Rh(I)-catalyzed intramolecular hetero-[4+2] cycloaddition of ω-alkynyl-vinyl oximes

Cationic rhodium(I) catalyst derived from [RhCl(cod)]₂ and AgSbF₆ in hexafluoroisopropanol (HFIP) efficiently catalyzed the formation of bicyclic pyridine derivatives by intramolecular hetero-[4+2] cycloadditions of ω-alkynyl-vinyl oximes.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Rh(I)-catalyzed mild intramolecular [4+2] cycloaddition reactions of ester-tethered diene-yne compounds

The cationic rhodium(I) species derived from [Rh(COD)Cl]₂ and AgSbF₆ efficiently catalyze intramolecular [4+2] cycloadditions of ester-tethered 1,3-diene-8-yne derivatives such as 2-propynyl penta-2,4-dienoate and 2,4-pentadienyl propiolate derivatives in fluorinated alcohols.     

N-Iodosaccharin (NISac): a new reusable catalyst for formal [2+4] cycloaddition of imines and enones

The first example of N-iodosaccharin (NISac)-catalyzed step, pot and atom economic synthesis of 1,3-oxazines via formal [2+4] cycloaddition of imines and enones has been reported. No by-product formation, operational simplicity, ambient temperature and high yields (85-95%) are the salient features of the present synthetic protocol. After isolation of the product, the catalyst NISac can be easily recovered and reused without any loss of efficiency.     

Isolation of p-tricyanovinylphenyldicyanomethide ion via a [2+2] cycloaddition of 7,7,8,8-tetracyanoquinodimethane (TCNQ) molecules

In the presence of CoCl₂·6H₂O and dppm (bis(diphenylphosphino) methane), the reaction of TCNQ (7,7,8,8-tetracyanoquinodimethane) molecules by [2+2] cycloaddition forms a p-tricyanovinylphenyldicyanomethide ion (PCQ⁻), which has been obtained as one anion unit in one new compound [Co(dppmdo)₃][PCQ⁻]₂·H₂O 1 (dppmdo = bis(diphylphospine oxide) methane). Its structure was determined by X-ray crystallography: 1 crystallizes in with a = 14.174(3) Å, b = 19.553(4) Å, c = 19.776(4) Å, α = 112.72(3)°, β = 95.43(3)°, γ = 110.79(3)°, and Z = 2. It was characterized by IR spectra, UV–Vis spectra, and cyclic voltammogram. Magnetic properties indicate that no magnetic coupling between PCQ⁻ and [Co(dppmdo)₃]²⁺ unit.     

Shape- and Size-Tunable Synthesis of Covalent Organic Cages through Rh-Catalyzed Regioselective [2+2+2] Cycloaddition

Covalent organic cages have potential applications in molecular inclusion/recognition and porous organic crystals. Bridging arene units with sp³ atoms enables facile construction of rigid isolated internal vacancies, and various prismatic arene cages have been synthesized by kinetically controlled covalent bond formation. However, the synthesis of a tetrahedral one, which requires twice as much bond formation as prismatic ones, has been limited to a thermodynamically controlled dynamic S_NAr reaction, and this reversible covalent bond formation made the resulting cage product chemically unstable. Here we report the Rh-catalyzed high-yielding and highly 1,3,5-selective room temperature [2+2+2] cycloaddition of push-pull alkynes and its application to the synthesis of chemically stable aryl ether cages of various shapes and sizes, including prismatic and tetrahedral forms. These aryl ether cages are highly crystalline and intertwine with each other to form regular packing structures. Some aryl ether cages encapsulated isolated water molecules in their hydrophobic cavity by hydrogen bonding with the multiple ester moieties.     

A rhodium(I)-xylyl-BINAP catalyzed asymmetric ynamide-[2+2+2] cycloaddition in the synthesis of optically enriched N,O-biaryls

A rhodium(I)-xylyl-BINAP catalyzed asymmetric [2+2+2] cycloaddition of achiral conjugated aryl ynamides with various diynes is described here. This asymmetric cycloaddition provides a series of structurally interesting chiral N,O-biaryls with excellent enantioselectivity along with a modest diastereoselectivity with respect to both C-C and C-N axial chirality.     

Annulation of furan-bridged 10-membered rings on N-heterocycles through [8+2] cycloaddition of dienylazaisobenzofurans and dimethyl acetylenedicarboxylate

One-pot three-component coupling of o-alkynylheteroaryl carbonyl derivatives with α,β-unsaturated Fischer carbene complexes and dimethyl acetylenedicarboxylate leading to the synthesis of heterocyclic analogues of furanophane derivatives has been explored. This involves the generation of conformationally flexible dienylazaisobenzofuran intermediate as transient intermediates, which undergo [8+2] cycloaddition reaction with dienophile. In some cases, this intermediate undergoes twofold Diels-Alder reaction to afford heterolignan derivatives in a single step.     

Organocatalytic intermolecular [2+2] cycloaddition of norbornadienes by a stable organic radical compound

An organocatalytic [2+2] cycloaddition reaction of norbornadienes (NBDs) using catalytic amount of TEMPO was reported. Single crystal X-ray diffraction of the product revealed its detailed multicyclic structure containing a 4-membered ring, formed in intermolecular reaction. Addition of AIBN to the current catalytic system improved the product yield. Quantitative reaction of the NBD and TEMPO gave a 2:2 adduct of NBD and TEMPO, which was confirmed by HR-MS. This catalytic [2+2] addition of NBDs has great advantage in selective intermolecular coupling in comparison with [2+2] photocycloaddition.     

Novel formal [2+3] cycloaddition between substituted phenols and furan

Treatment of various substituted phenols in the presence of furan, iodobenzene diacetate, and trifluoroethanol promotes oxidative formal [2+3] cycloaddition in moderate to useful yields.     

Stereospecific [2+2] cycloaddition reactions of diphosphorus with alkenes

[2+2] Cycloaddition reactions of P₂ with alkenes were predicted to have concerted paths, that is, pseudoexcitation, distorted 2π_s+2π_s, and 2π_s+2π_a processes without any interventions of intermediates. The pseudoexcitation and/or distorted 2π_s+2π_s paths with retention of configuration of alkenes are kinetically preferred to the 2π_s+2π_a path with inversion of configuration. The reactions were predicted from the appreciable difference in the calculated enthalpies of activation to be stereospecific.     

Thiourea-catalyzed asymmetric formal [3+2] cycloaddition of azomethine ylides with nitroolefins

A chiral thiourea catalyst possessing an amine function catalyzes an asymmetric [3+2] cycloaddition of azomethine ylides to nitroolefins to provide highly functionalized pyrrolidines with high diastereo- and enantioselectivities (up to 98:1:1 dr, 92% ee). The reaction proceeds in a stepwise manner consisting of Michael addition and subsequent intramolecular aza-Henry reaction. Both reactions are promoted by the thiourea catalyst, and the reaction rate of the latter step is efficiently enhanced by the addition of 2,2,2-trifluoroethanol.     

SiO2-NHC-Cu(I): an efficient and reusable catalyst for [3+2] cycloaddition of organic azides and terminal alkynes under solvent-free reaction conditions at room temperature

A novel SiO₂-NHC-Cu(I) 3b was developed and used as a highly efficient catalyst for [3+2] cycloaddition of organic azides and terminal alkynes. In the presence of SiO₂-NHC-Cu(I) 3b (1 mol %), the reactions of terminal alkynes with organic azides underwent smoothly to generate the corresponding regiospecific 1,4-disubstituted 1,2,3-triazoles in excellent yields under solvent-free reaction conditions at room temperature. Furthermore, catalyst 3b was quantitatively recovered from the reaction mixture by a simple filtration and reused for 10 cycles without loss of its activity.     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.     

Expeditious synthesis of cis-1-methyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo-[3,2h]isoquinoline/[2,3-f]quinoline via azomethine ylide-alkene [3+2] cycloaddition

Expeditious syntheses of cis-1-methyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo-[3,2h]isoquinoline/[2,3-f]quinoline have been developed. The syntheses started with commercially available materials and afforded excellent overall yields in straightforward steps. Intramolecular azomethine ylide-alkene [3+2] cycloaddition is the key step in the construction of these pyrroloisoquinoline and pyrroloquinoline scaffolds. This route is much more atom-economic than those reported in the literature and is appropriate for scale-up synthesis.     

The Lewis acid-catalyzed [3+1+1] cycloaddition of azomethine ylides with isocyanides

A Lewis acid-catalyzed [3+1+1] cycloaddition reaction between aliphatic isocyanides and azomethine ylides generated in situ from aziridines, leading to pyrrolidine derivatives, has been developed. This reaction proceeds smoothly under mild conditions and can also be modified by employing aromatic isocyanides to generate four-membered heterocycles, azetidines, through a [3+1] cycloaddition reaction.     

Cyclopentadienone synthesis by rhodium(I)-catalyzed [3 + 2] cycloaddition reactions of cyclopropenones and alkynes

The Rh(I)-catalyzed [3 + 2] cycloaddition of cyclopropenones and alkynes is found to provide a highly efficient and regiocontrolled route to cyclopentadienones (CPDs), building blocks of widespread use in the synthesis of natural and non-natural products, therapeutic leads, polymers, dendrimers, devices, and antigen presenting scaffolds. The versatility of the method is explored with 23 examples representing a wide range of alkyne variations (arylalkyl-, dialkyl-, heteroarylalkyl-) and diaryl- as well as arylalkylcyclopropenones. The reactions often proceed in high yield using minimal catalyst loadings and in all cases examined proceed with high or complete regioselectivity. The reaction is readily scalable to produce gram quantities of cycloadduct and provides a unique and versatile route to CPDs that would be otherwise difficult to obtain.     

Hydroxyapatite-supported copper(II)-catalyzed azide-alkyne [3+2] cycloaddition with neither reducing agents nor bases in water

Copper(II)-exchanged hydroxyapatite, prepared by ion-exchanging of Ca(II) in calcium hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂] with Cu(NO₃)₂ at 70 °C in water, functions as a reusable heterogeneous catalyst with neither reducing agents nor bases for azide-alkyne [3+2] cycloaddition at 50 °C in water under air.     

Intramolecular formal [4+2] cycloaddition reactions of secondary and tertiary aryldiacetylene alcohols

Thermal and thionyl chloride induced cycloaromatizations of secondary and tertiary aryldiacetylene alcohols were studied. The secondary alcohol did not respond to thionyl chloride, but in all the other cases presumptive biradical intermediates evolved either by intramolecular radical coupling or, when derived from a xanthene scaffold, by intramolecular radical acylation to a diketone that finally afforded a p-methylene-quinone.