AbstractA novel cyclization reaction of methylenemalonate with indoles is reported, and it provides efficient access to a variety of hexahydrocarbazoles. The enantioselective version was realized by a finely tuned ligand/CuII catalyst. The optically active hexahydrocarbazoles contain three quaternary carbon centers and are obtained in up to 99 % yield with greater than 99:1 d.r. and up to greater than 99 % ee. This reaction can be carried out on gram scale and stereoselective transformation of the product led to the core structure of a series of alkaloids from Kopsia plants.

AbstractA novel cyclization reaction of methylenemalonate with indoles is reported, and it provides efficient access to a variety of hexahydrocarbazoles. The enantioselective version was realized by a finely tuned ligand/CuII catalyst. The optically active hexahydrocarbazoles contain three quaternary carbon centers and are obtained in up to 99 % yield with greater than 99:1 d.r. and up to greater than 99 % ee. This reaction can be carried out on gram scale and stereoselective transformation of the product led to the core structure of a series of alkaloids from Kopsia plants.

A highly diastereoselective and enantioselective Cu(II)/SaBOX-catalyzed [2 + 2] cycloaddition of methylidenemalonate and multisubstituted alkenes was developed to furnish optically active cyclobutanes in high yields with >99/1 dr and up to >99% ee. By application of the newly developed method, the total synthesis of (+)-piperarborenine B was completed in eight steps from methylidenemalonate and olefin in 17% overall yield with >99/1 dr and 99% ee.

The first catalytic enantioselective ring-opening reaction of donor–acceptor cyclopropanes with water is described. By employing Cy-TOX/Cu(II) as catalyst, the reaction performed very well over a broad range of substrates, leading to the ring-opening products in 70–96% yields with up to 95% ee under mild conditions. The current method provides a new approach to direct access to γ-substituted GBH derivatives very efficiently. Importantly, Cu(ClO4)2·6H2O proves to serve as both a Lewis acid and a source of water, which affords a fine system to controllably release water as a nucleophile in the asymmetric catalysis.

The first highly diastereoselective and enantioselective catalytic formal [4 + 3] cycloaddition of 1,1-cyclobutane diester with nitrone has been developed. Sterically hindered chiral SaBOX/Cu(II) complex promotes the reaction efficiently with a broad substrate scope, producing a range of multifunctionalized optically active 1,2-oxazepanes with excellent stereocontrol (up to >99/1 dr and 97% ee).

A one-pot asymmetric synthesis of 1,2,3,4-tetrahydrocarbazoles has been developed via an enantioselective [3 + 3] annulation of 2-alkynylindoles and donor–acceptor cyclopropanes. In the presence of chiral Lewis acids as catalysts, a series of optically active tetrahydrocarbazoles were furnished in high yields (63–87%) with good to excellent levels of enantioselectivity (up to 94% ee).

Stereocontrol in the synthesis of structurally complex molecules, especially those with all-carbon quaternary stereocenters, remains a challenge. Here, we reported the preparation of a class of tetracyclic cyclopenta-fused spiroindoline skeletons through Cu(II)-catalyzed intramolecular [3 + 2] annulation reactions of donor–acceptor cyclopropanes with indoles. Both cis- and trans-diastereomers of tetracyclic spiroindolines are accessed with high selectivities by altering the remote ester groups of cyclopropanes. The origins of this stereocontrol are identified using DFT calculations: attractive interactions between the ester group and arene favor the generation of the trans isomer, while the formation of the cis isomer is preferred when steric repulsions become predominant.

A highly diastereo- and enantioselective BOX/Cu(II)-catalyzed C2,C3-cyclopentannulation of indoles with donor–acceptor cyclopropanes has been developed on the basis of asymmetric formal [3 + 2] cycloaddition of indoles. This reaction provides rapid and facile access to a series of enantioenriched cyclopenta-fused indoline products and can be further extended to the construction of tetracyclic pyrroloindolines. The synthetic potential of the reaction was demonstrated in a four-step synthesis of the core structure of borreverine.

Highly efficient synthesis of chiral tetrasubstituted 2,3-dihydrofuran derivatives has been realized by Cu-catalyzed asymmetric [4 + 1] cycloadditions of α-benzylidene-β-ketoester with a diazo compound. Following this methodology, a series of optically active multifunctionalized dihydrofurans were prepared in high yield with up to 96% ee and 99/1 dr.Keywords: asymmetric; copper carbene; dihydrofurans; [4 + 1] cycloadditions

An efficient synthetic approach to benzoheterocycles has been developed based on the hydrolysis of key ylide intermediates in a tandem reaction, upon which a variety of 3-alkylidene dihydrobenzofurans and related benzoheterocyclic products can be obtained in high yields with excellent Z/E selectivity.

A Ni-catalyzed asymmetric ring-opening reaction of 2-substituted cyclopropane-1,1-dicarboxylates with aliphatic amines has been accomplished using the chiral indane–trisoxazoline (In-TOX) ligand. This highly enantioselective reaction provides an efficient approach to a variety of chiral γ-substituted γ-amino acid derivatives, which are readily transformed into multifunctionalized piperidines and γ-lactams. The single-crystal X-ray structure of the TOX–Ni complex is provided, and the role of the side arm in the chiral ligand is discussed.

A pyridine-catalyzed ylide cyclization affording dihydrofurans and dihydropyrroles has been developed. In the presence of a catalytic amount of pyridine and Fe(Tcpp)Cl, α-ylidene-β-diketones and α,β-unsaturated imines react with diazoacetates providing dihydrofurans and dihydropyrroles respectively, in up to 96% yield with high diastereoselectivities.

A new cationic [N–O–S]zirconium complex (cat.) was developed to be an excellent catalyst for the intramolecular hydroamination of aminoalkenes with a large substrate scope from terminal alkenes to internal alkenes, and primary amines to secondary amines. The catalyst system can also tolerate various functional groups and perform sequential hydroamination of primary aminodienes.

Highly diastereoselective synthesis of cis-trisubstituted vinylaziridines containing a quaternary carbon center is realized by a one-pot protocol in which the combination of sulfur ylide-mediated aziridination of cyclic ketimines and Pd(0)-catalyzed isomerization is employed successfully.

The reaction of a crotonate-derived chiral phosphonium salt with α,β-unsaturated carbonyl compounds in the presence of Cs2CO3 affords optically active cyclohexa-1,3-diene derivatives with up to 90% ee in good yields.

A series of [O−NS]TiCl3 complexes 5a–l derived from β-carbonylenamine were synthesized and characterized. In the presence of modified methylaluminoxane (MMAO), complexes 1, 5a–i and 5l are highly active for ethylene polymerization and copolymerization of ethylene with 1-hexene, CPE and NBE. Up to 5.12 × 106 g mol−1 h−1 atm−1 of activity for the copolymerization of ethylene with 1-hexene is achieved with a 28.9 mol% incorporation ratio.

In the presence of 20 mol % of tributylphosphine, tert-butyl carbonate substrate 3a undergoes smoothly an intramolecular formal [3 + 2] cycloaddition reaction at room temperature to give benzobicyclo[4.3.0] compounds in 99% yield with a 19/81 ratio of 2a and 2a′. The mechanism of the isomerization of the product 2a into 2a′ has been investigated in detail. On the basis of this mechanism, two strategies, using 20 mol % of triphenylphosphine or 10 mol % of tributylphosphine in the presence of 20 mol % of Ti(OiPr)4, have been established for the selective construction of benzobicyclo[4.3.0] compounds. Under neutral conditions, the reactions of compounds 3a−g afford benzobicyclo[4.3.0] compounds 2a−g with high selectivities in good to excellent yields. In addition, α-methyl α,β-unsaturated ester 3h also works well to give the corresponding product 2h with one quaternary carbon center in 99% yield under neutral and room temperature conditions.

Nucleophilic phosphine catalysis has proven to be a powerful tool in organic synthesis, which can provide easy access to cyclic, bicyclic or polycyclic carbocycles and heterocycles. Owing to their comparatively strong and readily tunable nucleophilicity, phosphines can be easily tailored to efficient annulation reactions with good control over reaction selectivity. This has resulted in a tremendous increase in their scope and in a concomitant number of reports where phosphine-triggered annulation reactions occur. This tutorial review summarizes the recent achievements in this area.

Ylides are nucleophiles that bear a unique leaving group, LnM, and can attack aldehydes, ketones, imines, and electron-deficient alkenes. Over the course of the reaction, they react with C═X (X = C, N, O, etc.) double bonds to form betaine or oxetane intermediates, which further eliminate the heteroatom-containing group in one of two ways to give the corresponding olefination or cyclization product. Since the discovery of the Wittig reaction, ylide olefination has developed as one of the most useful approaches in constructing carbon−carbon double bonds. These reactions provide unambiguous positioning of the C−C double bond and good stereoselectivity. Researchers have also widely used ylides for the synthesis of small ring compounds such as epoxides, cyclopropanes, and aziridines. However, the use of ylides to prepare larger cyclic structures was very limited. This Account outlines our recent work on ylide-initiated Michael addition/cyclization reactions. By altering the heteroatoms and the ligands of the ylides, we have modulated the reactivity of ylides. These modified ylides provide easy access to diverse cyclic compounds with the ability to control regioselectivity, chemoselectivity, diastereoselectivity, and enantioselectivity. Reactions using these ylides produce the structural components of many biologically active compounds and valuable intermediates in organic synthesis. Allylic telluronium and sulfonium ylides can react with α,β-unsaturated esters, ketones, amides, and nitriles to afford multisubstituted vinylcyclopropanes with high selectivities. Telluronium allylides react with aromatic N-phenyl aldimines to give trans-vinylaziridines and with chiral N-tert-butylsulfinylimines to afford the optically active cis-2-substituted vinylaziridines, both with high diastereoselectivities. We also used sulfonium and telluronium allylides to prepare vinylepoxides. In addition, ylides are good reagents for the synthesis of five-membered heterocyclic compounds. By treatment of stable camphor-derived sulfur ylides with α-ylidene-β-diketones, we obtained multisubstituted dihydrofurans with high diastereo- and enantioselectivities. Ammonium salts derived from cinchonidine and cinchonine react smoothly with 3-aryl and 3-heteroaryl-2-nitro acrylates, affording both enantiomers of isoxazoline N-oxides with up to 99% ee. Ylides can initiate tandem cyclizations for the synthesis of chromenes, bicyclic compounds, and cyclohexadiene epoxides. Varying the choice of base allows access to 2H-chromenes and 4H-chromenes from 3-(2-(bromomethyl)phenoxy)acrylates via a tandem ylide Michael addition/elimination/substitution reaction. Phosphines can catalyze an intramolecular ylide [3 + 2] annulation constructing bicyclo[n.3.0] ring systems with three contiguous stereogenic centers. The reaction of crotonate-derived sulfur ylides with α,β-unsaturated ketones affords cyclohexadiene epoxides with excellent diastereoselectivities (>99/1) in good to high yields. Using a camphor-derived sulfonium salt, we have produced asymmetric cyclohexadiene epoxides with high eeʼs. Overall, these results illustrate the versatility and tunability of ylides for the preparation of cyclic systems containing more than three atoms.

The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.

A simple and practical one-step method for the screening of new titanium catalysts for olefin polymerization has been developed, which allows to combine ligands such as enamine and salicylaldehyde-derived imines with TiCl4(THF)2 in situ for direct activity evaluation. By this strategy, β-carbonylenamine made TiCl4(THF)2, a highly active and single-site-like catalyst for ethylene polymerization and copolymerization. A rationale involving a newly formed titanium complex that was characterized by X-ray analysis is discussed.

Ni(II) and Pd(II) complexes based on N-((1H-pyrrol-2-yl)methylene)-2-(diphenylphosphino)benzenamine were synthesized and characterized. X-ray diffraction studies on complexes 1, 2, and 4 revealed that N, N, P, and halogen atoms coordinated to metal, with distorted square planar geometries in all cases. Upon treatment with modified methylaluminoxane (MMAO), the [N−NP]Ni(II)X complexes are robust and exhibit high activity for the vinyl addition polymerization of norbornene (up to 5.46 × 107 g PNB/mol(Ni)·h·atm).

A series of titanium complexes of the general formula [N-(3,5-di-tert-butylsalicylidene)-2-alkyl-sulfanylanilinato]Ti(IV)Cl3 (5a, b, e and f) exhibited very high catalytic activities in ethylene homo- and copolymerization with various α-olefins in the presence of modified methylaluminoxane (MMAO). The results showed that steric hindrance of the alkylthio groups in 5a–f strongly influenced the polymerization behavior. An increase in the steric hindrance of these alkyl units led to the decrease in both catalytic activity and comonomer incorporation ratio. On the other hand, the amount of α-olefin incorporated into the copolymer chain depended on the molar ratio of the monomers in the polymerization reaction and was slightly influenced by the chain length of α-olefin. Comparisons between alkylthio and arylthio substituents on catalyst performance were also discussed in this article.In the presence of MMAO, the [O−NSR]TiCl3 complexes containing phenoxyimine ligands with appended alkylthio groups were very active catalysts for ethylene homo- and copolymerization with α-olefin. Steric hindrance of the alkylthio groups (SR) was proved to strongly influence the polymerization behavior. Comparisons between alkylthio and arylthio substituents on catalyst performance were also discussed.

A highly enantioselective cyclopropanation of alkenes with phenyldiazoacetates catalyzed by CuPF6(CH3CN)4/trisoxazoline has been developed.

Pseudo-C2-symmetric chiral phosphorus ylides have been designed and synthesized for the enantioselective preparation of allenic esters, and up to 92% ee has been achieved.

A tandem ring-opening–cyclization reaction of cyclopropanes with imines in the presence of 5 mol% of scandium triflate was developed for the highly diastereoselective synthesis of multisubstituted pyrrolidines.

The development of suitable ligands that upon coordination to a metal facilitate enantioselective reactions or are able to selectively recognize a molecule are fundamental endeavours in organic chemistry. Chiral ligands that contain one or two oxazoline groups have been extensively studied and applied successfully to many metal catalyzed reactions. Accordingly, the development and application of chiral trisoxazolines has received increasing attention in the last decade. This tutorial review covers the synthetic methods for the preparation of chiral trisoxazolines, the application of chiral trisoxazolines in asymmetric catalysis and molecular recognition.

The cheap and simple iPr-bisoxazoline–Cu(OTf)2 proves to be an efficient catalyst in the asymmetric Friedel–Crafts reaction of indole with arylidene malonates. In iBuOH, the S-enantiomer was obtained in up to 97% ee, while the opposite enantiomer was obtained in up to 78% ee in CH2Cl2 or TTCE.

The reaction of telluronium allylides with alkylimines, generated in situ from α-amidoalkyl sulfones, affords cis-alkylvinylarizidines with good stereoselectivity in good yields. However, the same ylides react with N-aryl imines to provide trans-vinylaziridines.

Air- and water-stable chiral catalyst trisoxazolines 4–6/Cu(ClO4)2·6H2O have been used in the Diels–Alder reaction of cyclopentadiene with acryloyl-2-oxazolidinones or ketoesters. The reaction is carried out in air and up to 82% ee was achieved.

Access to vinyloxiranes using aldehydes and allylic bromides in the presence of 1–5 mol% tetrahydrothiophene is reported. Both aliphatic and aromatic aldehydes work well in this reaction and the catalyst loading could be reduced as low as 0.5 mol%.

Novel chiral iPr-tris(oxazoline)/Cu(ClO4)2·6H2O catalyzed coupling of terminal acetylenes and nitrones to afford cis-disubstituted β-lactams is described; the choice of base proves essential to both the diastereoselectivity and the enantioselectivity.

A highly enantioselective cyclopropanation of alkenes with phenyldiazoacetates catalyzed by CuPF6(CH3CN)4/trisoxazoline has been developed.

A facile approach for the synthesis of benzo[3.1.0]bicycloalkanes via alkylation/cyclopropanation cascade reactions of benzyl bromide with triphenylphosphonium bromide has been developed. By elaborate designing of starting materials, this multistep cyclization proceeded smoothly with a wide range of substrates, providing the benzo[3.1.0]bicycloalkanes in 52–90% yields with exclusive diastereoselectivity.

The reaction of a crotonate-derived chiral phosphonium salt with α,β-unsaturated carbonyl compounds in the presence of Cs2CO3 affords optically active cyclohexa-1,3-diene derivatives with up to 90% ee in good yields.

A pyridine-catalyzed ylide cyclization affording dihydrofurans and dihydropyrroles has been developed. In the presence of a catalytic amount of pyridine and Fe(Tcpp)Cl, α-ylidene-β-diketones and α,β-unsaturated imines react with diazoacetates providing dihydrofurans and dihydropyrroles respectively, in up to 96% yield with high diastereoselectivities.

The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.

Nucleophilic phosphine catalysis has proven to be a powerful tool in organic synthesis, which can provide easy access to cyclic, bicyclic or polycyclic carbocycles and heterocycles. Owing to their comparatively strong and readily tunable nucleophilicity, phosphines can be easily tailored to efficient annulation reactions with good control over reaction selectivity. This has resulted in a tremendous increase in their scope and in a concomitant number of reports where phosphine-triggered annulation reactions occur. This tutorial review summarizes the recent achievements in this area.

A series of [O−NS]TiCl3 complexes 5a–l derived from β-carbonylenamine were synthesized and characterized. In the presence of modified methylaluminoxane (MMAO), complexes 1, 5a–i and 5l are highly active for ethylene polymerization and copolymerization of ethylene with 1-hexene, CPE and NBE. Up to 5.12 × 106 g mol−1 h−1 atm−1 of activity for the copolymerization of ethylene with 1-hexene is achieved with a 28.9 mol% incorporation ratio.