While remarkable progress has been made over the past decade, new design strategies for chiral catalysts in enantioselective C(sp 3 )−H functionalization reactions are still highly desirable. In particular, the ability to use attractive noncovalent interactions for rate acceleration and enantiocontrol would significantly expand the current arsenal for asymmetric metal catalysis. Herein, we report the development of a highly enantioselective Ir(III)-catalyzed intramolecular C(sp 3 )−H amidation reaction of dioxazolone substrates for synthesis of optically enriched γ-lactams using a newly designed α-amino-acid-based chiral ligand. This Ircatalyzed reaction proceeds with excellent efficiency and with outstanding enantioselectivity for both activated and unactivated alkyl C(sp 3 )−H bonds under very mild conditions. It offers the first general route for asymmetric synthesis of γ-alkyl γlactams. Water was found to be a unique cosolvent to achieve excellent enantioselectivity for γ-aryl lactam production. Mechanistic studies revealed that the ligands form a well-defined groove-type chiral pocket around the Ir center. The hydrophobic effect of this pocket allows facile stereocontrolled binding of substrates in polar or aqueous media. Instead of capitalizing on steric repulsions as in the conventional approaches, this new Ir catalyst operates through an unprecedented enantiocontrol mechanism for intramolecular nitrenoid C−H insertion featuring multiple attractive noncovalent interactions.

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A Pd-catalyzed carboxamide-directed enantioselective 1,2-carboboration reaction of unactivated alkenes with C−H nucleophiles and B 2 Pin 2 has been developed using a second generation of chiral monodentate oxazoline (MOXca) ligand. The MOXca ligand featuring a modular design of a Nlinked carbazole side arm can be readily synthesized from serine and NH-carbazoles and provided further improved enantiocontrol of the AQ-directed nucleopalladation over MOXin ligand. The use of KTFA additive and TFE solvent was critical to obtain high reactivity in this difunctionalization reaction system. Preliminary study showed that 1,2-aminoboration of 3-butenamide with imide N-nucleophiles and B 2 Pin 2 under the same conditions proceeded in good yield and high enantioselectivity.

Sulfur–heteroatom bonds such as S–S and S–N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S–N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis of N-acyl sulfenamides via copper-catalyzed nitrene-mediated S-amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resulting N-acetyl sulfenamides are highly effective S-sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. The S-sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means.

A Pd-catalyzed carboxamide-directed hydrocarbofunctionalization reaction of unactivated alkenes with different alkynes has been developed. An 8-aminoquinoline auxiliary was utilized to increase the reactivity of the alkene and control the regioselectivity via the formation of thermodynamically favored five-membered palladacycle intermediate. 3-Alkene carboxamides bearing a C4-substituted alkene group reacted with a variety of terminal alkynes in the presence of an ortho-phenyl benzoic acid promoter, yielding γ-alkynylated products with high yields and regioselectivity. 3-Butenamide underwent a three-component coupling reaction with internal alkynes and carboxylic acids to give vinyl ester products. Preliminary mechanistic studies indicate that the intramolecular migratory insertion of alkynyl or vinyl palladium species into the CC bond is responsible for the γ-selective alkynylation or alkenylation of the alkene group.