Vinyl Cyclopropanes Research Articles

A computational triage approach to the synthesis of novel difluorocyclopentenes and fluorinated cycloheptadienes using thermal rearrangements

Electronic structure calculations have been used for the effective triage of substituent effects on difluorinated vinylcyclopropane precursors and their ability to undergo vinyl cyclopropane rearrangements (VCPR). Groups which effectively stabilised radicals, specifically heteroarenes, were found to result in the lowest energy barriers. Ten novel precursors were synthesised to test the accuracy of computational predictions; the most reactive species which contained heteroarenes underwent thermal rearrangements at room temperature to afford novel difluorocyclopentenes and fluorinated benzocycloheptadienes through competing VCPR and [3,3]-rearrangement pathways, respectively. More controlled rearrangement of ethyl 3-(1'(2'2'-difluoro-3'-benzo[d][1,3]dioxol-5-yl)cyclopropyl)propenoate (22) allowed these competing pathways to be monitored at the same time and activation energies for both reactions were determined; Ea(VCPR) = (23.4 ± 0.2) kcal mol-1 and Ea([3,3]) = (24.9 ± 0.3) kcal mol-1. Comparing our calculated activation energies with these parameters showed that no single method stood out as the most accurate for predicting barrier heights; (U)M05-2X/6-31+G* methodology remained the best for VCPR but M06-2X/6-31G* was better for the [3,3]-rearrangement. The consistency observed with (U)B3LYP/6-31G* calculations meant that it came closest to a universal method for dealing with these systems. The developed computational design model correctly predicted the observed selectivity of rearrangement pathways for both our system and literature compounds.

Asymmetric preparation of polysubstituted cyclopentanes by synergistic Pd(0)/amine catalyzed formal [3+2] cycloadditions of vinyl cyclopropanes with enals.

We report herein a novel diastereo- and enantiocontrolled preparation of polysubstituted cyclopentanes by the formal [3+2] cycloadditions of vinyl cyclopropanes with enals. In constrast with previously developed strategies, our original approach is based on the synergistic merger of iminium/enamine organocatalysis with palladium(0) catalysis.

ChemInform Abstract: Transition Metal‐Catalyzed Cycloadditions of Cyclopropanes for the Synthesis of Carbocycles: C‐C Activation in Cyclopropanes

AbstractReview: 140 refs.

Preparation of Vinylcyclopropanes by Sodium Mediated Reductive Isomerization of Methylenecyclopropanes.

We disclosed therein a new reaction of reductive isomerization of methylenecyclopropanes (MCPs) to vinylcyclopropanes (VCPs). On treatment with sodium metal in liquid ammonia, MCPs bearing a C-O bond at allylic position undergo both a reductive cleavage of the C-O bond and an isomerization of the C-C double bond giving rise to VCPs. The scope of the reductive isomerization was investigated and showed a broad applicability since various functional groups are tolerated. MCP substrates were straightforwardly prepared by a palladium-promoted [2 + 1] cycloaddition between norbornene derivatives with alkynes.

ChemInform Abstract: Transition‐Metal‐Free Coupling Reaction of Vinylcyclopropanes with Aldehydes Catalyzed by Tin Hydride.

AbstractHydrostannation of vinylcyclopropanes (VCPs) followed by reaction with aldehydes gives access to homoallylic alcohols without the use of transition‐metal catalysts.

ChemInform Abstract: Pd‐Catalyzed Three‐Component Coupling of Terminal Alkynes, Arynes, and Vinyl Cyclopropane Dicarboxylate.

AbstractThe efficient protocol provides access to 1‐allyl‐2‐alkynylbenzenes.

ChemInform Abstract: Enantioselective Cycloadditions of Vinyl Cyclopropanes and Nitroolefins for Functionally and Optically Enriched Nitrocyclopentanes.

AbstractThe two diastereomers can be easily separated by column chromatography.

Transition-metal-free coupling reaction of vinylcyclopropanes with aldehydes catalyzed by tin hydride.

Donor-acceptor cyclopropanes are useful building blocks for catalytic cycloaddition reactions with a range of electrophiles to give various cyclic products. In contrast, relatively few methods are available for the synthesis of homoallylic alcohols through coupling of vinylcyclopropanes (VCPs) with aldehydes, even with transition-metal catalysts. Here, we report that the hydrostannation of vinylcyclopropanes (VCPs) was effectively promoted by dibutyliodotin hydride (Bu2 SnIH). The resultant allylic tin compounds reacted easily with aldehydes. Furthermore, the use of Bu2 SnIH was effectively catalytic in the presence of hydrosilane as a hydride source, which established a coupling reaction of VCPs with aldehydes for the synthesis of homoallylic alcohols without the use of transition-metal catalysts. In contrast to conventional catalytic reactions of VCPs, the presented method allowed the use of several VCPs in addition to conventional donor-acceptor cyclopropanes.

Pd-Catalyzed Three-Component Coupling of Terminal Alkynes, Arynes, and Vinyl Cyclopropane Dicarboxylate

A palladium-catalyzed three-component coupling involving in situ generated arynes, terminal alkynes, and vinyl cyclopropane dicarboxylate has been developed. The process demonstrates the first example of aryne chemistry combined with the ring opening of vinyl cyclopropanes. This efficient method using readily available starting materials generates two new carbon-carbon bonds in one pot.

Designed enzymatically degradable amphiphilic conetworks by radical ring-opening polymerization

A simple and versatile route for making functional biodegradable amphiphilic conetworks (APCNs) with unique swelling property and excellent enzymatic degradability is presented. The APCNs were made by radical ring-opening copolymerization of cyclic ketene acetal and vinyl cyclopropane derivative.

Cover Picture: Enantioselective Cycloadditions of Vinyl Cyclopropanes and Nitroolefins for Functionally and Optically Enriched Nitrocyclopentanes (Asian J. Org. Chem. 1/2015)

Cover Picture: Enantioselective Cycloadditions of Vinyl Cyclopropanes and Nitroolefins for Functionally and Optically Enriched Nitrocyclopentanes (Asian J. Org. Chem. 1/2015)

Diversity-oriented synthesis of acyclic nucleosides via ring-opening of vinyl cyclopropanes with purines.

The diversity-oriented synthesis of acyclic nucleosides has been achieved via ring-opening of vinyl cyclopropanes with purines. With Pd2(dba)3·CHCl3 as a catalyst, the 1,5-ring-opening reaction proceeded well and afforded N9 adducts as the major form, in which the C=C bonds in the side chain were exclusively E-form. In the presence of AlCl3, the 1,3-ring-opening reaction occurred smoothly, giving N9 adducts as the dominate products. Meanwhile, when MgI2 was used as the catalyst, the 1,3-ring-opening reaction also worked well to form N7 adducts.

Palladium-catalyzed asymmetric cycloadditions of vinylcyclopropanes and in situ formed unsaturated imines: construction of structurally and optically enriched spiroindolenines.

A palladium-catalyzed (3 + 2) cycloaddition of vinyl cyclopropane and α,β-unsaturated imines generated in situ from aryl sulfonyl indoles is reported. The reaction proceeds with high diastereoselectivity to provide the optically enriched spirocyclopentane-1,3'-indolenines in up to 74% yield and with up to 97% ee, which contains an all-carbon quaternary center and two tertiary stereocenters. The reaction involves a first conjugate addition of the carbon anion of zwitterionic π-allylpalladium complex from vinyl cyclopropane to the in situ formed unsaturated imine followed by a palladium-catalyzed intramolecular C3-allylation of indole.

Highly enantioselective [3+2] cycloaddition of vinylcyclopropane with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert-amine) ligand.

An enantioselective [3+2] cycloaddition of vinyl cyclopropane derived from 1,3-indanedione with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert-amine) ligand was developed in high yields with good diastereoselectivities and excellent enantioselectivities. The resulting bis(tert-amine)-palladium complex proved to be a highly efficient catalyst for this cycloaddition.

Reactivity and chemoselectivity of allenes in Rh(I)-catalyzed intermolecular (5 + 2) cycloadditions with vinylcyclopropanes: allene-mediated rhodacycle formation can poison Rh(I)-catalyzed cycloadditions.

Allenes are important 2π building blocks in organic synthesis and engage as 2-carbon components in many metal-catalyzed reactions. Wender and co-workers discovered that methyl substituents on the terminal allene double bond counterintuitively change the reactivities of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with vinylcyclopropanes (VCPs). More sterically encumbered allenes afford higher cycloadduct yields, and such effects are also observed in other Rh(I)-catalyzed intermolecular cycloadditions. Through density functional theory calculations (B3LYP and M06) and experiment, we explored this enigmatic reactivity and selectivity of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with VCPs. The apparent low reactivity of terminally unsubstituted allenes is associated with a competing allene dimerization that irreversibly sequesters rhodium. With terminally substituted allenes, steric repulsion between the terminal substituents significantly increases the barrier of allene dimerization while the barrier of the (5 + 2) cycloaddition is not affected, and thus the cycloaddition prevails. Computation has also revealed the origin of chemoselectivity in (5 + 2) cycloadditions with allene-ynes. Although simple allene and acetylene have similar reaction barriers, intermolecular (5 + 2) cycloadditions of allene-ynes occur exclusively at the terminal allene double bond. The terminal double bond is more reactive due to the enhanced d−π* backdonation. At the same time, insertion of the internal double bond of an allene-yne has a higher barrier as it would break π conjugation. Substituted alkynes are more difficult to insert compared with acetylene, because of the steric repulsion from the additional substituents. This leads to the greater reactivity of the allene double bond relative to the alkynyl group in allene-ynes.

Iridium catalyzed carbocyclizations: efficient (5+2) cycloadditions of vinylcyclopropanes and alkynes.

Third-row transition metal catalysts remain a largely untapped resource in cycloaddition reactions for the formation of medium-sized rings. Herein, we report the first examples of iridium-catalyzed inter- and intramolecular vinylcyclopropane (VCP)-alkyne (5+2) cycloadditions. DFT modeling suggests that catalysis by iridium(I) proceeds through a mechanism similar to that previously reported for rhodium(I)-catalyzed VCP-alkyne cycloadditions, but a smaller free energy span for iridium enables substantially faster catalysis under favorable conditions. The system is characterized by up to quantitative yields and is amenable to an array of disubstituted alkynes and vinylcyclopropanes.

Enantioselective Cycloadditions of Vinyl Cyclopropanes and Nitroolefins for Functionally and Optically Enriched Nitrocyclopentanes

AbstractPalladium‐catalyzed enantioselective cycloaddition of vinyl cyclopropane dicarbonitriles and nitroolefins was achieved to generate structurally and optically enriched nitrocyclopentanes with three consecutive chiral carbon centers in up to 96 % yield and with up to 92 % ee. The two diastereoisomers produced in each reaction are readily separable by simple chromatography. The present method allows the preparation of both diastereoisomers in optically enriched form.

Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes: experimental and computational studies of rearrangement stereospecificity.

Vinyl cyclopropane rearrangement (VCPR) has been utilised to synthesise a difluorinated cyclopentene stereospecifically and under mild thermal conditions. Difluorocyclopropanation chemistry afforded ethyl 3-(1'(2'2'-difluoro-3'-phenyl)cyclopropyl) propenoate as all four stereoisomers (18a, 18b, 22a, 22b) (all racemic). The trans-E isomer (18a), prepared in 70 % yield over three steps, underwent near quantitative VCPR to difluorocyclopentene 23 (99 %). Rearrangements were monitored by (19) F NMR (100-180 °C). While cis/trans cyclopropane stereoisomerisation was facile, favouring trans-isomers by a modest margin, no E/Z alkene isomerisation was observed even at higher temperatures. Neither cis nor trans Z-alkenoates underwent VCPR, even up to much higher temperatures (180 °C). The cis-cyclopropanes underwent [3,3]-rearrangement to afford benzocycloheptadiene species. The reaction stereospecificity was explored by using electronic structure calculations, and UB3LYP/6-31G* methodology allowed the energy barriers for cyclopropane stereoisomerisation, diastereoisomeric VCPR and [3,3]-rearrangement to be ranked in agreement with experiment.

σ-Ferrier rearrangement of carbohydrate derived vinylcyclopropanes: a facile approach to oxepane analogs

This article presents our work on the σ-Ferrier ring-expansion of carbohydrate derived vinylcyclopropanes (VCPs) under electrophilic conditions mediated by chloramine-T and a phase-transfer catalyst. The present work serves as the first example on the studies of the reactivity of carbohydrate VCPs towards the synthesis of densely functionalized oxepane analogues. The work elaborates on a reasonable mechanism for the product formation and our observations on the diastereoselectivity based on control experiments and gas-phase calculations.

Fe or Fe-NO catalysis? A quantum chemical investigation of the [Fe(CO)3(NO)](-)-catalyzed Cloke-Wilson rearrangement.

A quantum chemical investigation of the Bu4N[Fe(CO)3(NO)]-catalyzed Cloke-Wilson rearrangement of vinyl cyclopropanes is reported. It was found that allylic C-C bond activation can proceed through a SN2' or SN2-type mechanism. The application of the recently reported intrinsic bond orbital (IBO) method for all structures indicated that one Fe-N π bond is directly involved. Further analysis showed that during the reaction oxidation occurs at the NO ligand exclusively.