Shi-Chao Ren

The cross-dehydrogenative coupling of cyclic aldimines (C–H) and corresponding nucleophiles (X–H) provides one of the most straightforward synthetic methods for cyclic imidic acid derivatives. However, the method is currently limited to the cross-coupling of aldimines with amines to prepare amides. A robust and general synthetic method that enables the involvement of amines, alcohols, and even thiols as nucleophiles to divergently synthesize imidic acid derivatives is unknown. Herein, we disclose a carbene-catalyzed cross-dehydrogenative coupling between cyclic aldimines and amines, alcohols, and thiols, enabling efficient and divergent synthesis of cyclic imidic-acid-derived amidines, imidates, and imidothioates. The mild reaction conditions enable an excellent tolerance of various functional groups, allowing for the modification of complex natural products and pharmaceuticals. The practical utility of the current method is demonstrated by its successful application to the divergent synthesis of a wide range of substituted probenazole and dichlobentiazox (two marketed pesticide molecules).

Indanone-3-carboxylates are key organic synthetic intermediates for a range of bioactive molecules. However, their efficient synthesis, particularly for structurally complex indanone-3-carboxylates, still faces challenges such as cumbersome steps and harsh conditions. Herein, we report a photocatalytic imidazolium ester- and phosphine-mediated dehydroxylative cyclization/acylation of 2-vinylbenzoic acids. This radical relay strategy enables the efficient preparation of structurally diverse indanone-3-carboxylates from readily available 2-vinylbenzoic acids and nitrogen heterocyclic carbene (NHC)-based azolium salts under mild conditions. The reaction exhibits broad substrate scope and, notably, allows facile access to carbon-cycle-fused indanone-3-carboxylate scaffolds that are challenging to obtain using conventional methods. Preliminary bioactivity assays reveal that several products possess good antifungal activity, demonstrating the potential of this method to advance the development of indanone-3-carboxylate-related bioactive molecules.

An NHC-catalyzed dehaloacylation of α-bromo phosphonates for efficient access to α-substituted β-keto phosphonates was disclosed.

NHC and palladium cooperatively catalyzed efficient access to bioactive 5-acylated benzoxasilepines was disclosed.

The key progress in the field of N-heterocyclic carbene (NHC) organocatalysis during the period of 2015 to 2024 is systematically summarized and discussed in this review.

A chiral phosphoric acid-catalyzed kinetic resolution of racemic biaryl oxazepines with alcohols was developed, which afforded biaryl oxazepines and imidates bearing a chiral center in high enantioselectivities.

Enantiodivergent synthesis using a single catalyst or catalysts with the same chiral scaffold has evolved as a particularly attractive tool to access both enantiomers of chiral molecules. Progress in this field mainly comes from the enantiodivergent construction of central chirality as well as axial chirality. We report herein a carbene-catalyzed base-controlled enantiodivergent synthesis of saddle-shaped eight-membered lactones with inherent chirality. With the use of the same carbene catalyst or the carbene catalysts with the same chiral scaffold, both enantiomers of the inherently chiral eight-membered lactones could be obtained under different base conditions in high yields with good to excellent enantioselectivities. The resulting inherently chiral eight-membered lactones allow further stereospecific derivatizations and exhibit notable antibacterial activity. Preliminary DFT calculations unraveled the origins of this base-controlled enantiodivergent process.