Vinyl Carbene Research Articles

The first examples of a meta-benzannulation from the reaction of Fischer carbene complexes with alkynes.

The intramolecular benzannulations of carbene complexes with alkynes are examined where the alkyne is tethered to the alpha-carbon of the vinyl carbene complex. These reactions are sensitive to the length of the tether and to the nature of the solvent. With a tether length of 16 methylenes, the reaction occurs in the same fashion as the intermolecular reactions to give a p-cyclophane. With intermediate tether lengths (n = 10, 13), the reaction gives an additional p-cyclophane in which the two oxygen substituents are meta on the arene ring. This type of product is unprecedented from the reaction of carbene complexes and alkynes and is quite surprising because the formation of this product requires that the carbon-carbon bond between the alpha- and beta-carbons of the vinyl carbene complex is broken. A mechanism is proposed to account for this process which involves the crossed intramolecular [2 + 2] cycloaddition of the alkene and a ketene in a conjugated dienyl ketene to give a benzvalenone paddalane intermediate.

Synthesis and chemistry of tricyclic cyclopropene-tricyclo[3.2.2.0 2,4]nona-2(4),6-diene

The 1,2-bridged tricyclic cyclopropene, tricyclo[3.2.2.0 2,4]nona-2(4),6-diene ( 1 ), has been synthesized by the elimination of 2-bromo-4-chlorotricyclo[3.2.2.0 2,4]-non-6-ene ( 5 ). Cyclopropene 1 will undergo different isomerizations in ether solution and in neat conditions. Compound 1 rearranged to an anti-Bredt compound 4 via diradical mechanism in ether and tricyclic compound 6 via vinyl carbene mechanism in neat conditions. Compound 1 can be trapped with DPIBF at different temperatures yielding different results: the exo– endo adduct 2 ( exo-addition from the view of the cyclopropene and endo-addition from the view of bicyclo[2.2.2]octene) is a sole product at 0°C by slowly addition of methyllithium, and the exo– endo adduct 2 , endo– endo adduct 9 , anti-Bredt adduct 3 , and styrene 8 are isolated at ether refluxing temperature. Styrene 8 is proposed to be formed from endo– endo adduct 9 by diradical mechanism. The chemistry of exo– endo adduct 2 and endo– endo adduct 9 is as well studied. The exo– endo adduct 2 undergoes hydration in trifluoroacetic acid to generate 1,3- cis-diol 11 followed by eliminations of water and formaldehyde to give naphthalene 12 . The endo– endo adduct 9 reacts with water in tetrahydrofuran-containing silica gel to yield 1,4- cis-diol 10 . Both 9 and 10 react with trifluoroacetic acid to form trans-3-hydroxy trifluoroacetate 13 . Compound 13 will undergo hydrolysis and isomerization to generate 1,3- cis-diol 11 in trifluoroacetic acid.

Formation of cis-enediyne complexes from rhenium alkynylcarbene complexes.

Dimerization of the alkynylcarbene complex Cp(CO)(2)Re=C(Tol)C(triple bond)CCH(3) (8) occurs at 100 degrees C to give a 1.2:1 mixture of enediyne complexes [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)CC(CH(3))=C(CH(3))C(triple bond)CTol] (10-Eand 10-Z), showing no intrinsic bias toward trans-enediyne complexes. The cyclopropyl-substituted alkynylcarbene complex Cp(CO)(2)Re=C(Tol)C(triple bond)CC(3)H(5) (11) dimerizes at 120 degrees C to give a 5:1 ratio of enediyne complexes [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)C(C(3)H(5))C=C(C(3)H(5))C(triple bond)CTol] (12-E and 12-Z); no ring expansion product was observed. This suggests that if intermediate A formed by a [1,1.5] Re shift and having carbene character at the remote alkynyl carbon is involved, then interaction of the neighboring Re with the carbene center greatly diminishes the carbene character as compared with that of free cyclopropyl carbenes. The tethered bis-(alkynylcarbene) complex Cp(CO)(2)Re=C(Tol)C(triple bond)CCH(2)CH(2)CH(2)C(triple bond)CC(Tol)= Re(CO)(2)Cp (13) dimerizes rapidly at 12 degrees C to give the cyclic cis-enediyne complex [Cp(CO)(2)Re](2)[eta(2),eta(2)-TolC(triple bond)CC(CH(2)CH(2)CH(2))=CC(triple bond)CTol] (15). Attempted synthesis of the 1,8-disubstituted naphthalene derivative 1,8-[Cp(CO)(2)Re=C(Tol)C(triple bond)C](2)C(10)H(6) (16), in which the alkynylcarbene units are constrained to a parallel geometry, leads to dimerization to [Cp(CO)(2)Re](2)(eta(2),eta(2)-1,2-(tolylethynyl)acenaphthylene] (17). The very rapid dimerizations of both 13 and 16 provide compelling evidence against mechanisms involving cyclopropene intermediates. A mechanism is proposed which involves rate-determining addition of the carbene center of A to the remote alkynyl carbon of a second alkynylcarbene complex to generate vinyl carbene intermediate C, and rearrangement of C to the enediyne complex by a [1,1.5] Re shift.

α-Phosphonovinyl Carbanions in Organic Synthesis

The generation of several α-phosphono-substituted vinyl carbanions is described. The α-phosphonovinyl carbanions have been used to afford versatile vinylphosphonate reagents capable of a wide range of synthetic transformations.

Formation of Acetylenes by Ring-Opening of 1,1,2-Trihalocyclopropanes

This review describes studies into the conversion of substituted 1,1,2-trihalocyclopropanes into acetylenic acetals and acetylenic ketals by application of alcohols or alkoxides under basic conditions. The acetal/ketal ratio turned out to depend both on the substituents attached to the ring and on the reaction conditions prevailing during the reaction. Under the right conditions, however, completely regioselective ring-opening occurs to give either acetylenic acetals or acetylenic ketals, with formation of either no or only minor amounts of other products. The reactions are thought to involve cyclopropene intermediates, which are consumed by nucleophilic attack of alcohol or alkoxide. In some cases, the cyclopropene intermediates rearrange to the corresponding vinyl carbenes, which undergo insertion reactions with protic species present in the reaction mixture and give various 2-propenal derivatives as by-products.

Formation of Acetylenes by Ring-Opening of 1,1,2-Trihalocyclopropanes

This review describes studies into the conversion of substituted 1,1,2-trihalocyclopropanes into acetylenic acetals and acetylenic ketals by application of alcohols or alkoxides under basic conditions. The acetal/ketal ratio turned out to depend both on the substituents attached to the ring and on the reaction conditions prevailing during the reaction. Under the right conditions, however, completely regioselective ring-opening occurs to give either acetylenic acetals or acetylenic ketals, with formation of either no or only minor amounts of other products. The reactions are thought to involve cyclopropene intermediates, which are consumed by nucleophilic attack of alcohol or alkoxide. In some cases, the cyclopropene intermediates rearrange to the corresponding vinyl carbenes, which undergo insertion reactions with protic species present in the reaction mixture and give various 2-propenal derivatives as by-products.

Studies on Intramolecular Alkylation of an α-Sulfinyl Vinylic Carbanion: a Novel Route to Chiral 1-Cycloalkenyl Sulfoxides

Intramolecular alkylation of various β-(ω-haloalkyl) substituted vinylic sulfoxides was investigated. Upon treatment with LDA in THF at −78°C, α-sulfinyl carbanion generated from vinylic sulfoxides cyclized at the α-sulfinyl position to give 1-cycloalkenyl sulfoxides with a five- to seven-membered ring. Although iodide or bromide is normally a good leaving group, chloride affords better results than the corresponding iodide and bromide when the reaction takes place at the benzylic position. The cyclization proceeded even with the secondary iodide in moderate yield. Not only the ( E)-isomer but also the ( Z)-isomer cyclized via rapid inversion of the olefin geometry. No loss of optical purity was observed during isomerization. Various 1-cycloalkenyl sulfoxides including a fused ring and a polyoxygenated rings were synthesized in good to moderate yields.

Reactions of Alkynes with [Fe2(CO)6(μ-PPh2){μ-η1:η2α,β-(H)CαCβCγH2}]: Formation of Diphenylvinylphosphine-Functionalized Vinyl Carbenes via Carbon−Carbon and Carbon−Phosphorus Bond Formation and Hydrogen Migration

Reaction of [Fe2(CO)6(μ-PPh2){μ-η1:η2α,β-(H)CαCβCγH2}] (1) with PhC⋮CPh results in allenyl−alkyne−phosphido coupling to give [Fe2(CO)6(μ-PPh2){μ-η1(P):η3(C):η1(C)-C(Ph)C(Ph)C(H)C(CH2)PPh2}] (2), br...

The reaction of benzene with a ground state carbon atom, C(3Pj)

The reaction between benzene and a single ground state carbon atom, C(3Pj), which yields a C7H5 radical without a barrier in the exit channel, has been studied using density functional theory (B3LYP), Møller–Plesset perturbation theory, and the G2(B3LYP/MP2) and complete basis set (CBS) model chemistries. Comparing the computed reaction energies for the formation of various C7H5 radicals with experimental data suggests that the 1,2-didehydrocycloheptatrienyl radical (15) is observed in crossed-beams experiments at collision energies between 2 and 12 kcal mol−1. The carbon atom attacks the π-electron density of benzene and forms without entrance barrier a Cs symmetric complex (17T) in which the carbon atom is bound to the edge of benzene. From 17T, the insertion of the C atom into a benzene CC bond to yield triplet cycloheptatrienylidene (9T) is associated with a much lower barrier than the insertion into a CH bond to give triplet phenylcarbene (7T). As both steps are strongly exothermic, high energy vinyl carbene rearrangements on the triplet C7H6 potential energy surface provide pathways between 9T and 7T below the energy of separated reactants. In addition, intersystem crossing in the vicinity of 17T and 9T might give rise to singlet cycloheptatetraene (12S). The monocyclic seven-membered ring compounds 9T or 12S are precursors of the 1,2-didehydrocycloheptatrienyl radical: the dissociation of a CH bond α to the divalent carbon atom proceeds without an exit barrier, in agreement with experiment. In contrast, a direct carbon–hydrogen exchange reaction pathway analogous to the aromatic electrophilic substitution followed by rearrangement of phenylcarbyne (13) to 15 involves high barriers (39 kcal mol−1 with respect to separated reactants) and is thus not viable under the experimental conditions.

Photolysis of 3-methyl- and 3-isopropyl-3-ferrocenylcyclopropenes

The photochemistry of 3-methyl- and 3-isopropyl-3-ferrocenylcyclopropenes ( 10 and 11) has been studied. Upon triplet excitation (sensitized irradiation) both cyclopropenes are dimerized to a tricyclohexane dimers whereas in the singlet state (direct irradiation) cyclopropene 10 is converted to 3-ferrocenyl-3-methylidenepropyne and trans-2-ferrocenyl-2-butene indicating that there is an intermediate vinyl carbene. Cyclopropene 11 is converted to 1-ferrocenyl-4,4-dimethylcyclobutene. Direct irradiation of the mixture of 11 with 2-ferrocenyl-3-methyl-1-butene leads to the formation of 1,3-diferrocenyl-6,6-dimethyl-3-isopropenylcyclohexene ( 24). A possible reaction pathway via intermediate radicals is discussed. X-ray structural data are presented for 3,6-diferrocenyl-3,6-diisopropyltricyclo[3.1.0.0. 2,4]hexane and compound 24.

Direct Synthesis of Thermally Stable PCP-Type Rhodium Carbenes

Dinitrogen rhodium(I) complexes with bis-chelating diphosphine ligands are shown to be robust precursors toward Rh carbene complexes. While the Rh aryl N2 complex 1 reacts with phenyldiazomethane, giving the phenylcarbene complex 2, the Rh alkyl N2 precursor 3 reacts with 2 equiv of phenyldiazomethane to yield the Rh vinyl carbene complex 5. The more stable diphenyldiazomethane does not form carbene complexes under similar conditions, giving instead the stable diazomethane complex 10.

Electronic Tuning of Fischer Carbene Complexes in the Preparation of Bicyclo[3.1.1]heptanones as Taxane A-ring Synthons

A synthetic route to taxol and other Taxus diterpenes is described which employs as a key step the reaction between a Fischer carbene complex and a 1,6 enyne to construct 1-substituted-7,7-dimethyl-2-methylenebicyclo[3.1.1]heptan-6-ones. It was found that the reaction between complex 2 and 7-methyl-3-methylene-6-octen-1-yne (dienyne 30) yielded a mixture of bicyclo[3.1.1]heptanone 35 and cyclobutenone 36, the latter possibly arising from the migration of the chromium fragment from an electron-rich alkene to a less electron-rich alkene in the vinyl carbene complex intermediate (i.e. 40– 42). On this basis, it was expected that bicycloheptanone yields would increase with increasing electron deficiency in the intermediate 40 since this should lead to more competitive CO insertion. This was observed with a series of electronically modified carbene complexes ( 45 and 48a– d). The more electron deficient complexes gave good yields of bicycloheptanones, thus providing an efficient means for preparing taxane A-ring synthons.

(1-1)-Linked C-Disaccharides – Synthesis of Bis(β-D-Galactopyranosyl)Methane

ABSTRACT Bis[C-(galactal-1-yl)]carbinol derivative 2, which is readily obtained by transformation of galactal into a vinyl carbanion and then reaction with a C1-electrophile, was transformed into the title compound (1b). The procedure required first temporary protection of the carbinol hydroxy group and subsequent transformation of the galactal moiety into the galactopyranosyl moiety. Then deoxygenation of the carbinol and final deprotection could be carried out.

Organotransition metal modified sugars 14. Activation of sugar-based alkynols at a metal carbonyl template: a metal vinyl carbene functionalization of carbohydrates and non-conventional route to organometallic disaccharides

Abstract Chromium and tungsten alkenyl carbene modified carbohydrates have been synthesized by activation of sugar-based propargylic alcohols with pentacarbonyl–THF complexes followed by addition of methanol. This method has also been exploited in disaccharide synthesis. Higher functionalized carbohydrate skeletons are accessible by Diels–Alder and Michael-type addition reactions.

Mechanistic Studies on the Reaction of Fischer Carbene Complex with Alkynes: Does the Alkyne Insertion Intermediate Form Irreversibly?

The regioselectivity of the formation of three different products from the reaction of 1-phenylpropyne with (methoxy)(2-methoxyl-1-phenyl)methylene pentacarbonyl chromium 12 was examined in detail. The phenol product is formed with a substantial regioselectivity which is temperature-dependent, but the indene products (obtained as two compounds: indene and indenone) are formed as a nearly equal mixture of regioisomers. The proportion of indene and phenol products is dependent on the concentration with greater amounts of phenol products being formed at higher concentrations. The total regioselectivity of all of the products is also a function of the concentration. This result could be due either to an equilibration of the η1,η3-vinyl carbene intermediates in this reaction or to a change in mechanisms in the formation of the η1,η3-vinyl carbene intermediates from one involving a dissociative incorporation of the alkyne to one involving an associative incorporation of the alkyne. Kinetic studies reveal that at 45 °C and at 0.5 M (but not 0.0001 M) the reaction is bimolecular with a first-order dependence on both the carbene complex and the alkyne. However, at 90 °C the reaction is first-order in carbene complex and zero-order in alkyne over the concentration range of 0.05−0.005 M where the total regioselectivity changes from 2.5:1.0 to 1.5:1. This observation constitutes the first experimental evidence for the equilibration of regioisomeric vinyl carbene intermediates during the benzannulation reaction. This equilibration could occur as a result of a deinsertion of the alkyne or via a cyclopropene intermediate. Finally the generality of the unprecedented bimolecular reaction of complex 12 with 1-phenylpropyne at high concentrations was examined for the reaction methoxy(phenyl)methylene pentacarbonyl chromium 28 with diphenylacetylene and phenylacetylene at 0.5 M, and it was found that both reactions are first-order in carbene complex only.

Intramolecular alkylation of an α-sulfinyl vinylic carbanion without loss of optical purity: a novel access to chiral cyclic vinylic sulfoxides

Novel cyclisation via intramolecular α-alkylation of vinylic sulfoxides was studied and cyclic vinylic sulfoxides of various ring sizes (5–7) were synthesised from both (E)- and (Z)-isomers without loss of optical purity.

Stereoelectronic Effects on Product Formation from the E- and Z-Isomers of η1,η3-Vinyl Carbene Complexed Intermediates in the Reactions of Fischer Carbene Complexes with Alkynes

The reactions of 2-dihydropyranyl(methoxy)methylene pentacarbonyl chromium 19 with the series of five acetylenic ketones CH3(CH2)2C⋮C(O)(p-X−C6H4) 26 (X = CF3, Cl, H, OCH3, NMe2) gave a mixture of phenol and lactone products. The most electron-rich alkyne (X = NMe2) gave a greater proportion of the phenol product 27 (81:19), and the most electron-poor alkyne (R = CF3) gave the lactone 28 as the major product (64:36). Since the lactone product must come from a Z-isomer of a vinyl carbene complexed intermediate and the phenol product must come an E-isomer, this reveals that the stereochemistry of the reactive intermediates involved can be influenced by electronic effects of the substituents on the alkyne. A similar set of experiments with 3-hexyn-2-one 20 and the series of five phenoxy carbene complexes (CO)5CrC(C5H6O)O(p-X−C6H4) 29 (X = CF3, Cl, H, OCH3, NMe2) produced the opposite result, where predominantly the phenol product was produced from the most electron-poor carbene complex (X = CF3) and for the ...

Regioselective Nucleophilic Addition to Vinyl Carbenes (Metallabutadienes): Crystal Structure of [Ru{CH(CHCPh2)SC(NMe2)S}(S2CNMe2)(CO)(PPh3)

The new vinyl carbene salt [Ru(CαHCβHCγPh2)(CO)(S2CNMe2)(PPh3)2]PF6 (obtained from [RuHCl(CO)(PPh3)3], HC⋮CCPh2OH, Na[S2CNMe2], and HPF6) reacts with fluoride, alkoxide, borohydride and hydroxide at Cγ to give γ-functionalized σ-vinyl complexes, but with dithiocarbamate salts, attack occurs at Cα to provide the structurally characterized metallacycle [Ru{CH(CHCPh2)SC(NMe2)S}(S2CNMe2)(CO)(PPh3)].

Reactivity of Ru(H)(H2)Cl(PCy3)2 with Propargyl and Vinyl Chlorides: New Methodology To Give Metathesis-Active Ruthenium Carbenes

A procedure for generating the ruthenium hydride complex Ru(H)(H2)Cl(PCy3)2 in 95% yield is presented. Following a novel insertion−elimination pathway, this hydride can react with propargyl or vinyl halides to make metathesis-active vinyl and alkyl carbene species with the general formulas (PCy3)2Cl2RuCH−CHCR2 and (PCy3)2Cl2RuCHR, respectively. Tertiary propargyl chlorides work best, giving Ru−vinyl carbenes in extremely high yield.

The chemistry of perfluoroisobutylene (PFIB) with nitrone and nitroso spin traps: an EPR/Spin trapping study

While applying electron paramagnetic resonance (EPR)/Spin Trapping techniques, several reactive intermediate species were identified in the reaction of perfluoroisobutylene (PFIB) with nitrone and nitroso spin trap agents: the carbon dioxide radical anion (CO 2 −), a carbonyl fluoride intermediate (COF), and vinyl carbanions of PFIB. The reaction of PFIB with N- t-butyl- α-phenylnitrone (PBN) forms a dipolar ion which undergoes electron transfer reactions generating stable nitrone spin adducts. Nitroso compounds reacted with carbanions derived from PFIB, which raises the possibility that electron transfer reactions of this type might account for the observed nitroxides. Our results suggest that PFIB undergoes some type of electron transfer reaction leading to several reactive intermediate species (RIS). The implications of these observations on pulmonary damage caused by inhalation of PFIB are discussed.