Rationally Designing Regiodivergent Dipolar Cycloadditions: Frontier Orbitals Show How To Switch between [5+3] and [4+2] Cycloadditions

A pyridinium zwitterion substrate is employed with two different types of transition metal catalysts to develop a regiodivergent cycloaddition. The pyridinium zwitterion is a highly reactive dipolar substrate that can undergo a dipolar cycloaddition with various reactants. It has multiple reaction sites, and the chemoselectivity is determined by the electronic demand of the catalyst substrate complex. The reaction with nucleophilic Pd reagents affords fused N-heterocyclic compounds via regioselective [4 + 2] cycloaddition. The origin of the site selectivity and the mechanism of this reaction are investigated in this combined experimental and computational study. We found that the pyridinium zwitterion plays a completely different role in the palladium(0)-catalyzed [4 + 2] cycloaddition reaction and in the rhodium(II)-catalyzed [5 + 3] cycloaddition, which was examined experimentally in a previous study. The frontier molecular orbitals of the pyridinium substrate and activated catalyst complex reveal that the pyridinium zwitterion can act as both a nucleophile and an electrophile depending on the reaction partner in a manner much more defined than that of conventional substrates, leading to the observed regiodivergent chemical reactivity

Cu(I)-Catalyzed Enantioselective [5 + 1] Cycloaddition of NAromatic Compounds and Alkynes via Chelating-Assisted 1,2-Dearomative Addition

© 2020 American Chemical Society. Copper-catalyzed [5 + 1] cycloadditions of N-aromatic zwitterions have been accomplished by chelation-assisted 1,2-dearomative addition of electron-deficient terminal alkynes. The unique modular skeleton of pyrazino[1,2-a]quinoline could be obtained from the regio- and stereoselective cascade annulation process, which was supported by computational studies. Further, an asymmetric variant of the developed strategy has been successfully extended for enabling access to optically enriched six-member cyclic systems11Nsciescopu

Cu(I)-Catalyzed Enantioselective [5+1] Cycloaddition of N-Aromatic Compounds and Alkynes via Chelating-Assisted 1,2-Dearomative Addition

© 2020 American Chemical Society. Copper-catalyzed [5 + 1] cycloadditions of N-aromatic zwitterions have been accomplished by chelation-assisted 1,2-dearomative addition of electron-deficient terminal alkynes. The unique modular skeleton of pyrazino[1,2-a]quinoline could be obtained from the regio- and stereoselective cascade annulation process, which was supported by computational studies. Further, an asymmetric variant of the developed strategy has been successfully extended for enabling access to optically enriched six-member cyclic systems11Nsciescopu

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

© 2019 American Chemical Society.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 demonstrate

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. © 2017 American Chemical Society111sciescopu

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

Rationally Designing Regiodivergent Dipolar Cycloadditions: Frontier Orbitals Show How To Switch between [5 + 3] and [4 + 2] Cycloadditions

A pyridinium zwitterion substrate is employed with two different types of transition metal catalysts to develop a regiodivergent cycloaddition. The pyridinium zwitterion is a highly reactive dipolar substrate that can undergo a dipolar cycloaddition with various reactants. It has multiple reaction sites, and the chemoselectivity is determined by the electronic demand of the catalyst–substrate complex. The reaction with nucleophilic Pd reagents affords fused N-heterocyclic compounds via regioselective [4 + 2] cycloaddition. The origin of the site selectivity and the mechanism of this reaction are investigated in this combined experimental and computational study. We found that the pyridinium zwitterion plays a completely different role in the palladium(0)-catalyzed [4 + 2] cycloaddition reaction and in the rhodium­(II)-catalyzed [5 + 3] cycloaddition, which was examined experimentally in a previous study. The frontier molecular orbitals of the pyridinium substrate and activated catalyst complex reveal that the pyridinium zwitterion can act as both a nucleophile and an electrophile depending on the reaction partner in a manner much more defined than that of conventional substrates, leading to the observed regiodivergent chemical reactivity

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‑<i>a</i>]pyridines as Color-Tunable Fluorophores

A new protocol for the synthesis of color-tunable fluorescent 3,5-diarylimidazo­[1,2-<i>a</i>]­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-<i>a</i>]­pyridines. The emission wavelengths of imidazo­[1,2-<i>a</i>]­pyridines increase as a function of the electron-withdrawing nature of the substituent on the C5-aryl group of imidazo­[1,2-<i>a</i>]­pyridine as a result of inductive effects on the LUMO levels. Varying the substituent on the C3-aryl group imidazo­[1,2-<i>a</i>]­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-<i>a</i>]­pyridines, the developed method provides an efficient approach for understanding and preparing strongly fluorescent bioprobes