Chunlin Zhang

• Ph.D.
• ap at Institute of Chemistry, Chinese Academy of Sciences

C─B axially chiral architectures are valuable in materials science and medicinal chemistry, but their enantioselective synthesis remains a challenge. Herein, we report an efficient method for the enantioselective synthesis of C─B axially chiral 1,2‐azaborines through N‐heterocyclic carbene‐catalyzed dynamic kinetic resolution. The treatment of race...

C‐B axially chiral architectures are valuable in materials science and medicinal chemistry, but their enantioselective synthesis remains a challenge. Herein, we report an efficient method for the enantioselective synthesis of C‐B axially chiral 1,2‐azaborines through N‐heterocyclic carbene‐catalyzed dynamic kinetic resolution. Treatment of racemic...

N‐heterocyclic carbene catalysis has been developed as a versatile method for the enantioselective synthesis of complex organic molecules in organic chemistry. Merging of N‐heterocyclic carbene catalysis with transition metal catalysis holds the potential to achieve unprecedented transformations with broad substrate scope and excellent stereoselect...

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access diaryl ether atropisomers. Herein, we report the N‐heterocyclic carbene‐catalyzed enantioselective synthesis of axially chiral diaryl ethers via desymmetrization of pr...

Axially chiral diaryl ethers present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access diaryl ether atropisomers. Herein, we report the N‐heterocyclic carbene‐catalyzed enantioselective synthesis of axially chiral diaryl ethers via desymmetrization of prochi...

An NHC-catalyzed atroposelective synthesis of axially chiral α-carbolinones from α,β-unsaturated iminoindole derivatives and α-chloroaldehydes was developed. The reaction proceeds through a cascade process including [4 + 2] annulation and then oxidative dehydrogenation with concomitant central-to-axial chirality conversion under mild conditions. Th...

Direct synthesis of ketones from aldehydes features high atom- and step-economy. Yet, the coupling of aldehydes with unactivated alkyl C(sp³)-H remains challenging. Herein, we develop the synthesis of ketones from aldehydes via alkyl C(sp³)-H functionalization under photoredox cooperative NHC/Pd catalysis. The two-component reaction of iodomethylsi...

N‐heterocyclic carbene (NHC)‐catalyzed enantioselective Mannich‐type reactions of the biomass‐derived platform compound 5‐(chloromethyl)furfural (CMF) with imines were developed. A series of high‐value‐added chiral amines were afforded in good to high yields with excellent regio‐ and enantioselectivities. The bifunctional NHC derived from ʟ‐pyroglu...

N‐heterocyclic carbene (NHC)‐catalyzed enantioselective Mannich‐type reactions of the biomass‐derived platform compound 5‐(chloromethyl)furfural (CMF) with imines were developed. A series of high‐value‐added chiral amines were afforded in good to high yields with excellent regio‐ and enantioselectivities. The bifunctional NHC derived from ʟ‐pyroglu...

The iminoacylation of alkenes via photoredox N-heterocyclic carbene catalysis is developed with the employment of alkene-tethered α-imino-oxy acids and acyl imidazoles. The corresponding substituted 3,4-dihydro-2H-pyrroles were afforded in moderate to good yields with good to high diastereoselectivities in most cases. The reaction involves the 5-ex...

The NHC-catalyzed benzannulation of enals and β-trifluoromethylenones is developed for the synthesis of benzotrifluorides. This process involves NHC-catalyzed [4+2] annulation/lactonization/decarboxylation/oxidative aromatization cascade. The reaction features mild reaction conditions, excellent functional...

Three-component carboacylation of simple alkenes with readily available reagents is challenging. Transition metal-catalysed intermolecular carboacylation works for alkenes with strained ring or directing groups. Herein, we develop a photoredox cooperative N-heterocyclic carbene/Pd-catalysed alkylacylation of simple alkenes with aldehydes and unacti...

The cooperative N-heterocyclic carbene/nickel-catalyzed redox-neutral hydroacylation of 1,3-dienes with aldehydes in water was reported. A wide range of aliphatic and aromatic aldehydes were directly coupled with 1,3-dienes, providing synthetically useful β,γ-unsaturated ketones or the corresponding ketones after hydrogenation in moderate to high y...

N-heterocyclic carbene-catalyzed intramolecular aza-Michael addition of alkyl amines to α,β-unsaturated carboxylic acid has been realized. The corresponding pyrrolidine and piperidine derivatives can be obtained in good to excellent yields. Reaction using chiral NHC catalyst showed promising enantioselectivities up to 55% ee. Further chemical trans...

Axially chiral biaryl scaffolds are prevalent in natural products, chiral ligands, and organocatalysts. However, N‐heterocyclic carbene (NHC) catalyzed de novo construction of an aromatic ring with concomitant axial chirality induction for the synthesis of biaryl atropisomers is far less developed, and the efficient synthesis of axially chiral tetr...

The N‐heterocyclic carbene catalyzed enantioselective de novo synthesis of axially chiral benzothiophene/benzofuran‐fused biaryls from enals and 2‐benzylbenzothiophene/benzofuran‐3‐carbaldehydes has been developed. This cascade process comprises a [2+4] annulation, decarboxylation, and oxidative aromatization with central‐to‐axial chirality convers...

Following the well-recognized dynamic kinetic resolution (DKR) of hemiaminals with α-hydrogen under lipase and chiral DMAP catalysis, the unprecedented DKR of hemiaminals without α-hydrogen was developed via N-heterocyclic carbene catalyzed O-acylation of 3-hydroxy-3-trifluoromethylbenzosultams. The racemic hemiaminals without α-hydrogen were effec...

N-heterocyclic carbene/copper-cocatalyzed [4 + 3] annulation of salicylaldehydes with aziridines was developed, giving the corresponding 1,4-benzoxazepinones in good yields with exclusive regioselectivity. Copper serves as a Lewis acid to activate the small strained aziridines, and the formation of NHC-salicylaldehyde adduct plays an important role...

A general strategy for the synthesis of tetrahydroquinolines and 1,4‐benzoxazepines has been developed via palladium‐catalyzed [4+2] and [5+2] annulations of propargyl carbonates with malonate‐tethered anilines and 2‐aminobenzylic alcohols. A series of six‐ and seven‐membered heterocycles with potential bioactivities was obtained in good to excelle...

The N-heterocyclic carbene-catalyzed β-addition of enals to 3-alkylenyloxindoles was developed. All of β-aryl, β-alkenyl and β-alkyl enals worked well for the reaction to give the corresponding 3,3-disubstituted oxindoles bearing contiguous...

The N‐heterocyclic carbene catalyzed [8+2] oxidative annulation of tropone with aldehydes was developed, giving cycloheptatriene‐fused furanones in moderate to good yields. Further reduction of the cycloadducts afforded cycloheptane‐fused furanones and dihydrofuranones in good yields. image

The N‐heterocyclic carbene (NHCs)‐catalyzed generation of azolium enolates has been well developed from various organic compounds. The first reported NHC‐catalyzed reaction involving azolium enolate intermediate was the redox reaction a‐functionalized aldehydes. In recent years, NHCs have also been demonstrated as efficient catalysts for the cycloa...

A metal-free photocatalytic protocol for the synthesis of internal alkynes via the radical C(sp3)–C(sp) coupling of alkynyl bromides and Hantzsch esters was developed. The reaction went smoothly under mild conditions...

The N‐heterocyclic carbene‐catalyzed [4+2] annulation of enals with α‐iminophosphonates was developed to give the corresponding cyclic α‐aminophosphonates in high yields with excellent enantioselectivities. Organocatalysis: The NHC‐catalyzed [4+2] annulation of enals and α‐iminophosphonates was developed to give the corresponding α‐aminophosphonate...

A DBU-mediated synthesis of 1,3,5-trisubstituted benzenes was developed via the [2+4] annulation of in situ activated α,β-unsaturated carboxylic acids and α-cyano-β-methylenones. The dual role of DBU as Brønsted base and nucleophilic Lewis base is the key for the success of the reaction.

The switchable visible-light-mediated decarboxylative Heck-type reaction and oxo-alkylation reaction of N-hydroxyphthalimide esters under photocatalysis were developed. Disubstituted or trisubstituted alkenes were obtained in good yield with high E-selectivity in the presence of Brønsted acid as the additive, while ketones resulted in the absence o...

The N‐heterocyclic carbene‐catalyzed [2+3] and [2+4] annulations of α‐chloroaldehydes with γ‐/δ‐amino‐α,β‐unsaturated ketones were developed, giving the corresponding pyrrolidones and piperidones in good yields with exclusive trans‐selectivities and excellent enantioselectivities. Pyrrolidones and piperidones: The N‐heterocyclic carbene‐catalyzed [...

The N-heterocyclic carbene-catalyzed tandem reaction of bromoenals and oxindoles was developed to give the corresponding chiral spirocyclopentene-oxindoles in good yields with good to high diastereo- and enantioselectivities.

A direct and efficient approach to 1,3,5-trisubstituted benzenes has been developed via N-heterocyclic carbene-catalyzed [2 + 4] annulation of α-bromoenals and α-cyano-β-methylenones. The reaction worked well for both aryl- and alkylenones.

The products are delivered in high yields and with excellent enantioselectivities.

An oxidative NHC‐catalyzed [2+4] annulation of enals and α‐cyano‐β‐methylenones was established for the rapid assembly of multi‐substituted benzenes. magnified image

The enantioselective N-heterocyclic carbene-catalyzed [2 + 4] cyclocondensation of α-chloroaldehydes and saccharine-derived 1-azadienes was developed, giving the corresponding saccharine-derived dihydropyridinones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

A new [3 + 2] annulation of α-bromoenals and 3-aminooxindoles is reported.

The chiral N-heterocyclic carbene-catalyzed [3 + 2] annulation of α-bromoenals and 3-aminooxindoles was developed, giving the corresponding spirocyclic oxindolo-γ-lactams in good yields with high diastereoselectivities and enantioselectivities.

The N-heterocyclic carbene-catalyzed generation of dienoate from α,β-unsaturated carboxylic acid via the in situ formed mixed anhydride, and the following [4 + 2] annulation with hydrazones and isatin-derived imines was developed, affording the corresponding dihydropyridinones and spirocyclic oxindolodihydropyridinones, respectively, in moderate to...

The N-heterocyclic carbene-catalyzed [3 + 3] cyclocondensation of bromoenals and hydrazones is developed to give the corresponding chiral 4,5-dihydropyridazones in good yields with excellent enantioselectivities.

The catalytic cyclocondensation of in situ activated α,β-unsaturated carboxylic acids was developed. N-heterocyclic carbenes efficiently catalyzed the generation of α,β-unsaturated acyl azolium intermediates from α,β-unsaturated carboxylic acids via in situ generated mixed anhydrides for the enantioselective [3+2] and [3+3] cyclocondensation with α...

The catalytic cyclocondensation of in situ activated α,β-unsaturated carboxylic acids was developed. N-heterocyclic carbenes efficiently catalyzed the generation of α,β-unsaturated acyl azolium intermediates from α,β-unsaturated carboxylic acids via in situ generated mixed anhydrides for the enantioselective [3+2] and [3+3] cyclocondensation with α...

Clofazimine, a member of the riminophenazine class, is one of the few antibiotics that are still active against multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). However, the clinical utility of this agent is limited by its undesirable physicochemical properties and skin pigmentation potential. With the goal of maintaining potent an...

An efficient and eco-friendly protocol for the chemoselective N-benzyloxycarbonylation of amines was described. The reaction of amines with benzyl chloroformate (Cbz-Cl) in the presence of PEG-600 at room temperature afforded the corresponding N-Cbz derivatives in excellent yields. The method is applicable to the N-Cbz protection of aliphatic (acyc...

A series of novel riminophenazine derivatives bearing an alkyl substituent attached to N-5 and imino nitrogen at C-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. All target compounds were prepared by utilizing simple and flexible...