods.

Cu-Catalyzed Generation of Alkyl Radicals from Alkylsilyl Peroxides and Subsequent C(sp3)-C(sp2) Cross-Coupling with Arylboronic Acids.

This work describes a novel and practical method for the Cu-catalyzed C(sp3)-C(sp2) cross-coupling of alkylsilyl peroxides with arylboronic acids. The reductive cleavage of the O-O bond of alkylsilyl peroxides and the desired cross-coupling reactions to afford alkyl-substituted aromatic rings proceed smoothly at room temperature promoted by simple Cu-based catalysts and do not require activation by visible light. The results of mechanistic investigations support a radical-mediated C(sp3)-C(sp2) bond formation via ß-scission of the alkoxy radicals generated from the alkylsilyl peroxides.

Transsulfinamidation of Sulfinamides with Amines.

Metal- and additive-free transsulfinamidation of N-unsubstituted sulfinamides and N-pivaloyl-protected sulfinamides with various amines is reported. With this method, both N-monosubstituted and N,N-disubstituted sulfinamides were obtained in good yields simply by heating. Preliminary experiments also indicate that alcohols can be used as nucleophiles instead of amines and can provide sulfinate esters.

Ni-Catalyzed C(sp2)-H alkylation of N-quinolylbenzamides using alkylsilyl peroxides as structurally diverse alkyl sources.

A Ni-catalyzed direct C-H alkylation of N-quinolylbenzamides using alkylsilyl peroxides as alkyl-radical precursors is described. The reaction forms a new C(sp3)-C(sp2) bond via the selective cleavage of both C(sp3)-C(sp3) and C(sp2)-H bonds. This transformation shows a high functional-group tolerance and, due to the structural diversity of alkylsilyl peroxides, a wide range of alkyl chains including functional groups and complex structures can be introduced at the ortho-position of readily available N-quinolylbenzamide derivatives. Mechanistic studies suggest that the reaction involves a radical mechanism.

N-Hydroxybenzimidazole as a structurally modifiable platform for N-oxyl radicals for direct C-H functionalization reactions.

Methods for direct functionalization of C-H bonds mediated by N-oxyl radicals constitute a powerful tool in modern organic synthesis. While several N-oxyl radicals have been developed to date, the lack of structural diversity for these species has hampered further progress in this field. Here we designed a novel class of N-oxyl radicals based on N-hydroxybenzimidazole, and applied them to the direct C-H functionalization reactions. The flexibly modifiable features of these structures enabled facile tuning of their catalytic performance. Moreover, with these organoradicals, we have developed a metal-free approach for the synthesis of acyl fluorides via direct C-H fluorination of aldehydes under mild conditions.