An iron(III)-catalyzed 1,3-dihydroisobenzofuran transferring reaction of indoles provides a practical synthetic protocol to access 3-substituted indoles under mild conditions. This is the first example of a 1,3-functional group transposition of a N-protected indole to give a 3-substituted indole derivative in good yield. A plausible mechanism has been proposed on the basis of deuterium-labeling and control experiments. Furthermore, after a simple oxidation, the obtained product could be easily transformed into 3-phthalide indole, a drug candidate for treating Alzheimer′s disease.

On the basis of asymmetric regioselective [3+2] or [3+2]/[4+2] cascade reaction of 3-isothiocyanato oxindoles with C=C and C=N bonds of α,β-unsaturated methanesulfonamides, diversified S-containing heterocyclic spirooxindole derivatives could be obtained in high yields along with good to excellent diastereo- and enantioselectivities under mild conditions in the presence of cinchona alkaloid-derived organocatalysts.

A novel and convenient palladium-initiated radical cascade stereoselective iodofluoroalkylation/cycloisomerization of ene-vinylidenecyclopropanes with fluoroalkyl iodides has been developed. The reaction proceeds under mild reaction conditions with high atom economy and stereoselectivity, thereby allowing an efficient access to a variety of difluoromethylated or perfluoroalkylated pyrrolidines tethered with an alkyl iodide. Two plausible radical pathways for the transformation have been proposed on the basis of the results of control experiments and previous reports, which in one case it was thought that palladium(0) was an initiator rather than a catalyst.

The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one-pot asymmetric relay catalysis of chiral-phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good-to-excellent ee values under mild conditions, based on the asymmetric aza-Morita-Baylis–Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations.

A novel cinchona-alkaloid-derived organocatalyst has been developed to catalyze the asymmetric regioselective [3+2] cycloaddition of 3-isothiocyanato oxindoles with dibenzylidene ketones. A series of spirooxindole enols could be obtained in high yields with good-to-excellent diastereo- and enantioselectivities.

Homogeneous gold catalysts are interesting as they can act as potent carbophilic Lewis acids to activate the π bonds of alkynes, allenes, and alkenes. Many impressive applications for the formation of C−C or C−heteroatom bonds have been found due to the excellent functional group compatibility of these catalysts and the air and moisture tolerance of their reactions. Here, we have developed gold-catalyzed novel intramolecular cycloisomerizations of nitrogen or oxygen-tethered cyclopropenes with propargylic esters. The reaction proceeded through different pathways according to different substituent styles, affording 5-azaspiro[2.5]oct-7-enes and bicyclo[4.1.0]heptanes.

Gold- and silver-catalyzed novel intramolecular cycloisomerizations of nitrogen or carbon-tethered indolylcyclopropenes to furnish biologically and pharmaceutically valuable azepino-[4,5-b]indole and spiro[indoline-3,4′-piperidine] derivatives have been developed. Both reactions exhibit high chemoselectivity and stereospecificity through completely different reaction pathways. Based on mechanistic studies, it is well demonstrated that gold and silver catalysts act differently to promote the anti- and syn-addition and the steric effect of the catalysts play an important role to switch the addition mode, affording the catalyst-controlled-divergent synthesis.

The Lewis base catalyzed reactions of cyclopropenones with a variety of nucleophiles (alcohols, phenols, or water) were systematically investigated. We demonstrated that this kind of reaction could be used to synthesize allenic esters in moderate to excellent yields. Furthermore, more synthetically interesting axially chiral allenes in moderate to good yields and ee values were obtained in the corresponding asymmetric reaction in the presence of multifunctional chiral phosphine catalyst. The reaction mechanism was disclosed by using NMR tracing experiments, MS, and DFT calculations. Notably, the asymmetric reaction was proved to be a dynamic kinetic asymmetric transformation based on the control experiments, and the detailed mechanism of this transformation revealed by theoretical investigations.

Rh^II-catalyzed intermolecular [3+2] cycloaddition of 2 H-azirines with N-sulfonyl-1,2,3-triazoles is disclosed, in which a series of fully functionalized pyrroles is produced via rhodium azavinyl carbene intermediates. A distinct feature of this reaction is that the azavinyl carbene serves as a [2 C] equivalent, instead of as [1 C] or aza-[3 C] synthons, which have been reported previously in cyclopropanations and [3+n] cycloadditions. Moreover, this methodology has also been successfully applied in the total synthesis of URB447 as well as the formal synthesis of Atorvastatin (Lipitor).

A novel iron(III)-catalyzed intramolecular cycloisomerization of acetal–vinylidenecyclopropanes to afford a series of halogenated 1,2-disubstituted cyclobutenes tethered with a tetrahydropyrrole has been developed. The reaction is thought to proceed through a formal iron-catalyzed Prins cyclization followed by a ring-enlarging rearrangement of the methylenecyclopropane carbocation. The present protocol provides an alternative route to functionalized disubstituted cyclobutenes and the corresponding products could be successfully transformed into eight-membered oxacyclic products.

A gold-catalyzed intramolecular cycloisomerization of α-yne-furans 1 is described in this contribution. A variety of cyclic α,β-unsaturated aldehyde or ketone derivatives and nitrogen-containing tricyclic adducts were obtained selectively in moderate to excellent yields under mild conditions by varying the substituents on the standard substrates.

The phosphane- and amine-catalyzed ring-opening reactions of cyclopropenones with isatin derivatives give different reaction outcomes. Under phosphane catalysis, carboxylated 1H-indoles are afforded in good yields, and under amine catalysis, multisubstituted 2H-pyran-2-ones are provided in moderate yields. The mechanistic aspects of these reactions are discussed on the basis of control experiments.

Highly efficient diastereo- and enantioselective Michael addition reactions between 3-substituted oxindoles and trifluoromethylated nitro olefins catalyzed by a quinine-derived squaramide have been investigated. The corresponding adducts, each bearing a chiral tertiary carbon center attached to a trifluoromethyl group and adjacent to a quaternary stereocenter at the C3 position of the oxindole, were obtained in good to excellent yields (up to 99 %) and with high diastereoselectivities (up to >20:1 dr) and excellent enantioselectivities (up to 99 % ee).

The reaction of methylenecyclopropanes (MCPs) with tetrahydrofuran (THF) proceed smoothly in the presence of AgOC(O)CF₃ and electrophilic halogenation reagents to give the corresponding 4-(3-halobut-3-enyloxy)butyl 2,2,2-trifluoroacetate derivatives in moderate yields through dual cleavage of C–C and C–O bonds under mild conditions.

A highly efficient palladium(0)-catalyzed asymmetric [3+2] cycloaddition using 3-diazooxindoles serving as dipolarophiles affords functionalized pyrazolidine derivatives in an atom-economical way. In addition, by trapping the pyrazolidine derivatives with maleimides, the corresponding spiropyrazolidine oxindoles containing multiple stereogenic centers have been obtained in high yields along with moderate to good levels of diastereoselectivity and enantioselectivity under mild conditions. Thus, a novel three-component one-pot tandem reaction has been developed.

Chiral phosphines are versatile Lewis basic catalysts that are capable of promoting a wide range of asymmetric reactions. In particular, recently designed chiral phosphines based on the concept of bi-/multifunctionality have been demonstrated to be effective catalysts for many types of asymmetric reactions, such as (aza)-MBH reactions, cycloaddition reactions, and nucleophilic addition reactions. This short overview summarizes the recent advances in this field and highlights the most-significant achievements.

A highly regio- and stereoselective synthesis of bispirooxindoles by 1,3-dipolar cycloaddition of in situ generated azomethine ylides from isatin and proline to different electron-deficient alkenes has been developed. The synthesis affords the desired bispiro scaffold compounds in excellent yields with high regioselectivity under mild conditions. The stereochemistry was determined by single-crystal X-ray analysis.

A convenient and efficient synthetic method has been developed to construct highly functionalized N-bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular CH functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.

A novel phosphine-catalyzed [4+1] annulation of maleimides with 4,4-dicyano-2-methylenebut-3-enoates has been developed to afford spirocyclic products, and the maleimides serves as C₁ synthons. Moreover, a phosphine-catalyzed formal [3+2] annulation between 4,4-dicyano-2-methylenebut-3-enoates and maleic anhydride has been also achieved, and maleic anhydride behaved as a C₃ synthon in the reaction, thus efficiently affording the functionalized cyclopentenones. A stable phosphinium-containing zwitterionic compound is the key reactive intermediate in both annulations and was successfully isolated. Plausible mechanisms have been proposed on the basis of control experiments and deuterium-labeling experiments.

A novel phosphine-catalyzed [4+1] annulation of maleimides with 4,4-dicyano-2-methylenebut-3-enoates has been developed to afford spirocyclic products, and the maleimides serves as C₁ synthons. Moreover, a phosphine-catalyzed formal [3+2] annulation between 4,4-dicyano-2-methylenebut-3-enoates and maleic anhydride has been also achieved, and maleic anhydride behaved as a C₃ synthon in the reaction, thus efficiently affording the functionalized cyclopentenones. A stable phosphinium-containing zwitterionic compound is the key reactive intermediate in both annulations and was successfully isolated. Plausible mechanisms have been proposed on the basis of control experiments and deuterium-labeling experiments.

A novel Ru⁰- and Rh^I-catalyzed noncarbonylative and carbonylative cycloisomerization of readily available 3-alkynyl imine derivatives has been developed to provide 3,4-fused or nonfused pyrrole derivatives efficiently in moderate to excellent yields. The key steps involve the formation of a ruthenium carbenoid intermediate or a rhodacycle intermediate, respectively. In these reactions, CO can serve as a ligand or a reagent.

A novel type of yne-vinylidenecyclopropanes (VDCPs) has been synthesized and applied in gold-catalyzed cycloisomerization reactions. It was found that these compounds can undergo an intramolecular cycloisomerization and perform as a three-carbon synthon for [3+2] cycloaddition under gold catalysis to give fused [4.3.0] and [5.3.0] bicyclic derivatives and VDCP rearranged products in moderated to good yields under mild conditions. The substrate scope of these novel transformations has been explored and plausible reaction mechanisms have been presented on the basis of deuterium labeling experiments and DFT calculations.

Catalytic asymmetric [3+2] cycloadditions of C,N-cyclic azomethine imines with δ-substituted allenoates have been developed in the presence of (S)-Me-f-KetalPhos, affording functionalized tetrahydroquinoline frameworks in good yields with high diastereo- and good enantioselectivities under mild condition. The substrate scope has been also examined. This is the first time that δ-substituted allenoates have been applied as a δ,γ-CC bond participated C₂ synthon in asymmetric synthesis.

An efficient diastereo- and enantioselective [3+2] cycloaddition reaction of α-aryl isocyanoacetates to isatins catalyzed by a quinine-derived bifunctional amine-thiourea-bearing sulfonamide as multiple hydrogen-bonding donor catalyst has been investigated. The corresponding adducts, which bear a spirocyclic quaternary stereocenter at the C-3 position of the oxindole, were obtained in good yields (51–95%), high diastereoselectivities (up to >20:1 dr) and good to excellent enantioselectivities (up to 97% ee).

A highly regio- and stereoselective synthesis of pyrazolidine analogues by the use of N,N′-cyclic or C,N-cyclic azomethine imines with two different trifluoromethyl-containing olefins has been developed. The method affords highly functionalized trifluoromethyl-containing pyrazolidine analogues in excellent yields with high diastereoselectivities under mild conditions.

An Au^I/Au^III catalytic system was found to be effective for the cascade oxidative arylation and cyclization of allenoates with arylboronic acids to give the corresponding cyclic adducts in moderate yields. This reaction system constitutes a new method for the synthesis of β-aryl-γ-butenolides under mild conditions. Based on the previous mechanistic studies, a proposed Au^I/Au^III redox catalytic cycle has been outlined.

The catalytic asymmetric [3+2] cycloaddition of (3-isothiocyanato)oxindoles with azodicarboxylates has been explored in the presence of (DHQD)₂PHAL. It affords spirooxindoles having two heterocycles at their C3′-position in excellent yields, with high enantioselectivities, and under mild conditions within 5 min. Moreover, another spirooxindole derived from the reaction of (3-isothiocyanato)oxindole with two molecules of azodicarboxylate could also be formed in excellent yields with the same high enantioselectivities under the standard conditions.

[2+2+2] Cycloadditions can be applied to specifically build up derivatives of benzene and cyclohexadiene and, therefore, have attracted much attention. Herein, we present an intramolecular [2+2+2] cycloaddition of triynes catalyzed by the first-generation Grubbs ruthenium complex (Ru gen-1), which can efficiently afford benzene derivatives in good yields under mild conditions. Moreover, we also report on a novel tandem cross-metathesis transformation of intramolecular enediynes also catalyzed by Ru gen-1, which has not been observed previously in related reports. On the basis of deuterium labeling experiments, a possible reaction mechanism is presented.

Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1-methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments.

Efficient cyclization of 1-(indol-3-yl)-3-alkyn-1-ols in the presence of a cationic gold(I) complex, leading to annulated or specific substituted carbazoles, was observed. Depending on the reaction conditions and substitution pattern, divergent reaction pathways were discovered, furnishing diversified carbazole structures. Cycloalkyl-annulated [b]carbazoles are obtained through 1,2-alkyl migration of the metal-carbene intermediates; cycloalkyl-annulated [a]carbazoles are formed through a Wagner–Meerwein-type 1,2-alkyl shift; carbazole ethers are constructed through ring-opening of the cyclopropyl group by nucleophilic attack of water or an alcohol.

The first example of a β-isocupreidine (β-ICD)-catalyzed highly enantioselective [2+2] annulation of allenoates with trifluoromethyl ketones has been disclosed, allowing the synthesis of optically active 2-alkyleneoxetanes in moderate to good yields along with good to high enantioselectivities and high diastereoselectivities. Further transformations of the cycloadducts have been also disclosed to afford biologically interesting 6-trifluoromethyl-5,6-dihydropyran-2-ones and trifluoromethyl β-keto acids in good yields.

On the basis of the design and synthesis of multifunctional thiourea-phosphines, a catalytic method for the asymmetric [3+2] annulation of Morita–Baylis–Hillman carbonates with trifluoroethylidenemalonates has been developed, affording highly functionalized trifluoromethyl-bearing cyclopentenes in excellent yields, high diastereoselectivities and enantioselectivities under mild conditions.

We developed a synthetic method to prepare chiral multifunctional thiourea–phosphane catalysts for the asymmetric allylic substitution reaction of Morita–Baylis–Hillman carbonates with diphenyl phosphite or diphenylphosphane oxide to give allylic phosphites and allylic phosphane oxides in high yields with excellent enantioselectivity.

LDA-mediated cascade carbolithiation reactions of vinylidenecyclopropanes with enones and N-sulfonated imines as well as nitroalkene and (phenylmethylidene)malononitrile in THF at –78 °C have been realized; the corresponding novel adducts were produced in moderate to good yields with moderate to high diastereoselectivities. The scope and limitations are discussed as well as a plausible reaction mechanism based on control experiments performed in this work and previous literature reports.

Nitrogen- and phosphorus-containing Lewis base catalyzed [4+2] and [3+2] annulations of isatins with but-3-yn-2-one proceeded smoothly to give the corresponding spiro[indoline-3,2′-pyran]-2,4′(3′H)-diones and spiro[furan-2,3′-indoline]-2′,4(5H)-diones in good-to-excellent yields under mild conditions. The substrate scope has been carefully examined. Moreover, the additive effect of water has also been investigated in detail along with plausible reaction mechanisms based on previous literature and our own investigations.

A comprehensive mechanistic investigation on the reduction of activated carbonyl groups using alkylphosphanes as reducing agents has been conducted through a combination of experimental as well as computational studies. Both approaches show that this kind of reduction proceeds either through proton transfer from alkylphosphanes and cleavage by water during work-up or through another reaction pathway involving the participation of water at the initial stage and a two-fold proton transfer to afford the product.

Treatment of pyridine and dimethyl acetylenedicarboxylate derivatives with N-substituted isatylidene derivatives resulted in three-component condensations, affording 1′,9a′-dihydrospiro[indoline-3,2-quinolizin]-2-one derivatives in high yields and with good diastereoselectivities through 1,4-dipolar cycloadditions.

Phosphorus containing Lewis base catalyzed cascade reactions of isatin-derived oximes with allenic esters afford the corresponding functionalized nitrones. Further Lewis acid catalyzed highly regioselective intramolecular [3+2] cyclizations give the corresponding bridged cycloadducts. Moreover, a combined “one-pot” reaction is also feasible for the above two catalytic reactions.

An efficient enantioselective allylic amination of Morita–Baylis–Hillman (MBH) carbonates derived from methyl acrylate and aromatic aldehydes with isatins has been realized in the presence of commercially available cinchona alkaloids. The allylic amination products were obtained in moderate-to-good yields (46–74 %) with moderate-to-good enantioselectivities (up to 89 % ee) under mild conditions. The synthetic utility of the amination products has been well demonstrated by the facile synthesis of methyl (3R,4R)-10-oxo-4-phenyl-2,3,4,10-tetrahydropyrimido[1,2-a]indole-3-carboxylate.

We found that nitrogen-containing Lewis base mediated [4+2] annulation of but-3-yn-2-one with activated ketones could proceed efficiently to give the corresponding 2,3-dihydropyran-4-ones in moderate to good yields under mild conditions. The substrate scope has been carefully examined. Moreover, a plausible reaction mechanism for the [4+2] annulation of but-3-yn-2-one with activated ketones mediated by DABCO has been proposed on the basis of previous literature and our own investigations.

Chiral C₂-symmetric N-heterocyclic carbene (NHC) palladium diaquo complex 5b prepared from (S)-BINAM was found to be a fairly effective catalyst for the enantioselective asymmetric fluorination of oxindoles to give the corresponding products in moderate enantioselectivities along with good to excellent yields.

The addition of nucleophiles to CN bonds offers a highly efficient synthetic strategy for accessing nitrogen-containing molecules.1 Among the well-developed addition reactions, such as the highly efficient Mannich reaction, various CH bond-activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines.2 However, employing new nucleophiles without activated CH bonds, such as internal alkynes and allenic esters are limited when using metal catalysts.3 Herein, we wish to report a new addition of allenic esters to CN bonds initiated by a silver-catalyzed 1,3-migration of propargylic esters.

Lewis base-catalyzed cyclization reactions of allenoates with electron-deficient olefins and imines have been demonstrated by the preparation of biologically active natural products and pharmaceutically interesting substances and have emerged as powerful synthetic tools in the rapid construction of cyclic molecular complexity. In contrast to phosphine-containing Lewis bases, nitrogen-containing Lewis base amines display markedly different reaction profiles; however, this area is not well-developed. Herein we summarize the recent progress in this emerging field and outline the challenges ahead.

A highly regio- and enantioselective asymmetric vinylogous Mannich reaction of readily available fluorinated aldimines bearing a chiral auxiliary [(S)-1-phenylethyl group] with siloxyfurans to afford chiral fluorine-containing γ-butenolide or γ-lactone derivatives has been developed in the presence of silver acetate (10 mol%) and axially chiral phosphine-oxazoline ligand L1 (11 mol%). In most cases, the corresponding fluorinated adducts were obtained in high yields, good to excellent enantiomeric excesses and up to>20:1 dr.

The 1,4-diazabicyclic[2.2.2]octane (DABCO)-catalyzed intermolecular Rauhut–Currier reaction of maleimides with electron-deficient allenes has been investigated, affording the corresponding products in good to high yields under mild conditions. The first example of a β-isocupreidine (β-ICD)-catalyzed highly enantioselective intermolecular Rauhut–Currier reaction of maleimides with allenoates and penta-3,4-dien-2-one has been also developed, allowing the synthesis of optically active functionalized allene derivatives in good to high yields along with good to excellent enantioselectivities.

A series of new chiral bifunctional thiourea–phosphane catalysts was synthesized and successfully applied in the catalytic, asymmetric allylic amination of Morita–Baylis–Hillman (MBH) acetates derived from the methyl vinyl ketone (MVK) or ethyl vinyl ketone (EVK) system, with phthalimide, affording the amination products in up to over 99 % yield and 90 % ee for a wide range of substrates derived from different aromatic aldehydes.

The phosphane-catalyzed umpolung addition of various nucleophiles to ethyl 2-methyl-2,3-butadienoate is described. Oxygen, nitrogen, and carbon nucleophiles smoothly reacted with ethyl 2-methyl-2,3-butadienoate to give the corresponding umpolung addition products in good to excellent yields by a similar reaction mechanism. For sulfur nucleophiles, the addition reactions with ethyl 2-methyl-2,3-butadienoate proceeded by a different mechanism.

Under mild reaction conditions, the C=C double bond inisatin-derived electron-deficient alkenes has been exclusively reduced in the presence of alkylphosphanes and water to afford the corresponding reduction products in good to excellent yields. A plausible mechanism is proposed on the basis of deuterium-labeling experiments.

1,6-Enynes can be transformed into 3-azabicyclo[3.1.0]hexanes and functionalized allenes in moderate to good yields along with moderate to high diastereoselectivities by controlling the reaction temperature in the presence of titanium(IV) chloride. A plausible mechanism is proposed.

A series of novel quinidine-derived organocatalysts was synthesized and utilized for the asymmetric substitution of O-Boc-protected Morita–Baylis–Hillman adducts with various carbamates and tosylcarbamates, affording the corresponding products in good to high yields (up to 91 % yield) with moderate to high ee values (up to 96 % ee) under mild conditions.

An interesting nitrene equivalent mediated metal-free ring expansion of methylenecyclopropanes was developed in the presence of iodosobenzene diacetate (PIDA) and 3-amino-2-ethyl-4(3H)-quinazolinone under mild conditions. A variety of cyclobutylidene hydrazine derivatives were obtained in moderate to excellent yields as separable (Z)/(E) isomeric mixtures.

A series of multifunctional, chiral amide–phosphane organocatalysts have been designed and synthesized for the allylic substitution of Morita–Baylis–Hillman (MBH) acetate with 2-trimethylsilyloxyfuran for butenolide synthesis. This reaction was achieved in good to excellent yield (42–98 %) and high ee (85–99 %) with respect to a wide range of substrates in absolute MeOH or CH₃CN, using chiral amide–phosphane organocatalysts with an amide moiety including an active proton. NMR tracing experiments identified the critical phosphonium intermediates involved in the catalytic cycles. Computational studies disclosed the origins of diastereo- and enantioselectivity, in particular, revealing that the active proton of the amide moiety is the critical factor for the catalyst to have high enantiofacial control.

Cyclopropylidenecycloalkanes, which are highly strained methylenecyclopropane (MCPs) containing a cycloalkane moiety, react with carbon dioxide smoothly to give the corresponding five-membered lactone derivatives in moderate to good yields through a cyclopropane ring-opening process in the presence of Pd⁰ catalyst and PCy₃ upon heating under 40 atm of CO₂. The relative configuration of the major diastereomers has been determined and a plausible reaction mechanism has also been proposed.

O-Benzoylquinidine is an effective organocatalyst for the asymmetric chlorination of 3-aryloxindoles by using easily available N-chlorosuccinimide (NCS) as chlorine source to give the corresponding 3-aryl-3-chlorooxindoles in excellent yields and up to 93 % enantiomeric excess.

Ring-opening reaction of vinylidenecyclopropanediesters catalyzed by Re₂(CO)₁₀ or Yb(OTf)₃ afforded 2H-pyran-2-one derivatives or α,β-unsaturated ketones in moderate to good yields through a highly regioselective carbon–carbon bond cleavage pathway. The substituents at the cyclopropane mainly determine the regioselectivity of the carbon–carbon bond cleavage, providing different products of tandem ring-opening and rearrangement reactions.

Oxidative isomerization of vinylidenecyclopropanes 1 produces dimethylenecyclopropane aldehydes 2 in moderate to good yields using tetrapropylammonium perruthenate (TPAP)/4-methylmorpholine N-oxide (NMO) as a catalytic system and the obtained dimethylenecyclopropanes 3 can be transformed to indene derivatives smoothly in the presence of Brønsted acid (HOTf). The scope and limitations as well as the plausible mechanisms have been discussed.

Aminochlorination of methylenecyclopropanes (MCPs) 1 can be achieved under CO₂ atmosphere using N,N-dichlorotoluenesulfonamine (TsNCl₂) as the nitrogen and halogen sources at room temperature to give the corresponding normal ring-remaining aminochlorinated products 2 along with/without the ring-opened aminochlorinated products 3 in moderate to good total yields. The present process takes the advantage of the green benign reaction conditions in the absence of any metal catalyst and solvent.

Chiral phosphine-Schiff base type ligand L8 prepared from (R)-(−)-2-(diphenylphosphino)-1,1'-binaphthyl-2'-amine was found to be a fairly effective ligand for Cu(I)-promoted enantioselective chlorination of β-keto esters to give the corresponding products in high yields and with moderate enantioselectivities. Chirality 2011. © 2010 Wiley-Liss, Inc.

Phosphane-mediated cyclizations between α-keto nitriles and methylidenemalononitriles, producing highly functionalized cyclopropanes in good to excellent yields, are reported. The presence of strongly electron-withdrawing cyano groups directly bound to the ketone carbonyl groups is believed to play a critical role in these transformations.

Isopropenylbiaryl derivatives were produced in moderate to good yields at high temperature from the reaction of methylenecyclopropanes (MCPs) 1 in the presence of palladium acetate under ambient atmosphere by tandem intramolecular C–H and C–C bond activation and aromatization through dehydrogenated rearrangement of MCPs 1. A plausible mechanism has been proposed on the basis of deuterium labeling and control experiments.

DABCO-catalyzed aza-MBH reactions of N-Boc imines with MVK and EVK have been thoroughly investigated in the paper. The asymmetric version of this aza-MBH reaction was also systematically investigated by using a chiral amine or a chiral phosphane catalyst. It was found that most of the N-protected imines are suitable substrates under the mild reaction conditions and are able to give the corresponding adducts in moderate yields with high ee values. The TQO- or LB1-catalyzed aza-MBH reactions of N-protected α-amidoalkyl phenyl sulfones or α-amidoalkyl p-tolyl sulfones with MVK could be well conducted, which provides a facile and direct route to obtain highly enantioselective aza-MBH adducts. The Boc protecting group of the aza-MBH product could be easily removed under acidic conditions to give the corresponding α-methylene-β-amino ketone or α-methylene-β-amino alcohol derivatives in good yields.

Several highly efficient DABCO (1,4-diazabicyclo[2.2.2]octane)-catalyzed Michael-type reactions of hydrazones with activated alkynes are described in this paper. This aza-Michael addition reaction can be applied to different types of hydrazones, such as hydrazones 1 and hydroxy-bearing hydrazones 5. The corresponding adducts are achieved in high yields under mild reaction conditions. DABCO-promoted aza-Michael addition reactions were successfully applied to a serious of hydrazones with activated alkynes to afford the corresponding adducts in moderate to good yields.

Gold(I) can catalyze the diacetoxylation of methylenecyclopropanes to produce the corresponding diacetoxylated products in moderate to good yields in acetic acid in the presence of iodosobenzene diacetate via C–C bond breaking under mild condition.

Tandem Wittig reaction/Cope rearrangement of methylenecyclopropyl aldehydes 1 with cinnamyltriphenylphosphonium bromide afforded a convenient method for the synthesis of cyclopentene derivatives 2 in moderate yields in a one-pot manner. Dialkyl 2-[(2-methylenecyclopropyl)methylene]malonates 3 derived from methylenecyclopropyl aldehydes 1 could produce two kinds of cyclopentene derivatives, 4 and 5, in good total yields through a thermally induced Cope rearrangement upon heating at 100 °C. Plausible reaction mechanisms are discussed on the basis of previous reports and on control experiments.

Pd-catalyzed reactions of 3-substituted methylenecyclopropanes (MCPs), in which the substituents can be either hydroxymethyl or formyl, have been thoroughly investigated in the presence or absence of an acid source. It was found that the Pd-catalyzed reactions of methylenecyclopropylcarbinols (Z)-1 in the presence of acetic acid, acetic acid 2-methylene-but-3-enyl esters 4 can be formed in moderate yields. It was also found that Pd alone can catalyze the isomerization of methylenecyclopropylcarbinols (E)-1 in the absence of an acid source to form pent-4-enals 3. The Pd-catalyzed reactions of methylenecyclopropanecarbaldehydes 5 were also carried out in the presence of acetic acid. It was found that when (E)-5 was used as the substrate, the isomerized product, penta-2,4-dienal 6, could be obtained in good to high yields, whereas the use of (Z)-5 gave 2-(3-formylpenta-2,4-dienylidene)cyclopropanecarbaldehyde 7 in moderate to good yields. Plausible mechanisms for all these transformations have been discussed on the basis of the obtained results and control experiments.

An efficient method to synthesize multisubstituted naphthalene and cyclobutanol derivatives through ring opening/ring enlargement of readily available methylenecyclopropane diaryl alcohols or dialkyl- and monoalkyl- as well as monoaryl alcohols in moderate to good yields has been described in this paper. The formation of naphthalene derivatives is a sequential reaction involving a cation-induced ring opening of cyclopropane, a Friedel–Crafts alkylation reaction, followed by aromatization. On the other hand, the production of cyclobutanol derivatives is a cation-induced ring-enlargement process. The scope and limitations have also been presented.

With the catalysis of Zn(OTf)₂, Mannich-type reactions of various aromatic hydrazones 1 with difluoroenoxysilane 2 proceeded smoothly to produce 2,2-difluoro-3-oxo-benzohydrazides in 27% –78% yields in THF or DCM under mild conditions. An unexpected monofluorination of hydrazone 1m with difluoroenoxysilane 2 was also disclosed in this paper. The first example of the asymmetric Mannich-type reaction of hydrazone 1a with difluoroenoxysilane 2 using chiral phosphine-oxazoline ligand has been reported, giving the adduct 3a in good yields and moderate enantioselectivities under mild conditions.

BF₃⋅OEt₂-catalyzed reactions of vinylidenecyclopropanes (VDCPs) 1 with bis(aryl)methanols 2 were thoroughly investigated. When VDCPs 1 reacted with electron-rich bis(aryl)methanols 2, diastereomeric rotamers of indene derivatives formed in excellent yields by a novel cationic 1,4-aryl migration between two carbon atoms and the subsequent intramolecular Friedel–Crafts reaction pathways in the presence of BF₃⋅OEt₂ under mild conditions. As for electron-deficient or less-electron-rich bis(aryl)methanols 2, either trialkene products formed in good yields by direct deprotonation, or another type of indene derivative was produced by direct intramolecular Friedel–Crafts reaction, depending on the substituents on the cyclopropane of VDCPs. In addition, DFT calculations were carried out to explain the experimental results. Plausible mechanisms for all these transformations are proposed on the basis of the experimental and computational results.

We report here the intramolecular reactions between α,β-epoxy ketones and alkynes cocatalyzed by gold(I) and Yb(OTf)₃. This new catalytic system based on a combination of gold(I) and Yb(OTf)₃ allows facile transformation of epoxy alkynes to give novel indene derivatives in moderate to good yields under mild conditions. Moreover, we describe here the first observation of a transfer of a carbonyl group in a five-membered carbocycle during gold-catalyzed reactions. This proposed mechanism is corroborated by isotope-labeling experiments (D and ¹³C). Furthermore, the probable role of each catalyst in this interesting domino reaction has been examined by ³¹P NMR experiments. The utilization of gold catalysts combined with rare-earth metal salts offers a new concept for the design of catalyst combinations for domino or cascade reactions.

A new asymmetric catalytic system for the Mannich reaction of aldimines with trimethylsiloxyfuran is described. The combination of an axially chiral phosphine-oxazoline ligand (S)-2-[(R)-2′-(diphenylphosphino)-1,1′-binaphthyl-2-yl]-4-phenyl-4,5-dihydrooxazole with silver acetate and 2,2,2-trifluoroacetic acid is a very effective catalytic system in the asymmetric Mannich reaction of various aldimines with trimethylsiloxyfuran in dichloromethane at −78 °C, affording the corresponding adducts in up to 99% yield, 99:1 (dr) and 99% ee (major diastereoisomer) under mild conditions.

Brønsted acid (TfOH) or solid acid (montmorillonite K-10) catalyzed aza-Diels–Alder reactions of methylenecyclopropanes with ethyl (arylimino)acetates were shown for the construction of the tetrahydroquinoline skeleton with the untouched cyclopropyl group in the 3,3′-position. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Gold(I)-catalyzed intramolecular cycloisomerization of ketone-substituted epoxides with alkynes to six- or seven-membered heterocyclic compounds is firstly introduced in this paper. This procedure involves a cascade isomerization of the ketone-substituted epoxides into 1,3-diketones in the presence of a Lewis acid and subsequent gold(I)-catalyzed selective intramolecular addition of an oxygen or a carbon nucleophile to the alkynes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Bis(4-methoxyphenyl)methanol (2a) can be transformed by BF₃·OEt₂-catalyzed reactions of (arylmethylene)cyclopropanes 1 to the corresponding polysubstituted cyclopentenes 3 as the major products along with methylenecyclobutanes and dienes as minor products. The reaction conditions are mild, yields are moderate to good. In the reactions of aliphatic methylenecyclopropanes with bis(4-methoxyphenyl)methanol (2a), cyclopentenes 3o–q were produced in good yields under the standard conditions. Interesting results were obtained from the reactions of 1-[cyclopropylidene(4-methoxyphenyl)methyl]-4-methoxybenzene (1e) with bis(4-alkoxyphenyl)methanols 2: polysubstituted cyclopentene derivatives 5 were obtained in good yields under mild reaction conditions. Plausible reaction mechanisms based on the deuterium-labeling and control experiments are proposed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A palladium-catalyzed cross-coupling reaction of diarylvinylidenecyclopropanes with 2-iodophenol and N-(2-iodophenyl)-4-methylbenzenesulfonamide provided a variety of cyclopropane-containing 2,2-diaryl-3-tetramethylcyclopropylidene-2,3-dihydrobenzofuran and 2,2-diaryl-3-tetramethylcyclopropylidene-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-indole derivatives in moderate-to-good yields.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

A new family of imidazole-coordinated monodentate NHC–metal complexes 9 was obtained as well as cis-chelatedbidentate NHC–metal complexes 10 from novel bis(imidazolium) salts 4 with a biphenyl backbone. The structures of complexes 9a and 10b were determined by X-ray crystal-structure diffraction, and their application in the Heck reaction showed good to excellent catalytic activities under very mild conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Novel axially chiral N-heterocyclic carbene (NHC) Pd(II) complexes were prepared from optically active 1,1′-binaphthalenyl-2,2′-diamine (BINAM) and H₈-BINAM and their crystal structures were unambiguously determined by X-ray diffraction. These chiral N-heterocyclic carbene (NHC) Pd(II) complexes were applied in the oxidative kinetic resolution of secondary alcohols using molecular oxygen as a terminal oxidant or under aerobic conditions, affording the corresponding sec-alcohols in good yields with moderate to good enantioselectivities. Copyright © 2009 John Wiley & Sons, Ltd.

Diarylvinylidenecyclopropanes undergo a novel rearrangement in the presence of the Brønsted acid Tf₂NH (Tf: trifluoromethanesulfonyl) to give the corresponding naphthalene derivatives in good to high yields upon heating, whereas in the presence of the Brønsted acid toluene-4-sulfonic acid (p-TSA), the corresponding triene derivatives are afforded in moderate to good yields under mild conditions. Corresponding mechanistic studies on the basis of density functional theory (DFT) with the Gaussian03 program by using the B3LYP method have revealed that the pK_a value of the Brønsted acid, as well as the entropy and solvent effects, plays a significant role in this reaction; these factors can discriminate the differences in the reactivity and regioselectivity among the Brønsted acids used in this reaction. In the presence of Lewis acid Sn(OTf)₂, a butatrienecyclopane can produce the corresponding ring-opened products in moderate yields.

Lewis acid or Brønsted acid catalyzed reactions of vinylidene cyclopropanes (VDCPs), 1, with activated carbon–nitrogen, nitrogen–nitrogen, and iodine–nitrogen double-bond-containing compounds have been thoroughly investigated. We found that pyrrolidine and 1,2,3,4-tetrahydroquinoline derivatives can be formed in good yields in the reactions of VDCPs 1 with ethyl (arylimino)acetates 2 by a [3+2] cycloaddition or intramolecular Friedel–Crafts reaction pathway. Based on these results, we found that activated carbon–nitrogen and nitrogen–nitrogen double-bond-containing compounds, such as N-toluene-4-sulfonyl (N-Ts) imines 5 and diisopropylazodicarboxylate (7), can also react with VDCPs 1 to give [3+2] cycloaddition products in moderate to good yields in the presence of a Lewis acid. When N-tert-butoxycarbonyl aldimine 9 was used as the substrate, six-membered cycloaddition products 10 and 11 were formed in moderate yields in the presence of a Brønsted acid, trifluoromethanesulfonic acid (TfOH). The reactions of VDCPs 1 with N-Ts-iminophenyliodinane (12) were also carried out in the presence of (CuOTf)₂⋅C₆H₆ and it was found that nitrogen-containing indene derivatives 13 were obtained, rather than the aziridination products. Plausible mechanisms for all of these transformations are discussed, based on the obtained results.

A series of polyether dendritic chiral phosphine Lewis bases was synthesized, and successfully applied to the asymmetric aza-Morita–Baylis–Hillman reaction of N-sulfonated imines (N-arylmethylidene-4-methylbenzenesulfonamides) with methyl vinyl ketone (MVK), ethyl vinyl ketone (EVK), and acrolein to give the adducts in good to excellent yields along with up to 97 % ee, which are more effective than our previously reported original chiral phosphine Lewis bases. In addition, the dendrimer-supported chiral phosphine Lewis bases can be easily recovered and reused.

A novel imidazole-mediated [2 + 2 + 2] annulation process that enables the diastereoselective synthesis of multiply substituted cyclohexanes 3 in a one-pot, three-component manner from two units of (arylmethylidene)malononitriles 1 and one unit of nitroalkenes 2 is described. These cyclohexane derivatives were obtained in moderate to good yields under mild conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A series of chiral sterically congested phosphane-amide bifunctional Lewis bases L1–L3 have been successfully synthesized and their application in asymmetric aza-Morita–Baylis–Hillman (aza-MBH) reactions of N-sulfonated imines with activated olefins such as methyl and ethyl vinyl ketone has been investigated under mild conditions. The corresponding aza-MBH adducts can be obtained in good-to-excellent yields (up to 98 %) and moderate-to-good enantioselectivities (up to 91 or 93 % ee) in dichloromethane at room temperature (20 °C) with these novel chiral bifunctional phosphane Lewis bases.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A series of novel bifunctional chiral phosphane Lewis bases having one phenyl group and an electron-donating alkyl group on the phosphorus atom was designed and successfully synthesized. The use of these bifunctional chiral phosphane Lewis bases in catalytic asymmetric aza-Morita–Baylis–Hillman reactions (aza-MBH reactions) of N-sulfonated imines with methyl vinyl ketone affords the corresponding adducts in good-to-excellent yields and moderate-to-good enantioselectivities within a few hours at room temperature. To the best of our knowledge, this is the fastest catalytic asymmetric MBH reaction reported thus far.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Axially chiral cis-chelated bidentate bis(N-heterocyclic carbene)–palladium(II) complexes with two weakly coordinating carboxylate ligands are effective catalysts for the asymmetric conjugate addition of arylboronic acids to cyclic enones, producing the corresponding adducts in moderate-to-high yields and with good-to-high enantioselectivities, in most cases under mild conditions.

The gold(I)-catalyzed cycloisomerization of epoxy alkynes in the presence of a nucleophile is an efficient protocol to provide ketal skeletons with high stereoselectivity. An intramolecular reaction of propargylic/homopropargylic alcohols with oxirane to produce ketal/spiroketals in moderate yields under mild conditions has been reported. Moreover, the mechanism of this kind of reaction has been discussed on the basis of a series of control and ¹⁸O tracer experiments.

The reactions of vinylidenecyclopropanes 1 with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers 2 in the presence of a Lewis acid selectively produce 4-dihydro-1H-cyclopenta[b]naphthalene derivatives 3 or 1,2,3,8-tetrahydrocyclopenta[a]indene derivatives 4 depending on the substituents on the cyclopropane. Good to high yields are obtained under mild conditions. A plausible cascade Meyer–Schuster rearrangement and Friedel–Crafts reaction mechanism has been proposed. Moreover, novel functionalized methylenecyclobutene derivatives 5 could also be obtained in moderate to good yields under similar conditions when strongly electron-donating methoxy groups were introduced into the benzene rings of 2.