Guoqiang Wang

Visible‐Light Photoredox‐Catalyzed C−H Difluoroalkylation of Hydrazones through an Aminyl Radical/Polar Mechanism

An unprecedented visible-light-induced direct C-H bond difluoroalkylation of aldehyde-derived hydrazones was developed. This reaction represents a new way to synthesize substituted hydrazones. The salient features of this reaction include difluorinated hydrazone synthesis rather than classical amine synthesis, extremely mild reaction conditions, high efficiency, wide substrate scope, ease in further transformations of the products, and one-pot syntheses. Mechanistic analyses and theoretical calculations indicate that this reaction is enabled by a novel aminyl radical/polar crossover mechanism, with the aminyl radical being oxidized into the corresponding aminyl cation through a single electron transfer (SET) process.

Homolytic Cleavage of a B−B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification

Density functional theory (DFT) investigations revealed that 4-cyanopyridine was capable of homolytically cleaving the B-B σ bond of diborane via the cooperative coordination to the two boron atoms of the diborane to generate pyridine boryl radicals. Our experimental verification provides supportive evidence for this new B-B activation mode. With this novel activation strategy, we have experimentally realized the catalytic reduction of azo-compounds to hydrazine derivatives, deoxygenation of sulfoxides to sulfides, and reduction of quinones with B2 (pin)2 at mild conditions.

Hantzsch Ester as a Photosensitizer for the Visible-Light-Induced Debromination of Vicinal Dibromo Compounds.

The debromination of vicinal dibromo compounds to generate alkenes usually requires harsh reaction conditions and the addition of catalysts. Just recently the visible-light-induced debromination of vicinal dibromo compounds emerged as a possible alternative to commonly used methods, but the substrate scope of this reaction is limited and a photocatalyst is necessary for the successful conversion of the starting compounds. A catalyst-free visible-light-induced debromination of vicinal dibromo compounds with a base-activated Hantzsch ester as photosensitizer is reported. The method has a wide substrate scope and a broad functional-group compatibility.

Intermolecular C-H Quaternary Alkylation of Aniline Derivatives Induced by Visible-Light Photoredox Catalysis.

The intermolecular direct C-H alkylation of aniline derivatives with α-bromo ketones to build a quaternary carbon center was reported with a visible-light catalysis procedure. The reaction covers a variety of functional groups with good to excellent yields. A regioselectivity favoring the ortho position for the amine group was observed and investigated with Fukui indices and spectral methods.

Rh(III)-catalyzed double C–H activation of aldehyde hydrazones: a route for functionalized 1H-indazole synthesis

A novel and straightforward strategy for functionalized 1H-indazoles is realized by the Rh(III)-catalyzed double C–H activation and C–H/C–H cross coupling of readily available aldehyde phenylhydrazones. The reaction is scalable and various 1H-indazoles could be afforded in moderate to high yields with good functional-group compatibility. Mechanism experiments and DFT calculations suggest the distinctive Rh(III)-catalyzed C–H/C–H cross coupling reaction underwent a cascade C(aryl)–H bond metalation, C(aldhyde)–H bond insertion and reductive elimination process.

Automatic Reaction Pathway Search via Combined Molecular Dynamics and Coordinate Driving Method

We proposed and implemented a combined molecular dynamics and coordinate driving (MD/CD) method for automatically searching multistep reaction pathways of chemical reactions. In this approach, the molecular dynamic (MD) method at the molecular mechanics (MM) or semiempirical quantum mechanical (QM) level is employed to explore the conformational space of the minimum structures, and the modified coordinate driving (CD) method is used to build reaction pathways for representative conformers. The MD/CD method is first applied to two model reactions (the Claisen rearrangement and the intermolecular aldol reaction). By comparing the obtained results with those of the existing methods, we found that the MD/CD method has a comparable performance in searching low-energy reaction pathways. Then, the MD/CD method is further applied to investigate two reactions: the electrocyclic reaction of benzocyclobutene-7-carboxaldehyde and the intramolecular Diels-Alder reaction of ketothioester with 11 effectively rotatable single bonds. For the first reaction, our results can correctly account for its torquoselectivity. For the second one, our method predicts eight reaction channels, leading to eight different stereo- and regioselective products. The MD/CD method is expected to become an efficient and cost-effective theoretical tool for automatically searching low-energy reaction pathways for relatively complex chemical reactions.

Combined Molecular Dynamics and Coordinate Driving Method for Automatic Reaction Pathway Search of Reactions in Solution

The combined molecular dynamics and coordinate driving (MD/CD) method is further refined in this work to automatically search reaction pathways for chemical reactions in solution. In this refined MD/CD method, the selective integrated tempering sampling based MD (SITS-MD) simulations are performed to efficiently sample conformers of the reactants in a realistic solution environment. Then, dozens of the reactant/solvent clusters from SITS-MD simulations were used in the subsequent CD step with the quantum mechanics/molecular mechanics (QM/MM) method to generate the reaction pathways. The present MD/CD method is able to search reaction pathways, in which solvent molecules may directly participate. This approach is applied to investigate two reactions without any prior knowledge of the reaction mechanism: Cope elimination of amine oxide in aqueous and dimethyl sulfoxide solutions, and dehydration of methanediol in aqueous solution. For both reactions, our calculations can locate a large number of low-energy reaction pathways. For the dehydration reaction in aqueous solution, free energy barriers for several reaction modes located by the MD/CD method have been obtained from the potential of mean force calculations. Our results show that the most likely reaction mode is the dehydration of methanediol catalyzed by two water molecules. These two illustrative applications demonstrate that the refined MD/CD method is a promising tool in predicting low-energy reaction pathways for reactions in solution.

Selective C−N Borylation of Alkyl Amines Promoted by Lewis Base

An efficient method for the metal-free deaminative borylation of alkylamines, using bis(catecholato)diboron as the boron source, to directly synthesize various alkyl potassium trifluoroborate salts is introduced. The key to this high reactivity is the utilization of pyridinium salt activated alkylamines, with a catalytic amount of a bipyridine-type Lewis base as a promoter. This transformation shows good functional-group compatibility (e.g., it is unimpeded by the presence of a ketone, indole, internal alkene, or unactivated alkyl chloride) and can serve as a powerful synthetic tool for borylation of amine groups in complex compounds. Mechanistic experiments and computations suggest a mechanism in which the Lewis base activated B2 cat2 unit intercepts an alkyl radical generated by single-electron transfer (SET) from a boron-based reductant.