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The first asymmetric [4 + 1] annulation of oxindole 3-pyridinium salts and hydrazones is realized by using a chiral N,N′-dioxide-Pr(OTf)3 complex. A range of bioactive chiral pyrazoline-spirooxindoles are obtained in good yields with excellent ee values.

Highly regio- and enantioselective hydrosilylation of aryl-substituted terminal/internal alkenes with primary silanes was achieved using a chiral La(iii)-bisoxazoline complex.

A visible-light-induced acyl radical conjugate addition to electron-deficient alkenes with acylsilane was realized by merging photoredox and Lewis acid catalysis under mild reaction conditions. Various tri- and tetra-substituted furans were obtained with good yield (up to 97%) from α,β-unsaturated ketones. Based on the experimental results and spectral analysis, a possible catalytic cycle involving 1,4-conjugate addition/ring-closure/arylation sequence was proposed. Beyond that, 1,6-acyl radical conjugate addition to para-quinone methides was also accomplished to deliver a series of α-aryl ketones by using this synergistic catalysis protocol.

Chiral Lewis acid-catalyzed enantioselective nitrooxylation and azidation of cyclic and acyclic β-keto amides/esters with hypervalent iodine(iii) reagents.

A series of novel chiral pyridine-oxazolines were synthesized via catalytic asymmetric Heine reaction of meso-N-(2-picolinoyl)-aziridines.

An asymmetric cascade reaction catalyzed by a chiral N,N′-dioxide–Dy(iii) complex was realized to construct the valuable [6,5,5,6] tetracyclic spiroindolines with good yields and enantioselectivities by a concise and one-step protocol.

An asymmetric IEDDA reaction of 2-pyrones with indenes catalyzed by a chiral N,N′-dioxide/Ni(OTf)2 complex has been disclosed to construct highly functionalized hexahydrofluorenyl bridged-lactone scaffolds in high yields and ee.

A type of new chiral nitrogen-donor hybrid ligand bearing acyclic guanidine, amide, and pyridine subunits was rationalized for Cu(i)-catalyzed asymmetric Sonogashira C(sp3)–C(sp) cross-coupling.

A new method has been developed for constructing vicinal quaternary stereocenters with an oxindole–butanolide hybrid framework through asymmetric vinylogous addition of a siloxyfuran to an indol-2-one in the presence of a readily available N,N′-dioxide–Ni(OTf)2 complex catalyst. Various oxindole–lactones were obtained in up to 98% yield with >19:1 dr and 97% ee under mild reaction conditions. A possible transition-state model is proposed to explain the origin of the asymmetric induction.

An enantioselective [3+2] cycloaddition of donor-acceptor aziridines with N-aryl protected imines were developed with a Ni(ClO4)2·6H2O/N,N'-dioxide catalyst system, providing a broad range of chiral trans-substituted imidazolidine compounds with good yields and excellent enantioselectivities (up to 99% yields, up to 98% ee). Control experiments indicated that the products could offer excellent diastereoselectivities with the control of chiral Ni(II)-N,N'-dioxide complex and the interaction of the substrates. The possible catalytic process was proposed to rationalize the stereocontrol.

Enantioselective formal (3 + 2) cyclization of cyclic β-keto esters with azonaphthalenes to synthesize cyclopenta[b]indoles in good yields with high diastereo- and enantioselectivity is established by using guanidine-amides as catalysts under mild reaction conditions.

The asymmetric catalytic synthesis of 3-cyclotryptamine substituted oxindoles through formal [4 + 2] cycloaddition/cyclization cascade is described. A wide range of cyclotryptamine derivatives were obtained in enantioenriched form under mild reaction conditions and were found to have potential anticancer activity. The strategy enables ready assembly of cyclotryptamine subunits at the C3a-C3a' positions with two quaternary stereogenic centers in cis-selectivity, leading to the concise synthesis of optically active cis-bis(hexahydropyrroloindole) and others of the cyclotryptamine alkaloid family.

The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) N,N'-dioxide as the Lewis acid catalyst. This reaction supplies a highly chemo-, regio-, and enantioselective pathway for the synthesis of optically active β-keto esters with an all-carbon quaternary center through highly selective alkyl-group migration of the ketones. Moreover, the ring expansion of cyclic ketones was accomplished under slightly modified conditions, affording a series of enantioenriched cyclic β-keto esters. Density functional theory calculations have been carried out to elucidate the reaction pathway and possible working models that can explain the observed regio- and enantioselectivity.

An enantioselective tandem Friedel-Crafts alkylation/annulation of indoles with diazoacetoacetate enones is realized in one pot. A series of dihydrocarbazoles were obtained in moderate yields with good to excellent ee values by using a RhII/ScIII dual-metallic catalyst system. Control experiments revealed that ScIII is critical to both the alkylation and annulation.

An asymmetric catalytic tandem cycloisomerization/[3 + 2] cycloaddition was achieved by a combined system of Au(I) and a chiral N,N′-dioxide–Dy(III) complex. Various enantioenriched 3H-spiroisobenzofuran-1,3′-pyrrolidine derivatives from a number of 2,2′-diester aziridines and 2-ethynyl benzyl alcohols were afforded in moderate to good yields with high diastereo- and enantioselectivities (up to 81% yield, >19 : 1 dr, 95% ee). On the basis of control experiments and the absolute configuration of the product, possible working modes were proposed to understand the origin of chiral control.

An easily available L-proline-derived guanidine-amide was found to be efficient at catalyzing a [4 + 2] cycloaddition of azlactones with 2-benzothiazolimines, affording various benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers in excellent yields at 2 mol% loading. The diastereoisomers of the main adducts differed from those in a previous bifunctional organocatalytic system.

An asymmetric organocatalytic nucleophilic aromatic substitution reaction of azlactones with electron-deficient aryls was established. A variety of α-aryl α-alkyl α-amino acid esters and peptides were obtained in decent yields and stereoselectivities. A new bifunctional catalytic mode involving charge-transfer interaction and hydrogen bonding is proposed to explain the enantioselectivity.

A unique chiral amine organocatalyst with a bispidine structure was found to be efficient for the diastereo- and enantioselective Mannich reaction of isatin ketimines with ketones. A series of 3-substituted 3-amino-2-oxindoles bearing vicinal tertiary and quaternary chiral stereogenic centers were obtained in excellent yields with excellent dr and ee values. The gram-scale synthesis and transformation of the product showed the practicability of this methodology. In addition, a possible transition state model was proposed to explain the origin of the stereoselectivity.

A highly atroposelective N-acylation reaction of aniline-derived sulfonamides has been developed with chiral isothiourea as the catalyst. This approach provides a facile and efficient route to an array of atropoisomeric sulfonyl substituted anilide products in good yields with high to excellent enantioselectivities.

A highly enantioselective acyloin rearrangement of cyclic α-ketols has been developed with a chiral Al(III)–N,N′-dioxide complex as catalyst. This strategy provided an array of optically active 2-a...

A number of nitrile-containing chiral molecules were synthesized via asymmetric nucleophilic addition of formaldehyde N,N-dialkylhydrazone as the nitrile equivalent. Chiral N,N′-dioxide/metal salt ...

Highly enantioselective ring-opening/cycloaddition reactions of cyclobutenones were achieved by employing chiral N,N'-dioxide/metal complexes as the catalysts. The Diels-Alder type cycloaddition with (E)-alkenyloxindoles yielded spirocyclohexaneoxindoles with excellent results. Meanwhile, a hetero-Diels-Alder process occurred with (E)-dioxopyrrolidines to afford spiropyrrolidinone-dihydropyranone derivatives.

An efficient kinetic resolution of propargyloxy dicarbonyl compounds via asymmetric [2,3]-Wittig rearrangement was achieved by using a chiral N,N'-dioxide/NiII complex catalyst. Various chiral α-allenyl alcohols were obtained in high enantioselectivities under mild conditions. The utility of this method was readily demonstrated in the asymmetric synthesis of the chiral 2,5-dihydrofuran derivative.

A highly efficient asymmetric imino-ene reaction of cyclic ketimines with silyl enol ethers was developed. Various chiral benzosultam derivatives were obtained in excellent yields (up to 99%), enantioselectivities (up to 99% ee), and diastereoselectivities (up to >19:1 dr) by utilizing a Ni(BF4)2·6H2O/N,N'-dioxide complex as the catalyst. A possible transition state model was proposed to explain the stereoinduction. Furthermore, the synthetic utility of the protocol provided quick access to optically pure HIV-1 inhibitor.

An asymmetric tandem cycloisomerization and intermolecular [5+2] cycloaddition reaction of 2-ethynylphenyl-substituted nitrones with methyleneindolinones was realized. The process includes the palladium(II)-promoted in situ formation of azomethine ylide and the following chiral N,N'-dioxide-Co(II) complex-catalyzed regio-, diastereo-, and enantioselective [5+2] cycloaddition reaction. The desired spiro-tropanyl oxindoles were obtained in good yields with excellent dr and ee values. On the basis of the determination of the catalyst structure, a possible transition state model was proposed.

The enantioselective [3 + 1]-cycloaddition of racemic donor-acceptor (D-A) aziridines with isocyanides was first realized under mild reaction conditions using a chiral

A highly diastereo- and enantioselective allylation of isatins with 3-substituted allylboronic compounds was achieved by the chiral N,N'-dioxide/Lu(OTf)3 complex. This approach provides an efficient route to useful enantioenriched 3-allyl-3-hydroxyoxindoles with adjacent tetrasubstituted tertiary or tetrasubstituted quaternary stereogenic centers. Density functional theory calculations were performed to understand the different diastereoselection between the background reaction and catalytic process. Moreover, allylation with potassium allyltrifluoroborate was accomplished by the chiral N,N'-dioxide/In(OTf)3 complex. The synthetic utility was demonstrated by further transformation of the product to a tetrahydrofuranyl oxindole derivative.

The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N'-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.

An enantioselective epoxidation of α-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N'-dioxide/ScIII complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.

An asymmetric three-component 1,3-dipolar cycloaddition of 3,4-dihydroisoquinolines, bromoacetates and α,β-unsaturated pyrazole amide is realized by using a chiral N,N'-dioxide-Y(OTf)3 complex as the catalyst. The process includes a base-promoted formation of dihydroisoquinolium ylides in situ, and a chiral Lewis acid-catalyzed asymmetric [3+2] cycloaddition with α,β-unsaturated pyrazole amides. A series of hexahydropyrrolo-isoquinolines are obtained in moderate to good yields with excellent diastereo- and enantioselectivities.

A highly enantioselective 1,3-dipolar cycloaddition of meso-diaziridines with chalcones was realized by utilizing the ScIII-N,N'-dioxide complex as the catalyst. In this transformation, the 1,3-dipole intermediates generated from the C-N bond cleavage of diaziridine were trapped by chiral N,N'-dioxide/scandium(III) complex activated chalcones to undergo enantioselective 1,3-dipolar cycloaddition. A range of chiral 1,5-diazabicylo[3.3.0]octane derivatives were readily synthesized in good yields with high diastereo- and enantioselectivities.

A highly enantioselective ring-opening desymmetrization of meso-aziridines with isocyanides was achieved in the presence of a chiral N,N′-dioxide/Mg(OTf)2 complex. The in situ generated chiral 1,4-...

A chiral Mg(II)/N,N′-dioxide complex was found to be highly effective in promoting the diastereo- and enantioselective 1,6-conjugate addition of various azaarylacetamides to p-quinone methides under mild reaction conditions. Various chiral azaarene derivatives containing gem(1,1)-diaryl skeletons were obtained in good yields, dr, and excellent ee values. Meanwhile, on the basis of insight gained from the control experiments as well as the single-crystal structure of the Mg(II)/N,N′-dioxide complex and product, a possible transition state was proposed to explain the origin of coordination and stereoinduction.

A highly efficient kinetic resolution of racemic 2-acyl-3-aryl-N-tosylaziridines is achieved through a chiral Lewis acid promoted ring-opening reaction with 2-mercaptobenzothiazoles as the nucleoph...

A highly diastereo- and enantioselective ring-opening/cycloaddition reaction of cyclobutenones with 2-hydroxyacetophenones or salicylaldehyde was achieved by employing a chiral N,N′-dioxide-scandium(III) complex as the catalyst. It provided various 3-phenylvinyl-4-hydroxy-dihydrocoumarins in good yields (up to 92%), high enantioselectivities (up to 93% ee), and excellent diastereoselectivities (>19:1 dr). Moreover, a possible catalytic cycle was proposed based on the control experiments and previous reports.

An efficient asymmetric vinylogous Michael–aldol domino reaction between α-arylidene pyrazolinones and β,γ-unsaturated-α-ketoesters catalyzed by a chiral N,N′-dioxide-ScIII complex in aqueous media has been established. A variety of spirocyclohexene pyrazolones with three stereocenters including vicinal tetrasubstituted stereocenters were obtained in excellent yields with good diastereoselectivities and enantioselectivities. A retro-aldol process was observed, which led to epimerization at the spirocyclic quaternary carbon center.

Regioselectivity is a crucial issue in Baeyer-Villiger (BV) oxidation. To date, few reports have addressed asymmetric BV oxidation of 3-substituted cycloketones due to the high difficulty of controlling regio- and stereoselectivity. Herein, we report the asymmetric BV oxidation of 3-substituted and meso-disubstituted cycloketones with chiral N,N'-dioxide/Sc(iii) catalysts performed in three ways: classical kinetic resolution, parallel kinetic resolution and desymmetrization. The methodology was applied in the total and formal synthesis of bioactive compounds and natural products. Control experiments and calculations demonstrated that flexible and adjustable catalysts played a significant role in the chiral recognition of substrates.

A highly enantioselective isocyanide-based multicomponent reaction catalyzed by a chiral N,N'-dioxide/MgII complex was reported. A wide range of substrates were tolerated in this reaction, including alkyl- and aryl-substituted isocyanides with alkylidene malonates and various phenols, affording the corresponding phenoxyimidate products in good to excellent yields (up to 94% yield) with good to excellent enantioselectivities (up to 95.5:4.5 er). A catalytic cycle and transition state were proposed to rationalize the reaction process and enantiocontrol.

A highly enantioselective three-component reaction of ynamides with carboxylic acids and 2,2'-diester aziridines has been realized by using a chiral N,N'-dioxide/Ho(OTf)3 complex as a Lewis acid catalyst. The process includes the formation of an α-acyloxyenamide intermediate through the addition of carboxylic acids to ynamides and the following enantioselective nucleophilic addition to in-situ-generated azomethine ylides induced by the chiral catalyst. A range of amino acyloxyenamides are delivered in moderate to good yields with good ee values. In addition, a possible catalytic cycle with a transition model is proposed to elucidate the reaction mechanism.

A chiral N,N' -dioxide-nickel(II) complex-catalyzed asymmetric amination reaction of 3-bromo-3-substituted oxindoles with anilines was developed. A series of alkyl or aryl 3-amino-indolinones with quaternary stereocenters were obtained in high yields with excellent ee values in one step (up to 99% yield, up to 96% ee). The method provided a readily route to optically active intermediates of 3-amino-2-oxindole-based bioactive compounds. Besides, a possible transition state model was proposed to elucidate the origin of the chirality induction based on the X-ray crystal structure of the catalyst and the adduct.

An enantioselective three-component reaction of diazoacetates, 2-oxo-3-ynoates, and nitrosoarenes has been developed by using a chiral N,N′-dioxide/Ni(OTf)2 complex. This catalytic manifold allows ...

A highly enantioselective three-component hydroacyloxylation/1,4-conjugate addition of ortho-hydroxybenzyl alcohols, ynamides and carboxylic acids was developed under mild reaction conditions in the presence of a chiral N,N'-dioxide/Sc(OTf)3 complex, which went through in situ generated ortho-quinone methides with α-acyloxyenamides, delivering a range of corresponding chiral α-acyloxyenamides derivatives containing gem(1,1)-diaryl skeletons in moderate to good yields with excellent ee values. The scale-up experiment and further derivation showed the practicality of this catalytic system. In addition, a possible catalytic cycle and transition state model was proposed to elucidate the origin of the stereoselectivity based on X-ray crystal structure of the α-acyloxyenamide intermediate and product.

A highly efficient enantioselective synthesis of multisubstituted tetrahydrobenzofuran derivatives with four contiguous stereocenters was established by the dual catalysis of a gold(I)/chiral N,N′-...

Intermolecular addition of enols and enolates to unactivated alkynes was proved to be a simple and powerful method for carbon-carbon bond formation. Up to date, a catalytic asymmetric version of alkyne with 1,3-dicarbonyl compound has not been realized. Herein, we achieve the catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes attributing to the synergistic activation of chiral N,N′-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) π-acid. A range of β-ketoamides, β-ketoesters and 1,3-diketones transform to the corresponding products with a tetra-substituted chiral center in good yields with good e.r. values. Besides, a possible catalytic cycle and a transition state model are proposed to illustrate the reaction process and the origin of chiral induction based on the experimental investigations., Although enols and enolates addition to unactivated alkynes is used for carbon-carbon bond modification a catalytic asymmetric alkyne with 1,3-dicarbonyl compound has been elusive. Here, the authors achieve this using the synergistic activation of chiral N,N′-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) π-acid.”

A 2-alkenoylpyridine-bound N,N'-dioxide-TbIII complex has been found to absorb visible light to reach the excited state, leading to the direct visible-light-excited catalytic enantioselective [2+2] cycloaddition of 2-alkenoylpyridines to various alkenes in the absence of an additional photosensitizer. Diverse enantioenriched cyclobutanes were successfully obtained (yields up to 70 %, >19:1 d.r., 92 % ee). The new chiral terbium(III) complex features a bathochromic shift, lower excitation energy, and facile intersystem crossing due to paramagnetic and heavy-atom effects, which enable the antenna 2-alkenoylpyridines to be excited. For comparison, a chiral N,N'-dioxide-ScIII complex in combination with [Ru(bpy)3 ]Cl2 was efficient in the enantioselective photocycloaddition reactions of 2'-hydroxychalcones with alkenes, thereby revealing that both substrates and metal salts have significant effects on the reaction.

Halofunctionalization methods enable the vicinal difunctionalization of alkenes with heteroatom nucleophiles and halogen moieties. As a fundamental transformation in organic synthesis, the catalytic asymmetric variants have only recently been reported. In sharp contrast to the asymmetric halocyclization of simple alkenes which involves a nucleophile-assisted alkene activation process, the asymmetric halofunctionalization of enones developed by our laboratory features an electrophile-assisted 1,4-addition pathway. Our work in this area has resulted in the development of several different types of regio-, diastereo-, and enantioselective processes, including inter- and intramolecular haloaminations, haloetherifications, and haloazidations. The scope, updated mechanism, limitations, and future perspective of these reactions are discussed.

A highly regio-, diastereo-, and enantioselective Diels-Alder reaction of β,γ-unsaturated α-ketoesters with ( E)-1-phenyl dienes has been accomplished by using a stable and easily available chiral N,N'-dioxide/zinc(II) complex as catalyst. Only one isomer of the corresponding cyclohexenes with three chiral centers was obtained in good to excellent yields with excellent ee values under mild reaction conditions. The configurations of the product and chiral N,N'-dioxide/zinc(II) catalyst were identified by X-ray diffraction analysis. In addition, a possible catalytic model was proposed to explain the origin of the asymmetric induction.