Direct cyclopropanation of activated N-heteroarenes via site- and stereoselective dearomative reactions.

A divergent cyclopropanation reaction has been accomplished via the dearomative addition of sulfur ylides to activated N-heteroarenes. A series of biologically significant molecular skeletons was obtained by the direct cyclopropanation of quinolinium zwitterions. Furthermore, a straightforward synthetic route to optically enriched cyclopropane-fused heterocycles was developed using sulfur ylides as chiral nucleophiles in the 1,4-dearomative reaction.

Catalytic Cascade Reaction To Access Cyclopentane-Fused Heterocycles: Expansion of Pd-TMM Cycloaddition.

A palladium-catalyzed reaction of N-aromatic zwitterion and trimethylenemethane that gives fused N-heterocycles via dearomative [3 + 2] cycloaddition and intramolecular cyclization is developed, and a cyclopentane-fused cyclic product is generated. Combining computational and experimental studies, the site-selective dearomatization and the mechanism of this novel reaction are investigated in detail, and the value of pyridinium zwitterion as a reactant is demonstrated.

Synthesis of Fused Polycyclic 1,4-Benzodiazepines via Metal-Free Cascade [5 + 2]/[2 + 2] Cycloadditions.

A metal-catalyst-free, mild, and efficient synthetic protocol for polycyclic 1,4-benzodiazepines via cascade [5 + 2]/[2 + 2] cycloadditions between pyridinium zwitterions and arynes is reported. Mechanistic experiments revealed that pyridinium zwitterions act as 1,5-dipoles in [5 + 2] cycloadditions with arynes for the construction of 1,4-benzodiazepines, which further undergo [2 + 2] cycloaddition resulting in the one-pot formation of one C-N bond and three C-C bonds.

3,5-Diarylimidazo[1,2-a]pyridines as Color-Tunable Fluorophores.

A new protocol for the synthesis of color-tunable fluorescent 3,5-diarylimidazo[1,2-a]pyridines has been achieved via palladium-catalyzed C-H amination of pyridinium zwitterions. Based on experimental results and computational analysis, we extracted a high correlation of photophysical properties with the theoretical concept and predicted emission wavelengths of 3,5-diarylimidazo[1,2-a]pyridines. The emission wavelengths of imidazo[1,2-a]pyridines increase as a function of the electron-withdrawing nature of the substituent on the C5-aryl group of imidazo[1,2-a]pyridine as a result of inductive effects on the LUMO levels. Varying the substituent on the C3-aryl group imidazo[1,2-a]pyridine changes the HOMO levels. Combining these two sites, the HOMO and LUMO levels can be tuned fairly decoupled from each other. This conceptual trend is demonstrated across a series where the C3 and C5 positions were functionalized independently and then utilizes a combination strategy where both sites are used to prepare fluorophores with a large window of emission wavelengths. In view of the biological properties of imidazo[1,2-a]pyridines, the developed method provides an efficient approach for understanding and preparing strongly fluorescent bioprobes.

Rhodium(II)-Catalyzed Cycloaddition Reactions of Non-classical 1,5-Dipoles for the Formation of Eight-Membered Heterocycles.

A new type of intermolecular rhodium(II)-catalyzed [5+3] cycloaddition has been developed. This higher-order cycloaddition between pyridinium zwitterion 1,5-dipole equivalents and enol diazoacetates enables the formation of eight-membered heterocyclic skeletons, which are otherwise difficult to construct. The optimized cycloaddition occurs efficiently under mild conditions with a wide range of pyridinium zwitterions and with high functional-group tolerance.