Understanding how charge-charge interaction affects the stereochemistry of enamine fluorination by chiral primary amine catalysis

Electrostatic interaction, especially electrostatic attraction, usually plays critical roles in controlling the reactivity and selectivity in catalytic transformations;however, the like-charge repulsion, which is ubiquitous in physical systems, is rarely applied in reaction control. Herein we disclosed an unexpected like-charge repulsion induced enantio-control mode in primary aminecatalyzed fluorination reactions with 1-fluoro-2,4,6-trimethylpyridinium triflate. The ionic reaction works favorably in both highly polar(methanol) and non-polar(hexane) solvents, a seldom observed phenomenon in asymmetric catalysis. Erying plot analysis showed that an inversion temperature existed in Me OH, which was explained by the solvent-solute cluster model under different temperatures. Density functional theory(DFT) study and energy decomposition analysis(EDA) verified that the likecharge repulsion takes effect in polar solvent methanol, while in nonpolar solvents, the steric repulsion associated with ion-pair was found to be the major effect for the observed enantioselectivity.

Bio-inspired Small Molecular Catalysis

What is the most favorite and original chemistry developed in your researchgroup?I hope it's always the next one.How do you get into this specific field?Could you please share some experiences with ourreaders?Nature provides many astonishing catalytic machineries for building up molecular complexity and harnessing energy in the most efficient ways.Nature's recipe for catalysis serves as a starting point to develop new catalyst for synthetic and energy chemistry.

Biomimetic asymmetric catalysis

Enzymes are the core for biological transformations in nature.Their structures and functions have drawn enormous attention from biologists as well as chemists since last century.The large demand of bioactive molecules and the pursuit of efficiency and greenness of synthesis have spurred the rapid development of biomimetic chemistry in the past several decades.Biomimetic asymmetric catalysis,mimicking the structures and functions of enzymes,has been recognized as one of the most promising synthetic strategies for the synthesis of valuable chiral compounds.This review summarizes the evolution of asymmetric catalysis inspired by aldolases,vitamin B_(1)/B_(6)-dependent enzymes,NAD(P)H,flavin,hydrogenases,heme oxygenases,nonheme oxygenases,and dinuclear/multinuclear metalloenzymes in aspects of biomimetic design,catalyst development and related catalytic transformations.Those well-established synthetic approaches originating from biological reactions have demonstrated the unique prowess of biomimetic asymmetric catalysis in bridging the gap between bio-catalysis and chemical synthesis.

Asymmetric α-Pentadienylation of β-Ketocarbonyls and Aldehydes by Synergistic Pd/Chiral Primary Amine Catalysis

Direct alkylation with skipped enynes or cyclopropropylacetylenes represents an ideal process for the installation of pentadienyl group in terms of atom- and step-economy.The development of catalytic asymmetric versions has been frequently pursued and most of the successes have been achieved with enolizable aldehydes.We herein describe a synergistic chiral primary amine/Pd catalysis for asymmetric α-pentadienylation of β-ketocarbonyls and aldehydes with skipped enynes or cyclopropropylacetylenes.The reaction features the construction of acyclic all-carbon quaternary centers with high enantioselectivity,and good functional group tolerance and scalability.

Recent Progress of Asymmetric Catalysis from a Chinese Perspective

The precise construction of chiral molecules is a core research area in chemical science and technology.Among the plethora of reported synthetic methods,asymmetric catalysis has emerged as one of the most efficient and direct ways to obtain optically pure chiral compounds.This article mainly reviews the recent progress of asymmetric catalysis made by Chinese chemists from the following aspects:the development of new chiral ligands,transition metal-catalyzed asymmetric reactions,asymmetric organocatalytic reactions,and new strategies for asymmetric catalysis.This review does not intend to be comprehensive;only representative examples are selected to highlight the important progress made in this field.Finally,a brief outlook is given on the development of novel chiral ligands/catalysts,new enantioselective reactions,and their applications in chiral drugs and agricultural chemicals.

Visible Light Promoted Direct Deuteration of Alkenes via Co(III)–H Mediated H/D Exchange

We report herein a visible light-mediated direct deuteration of alkenes with D_(2)O or deuterated methanol(MeOD)using a cobaloxime as a hydrogen/deuterium(H/D)exchange catalyst.The synergistic photoredox/Co catalysis enabled facile deuterium(D)-incorporation of a variety of terminal and internal alkenes at either terminal or benzylic positions.We proposed that this process proceeded through a sequence of reversible addition-elimination reactions and fast proton exchange involving Co(III)–H,which was generated in situ by photoreduction.

Visible Light Promoted β-C-H Alkylation of β-Ketocarbonyls via a β-Enaminyl Radical Intermediate

A 5πe carbonyl activation mode is reported on the basis of photo-induced single-electron-transfer （SET） oxidation of a secondary enamine. The resultant β-enaminyl radical intermediate was trapped by a wide range of Michael acceptors, producing β-alkylation products of β-ketocarbonyls in a highly efficient manner,

Asymmetric α-Alkylation of β-Ketocarbonyls via Direct Phenacyl Bromide Photolysis by Chiral Primary Amine

Enantioselective α-photoalkylation of β-ketocarbonyls without any external photosensitizer was described in this work. The photoalkylation reactions, enabled solely by a chiral primary amine catalyst, provided convenient constructions of all-carbon quaternary stereocenters with good activity and high enantioselectivity. Mechanism studies revealed α direct photolytic radical chain process under visible light irradiation.

Catalytic Asymmetric Addition and Telomerization of Butadiene with Enamine Intermediates

Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.

Primary-Tertiary Diamine/Brønsted Acid Catalyzed α-Allylation of Carbonyl Compounds with Allylic Alcohols

A simple and directα-allylic alkylation of unmodified aldehydes with allylic alcohols catalyzed by primary amine/Brønsted acid has been developed.The N,N-dimethylethylenediamine/TfOH was identified as the optimal catalyst to promote this transformation via an enamine process in high yields(up to 88%)and with good diastereoselectivities(up to 9∶1).

Bio-inspired quinone catalysis

Quinoproteins are an important type of redox enzymes for biological oxidation processes. Inspired by the quinone cofactors, particularly from copper amine oxidases, a number of small molecular quinone catalysts have been developed for C-H functionalizations of amines. Bio-inspired quinone catalysts have significantly expanded the substrate scope to include branched primary amines, secondary amines and tertiary amines, far beyond the scope of quinoproteins. This review summarizes the evolution of quinone catalysts, their mechanism and catalytic applications.

Catalytic asymmetric oxidative sulfenylation of β-ketocarbonyls using a chiral primary amine

Enantioselective oxidative construction of a C(sp^(3))–S bond has been achieved using a chiral primary amine catalyst in the presence of tert-butyl hydroperoxide and a catalytic amount of tetrabutylammonium iodide.The distinctive feature of the current reaction is coupling with nucleophilic sulfur reactants under oxidative conditions.This protocol provides facile access to chiral thioethers bearing S-containing quaternary stereocenters with good chemo-and enantiocontrol.