Cycloaddition Of Vinylcyclopropanes Research Articles

3+2] Cycloaddition of Vinyl Cyclopropane and Hydroxylamines via Isocynate Intermediate to γ‐Lactams

Comprehensive SummaryA general and efficient strategy for the synthesis of γ‐lactams has been reported. The hydroxylamines form Lossen rearrangement products of electron‐deficient group migration with base and then undergo [3+2] cycloaddition reaction with vinyl cyclopropane, which could be performed with broad substrate scope, excellent functional group tolerance and high efficiency to produce the desired products. It also allowed further modification to other derivatives of these γ‐lactams.

Enantioselective [3 + 2] Cycloaddition of Vinylcyclopropanes with Alkenyl N-Heteroarenes Enabled by Palladium Catalysis.

The first catalytic enantioselective [3 + 2] cycloaddition reaction between vinylcyclopropanes and alkenyl N-heteroarenes in the presence of LiBr and a Pd(0)/SEGPHOS complex was developed. LiBr plays a key role in improving the reactivity of alkenyl N-heteroarenes as a mild Lewis acid.

Cooperative Palladium/Isothiourea Catalyzed Enantioselective Formal (3+2) Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Esters.

A protocol for the enantioselective synthesis of substituted vinylcyclopentanes has been realised using cooperative palladium and isothiourea catalysis. Treatment of vinylcyclopropanes with Pd(PPh3)4 generates a zwitterionic π‐allyl palladium intermediate that intercepts a catalytically generated α,β‐unsaturated acyl ammonium species prepared from the corresponding α,β‐unsaturated para‐nitrophenyl ester and the isothiourea (R)‐BTM. Intermolecular formal (3+2) cycloaddition between these reactive intermediates generates functionalised cyclopentanes in generally good yields and excellent diastereo‐ and enantiocontrol (up to >95 : 5 dr, 97 : 3 er), with the use of LiCl as an additive proving essential for optimal stereocontrol. To the best of our knowledge a dual transition metal/organocatalytic process involving α,β‐unsaturated acyl ammonium intermediates has not been demonstrated previously.

Cooperative Palladium/Isothiourea Catalyzed Enantioselective Formal (3+2) Cycloaddition of Vinylcyclopropanes and α,β‐Unsaturated Esters

AbstractA protocol for the enantioselective synthesis of substituted vinylcyclopentanes has been realised using cooperative palladium and isothiourea catalysis. Treatment of vinylcyclopropanes with Pd(PPh3)4 generates a zwitterionic π‐allyl palladium intermediate that intercepts a catalytically generated α,β‐unsaturated acyl ammonium species prepared from the corresponding α,β‐unsaturated para‐nitrophenyl ester and the isothiourea (R)‐BTM. Intermolecular formal (3+2) cycloaddition between these reactive intermediates generates functionalised cyclopentanes in generally good yields and excellent diastereo‐ and enantiocontrol (up to >95 : 5 dr, 97 : 3 er), with the use of LiCl as an additive proving essential for optimal stereocontrol. To the best of our knowledge a dual transition metal/organocatalytic process involving α,β‐unsaturated acyl ammonium intermediates has not been demonstrated previously.

Enantioselective 1,3-Dipolar (5+3) Cycloadditions of Oxidopyrylium Ylides and Vinylcyclopropanes toward 9-Oxabicyclononanes.

We have developed an efficient and mild enantioselective palladium-catalyzed (5+3) cycloaddition of vinylcyclopropanes and oxidopyrylium ylides generated in situ from benzopyranones, in the presence of a chiral PHOX ligand. These reactions afford various highly functionalized bridged oxa-[3.3.1]carbocycles with three stereogenic centers that are challenging to synthesize, in moderate to good yields and enantioselectivities.

Recent Advances in [5+2] Cycloadditions

Abstract: The existence of a seven-membered cyclic core in several natural products and biomolecules vitalized the research on its synthesis. [5+2] cycloaddition has become a promising strategy for the construction of seven-membered ring systems by the formation of carboncarbon bonds in a single step, with strong regioselectivity and stereoselectivity. This review mainly focuses on recent developments in the area of [5+2] cycloaddition since 2019. Total synthesis of natural products involving [5+2] cycloaddition as a key step leading to the heptacyclic core has also been discussed. Synthesis of fused and bridged ring systems via the reactions involving inter and intramolecular [5+2] cycloadditions like oxidopyrylium-mediated [5+2] cycloadditions, [5+2] cycloadditions of vinyl cyclopropanes (VCPs), vinyl phenols, etc. is explained in the review with the latest examples. This review provides a useful guide for researchers exploring this powerful strategy to create more elegant heptacycles in their future research.

B(C6F5)3-Catalyzed Diastereoselective Formal (4 + 1)-Cycloaddition of Vinylcyclopropanes and Et2SiH2.

A formal (4 + 1)-cycloaddition of vinylcyclopropanes and Et2SiH2 to afford 3,4-disubstituted silolanes is reported. The reaction sequence commences with the known B(C6F5)3-catalyzed alkene hydrosilylation with dihydrosilanes. Cleavage of the remaining Si-H bond in the hydrosilylation product assisted by B(C6F5)3 leads to formation of a cyclopropane-stabilized silylium ion. The activated cyclopropane ring is then opened by the in situ-generated borohydride accompanied by ring closure to the silolane. The diastereoselectivity is rationalized by a mechanistic model.

Palladium-Catalyzed Diastereo- and Enantioselective [3 + 2] Cycloaddition of Vinylcyclopropanes with Azadienes: Efficient Access to Chiral Spirocycles.

Benzofuran-derived azadienes (BDAs) have been widely used as four-atom synthons in transition-metal-mediated cycloaddition reactions, while the exploitation of their reactivity as a two-atom unit to construct spirocycles is still underdeveloped. Herein, we reported the first palladium(0)-catalyzed diastereo- and enantioselective [3 + 2] annulation of vinylcyclopropanes (VCPs) and BDAs. This transformation is featured with a broad substrate scope (31 examples), allowing for facile access to a variety of enantioenriched spirocycles bearing a quaternary stereogenic center in good yields with excellent regio-, diastereo-, and enantioselectivities (up to 93% yield, >20:1 dr, and mostly >99% ee) under mild reaction conditions. Moreover, the spirocyclic products could be efficiently converted to structurally complex tricyclo[8.3.0.01,5]-azatridecane and tricyclo[7.3.0.01,5]-azadodecane skeletons.

Utilizing Vinylcyclopropane Reactivity: Palladium-Catalyzed Asymmetric [5+2] Dipolar Cycloadditions.

Vinylcyclopropanes (VCPs) are commonly used in transition-metal-catalyzed cycloadditions, and the utilization of their recently realized reactivities to construct new cyclic architectures is of great significance in modern synthetic chemistry. Herein, a palladium-catalyzed, visible-light-driven, asymmetric [5+2] cycloaddition of VCPs with α-diazoketones is accomplished by switching the reactivity of the Pd-containing dipolar intermediate from an all-carbon 1,3-dipole to an oxo-1,5-dipole. Enantioenriched seven-membered lactones were produced with good reaction efficiencies and selectivities (23 examples, 52-92 % yields with up to 99:1 er and 12.5:1 dr). In addition, computational investigations were performed to rationalize the observed high chemo- and periselectivities.

Asymmetric Synthesis of Tetrahydrofurans through Palladium(0)-Catalyzed [3 + 2]-Cycloaddition of Vinylcyclopropanes with Ketenes.

In this article we describe a new asymmetric synthesis of highly substituted tetrahydrofurans through a Pd(PPh3)4-catalyzed formal [3 + 2]-cycloaddition of donor-acceptor cyclopropanes and ketenes. The desired structural motif was formed in moderate to excellent yields (42-84% for 16 examples), with excellent Z:E isomer diastereoselectivity (≥19:1 for 16 examples), and with good to excellent enantioselectivity in all cases examined (83-97% ee for 6 examples). The synthetic utility of the products was illustrated by a number of diastereoselective transformations into reduced tetrahydrofurans and spirocyclic tetrahydrofuran-barbiturate derivatives.

Palladium-Catalyzed [3+2] Cycloaddition of Vinylcyclopropane and Ketones

A Pd-catalyzed [3+2] cycloaddition reaction of vinylcyclopropane and trifluoromethyl ketones as well as α-keto esters were developed, affording tetrahydrofurans in high yield.

Palladium-catalyzed diastereo- and enantioselective formal [3 + 2] cycloaddition of vinyl cyclopropanes with cyclic 1-azadienes

We have developed highly efficient and stereoselective Pd-catalyzed formal [3 + 2] cycloadditions of vinyl cyclopropanes with cyclic 1-azadienes.

Intermolecular scandium triflate-promoted nitrene-transfer [5 + 1] cycloadditions of vinylcyclopropanes.

Sc(OTf)3-promoted [5 + 1] cycloaddition of vinylcyclopropanes with PhINTs is reported, enabling the regioselective preparation of a range of 1,2,3,6-tetrahydropyridine scaffolds under mild conditions. This represents the second example of a [5 + 1] nitrene-transfer cycloaddition and exhibits complementary substrate scope to the antecedent work, expanding the range of N-heterocycles accessible via this strategy.

A photoinduced Wolff rearrangement/Pd-catalyzed [3+2] cycloaddition sequence: an unexpected route to tetrahydrofurans.

A novel sequential reaction that combines a visible light-induced Wolff rearrangement of α-diazoketones and a Pd-catalyzed [3+2] cycloaddition of vinyl cyclopropanes with the resulting ketenes is described in this work. Selective O-allylic alkylation was observed over C-allylic alkylation, which unexpectedly led to a series of highly functionalized tetrahydrofurans with high efficiency (20 examples, 58-99% yields).

Palladium(0)-Catalyzed Diastereoselective (3+2) Cycloadditions of Vinylcyclopropanes with Sulfonyl-Activated Imines

We report herein a palladium(0)-catalyzed (3+2)-cycloaddition process between vinylcyclopropanes and cyclic or acyclic sulfonylimines. This reaction, which operates under low catalyst loading and practical reaction conditions, gives access to a wide variety of N-heterocyclic derivatives in good to excellent yields and high levels of diastereoselectivity.

Mechanistic understanding of [Rh(NHC)]-catalyzed intramolecular [5 + 2] cycloadditions of vinyloxiranes and vinylcyclopropanes with alkynes.

Zhang and co-workers have recently advanced the carbon [5 + 2] cycloaddition of vinylcyclopropane and alkyne (VCP-alkyne) to the hetero-[5 + 2] cycloaddition of vinyloxirane with alkyne (VOR-alkyne). Herein, we present a systematic computational study to gain insights into the detailed reaction mechanisms and origins of mechanistic differences of the two types of cycloadditions (all-carbon [5 + 2] cycloaddition vs. hetero-[5 + 2] cycloaddition). Instead of the general mechanism of rhodium-catalyzed VCP-alkyne cycloaddition that involves cyclopropane cleavage, alkyne insertion and reductive elimination, the rhodium-catalyzed VOR-alkyne cycloaddition occurs via oxidative alkyne-alkene cyclization, oxirane cleavage and reductive elimination. The cycloaddition of VOR-alkyne represents the first example of preferring the oxidative alkyne-alkene cyclization mechanism within rhodium-catalyzed [5 + 2] cycloadditions. The origins of the mechanistic difference are derived from the stabilizing effects due to the favorable ligand-substrate C-H/π dispersion interaction and the substrate-substrate C-HO hydrogen-bond interaction in the oxidative alkyne-alkene cyclization step of the hetero-[5 + 2] cycloaddition. The VOR-alkyne cycloaddition gives a bicyclo[5.3.0] product featuring a 2,5-dihydrooxepin moiety, which can further undergo a [3,3]-sigmatropic rearrangement giving the final bicyclo[3.1.0] product, because a carbonyl structure is more favorable than an enolate structure.

Pd-catalyzed [3 + 2] cycloaddition of vinylcyclopropanes with 1-azadienes: synthesis of 4-cyclopentylbenzo[e][1,2,3]oxathiazine 2,2-dioxides.

The palladium-catalyzed [3 + 2] cycloaddition of vinylcyclopropanes and 1-azadienes has been developed under mild reaction conditions, giving the multisubstituted cyclopentane derivatives in good to excellent yields with moderate to good diastereoselectivities. The relative configuration of both diastereomers of the products have been determined through X-ray crystallographic diffraction.

Pd-Catalyzed diastereoselective [3 + 2] cycloaddition of vinylcyclopropanes with sulfamate-derived cyclic imines.

The palladium-catalyzed diastereoselective [3 + 2] cycloaddition reaction of vinylcyclopropanes with sulfamate-derived cyclic imines worked efficiently under mild reaction conditions, providing 2,3-dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]oxathiazine 5,5-dioxide derivatives in good to excellent yields.

Ynol Ethers as Ketene Equivalents in Rhodium-Catalyzed Intermolecular [5 + 2] Cycloaddition Reactions.

The previously unexplored metal-catalyzed [5 + 2] cycloadditions of vinylcyclopropanes (VCPs) and electron-rich alkynes (ynol ethers) have been found to provide a highly efficient, direct route to dioxygenated seven-membered rings, a common feature of numerous natural and non-natural targets and building blocks for synthesis. The reactions proceed in high yield at room temperature and tolerate a broad range of functionalities. Substituted VCPs were found to react with high regioselectivity.

ChemInform Abstract: Fe2(CO)9‐Mediated [5 + 1] Cycloaddition of Vinylcyclopropanes and CO for the Synthesis of α, β‐Cyclohexenones.

Abstract A Fe2(CO)9-mediated [5+1] cycloaddition of vinylcyclopropanes (VCPs) and CO to α, β-cyclohexenones has been developed. The reaction can tolerate aryl and aliphatic groups at the α-position of VCPs, while VCP substrates with vinyl or alkynyl substitutions are not suitable ones. In addition, this reaction can also be used to synthesize bicyclic rings if an aryl group is attached to the vinyl moiety of the substrate. Compared to the Fe(CO)5-mediated [5+1] reaction, the use of cheap and safe Fe2(CO)9 and abandoning the photo-irradiation conditions are the two major advantages of the present method.