Song Ye

• 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...

Organocatalyzed direct and asymmetric functionalization of benzylic C(sp³)─H bond is attractive yet challenging. Herein, we report the enantioselective acylation of benzylic C(sp³)─H bond via a cooperative photoredox and N‐heterocyclic carbene (NHC) catalysis, affording the corresponding chiral α‐aryl ketones in moderate to good yields with good to...

Organocatalyzed direct and asymmetric functionalization of benzylic C(sp3)−H bond is attractive yet challenging. Herein, we report the enantioselective acylation of benzylic C(sp3)−H bond via a cooperative photoredox and N‐heterocyclic carbene (NHC) catalysis, affording the corresponding chiral α‐aryl ketones in moderate to good yields with good to...

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...

Both furan and 1,4‐dihydropyridine (1,4‐DHP) are key structural motifs in pharmaceuticals. Herein, we report the synthesis of 4‐(furan‐2‐ylmethyl)‐1,4‐dihydropyridines from pyridiniums and furfural derivatives under NHC catalysis. This reaction involves the generation of NHC‐bounded trienolates from furfural derivatives and following addition to th...

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...

The cooperative visible-light mediated and NHC-catalyzed dearomative arylation-acylation of N-(2-bromobenzoyl)indoles with aldehydes was developed, affording the corresponding highly functionalized polycyclic indolines in moderate to good yields with exclusive diastereoselectivities. Mechanism investigations support the activation of CAr–Br bond vi...

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...

Deuterium incorporation at selective sites of organic compounds has long attracted the interest of pharmaceutical industry. Here, we present a distal p-benzylic deuteration via N-heterocyclic carbene catalyzed ring-opening of cyclopropylbenzaldehydes...

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 se...

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 enantioselective α‐oxidative coupling of enals with carboxylic acids was developed via the umpolung of an NHC‐bound enolate with an iodine(III) reagent. The corresponding α‐acyloxyl‐β,γ‐unsaturated esters were afforded in good yields, with high regio‐ and enantioselectivities. The key step of the reaction involves the formation of enol iodine(I...

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 enantioselective α‐oxidative coupling of enals with carboxylic acids was developed via the umpolung of NHC‐bound enolate with iodine(III) reagent. The corresponding α‐acyloxyl‐β,γ‐unsaturated esters were afforded in good yields, with high regio‐ and enantioselectivities. The key step of the reaction involves the formation of enol iodine(III) in...

β-Lactones are common substructures in bioactive molecules. Herein, we developed an enantioselective N‑heterocyclic carbene (NHC)-catalyzed rearrangement of enol ε-lactones for the construction of bicyclic β-lactones. The reaction works well for...

The ε-benzylation of γ-alkenyl-γ-oxidized enals via dual photoredox and N-heterocyclic carbene catalysis has been developed, affording the corresponding ε-benzyl-α,β-γ,δ-bisunsaturated esters in moderate to good yields with exclusive regioselectivities. The reaction is proposed via the generation of benzyl radical under photocatalysis, followed by...

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...

By the cooperative photoredox and N-heterocyclic carbene catalysis, the γ-difluoroalkylation of γ-preoxidized enals was developed for the synthesis of γ-difluoroalkyl-α,β-unsaturated esters with all-carbon quaternary centers. This method provides efficient catalytic C(sp3)-CF2R bond formation at the γ-position of carbonyl compounds for the first ti...

The N-heterocyclic carbene (NHC)-catalyzed reactions involving two-electron reaction pathway have been well-established. However, the development of NHC-catalyzed radical reactions is still in its infancy in terms of reaction types and enantioselectivity. In the past decade, several elegant NHC-catalyzed radical reactions have been developed, inclu...

Nature produces ∼170 billion tons of biomass per year; meanwhile, only a small percentage is used. Cellulose is the most abundant component in biomass; thus, the selective transformation of cellulose to high-value-added products is one of the most promising pathways to sustainable society. Here, we report an N-heterocyclic carbene-catalyzed umpolun...

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...

An N‐heterocyclic carbene catalyzed photooxidation reaction via intramolecular cross dehydrogenative coupling of tetrahydroisoquinoline‐tethered aldehydes was developed, giving the corresponding oxidative cyclization products in moderate to good yields. This reaction features mild conditions with oxygen as the terminal oxidant in the absence of pho...

ConspectusIn nature, enzymes are a powerful medium for the construction of enantiomerically pure chemicals, which always inspires synthetic chemists to explore new catalysts to imitate the enzyme machinery for asymmetric transformations. Vitamin B1, a bifunctional thiazolium N-heterocyclic carbene (NHC) precursor, is the coenzyme for transketolase....

An unprecedented photo/NHC-co-catalyzed ring-opening C-C bond cleavage of cyclopropane enal and the following γ-alkylation with a halogenated compound via radicals were established, affording the corresponding γ-alkylated α,β-unsaturated esters in moderate to good yields.

The N-heterocyclic carbene/photo-cocatalyzed oxidative Smiles rearrangement of O -aryl salicylaldehydes was developed. Both electron-deficient and electron-rich aryls worked well as the migrating group, giving the corresponding aryl salicylates in good yields....

An unprecedented NHC-catalyzed generation of p-quinodimethanes via ε-umpolung of 4-(chloromethyl)benzaldehydes and the following ε-addition to active ketones was developed. A series of active ketones, such as trifluoromethyl ketones and 1,2-dicarbonyl compounds worked well for the reaction, giving the corresponding trifluoromethyl alcohols and α-hy...

The merging of photoredox catalysis and N‐heterocyclic carbene (NHC) catalysis for γ‐ and ϵ‐alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ‐oxidized enals with alkyl halides worked well for the synthesis γ‐multisubstituted‐α,β‐unsaturated esters, including those with challenging vicinal all‐carbon quaternary cent...

The merging of photoredox catalysis and N‐heterocyclic carbene (NHC) catalysis for γ‐ and ϵ‐alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ‐oxidized enals with alkyl halides worked well for the synthesis γ‐multisubstituted‐α,β‐unsaturated esters, including those with challenging vicinal all‐carbon quaternary cent...

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...

Visible light promtoed oxo-difluoroalkylation (acetylation and acetamidation) of alkenes with DMSO as both the solvent and the oxidant was developed, affording the corresponding α,α-difluoro-γ-ketoacetates and acetamides in good yields. Both terminal and internal alkenes worked well for the reaction. This reaction features simple starting materials...

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

A visible light mediated oxidative lactonization of 2-methyl-1,1’-biaryls was developed, giving benzocoumarins in good yields. The reaction features multiple C-H functionalization with oxygen as the final oxidant. The corresponding 2-aldehdyes,...

Annulation: N‐heterocyclic carbene‐catalyzed synthesis of 2,2′‐dihydroxybenzophenones from β‐methylenals and aurones was developed. The cleavage of the C−O bond by retro‐Michael addition is the key step from the spirocyclic intermediate to final product (see scheme). 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...

The bifunctional N-heterocyclic carbene catalyzed [3+4] annulation of acyclic enals with aurone-derived azadienes was reported. The challenging β,β-disubstituted enals and β-monosubstituted enals reacted well to afford the corresponding benzofuroazepinones in...

The S factor: The enantioselective N‐heterocyclic carbene (NHC) catalyzed [3+3] annulation of α‐bromoenals by dynamic kinetic resolution (DKR) of enamines, and normal resolution of α,α‐disubstituted imines were developed. The corresponding substituted dihydropyridones were isolated in good yields with excellent diastereo‐ and enantioselectivities,...

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 enantioselective N‐heterocyclic carbene catalyzed [3+3] annulation of α‐bromoenals by dynamic kinetic resolution (DKR) of enamines and normal resolution of α,α‐disubstituted imines were developed. The corresponding substituted dihydropyridones were isolated in good yields with excellent diastereo‐ and enantioselectivities, and a high selective...

Herein, we report an enantioselective synthesis of azepinones via the N-heterocyclic carbene (NHC) catalyzed [3 + 4] annulation reaction of isatin-derived enals and aurone-derived azadienes. The corresponding spirocyclic oxindole-benzofuroazepinones were obtained in good yields, with excellent diastereo- and enantioselectivities. The resulted azepi...

The [3 + 4] and [2 + 4] annulations of bromoenals and 1,2-benzenedithiol were developed in the presence or absence of N-heterocyclic carbene, respectively. Control experiment and kinetic investigation revealed the [3 + 4] annulation involves the base-promoted [2 + 4] annulation and the following carbene-catalyzed ring-expansion.

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 chiral N-heterocyclic carbene-catalyzed [4 + 2] annulation of α-chloroaldehydes and aurones was developed, giving the corresponding benzofuran–fused dihydropyranones in good to high yields with good diastereoselectivities and excellent enantioselectivities. The catalytic cycle features with the generation of enolate from chloroaldehdye and its...

The oxidative N-heterocyclic carbene-catalyzed [3 + 2] annulation of β,β-disubstituted enals and dioxindoles was developed, giving the spirocyclic oxindole-γ-lactones bearing two contiguous tetrasubstituted stereocenters in good yields with excellent diastereo- and good enantioselectivities.

DFT computations have been performed to gain insight into the mechanisms of formylation/methylation of amines (e.g. methylaniline(1a)/2,2,4,4,-tetramethylpiperidine (2a)) with CO2 and hydrosilane ([Si]H2, [Si]=Ph2Si), catalyzed by 1,3,2-diazaphospholene ([NHP]H). Different from the generally proposed sequential mechanism for methylation of amine wi...

The [4+2] and [3+2] annulations of α‐chloroaldehydes with dithioesters are reported. In the presence of an N‐heterocyclic carbene (NHC) catalyst, the [4+2] annulation went smoothly to afford highly substituted 1,4‐oxathiin‐2(3 H )‐ones, while the [3+2] annulation was observed to give 1,3‐oxathioles in the absence of an NHC. magnified image

The N-heterocyclic carbene catalyzed [3 + 3] annulation of indolin-2-imines and bromoenals was developed to give dihydropyridinone-fused indoles in good to high yields, which were transformed to α-carbolines with different 2-subsituents by a process of dehydrogenation, tosylation, and palladium catalyzed C–C or C–N coupling reaction.

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 N‐heterocyclic carbene‐catalyzed [3+3] annulation of indoline‐2‐thiones and bromoenals has been developed, giving the corresponding indolo[2,3‐ b ]dihydrothiopyranones in high yields. magnified image

The N-heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindole and enals was developed, giving the corresponding spirocyclic oxindole-γ-lactones in good yields with high to excellent diastereo- and enantioselectivities. The challenging aliphatic enals worked effectively using this strategy. The oxidative cross coupling of homoenola...

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.

The bifunctional N-heterocyclic carbene catalyzed [3+4] annulation of enals and 5-alkenyl thiazolones was developed, giving the corresponding thiazole-fused Epsilon-lactones in high yields with excellent diastereoselectivties and enantioselectivities. The thiazole-fused Epsilon-lactone could be isomerized to the spirocyclic thiazolone-cyclopentanon...

In the presence of quinone, a Brønsted acid catalyzed intramolecular C-N bond formation of o-vinyl anilines via electrophilic cyclization was developed, giving the corresponding N-arylindoles in good to high yields. The reaction worked well for the o-vinyl anilines with terminal and internal C-C double bonds.

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 cascade reaction of enals with malonates to give bicyclic δ-lactones was developed. The cyclopentane- and cyclohexane-fused δ-lactones with three continued stereocenters were obtained in high yields with excellent diastereo- and high enantioselectivities.

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 N-heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals with aldimines was developed to give the corresponding dihydropyridinones in good yields with excellent enantioselectivies.

The chiral N-heterocyclic carbene-catalyzed [4 + 2] annulation of alpha-chloroaldehydes and arylidene indanediones was developed, giving the corresponding indenopyrones in good yields with high diastereoselectivities and enantioselectivities.

An N-heterocyclic carbene-catalyzed enantioselective [2 + 3] cyclocondensation of α-chloroaldehydes with azomethine imines was developed. The corresponding pyrazolidinones were obtained in good yields with moderate to good diastereoselectivities and excellent enantioselectivities.

The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of alpha-chloroaldehydes and trifluoromethyl N-Boc azadienes was developed, giving the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

Although the NHC-catalyzed cyclization reactions have been well established for the synthesis of various heterocycles, the corresponding all carbon cyclization reaction for the synthesis of carbocycles is far less established. In this note, the NHC-catalyzed all carbon [4+2] cyclocondensation of α,β-unsaturated acyl chlorides and 3-alkenyloxindoles...

The N-heterocyclic carbene catalyzed (NHC-catalyzed) generation of unsubstituted dienolate (butadienolate) and subsequent [4+2] annulation reactions with isatins afford chiral spirocyclic oxindolodihydropyranones in moderate to good yields with moderate to good enantioselectivities.

Bifunctional N-heterocyclic carbenes with a free hydroxy group are demonstrated as efficient catalysts for the [3+4] annulation of enals with aurones to give the corresponding benzofuran-fused ε-lactones in good yields with good diastereoselectivities and excellent enantioselectivities. Control experiments reveal that the [3+4] cycloadducts are kin...

The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of 2-aryl carboxylic acids and enones was developed, affording the corresponding chiral δ-lactones in good yields with good diastereo- and high enantioselectivities.

The N-heterocyclic carbene-catalyzed enantioselective [3+3] cyclocondensation of bromoenals and ketimines was developed. The reaction gives the corresponding dihydropyridinones in high yields with high enantioselectivity.

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...

The N-heterocyclic carbene (NHC)-catalyzed enantioselective cycloaddition reactions of ketenes are powerful methods for the synthesis of chiral heterocycles. Followed by the previous reported NHC-catalyzed [2+2] and [4+2] cycloaddtion of ketenes with imines, ketones and various heterodienes, the NHC-catalyzed enantioselective [4+2] cycloaddition of...

The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin-derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl group were demonstrated as efficient catalysts for the reaction, giving the corresponding spirocyclic oxindolo-β-lactams in high yields with excellent diastereo- and enantioselectivities.

γ-Amination: The title reaction was developed to give the corresponding dihydropyridazinones in good yields with excellent enantioselectivities (see scheme; Mes=2,4,6-trimethylphenyl). The annulation reaction worked well for γ-aryl, γ-alkyl, or γ-alkenyl oxidized enals. Highly enantiopure tetrahydropyridazinones and γ-amino acid derivatives could b...

The cinchona alkaloid-catalyzed [4 + 2] cyclocondensation of α,β-unsaturated acyl chlorides with imines is developed to give the corresponding substituted dihydropyridinones in good yields with high to excellent enantioselectivities. Reduction of the dihydropyridinones gave highly optically active substituted tetrahydropyridinone and piperidine der...