EnT-Mediated Amino-Sulfonylation of Alkenes with Bifunctional Sulfonamides: Access to ß-Amino Sulfone Derivatives.

ß-Amino sulfones are commonly found structural motifs in biologically active compounds. Herein, we report a direct photocatalyzed amino-sulfonylation reaction of alkenes for the efficicient production of important compounds by simple hydrolysis without the need for additional oxidants and reductants. In this transformation, the sulfonamides worked as bifunctional reagents, simultaneously generating sulfonyl radicals and N-centered radicals which were added to alkene in a highly atom-economical fashion with high regioselectivity and diastereoselectivity. This approach showed high functional group tolerance and compatibility, facilitating the late-stage modification of some bioactive alkenes and sulfonamide molecules, thereby expanding the biologically relevant chemical space. Scaling up this reaction led to an efficient green synthesis of apremilast, one of the best-selling pharmceuticals, demonstrating the synthetic utility of the applied method. Moreover, mechanistic investigations suggest that an energy transfer (EnT) process was in operation.

Nickel/Photoredox-Catalyzed Direct Amidation of Aldehydes with Nitroarenes via Fully Catalytic Process.

A fully catalytic nickel-photoredox process for the direct amidation of aldehydes with nitroarenes was developed. In this system, aldehydes and nitroarenes were catalytically activated by the photocatalytic cycle without the addition of an additional reductant or oxidants, which facilitated the Ni-mediated cross-coupling of the C-N bond under mild conditions. A preliminary mechanistic study indicates a reaction pathway in which nitrobenzene is directly reduced to aniline as the nitrogen source.

Uranyl nitrate as a recyclable homogeneous photocatalyst for selective cross-coupling of N-substituted amines and indoles.

A homogeneous photocatalytic recyclable system for the selective radical-radical cross-coupling of N-substituted amines and indoles has been established. This system could conduct in water or acetonitrile, featuring the reuse of uranyl nitrate as the recyclable photocatalyst via a simple extraction. With this mild strategy in hand, good to excellent yields of cross-coupling products could be achieved even under the irradiation of sunlight, including 26 natural product derivatives and 16 natural product inspired re-engineered compounds. A radical-radical cross-coupling mechanism was newly proposed based on experimental evidence and reported literature. This strategy has been also applied to a gram scale synthesis to demonstrate its practical utility.

Chemo- and regioselective ring-opening of donor-acceptor oxiranes with N-heteroaromatics.

The first ring-opening of D-A oxiranes with N-heteroaromatics in a chemoselective C-C bond cleavage manner was achieved. In the presence of 5 mol% of Y(OTf)3 as the catalyst, diverse N-heteroaromatics, including benzotriazoles, purines, substituted benzimidazole, imidazole and pyrazole, reacted well with various D-A oxiranes, providing acyclic nucleoside analogues containing a N-glycosidic bond in up to 97% yield and up to >95 : 5 regioselectivity. Through simple transformation, the Ganciclovir analogue could also be obtained.

Asymmetric Synthesis of 3-Amine-tetrahydrothiophenes with a Quaternary Stereocenter via Nickel(II)/Trisoxazoline-Catalyzed Sulfa-Michael/Aldol Cascade Reaction: Divergent Access to Chiral Thionucleosides.

A generally useful Ni(II)/trisoxazoline-catalyzed asymmetric sulfa-Michael/Aldol cascade reaction is introduced to access chiral 3-amine-tetrahydrothiophene derivatives containing a quaternary stereocenter (32 examples, up to 93% yield, > 20:1 dr and 92% ee). Moreover, the novel strategy offers an efficient and convenient approach to construct chiral thionucleoside analogues.

Palladium-catalyzed asymmetric formal [3+2] cycloaddition of α-N-heterocyclic acrylates with vinyl epoxides for construction of isonucleoside analogs.

A highly efficient Pd-catalyzed asymmetric formal [3+2] cycloaddition using α-N-heterocyclic acrylates to react with vinyl epoxides has been achieved for the first time to access chiral functionalized tetrahydrofuran skeletons (34 examples, up to 93% yield, >20 : 1 dr and 99% ee). Meanwhile, using a palladium/(S,S)-tBu-FOXAP catalyst or a palladium/(R)-Segphos catalyst, purine or pyrimidine isonucleoside analogs are constructed in high yields and stereoselectivity, respectively. The commercial availability of the catalysts, broad substrate scope and easy transformation of the products make this methodology an attractive method in asymmetric synthesis.