Cobalt(Ⅲ)hydride HAT mediated enantioselective intramolecular hydroamination access to chiral pyrrolidines

Enantioenriched pyrrolidines and derivatives are ubiquitous substructures in compounds of importance to medicinal and biological chemistry.Herein,we report an efficient cobalt-catalyzed intramolecular asymmetric hydroamination reaction that produces chiral pyrrolidines with good to excellent yield and enantiocontrol.Compared with previously reported radicalinvolved methodologies for enantioenriched pyrrolidines,these conditions feature two elegant versatilities,enabling(1)the use of cobalt-catalyzed hydrogen atom transfer(HAT)to generate organocobalt intermediates that bring radical reaction to organometallic chemistry,and(2)enantioselective intramolecular C-N bond forging through an S_(N)2-like displacement involving dynamic kinetic resolution(DKR).This approach provides a new alternative and efficient methodology for enantioselective radical-involved C-N bond construction that can be used in the synthesis of both chiral pyrrolidines and homologous nitrogen heterocycles.

Recent Advances in Domino Synthesis of Fused Polycyclic N-Heterocycles Based on Intramolecular Alkyne Hydroamination under Copper Catalysis

Fused polycyclic N-heterocycles are very important scaffolds in biomedicinal chemistry and materials science.Intramolecular alkyne hydroamination is a powerful method for the construction of N-heterocycles.In the last two decades,copper-catalyzed domino reactions based on intramolecular alkyne hydroamination has emerged as a robust strategy for assembling various fused polycyclic N-heterocycles.Great progress has been achieved in this area.This short review covers the advances made in copper-catalyzed domino synthesis of fused polycyclic N-heterocycles based on the strategy from 2008 to 2023,and will hopefully serve as an inspiration towards the exploration of new copper-catalyzed versions of the transformation.The domino transformations are introduced and discussed from five aspects according to the different key processes involved in these reactions.

Asymmetric Access of γ-Amino Acids and γ-Amino Phosphonic Acid Derivatives via Copper-Catalyzed Enantioselective and Regioselective Hydroamination

γ-Aminobutyric acid is a major inhibitory neurotransmitter in the mammalian central nervous system that plays a substantial role in brain disorders.γ-Amino phosphonic acid is a unique surrogate of both natural and unnatural γ-amino acid.Because of their unique biological activity,γ-amino acid and γ-amino phosphonic acid derivatives have attracted considerable attention.However,an efficient and straightforward method for constructing chiral γ-substituted-γ-amino acid and γ-amino phosphonic acid derivatives remains a long-standing challenge.Herein,a highly efficient,versatile,and universal Cucatalyzed asymmetric hydroamination of cinnamyl esters,cinnamyl phosphonates,and cinnamyl phosphine oxides is presented for accessing γ-amino acid andγ-amino phosphonic acid derivatives in good yields with high levels of enantiocontrol and regioselectivity.

Copper-Catalyzed Asymmetric Hydroamination:A Unified Strategy for the Synthesis of Chiralβ-Amino Acid and Its Derivatives

Catalytic asymmetric aza-Michael represents one of the most convenient and atom-economical approaches for the rapid construction of biologically active chiralβ-amino acid frameworks.However,the direct enantioselective addition of nitrogen-based nucleophiles to intrinsically low reactivity ofα,β-unsaturated carboxylic acid,ester,and amide,as well as simpleα,β-unsaturated nitrile,remains a long-standing challenge.

An Efficient and Green Approach to Synthesizing Enamines by Intermolecular Hydroamination of Activated Alkynes

An efficient, atom-economic and green approach to synthesizing enamines was developed by intermolecular hydroamination of activated alkynes with high yields under catalyst- and solvent-free conditions. β-Dimethylamino-acrylate derivatives were also obtained with high yields. In the synthetic process of the derivatives, N,N-dimethylformamide（DMF） pretreated with metal Na, was used as reactant instead of dimethylamine gas. The proposed synthetic method can be used for the synthesis of （E）-ethyl-3-（dimethylamino）acrylate（3cl）, and provide a new possible way to the synthesis of Quinolones.

Cobalt-Catalyzed Intermolecular Hydroamination of Unactivated Alkenes Using NFSI as Nitrogen Source

Cheap metal(Fe,Mn,and Co)-catalyzed hydroamination of alkenes has been an attractive method for synthesis of amines because of biocompatibility of metal,excellent Markovnikov selectivity and chemoselectivity.However,most reports are limited to unsaturated nitrogen sources(nitric oxide,azos,azides,cyano,etc.),for which aminated products are very limited.Notably,while used widely for fluorinating reaction,N-fluorobenzenesulfonimide(NFsI)as amine source for hydroamination has seldom been reported.Here we developed a cobalt-catalyzed intermolecular hydroamination of unactivated alkenes using NFSl as nitrogen source under mild conditions.The reaction exhibits excellent chemo-and regio-selectivity with no hydrofluorination or linear-selectivity products.Notably,the reaction proceeded with excellent yield even though the amount of Co(salen)catalyst was reduced to 0.2 mol%.Recently,a similar work was also reported by Zhang and coworkers(ref.19).

Origins of catalyst-controlled enantiodivergent hydroamination of enones with pyridazinones:A computational study

Density functional theory calculations have been performed to investigate the dipeptide phosphinecatalyzed hydroamination of enones with pyridazinones.The computations reveal that a number of the N-H...O hydrogen-bonding interactions with the pyridazinone moiety and the C–H...O hydrogenbonding interactions with the enone moiety are present in the enantioselectivity-determining Michael addition transition states.The experimentally-observed catalyst-controlled enantiodivergence is mainly attributed to the significant impact of the substituent of the amide moiety of the dipeptide phosphine on the relative strength of the N-H...O hydrogen-bonding interactions,which was found to affect the Si face attack transition state,enabling the enantioselectivity switch upon change of chiral dipeptide phosphine catalyst.

Mesoporous silicon sulfonic acid as a highly efficient and stable catalyst for the selective hydroamination of cyclohexene with cyclohexylamine to dicyclohexylamine in the vapor phase

In this work,a new mesoporous silicon sulfonic acid catalyst derived from silicic acid has been successfully prepared by the chemical bonding method.The physicochemical properties of mesoporous silicon sulfonic acid catalysts have been systematically characterized using various techniques.The results demonstrate that sulfonic acid groups have been grafted on silicic acid by forming a new chemical bond(Si-O-S).The mesoporous silicon sulfonic acid exhibits excellent catalytic performance and stability in the vapor phase hydroamination reaction of cyclohexene with cyclohexylamine.Cyclohexene conversion of 61% and 97% selectivity to dicyclohexylamine was maintained after running the reaction for over 350 h at 280℃.The developed mesoporous silicon sulfonic acid catalyst shows advantages of low cost,superior acid site accessibility,and long term reactivity stability.Moreover,a possible catalytic hydroamination reaction mechanism over silicon sulfonic acid was suggested.It has been demonstrated that the sulfonic acid groups of the catalyst play an important role in the hydroamination.The present work provides a simple,efficient,and environmentally friendly method for the hydroamination of cyclohexene to valuable dicyclohexylamine,which also shows important industrial application prospects.

Visible-light-driven Hydroamination of Alkynes over a New Type of Activated Carbon Immobilized Cu^(2+)Photocatalyst

A new type of activated carbon immobilized copper(Cu/AC)photocatalyst was prepared by a facile impregnation-adsorption method,where Cu^2+is chemically adsorbed by abundant oxygenated functional groups on large-surface-area activated carbon surface.Cu/AC exhibited good activity and selectivity to imine for the hydroamination of alkynes at 60℃under visible light irradiation.The reaction is initialized by the activation of alkynes molecules at Cu active sites with the aid of light as evidenced by the solid-state NMR and laser photolysis measurements and the control experiments.This strategy for catalyst design is potentially extended to the immobilization of other metal homogeneous catalysts for various heterogeneous catalytic systems.

Stereoselective Synthesis of 2-Deoxy-α-N-Glycosides from Glycals with 1,4,2-Dioxazol-5-ones

The synthesis of N-glycosides has received significant attention due to their crucial role in carbohydrate chemistry.Despite considerable advancements developed in the construction of N-glycosides,methods for the stereoselective construction of 2-deoxy-α-N-glycosides are still limited.Herein,we disclosed a nickel-catalyzed hydroamination of glycals under mild conditions.This transformation could allow for the stereoselective synthesis of an array of 2-deoxy-α-N-glycosides with excellentα-stereoselectivity.Nickel-catalyzed glycosylation reactions,particularly those involving anomeric C(sp")-metal bond formation,have proven to be an effective and stereoselective strategy for producing various N-glycosides.Additionally,with highlight of the application of this reaction,y-sugar amino acidderivatives weresynthesized.

Cobalt-Catalyzed Difunctionalization of Styrenes via Ligand Relay Catalysis

Here,we report a cobalt-catalyzed sequential dehydrogenative Heck silylation/hydroamination of styrenes with hydrosilane and diazo compound to access 1-amino-2-silyl compounds with excellent regioselectivity.This difunctionalization reaction could undergo smoothly using 1 mol%catalyst loading with good functional group tolerance.Not only di-and tri-substituted hydrosilanes,but also alkoxysilane is suitable,which does explore the scope of the family of 1-amino-2-silyl compounds.The ligand relay phenomenon between neutral tridentate NNN ligand and anionic NNN ligand is observed for the first time via absorption spectral analysis in this one-pot,two-step transformations.The primary mechanism has been proposed based on the control experiments.

Synthesis and Insecticidal Structure-Activity Relationships of Novel Tonghaosu Analogs

Twenty-one tonghaosu analogs were synthesized via hydroamination or selective reduction of the endocyclic double bond of the corresponding dienol spiroketals. Structures of all the new compounds were confirmed by ^1H NMR, IR, MS, HREIMS or elemental analysis. Their antifeedant activity against large white butterfly （Pieris brassicae L） and larvicidal activity toward mosquito （Culex quinquefasciatus Say） were examined. Some of them exhibited antifeeding activities comparable to or stronger than tonghaosu Z-1. Based on the activity data, the preliminary structure-activity relationship was also discussed, which might be instructive for finding out lead compounds with better bioactivities in the future.