Rh(i)-catalyzed stereoselective desymmetrization of prochiral cyclohexadienones via highly exo-selective Huisgen-type [3 + 2] cycloaddition

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed. This method enables convergent construction of complex epoxy-bridged polycyclic ring systems with five contiguous stereocenters with excellent exo-selectivity and broad substrate scope. The highly atom-economical process involves 6-endo-dig cyclization of carbonyl oxygen onto an activated alkyne resulting in a highly reactive metal–benzopyrylium intermediate, which readily undergoes intramolecular [3 + 2] annulation/hydration. Asymmetric induction is also achieved for the first time in Rh(i)-catalyzed 1,3-dipolar cycloaddition using an easily accessible chiral diene as the ligand.

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed.     

Supramolecular-induced regiocontrol over the photochemical [4 + 4] cyclodimerization of NHC- or azole-substituted anthracenes

Thanks to the impressive control that microenvironments within enzymes can have over substrates, many biological reactions occur with high regio- and stereoselectivity. However, comparable regio- and stereoselectivity is extremely difficult to achieve for many types of reactions, particularly photochemical cycloaddition reactions in homogeneous solutions. Here, we describe a supramolecular templating strategy that enables photochemical [4 + 4] cycloaddition of 2,6-difunctionalized anthracenes with unique regio- and stereoselectivity and reactivity using a concept known as the supramolecular approach. The reaction of 2,6-azolium substituted anthracenes H₄-L(PF₆)₂ (L = 1a–1c) with Ag₂O yielded complexes anti-[Ag₂L₂](PF₆)₄ featuring an antiparallel orientation of the anthracene groups. Irradiation of complexes anti-[Ag₂L₂](PF₆)₄ proceeded under [4 + 4] cycloaddition linking the two anthracene moieties to give cyclodimers anti-[Ag₂(2)](PF₆)₂. Reaction of 2,6-azole substituted anthracenes with a dinuclear complex [Cl-Au-NHC–NHC-Au-Cl] yields tetranuclear assemblies with the anthracene moieties oriented in syn-fashion. Irradiation and demetallation gives a [4 + 4] syn-photodimer of two anthracenes. The stereoselectivity of the [4 + 4] cycloaddition between two anthracene moieties is determined by their orientation in the metallosupramolecular assemblies.

A supramolecular templating strategy that enables the photochemical [4 + 4] cycloaddition of 2,6-difunctionalized anthracene derivatives with unique stereoselectivity has been developed based on metal-NHC units.     

Magnesium-mediated sp3 C–H activation in cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes: efficient synthesis of carborane-fused cyclopentanes

This work reports an unprecedented cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes promoted by magnesium-mediated sp³ C–H activation. Treatment of 1-arylethynyl-2-alkyl-o-carboranes with MeMgBr gives a series of carborane-fused cyclopentanes in very good yields. Deuterium labelling and control experiments suggest that HMgBr, resulting in situ from the nucleophilic substitution of cage B–H bonds with Grignard reagent, initiates the reaction, in which magnesium-promoted intramolecular sp³ C–H activation serves as a key step. This work not only offers a new route for the synthesis of carborane-fused cyclopentanes, but also sheds some light on Mg-mediated C–H activation and functionalization.

An unprecedented cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes with Grignard reagent for synthesizing carborane-fused cyclopentanes has been disclosed, in which magnesium-mediated intramolecular sp³ C–H activation serves as a key step.     

Access to substituted cyclobutenes by tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition of dipropargylphosphonates under Ag/Co relay catalysis

We present herein an unconventional tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition of simple dipropargylphosphonates to deliver a range of bicyclic polysubstituted cyclobutenes and cyclobutanes under Ag/Co relay catalysis. An interesting switch from allene–allene to allene–alkyne cycloaddition was observed based on the substitution of the substrates, which further diversified the range of compounds accessible from this practical method. Significantly, preliminary biological screening of these new compounds identified promising candidates as suppressors of cellular proliferation.

In situ generation of allenes through [3,3]-sigmatropic rearrangement of propargylphosphonates. Divergent allene–allene or allene–alkyne cycloaddition by Ag/Co relay catalysis. Products as promising suppressors of cellular proliferation.     

BNN-1,3-dipoles: isolation and intramolecular cycloaddition with unactivated arenes

The mono-base-stabilized 1,2-diboranylidenehydrazine derivatives featuring a 1,3-dipolar BNN skeleton are obtained by dehydrobromination of [ArB(Br)NH]₂ (Ar = 2,6-diphenylphenyl (Dpp), Ar = 2,6-bis(2,4,6-trimethylphenyl)phenyl (Dmp) or Ar = 2,4,6-tri-tert-butylphenyl (Mes*)) with N-heterocyclic carbenes (NHCs). Depending on the Ar substituents, such species can be isolated as a crystalline solid (Ar = Mes*) or generated as reactive intermediates undergoing spontaneous intramolecular aminoboration of the proximal arene rings via [3 + 2] cycloaddition (Ar = Dpp or Dmp). The latter reactions showcase the 1,3-dipolar reactivity toward unactivated arenes at ambient temperature. In addition, double cycloaddition of the isolable BNN species with two CO₂ molecules affords a bicyclic species consisting of two fused five-membered BN₂CO rings. The electronic structures of these BNN species and the mechanisms of these cascade reactions are interrogated through density functional theory (DFT) calculations.

The mono-base-coordinated 1,2-diboranylidenehydrazine derivatives exhibiting the BNN-1,3-dipolar reactivity toward unactivated arenes and CO₂ are reported.     

Formal oxo- and aza-[3 + 2] reactions of α-enaminones and quinones: a double divergent process and the roles of chiral phosphoric acid and molecular sieves

A double divergent process has been developed for the reaction of α-enaminones with quinones through facile manipulation of catalyst and additive, leading to structurally completely different products. The two divergent processes, which involve formal aza- and oxo-[3 + 2] cycloaddition reactions, are mediated by chiral phosphoric acid and molecular sieves, respectively. While inclusion of phosphoric acid in the reaction switched the reaction pathway to favor the efficient formation of a wide range of N-substituted indoles, addition of 4 Å molecular sieves to the reaction switched the reaction pathway again, leading to enantioselective synthesis of 2,3-dihydrobenzofurans in excellent yields and enantioselectivities under mild conditions. Studies in this work suggest that the chiral phosphoric acid acts to lower the transition state energy and promote the formation of amide intermediate for the formal aza-[3 + 2] cycloaddition and the molecular sieves serve to facilitate proton transfer for oxo-[3 + 2] cycloaddition. The reactivity of α-enaminones is also disclosed in this work.

A double divergent process for [3 + 2] cycloadditions of α-enaminones with quinones led to the formation of N-substituted indoles and 2,3-dihydrobenzofurans.     

Site-selective [2 + 2 + n] cycloadditions for rapid,scalable access to alkynylated polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are attractive synthetic building blocks for more complex conjugated nanocarbons, but their use for this purpose requires appreciable quantities of a PAH with reactive functional groups. Despite tremendous recent advances, most synthetic methods cannot satisfy these demands. Here we present a general and scalable [2 + 2 + n] (n = 1 or 2) cycloaddition strategy to access PAHs that are decorated with synthetically versatile alkynyl groups and its application to seven structurally diverse PAH ring systems (thirteen new alkynylated PAHs in total). The critical discovery is the site-selectivity of an Ir-catalyzed [2 + 2 + 2] cycloaddition, which preferentially cyclizes tethered diyne units with preservation of other (peripheral) alkynyl groups. The potential for generalization of the site-selectivity to other [2 + 2 + n] reactions is demonstrated by identification of a Cp₂Zr-mediated [2 + 2 + 1]/metallacycle transfer sequence for synthesis of an alkynylated, selenophene-annulated PAH. The new PAHs are excellent synthons for macrocyclic conjugated nanocarbons. As a proof of concept, four were subjected to alkyne metathesis catalysis to afford large, PAH-containing arylene ethylene macrocycles, which possess a range of cavity sizes reaching well into the nanometer regime. Notably, these high-yielding macrocyclizations establish that synthetically convenient pentynyl groups can be effective for metathesis since the 4-octyne byproduct is sequestered by 5 Å MS. Most importantly, this work is a demonstration of how site-selective reactions can be harnessed to rapidly build up structural complexity in a practical, scalable fashion.

An orthogonal [2 + 2 + n] cycloaddition/alkyne metathesis reaction sequence enables streamlined access to conjugated macrocyclic nanocarbons.     

Catalytic asymmetric synthesis of spirocyclobutyl oxindoles and beyond via [2+2] cycloaddition and sequential transformations

Efficient asymmetric synthesis of a collection of small molecules with structural diversity is highly important to drug discovery. Herein, three distinct types of chiral cyclic compounds were accessible by enantioselective catalysis and sequential transformations. Highly regio- and enantioselective [2+2] cycloaddition of (E)-alkenyloxindoles with the internal C C bond of N-allenamides was achieved with N,N′-dioxide/Ni(OTf)₂ as the catalyst. Various optically active spirocyclobutyl oxindole derivatives were obtained under mild conditions. Moreover, formal [4+2] cycloaddition products occurring at the terminal C C bond of N-allenamides, dihydropyran-fused indoles, were afforded by a stereospecific sequential transformation with the assistance of a catalytic amount of Cu(OTf)₂. In contrast, performing the conversion under air led to the formation of γ-lactones via the water-involved deprotection and rearrangement process. Experimental studies and DFT calculations were performed to probe the reaction mechanism.

Three distinct types of chiral cyclic compounds were accessible by catalytic asymmetric synthesis of spirocyclobutyl oxindoles via [2+2] cycloaddition and sequential transformations.     

Discovery of an all-donor aromatic [2]catenane

We report herein the first all-donor aromatic [2]catenane formed through dynamic combinatorial chemistry, using single component libraries. The building block is a benzo[1,2-b:4,5-b′]dithiophene derivative, a π-donor molecule, with cysteine appendages that allow for disulfide exchange. The hydrophobic effect plays an essential role in the formation of the all-donor [2]catenane. The design of the building block allows the formation of a quasi-fused pentacyclic core, which enhances the stacking interactions between the cores. The [2]catenane has chiro-optical and fluorescent properties, being also the first known DCC-disulphide-based interlocked molecule to be fluorescent.

An all-donor [2]catenane has been synthesised via dynamic combinatorial chemistry. It features stacked benzodithiophenes which are quasi-pentacyclic through hydrogen bonding.     

Acyclic nitronate olefin cycloaddition (ANOC): regio- and stereospecific synthesis of isoxazolines

We report the first demonstrations of intra- and intermolecular acyclic nitronate olefin cycloaddition (ANOC) reactions that enable the highly efficient syntheses of isoxazolines bearing various functional groups. This general approach to accessing γ-lactone fused isoxazolines was hitherto unprecedented. The room temperature transformations reported herein exhibit wide substrate scopes, as evidenced by more than 70 examples, including the generation of five tricyclic isoxazolines. The robustness of this methodology was confirmed by a series of trials that afforded highly functionalized isoxazolines. Both experimental results and density functional theory calculations indicate that these transformations proceed via the in situ formation of acyclic nitronates together with concerted [3+2] cycloaddition and tert-butyloxy group elimination processes to give regio- and stereospecificity.

A novel acyclic nitronate olefin cycloaddition (ANOC) reaction was successfully established, which enabled facile construction of various isoxazolines.     

Formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloaddition reactions of donor–acceptor cyclobutenes,cyclopropenes and siloxyalkynes induced by Brønsted acid catalysis

Brønsted acid catalyzed formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloadditions of donor–acceptor cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium ions are reported. [4 + 2]-cyclization/deMayo-type ring-extension cascade processes produce highly functionalized benzocyclooctatrienes, benzocycloheptatrienes, and 2-naphthols in good to excellent yields and selectivities. Moreover, the optical purity of reactant donor–acceptor cyclobutenes is fully retained during the cascade. The 1,3-dicarbonyl product framework of the reaction products provides opportunities for salen-type ligand syntheses and the construction of fused pyrazoles and isoxazoles that reveal a novel rotamer-diastereoisomerism.

Brønsted acid catalysis realizes formal [4 + 4]-, [4 + 3]-, and [4 + 2]-cycloadditions of donor–acceptor cyclobutenes, cyclopropanes, and siloxyalkynes with benzopyrylium ions.

Medium-sized rings are the core skeletons of many natural products and bioactive molecules,¹ and a growing number of strategies have been developed for their synthesis.² Because of their enthalpic and entropic advantages, ring expansion is a highly efficient methodology for these constructions.^3–6 For example, Sun and co-workers have developed acid promoted ring extensions of oxetenium and azetidinium species formed from siloxyalkynes with cyclic acetals and hemiaminals (Scheme 1a).⁴ Takasu and co-workers have reported an elegant ring expansion with a palladium(ii) catalyzed 4π-electrocyclic ring-opening/Heck arylation cascade with fused cyclobutenes (Scheme 1b).⁵ Each transformation is initiated by the formation of fused bicyclic units followed by ring expansion or rearrangement to give medium-sized rings.Open in a separate windowScheme 1Cycloaddition/ring expansion background and this work.Strategies for the formation of fused bicyclic compounds rely on cycloaddition of dienes or dipoles with unsaturated cyclic compounds⁷ and, if the reactant cyclic compound is strained and chiral, the resulting bicyclic compound is activated toward ring opening that results in retention of chirality. We have recently reported access to donor–acceptor cycloalkenes by [3 + n] cycloaddition that have the prerequisites of unsaturated cyclic compounds suitable for cycloaddition.⁸ Donor–acceptor (D–A) cyclopropenes⁹ and cyclobutenes¹⁰ have sufficient strain in the resulting bicyclic compounds to undergo ring opening. We envision that the selection of a diene or dipolar reactant and suitable reaction conditions could realize cycloaddition and subsequent ring expansion. Benzopyrylium species,^11,12 which are generated by metal or acid catalysis, have attracted our attention. We anticipated that their high reactivity would overcome the conventional unfavorable kinetic and/or thermodynamic factors that typically impede medium-sized ring formation. From a mechanistic perspective, benzopyrylium species are often formed by transition metal catalyzed reactions with 2-alkynylbenzaldehydes.¹¹ Recently, the reaction between 1H-isochromene acetal and Brønsted acid catalyst forms the 2-benzopyrylium salts that could react with functional alkenes to give same cycloaddition products.¹² Consequently, we believed that the [4 + 2]-cyclization between benzopyrylium species and donor–acceptor cyclobutenes, cyclopropenes, or siloxyalkynes would give bridged oxetenium intermediates, which contain high strain energy that should provide the driving force for ring expansion. The “push and pull” electronic effect of donor–acceptor functional groups facilitates deMayo-type ring-opening of the cyclobutane or cyclopropane skeletons (Scheme 1c).¹³Here we report bis(trifluoromethanesulfonyl)imide (HNTf₂) catalyzed formal [4 + 4]-, [4 + 3]- and [4 + 2]-cycloaddition reactions of D–A cyclobutenes, cyclopropenes, and siloxyalkynes with benzopyrylium salts. Polysubstituted benzo-cyclooctatrienes, benzocycloheptatrienes and 2-naphthols, are produced in good to excellent yields and selectivities. Complete retention of configuration occurs using chiral cyclobutenes, and opportunities for further functionalization are built into these constructions.Initially, we conducted transition metal catalyzed reactions with 2-alkynylbenzaldehyde intending to produce the corresponding benzopyrylium ion and explore the possibility of cycloaddition/ring opening with donor–acceptor cyclobutene 2a. Use of Ph₃PAuCl/AgSbF₆, Pd(OAc)₂ and Cu(OTf)₂, which were efficient catalysts in previous transformations,¹¹ gave only a trace amount of cycloaddition product (Fig. 1). Spectral analysis showed that mostly starting material remained (Fig. 1-i and ii). Increasing the reaction temperature led only to decomposition of 2-alkynylbenzaldehyde (Fig. 1-iv) or donor–acceptor cyclobutene 2a (Fig. 1-iv).Open in a separate windowFig. 1Reaction of 2-alkynylbenzaldehyde with donor–acceptor cyclobutene 2a.From these disappointments we turned our attention to 1H-isochromene acetal 1a as the benzopyrylium ion precursor. Various Lewis acid catalysts were employed with limited success, but we were pleased to observe the formation of the desired formal [4 + 4]-cycloaddition benzocyclooctatriene product 3aa, albeit in low yields (Table 1, entries 1–6). Selection of the Brønsted super acid HNTf₂ (ref. 14) proved to be the most promising, producing 3aa in 40% yield (Table 1, entry 7). Increasing the amount of D–A cyclobutene 2a by 30% gave a much higher yield of 3aa (Table 1, entry 8 vs. 7). Optimization of the stoichiometric reaction between 1a and 2a by increasing the reaction temperature from rt to 35 °C led to the formation of the desired product in 76% isolated yield (Table 1, entry 9 vs. 8). However, a further increase in the reaction temperature (Table 1, entry 10) or reducing the catalyst loading to 5 mol% did not improve the yield of 3aa (Table 1, entry 11).Optimization of reaction conditions^a

Reaction of carboryne with styrene and its derivatives

Reaction of carboryne generated from 1-I-2-Li-1,2-C₂B₁₀H₁₀ with styrene and its derivatives has been studied. In addition to [2+2] cycloaddition reaction and/or ene reaction, an extra-annular [4+2] cycloaddition reaction is also observed, depending upon the substituents on the vinyl unit. The resulting [4+2] cycloaddition intermediates are so reactive that they immediately undergo rearomatization via either a formal 1,3-hydrogen rearrangement or dehydrogenation initiated by hydrogen abstraction with carboryne in biradical form, to give 3,4-dihydronaphtho[1,2]-o-carboranes and naphtho[1,2]-o-carboranes, respectively. In sharp contrast to that of benzyne, further additions of carboryne onto the primary cycloadducts are not observed.     

Redox-induced reversible [2 + 2] cycloaddition of an etheno-fused diporphyrin

3,5-Ethenoporphyrin is a π-extended porphyrin containing a fused ethene unit between the meso- and β-positions, exhibiting unique contribution of macrocyclic antiaromaticity. We have recently reported that its analogue, etheno-fused diporphyrin, underwent thermal [2 + 2] cycloaddition to furnish X-shaped cyclobutane-linked tetraporphyrins. Here we demonstrate that the cyclobutane-ring formation is dynamically redox-active. Namely, the tetraporphyrin underwent two-step four-electron oxidation to afford two etheno-fused diporphyrin dications. The reduction of the resulting dication regenerated the cyclobutane-linked tetraporphyrin. The dication was sufficiently stable to allow its isolation under ambient conditions. The structure of the dication has been confirmed by ¹H NMR spectroscopy and X-ray diffraction analysis. Importantly, the simultaneous double C–C bond cleavage in the cyclopropane ring in the tetraporphyrin is exceptional among dynamic redox (dyrex) systems to achieve large structural changes, thus offering new insights for the design of novel redox-active functional organic materials for electrochromic dyes, organic batteries, and organic memories.

A four-electron oxidation of an X-shaped tetraporphyrin affords stable etheno-fused diporphyrin dications through double C–C bond cleavage. The reduction of the dication recovers the tetraporphyrin via a thermal [2 + 2] cycloaddition.     

Asymmetric construction of pyrido[1,2-a]-1H-indole derivatives via a gold-catalyzed cycloisomerization

Pyrido[1,2-a]-1H-indoles are important scaffolds found in many biologically active compounds. Herein, we first developed an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of N-1,3-disubstituted allenyl indoles affording pyrido[1,2-a]-1H-indoles. Then the axial-to-central chirality transfer starting from enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles has been realized in excellent yields and enantioselectivities. A mechanism has been proposed based on mechanistic studies. Synthetic applications have also been demonstrated.

We reported an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles in excellent yields and enantioselectivities.     

Understanding the mechanism of direct visible-light-activated [2 + 2] cycloadditions mediated by Rh and Ir photocatalysts: combined computational and spectroscopic studies

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques. Experimental observations show that the Rh-based photocatalyst produces excellent yield and enantioselectivity whereas the Ir-photocatalyst yields racemates. Two different mechanistic features were found to compete with each other, namely the direct photoactivation of the catalyst–substrate complex and outer-sphere triplet energy transfer. Our integrated analysis suggests that the direct photocatalysis is the inner working of the Rh-catalyzed reaction, whereas the Ir catalyst serves as a triplet sensitizer that activates cycloaddition via an outer-sphere triplet excited state energy transfer mechanism.

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques.     

1,2-Addition and cycloaddition reactions of niobium bis(imido) and oxo imido complexes

The bis(imido) complexes (BDI)Nb(N^tBu)₂ and (BDI)Nb(N^tBu)(NAr) (BDI = N,N′-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate; Ar = 2,6-diisopropylphenyl) were shown to engage in 1,2-addition and [2 + 2] cycloaddition reactions with a wide variety of substrates. Reaction of the bis(imido) complexes with dihydrogen, silanes, and boranes yielded hydrido-amido-imido complexes via 1,2-addition across Nb-imido π-bonds; some of these complexes were shown to further react via insertion of carbon dioxide to give formate-amido-imido products. Similarly, reaction of (BDI)Nb(N^tBu)₂ with tert-butylacetylene yielded an acetylide-amido-imido complex. In contrast to these results, many related mono(imido) Nb BDI complexes do not exhibit 1,2-addition reactivity, suggesting that π-loading plays an important role in activating the Nb–N π-bonds toward addition. The same bis(imido) complexes were also shown to engage in [2 + 2] cycloaddition reactions with oxygen- and sulfur-containing heteroallenes to give carbamate- and thiocarbamate-imido complexes: some of these complexes readily dimerized to give bis-μ-sulfido, bis-μ-iminodicarboxylate, and bis-μ-carbonate complexes. The mononuclear carbamate imido complex (BDI)Nb(NAr)(N(^tBu)CO₂) (12) could be induced to eject tert-butylisocyanate to generate a four-coordinate terminal oxo imido intermediate, which could be trapped as the five-coordinate pyridine or DMAP adduct. The DMAP adducted oxo imido complex (BDI)NbO(NAr)(DMAP) (16) was shown to engage in 1,2-addition of silanes across the Nb-oxo π-bond; this represents a new reaction pathway in group 5 chemistry.

Another slice of pi: the addition of a second π-donor ligand engenders 1,2-addition and [2 + 2] cycloaddition reactivity across Nb-imido and Nb-oxo bonds.     

Selective propargylic C(sp3)–H activation of methyl-substituted alkynes versus [2 + 2] cycloaddition at a titanium imido template

The reaction of the titanium imido complex 1b with 2-butyne leads to the formation of the titanium azadiene complex 2a at ambient temperature instead of yielding the archetypical [2 + 2] cycloaddition product (titanaazacyclobutene) which is usually obtained by combining titanium imido complexes and internal alkynes. The formation of 2a is presumably caused by an initial propargylic C(sp³)–H activation step and quantum chemical calculations suggest that the outcome of this unexpected reactivity is thermodynamically favored. The previously reported titanaazacyclobutene I (which is obtained by reacting 1b with 1-phenyl-1-propyne) undergoes a rearrangement reaction at elevated temperature to give the corresponding five-membered titanium azadiene complex 2b.

An unexpected reactivity between a titanium imido complex and internal alkynes was unveiled yielding titanaazacyclobutenes instead of the expected [2 + 2] cycloaddition products.     

Rh(iii)-Catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkenylphenols with allenyl acetates

Herein, we report a mild and highly regioselective Rh(iii)-catalyzed non-oxidative [5 + 1] vinylic C–H annulation of 2-alkenylanilides with allenyl acetates, which has been elusive so far. The reaction proceeds via vinylic C–H activation, regioselective 2,3-migratory insertion, β-oxy elimination followed by nucleophilic cyclization to get direct access to 1,2-dihydroquinoline derivatives. The strategy was also successfully extended to C–H activation of 2-alkenylphenols for constructing chromene derivatives. In the overall [5 + 1] annulation, the allene serves as a one carbon unit. The acetate group on the allene is found to be crucial both for controlling the regio- and chemoselectivity of the reaction and also for facilitating β-oxy elimination. The methodology was scalable and also further extended towards late stage functionalization of various natural products.

A highly regioselective Rh(iii)-catalyzed non-oxidative [5 + 1] vinylic C–H annulation of 2-alkenylanilides and 2-alkenylphenols with allenyl acetates was described for accessing dihyroquinoline and chromene derivatives.     

Regiodivergent construction of medium-sized heterocycles from vinylethylene carbonates and allylidenemalononitriles

Medium-sized heterocycles exist in a broad spectrum of biologically active natural products and medicinally important synthetic compounds. The construction of medium-sized rings remains challenging, particularly the assembly of different ring sizes from the same type of substrate. Here we report palladium-catalyzed, regiodivergent [5 + 4] and [5 + 2] annulations of vinylethylene carbonates and allylidenemalononitriles. We describe the production of over 50 examples of nine- and seven-membered heterocycles in high isolated yields and excellent regioselectivities. We demonstrate the synthetic utility of this approach by converting a nine-membered ring product to an interesting polycyclic caged molecule via a [2 + 2] transannulation. Mechanistic studies suggest that the [5 + 2] annulation proceeds through palladium-catalyzed ring-opening/re-cyclization from the [5 + 4] adducts.

Here we report palladium-catalyzed, regiodivergent [5 + 4] and [5 + 2] annulations of vinylethylene carbonates and allylidenemalononitriles affording over 50 medium-sized heterocycles in high isolated yields with excellent regioselectivities.     

Metal-free tandem carbene N–H insertions and C–C bond cleavages

A metal-free C–H [5 + 1] annulation reaction of 2-arylanilines with diazo compounds has been achieved, giving rise to two types of prevalent phenanthridines via highly selective C–C cleavage. Compared to the simple N–H insertion manipulation of diazo, this method elegantly accomplishes a tandem N–H insertion/S_EAr/C–C cleavage/aromatization reaction, and the synthetic utility of this new transformation is exemplified by the succinct syntheses of trisphaeridine and bicolorine alkaloids.

A metal-free C–H [5 + 1] annulation reaction of 2-arylanilines with diazo compounds has been achieved, giving rise to two types of prevalent phenanthridines via highly selective C–C cleavage.