Eun Jeong Yoo

Mechanistic Studies on the Cu-Catalyzed Three-Component Reactions of Sulfonyl Azides, 1-Alkynes and Amines, Alcohols, or Water: Dichotomy via a Common Pathway

Combined analyses of experimental and computational studies on the Cu-catalyzed three-component reactions of sulfonyl azides, terminal alkynes and amines, alcohols, or water are described. A range of experimental data including product distribution ratio and trapping of key intermediates support the validity of a common pathway in the reaction of 1-alkynes and two distinct types of azides substituted with sulfonyl and aryl(alkyl) groups. The proposal that bimolecular cycloaddition reactions take place initially between triple bonds and sulfonyl azides to give N-sulfonyl triazolyl copper intermediates was verified by a trapping experiment. The main reason for the different outcome from reactions between sulfonyl and aryl(alkyl) azides is attributed to the lability of the N-sulfonyl triazolyl copper intermediates. These species are readily rearranged to another key intermediate, ketenimine, into which various nucleophiles such as amines, alcohols, or water add to afford the three-component coupled products: amidines, imidates, or amides, respectively. In addition, the proposed mechanistic framework is in good agreement with the obtained kinetics and competition studies. A computational study (B3LYP/LACV3P*+) was also performed confirming the proposed mechanistic pathway that the triazolyl copper intermediate plays as a branching point to dictate the product distribution.

Multicomponent [5 + 2] cycloaddition reaction for the synthesis of 1,4-diazepines: isolation and reactivity of azomethine ylides.

Air-stable azomethine ylides with an unusual pattern of charge distribution were efficiently prepared via the rhodium-catalyzed reaction between pyridines and 1-sulfonyl-1,2,3-triazoles. This reaction allowed for the first example of the catalytic multicomponent [5 + 2] cycloaddition reactions, thus resulting in the formation of biologically active 1,4-diazepine compounds.

A new route to indolines by the Cu-catalyzed cyclization reaction of 2-ethynylanilines with sulfonyl azides.

It is revealed that 2-sulfonyliminoindolines can be efficiently synthesized by the Cu-catalyzed cyclization reaction of N-alkyl- or aryl-substituted 2-ethynylanilines with sulfonyl azides. This new route to the indoline derivatives is characterized by mild reaction conditions, facile introduction of functional groups at the 2-position of the indoline ring, and the wide substrate scope. Selective transformation of indoline to oxindole and isatin analogs is also demonstrated.

A New Entry of Copper-Catalyzed Four-Component Reaction: Facile Access to α-Aryl β-Hydroxy Imidates

Alpha-aryl beta-hydroxy imidates are efficiently obtained by the four-component reaction of ethyl glyoxylates, aryl acetylenes, sulfonyl azides, and alcohols using a copper catalyst. The developed procedure is characterized by high selectivity, mild reaction conditions, a wide substrate scope, and an excellent functional group tolerance. Facile transformations of the obtained sulfonylimidate moiety to other carbonyl groups such as sulfonamides or esters were also demonstrated.

Efficient Synthesis of C–N-Coupled Heterobiaryls by Sequential N–H Functionalization Reactions

C-N-coupled heterobiaryls were synthesized by sequential N-H functionalization reactions: stereoselective rhodium-catalyzed N-H insertion, followed by regioselective palladium-catalyzed C-H amination. Because of the good substrate scope and excellent selectivity, the developed method presents a novel approach for the synthesis of heterobiaryls, which are potent antibiotics.

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.