Metal-catalyzed silacyclopropanation of mono- and disubstituted alkenes

As an alternative to the strongly reducing conditions necessary for the formation of silacyclopropanes, silylene transfer was developed as a mild, functional group tolerant method of silacyclopropanation. Complex silacyclopropanes were formed from functionalized alkenes using cyclohexane di-tert-butyl silacyclopropane, 1, as the source of t-Bu(2)Si. Di-tert-butyl silylene can be generated from 1 through the use of a catalytic amount of a metal salt. At -27 degrees C, silver triflate catalyzes the transfer of t-Bu(2)Si from 1 to mono- and disubstituted alkenes stereospecifically and diastereoselectively. In situ functionalization of silacyclopropanes with catalytic zinc bromide and methyl formate provides for an expedient one-flask synthesis of complex oxasilacyclopentanes from alkenes.     

Mechanism of silver-mediated di-tert-butylsilylene transfer from a silacyclopropane to an alkene

Kinetic studies of the reactions of cyclohexene silacyclopropane 1 and monosubstituted alkenes in the presence of 5 mol % of (Ph3P)2AgOTf suggested a possible mechanism for silver-mediated di-tert-butylsilylene transfer. The kinetic order in cyclohexene silacyclopropane 1 was determined to be one. Inverse kinetic saturation behavior (rate inhibition) was observed in monosubstituted alkene and cyclohexene concentrations. Saturation kinetic behavior in catalyst concentration was observed. A reactive intermediate, a silylsilver complex, was observed using low temperature 29Si NMR spectroscopy. Competition experiments between substituted styrenes and a deficient amount of 1 correlated well with the Hammett equation and provided a rho value of -0.62 +/- 0.02 using sigmap constants. These data support a mechanism involving reversible silver-promoted di-tert-butylsilylene extrusion from 1 followed by irreversible concerted electrophilic attack of the silylsilver intermediate on the alkene.     

Mechanism of di-tert-butylsilylene transfer from a silacyclopropane to an alkene

Kinetic and thermodynamic studies of the reactions of cyclohexene silacyclopropane 1 and monosubstituted alkenes suggested a possible mechanism for di-tert-butylsilylene transfer. The kinetic order in cyclohexene silacyclopropane 1 and cyclohexene were determined to be 1 and -1, respectively. Saturation kinetic behavior in monosubstituted alkene concentration was observed. Competition experiments between substituted styrenes and a deficient amount of di-tert-butylsilylene from 1 correlated well with the Hammett equation and provided a rho value of -0.666 +/- 0.008, using sigma(p) constants. These data supported a two-step mechanism involving reversible di-tert-butylsilylene extrusion from 1, followed by irreversible concerted electrophilic attack of the silylene on the monosubstituted alkene. Eyring activation parameters were found to be DeltaH++ = 22.1 +/- 0.9 kcal.mol(-1) and DeltaS++ = -15 +/- 2 eu. Competition experiments between cycloalkenes and allylbenzene determined cycloalkenes to be more efficient silylene traps (k(rel) =1.3, DeltaDeltaG++ = 0.200 kcal.mol(-1)). A summary of the data resulted in a postulated reaction coordinate diagram. The mechanistic studies enabled rational modification of reaction conditions that improved the synthetic utility of silylene transfer. Removal of the volatile cyclohexene from the reaction mixture into an evacuated headspace led to the formation of previously inaccessible cyclohexene-derived silacyclopropanes.     

Synthesis of (+/-)-epi-stegobinone utilizing silacyclopropanes as synthetic intermediates

The synthesis of (+/-)-1'-epi-stegobinone has been accomplished in ten steps and 17% overall yield from a recently reported silacyclopropane-derived diol. All stereocenters of the final product were established relative to the stereochemistry of the initial silacyclopropane. This synthesis represents the first time silacyclopropane reactivity has been employed in a target-directed synthesis.     

[Co(TPP)]-Catalyzed Formation of Substituted Piperidines

Radical cyclization via cobalt(III)-carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five-membered N-heterocyclic pyrrolidines catalyzed by Co^II porphyrins, the [Co(TPP)]-catalyzed formation of useful six-membered N-heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2-hydrogen-atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl-radical formation followed by radical-rebound ring closure to form the piperidines. Competitive 1,5-hydrogen-atom transfer from the β-position to the benzyl radical explained the formation of linear alkenes as side products.     

Photolysis of organopolysilanes. The reaction of photochemically generated methylphenylsilylene with conjugated dienes

Photolysis of 2-phenylheptamethyltrisilane (I) in the presence of acyclic and cyclic conjugated dienes has been investigated using both a high-pressure mercury lamp with a quartz filter and a low-pressure mercury lamp with a Vycor filter. Irradiation of I in the presence of 1,3-butadiene, isoprene or 2,3-dimethylbutadiene with a high-pressure mercury lamp gave a product arising from photochemical isomerization of a silacyclopropane derivative and a compound apparently formed by 1,4-silylene addition, along with a 1/1 “ene” adduct of the diene to a photo-rearranged intermediate containing the silicon—carbon double bond. Irradiation of I in the presence of the conjugated diene with a low-pressure mercury lamp, followed by treatment of the product with methanol, afforded a methoxysilane arising from methanolysis of the corresponding silacyclopropane, together with the isomerization product, silacyclopentene and rearranged addition product. Irradiation of I in the presence of cyclopentadiene with a high-pressure mercury lamp produced methylphenylsilylcyclopentadiene, while irradiation of a similar mixture with a low-pressure mercury lamp followed by treatment with methanol gave 4-(methoxymethylphenylsilyl)-1-cyclopentene. With 1,3-cyclooctadiene, the photochemically generated methylphenylsilylene afforded many types of addition product. Photolysis of I in the presence of 1,3-cyclohexadiene, however, afforded none of the silylene addition products.     

The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes using pyrrolidine as an organocatalyst

The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes has been developed. Nitroso alkenes were generated in situ from alpha-halooximes and underwent [4 + 2]-cycloadditions with enamines as dienophiles formed from aldehydes and pyrrolidine (10 mol%) as an organocatalyst. The presence of a suitable heterogeneous buffer system was found to be essential and best results were obtained with sodium acetate trihydrate. The resulting 5,6-dihydro-4H-oxazines were obtained in moderate to good yields under mild reaction conditions. A catalytic cycle has been proposed and evidence for the cycloaddition mechanism has been obtained. Moderate asymmetric induction (42% ee) was observed when a chiral secondary amine was used.     

Hyperbaric laser chemical vapor deposition of carbon fibers from the 1-alkenes, 1-alkynes, and benzene

The growth of long carbon fibers was investigated using hyperbaric-pressure laser chemical vapor deposition (HP-LCVD). Precursors included the unbranched alkenes with linear structure 1-C(x)H(2x) (where x = 2,4,5,6,7,8), the unbranched alkynes, i.e., 1-C(x)H(2)(x-2) (where x = 3,4,5,6,8), and benzene. Rate constants, reaction orders, and apparent activation energies were derived for each precursor over a range of experimental conditions. Axial growth rates from the alkenes were 1-2 orders of magnitude greater than for the alkynes, while growth rates for benzene exceeded 10 mm s(-1). Generalized expressions for the growth rate vs molecular weight were determined. For the alkenes, the growth rate was directly proportional to the square root of the precursor molecular weight, while the alkynes exhibited an inverse relationship. Two regions of differing reaction order were identified for the alkynes; at pressures less than 2.0-2.5 bar, the average reaction order was 3.07, while above 2.0-2.5 bar, reaction orders diverged. Expressions were derived for the fraction of carbon atoms deposited per alkyne molecule transported; the deposition efficiency decreased with molecular weight for the alkynes, due in part to the Soret effect. In contrast, the reaction order for the alkenes was 1.65, and for benzene was 2.25. A phase change in the deposit was observed for both the alkenes and alkynes, with the exceptions of pentene and pentyne. Complete axial rate equations for the alkenes and alkynes were derived, as well as volumetric growth equations for the alkynes. It was shown that the volumetric rate increases nonlinearly with laser power at sufficiently high pressures.     

Rhodium-catalyzed hydroformylation of olefins: Effect of [bis(2,4-di-tert-butyl) pentaerythritol] diphosphite (alkanox P-24) on the regioselectivity of the reaction

Rhodium (I) associated with [bis(2,4-di-tert-butyl) pentaerythritol] diphosphite (I) as a ligand represents an active catalyst system for highly regioselective hydroformylation of various alkenes. The commercially available bis(2,4-di-tert-butyl)pentaerythritol diphosphite (alkanox P-24) (I), which has been used so far as an antioxidant in the stabilization of polymers, was used as a diphosphite ligand for the selective hydroformylation reaction of olefins. Excellent selectivity towards linear aldehydes and excellent conversions were achieved in the hydroformylation of alkenes. The hydroformylation reaction was applied to various olefinic substrates including the internal alkenes.     

An improved methyltrioxorhenium-catalyzed epoxidation of alkenes with hydrogen peroxide

Methyltrioxorhenium (MTO)-catalyzed epoxidation of alkenes with H(2)O(2) has been significantly improved by using 3-methylpyrazole as an additive. A system consisting of 35% H(2)O(2) and MTO-3-methylpyrazole in CH(2)Cl(2) catalyzes the epoxidation of various alkenes in excellent yields. The catalytic activity of MTO-3-methylpyrazole surpasses MTO-pyrazole and MTO-pyridine catalysts. Quantitative yields of epoxides from cyclic and internal alkenes were obtained with only 0.05-0.1 mol% of MTO in the presence of 10 mol% of 3-methylpyrazole.     

Catalytic oxyalkylation of alkenes with alkanes and molecular oxygen via a radical process using N-hydroxyphthalimide

A novel catalytic method for the radical addition of alkanes and molecular oxygen to electron-deficient alkenes was achieved by the use of N-hydroxyphthalimide (NHPI) combined with a Co species as the catalyst. This reaction is referred to as oxyalkylation of alkenes with alkanes and O(2). For instance, the reaction of 1,3-dimethyladamantane with methyl acrylate under molecular oxygen in the presence of catalytic amounts of NHPI and Co(acac)(3) at 70 degrees C for 16 h gave oxyalkylated products in 91% yield. Other alkenes such as fumarate and acrylonitrile also serve as good acceptors of alkyl radicals and O(2) to afford the corresponding adducts in high yields. The generality of the present reaction was examined between various alkanes and alkenes under dioxygen. The behavior of Co ions during the reaction course was discussed. The present reaction involves (i) an alkyl radical generation via hydrogen abstraction of alkane by phthalimide N-oxyl generated in situ from NHPI and O(2) assisted by Co(II), (ii) the addition of the resulting alkyl radical to an electron-deficient alkene to form an adduct radical, (iii) trapping of the adduct radical by O(2) yielding a hydroperoxide, and (iv) the decomposition of the hydroperoxide by Co ions to form an adduct in which a hydroxy or a carbonyl function is incorporated.     

In situ diagnostics of the decomposition of silacyclobutane on a hot filament by vacuum ultraviolet laser ionization mass spectrometry

The gas-phase reaction products of silacyclobutane (SCB) and 1, 1-dideuterio-silacyclobutane (SCB-d(2)) from a hot-wire chemical vapor deposition (HWCVD) chamber were diagnosed in situ using vacuum ultraviolet (VUV) laser single-photon ionization (SPI) coupled with time-of-flight (TOF) mass spectrometry. The SCB molecule was found to decompose at a filament temperature as low as 900 degrees C. Both Si- (silylene, methylsilylene, and silene) and C-containing (ethene and propene) species were produced from the SCB decomposition on the filament. Ethene and propene were detected by the mass spectrometer. It is demonstrated that the formation of ethene is favored over that of propene. The experimental study of hot-wire decomposition of SCB-d(2) shows that propene is most likely produced by a process that is initiated by a 1,2-H(D) migration to form n-propylsilylene, followed by an equilibration with silacyclopropane, which then decomposes to propene. The detection of ethene in our experiment indicates that a competitive route of fragmentation exists for SCB decomposition on the filament. It has been shown that this competitive route occurs without H/D scrambling. The highly reactive silylene, silene, and methylsilylene species produced from SCB decomposition underwent either insertion reactions into the Si-H bonds of the parent molecule or pi-type addition reaction across the double and triple CC bonds. The dimerization product of silene, 1,3-disilacyclobutane, at m/z = 88 was also observed.     

Adducts of phenoxathiin and thianthrene cation radicals with alkenes and cycloalkenes

Phenoxathiin cation radical perchlorate (PO.+ClO4(-)) added stereospecifically to cyclopentene, cyclohexene, cycloheptene, and 1,5-cyclooctadiene to give 1,2-bis(5-phenoxathiiniumyl)cycloalkane diperchlorates (4-7) in good yield. The diaxial configuration of the PO+ groups was confirmed with X-ray crystallography. Unlike additions of thianthrene cation radical perchlorate (Th.+ClO4(-)) to these cycloalkenes, no evidence for formation of monoadducts was found in the reactions of PO.+ClO4(-). This difference is discussed. Addition of Th.+ClO4(-) to five trans alkenes (2-butene, 2-pentene, 4-methyl-2-pentene, 3-octene, 5-decene) and four cis alkenes (2-pentene, 2-hexene, 2-heptene, 5-decene) gave in each case a mixture of mono- and bisadducts in which the configuration of the alkene was retained. Thus, cis alkenes gave erythro monoadducts and threo bisadducts, whereas trans alkenes gave threo monoadducts and erythro bisadducts. In these additions to alkenes, cis alkenes gave predominantly bisadducts, while trans alkenes (except for trans-2-butene) gave predominantly monoadducts. This difference is explained. 1,2-Bis(5-phenoxathiiniumyl)cycloalkanes (4-7) and 1,2-bis(5-thianthreniumyl)cycloalkanes underwent fast elimination reactions on activated alumina forming, respectively, 1-(5-phenoxathiiniumyl)cycloalkenes (8-11) and 1-(5-thianthreniumyl)cycloalkenes (12-16). Among adducts of Th.+ClO4(-) and alkenes, monoadducts underwent fast ring opening on alumina to give (5-thianthreniumyl)alkenes, while bisadducts underwent fast eliminations of H+ and thianthrene (Th) to give (5-thianthreniumyl)alkenes also. Ring opening of monoadducts was a stereospecific reaction in which the configuration of the original alkene was retained. Thus, erythro monoadducts (from cis alkenes) gave (E)-(5-thianthreniumyl)alkenes and threo monoadducts (from trans alkenes) gave (Z)-(5-thianthreniumyl)alkenes. Among bisadducts, elimination of a proton and Th occurred and was more complex, giving both (E)- and (Z)-(5-thianthreniumyl)alkenes. These results are explained. Configurations of adducts and (5-thianthreniumyl)alkenes were deduced with the aid of X-ray crystallography and (1)H and (13)C NMR spectroscopy. In the NMR spectra of (E)- and (Z)-(5-thianthreniumyl)alkenes, the alkenyl proton of Z isomers always appeared at a lower field (0.8-1.0 ppm) than that of E isomers.     

Theoretical investigations of substituent effects in dimethyldioxirane epoxidation reactions

A detailed theoretical study of dimethyldioxirane-mediated epoxidations with a variety of differently substituted alkenes 3-21 is presented. Transition structures and activation barriers were determined in the gas phase and in acetone as solvent with the B3LYP/6-311+G(d) level of theory. Substituent effects were elucidated by frontier orbital analyses of the reacting species as well as by natural bond orbital (NBO) analysis of the transition structures. Epoxidations with alkenes carrying electron-donating groups such as OMe or NHAc commonly tend to have low activation energies and early transitions states, whereas using alkenes with electron-withdrawing moieties such as CN, SO2Me, CO2Me, CF3, CHO, and Cl higher activation barriers and late transition states are observed. In all cases a net charge transfer (CT) from the alkene to the dioxirane was observed substantiating the electrophilic character of dimethyldioxirane.     

A highly efficient palladacycle catalyst for hydrophenylation of C-, N-, and O-substituted bicyclic alkenes under aerobic condition

A new phosphine-free palladacycle catalyst 4 was prepared from benzyl oxazoline in high yield and fully characterized. With it as catalyst, hydrophenylation reactions of a wide range of bicyclic alkenes, not only norbornene and norbornadiene but also oxa- and aza-bicyclic alkenes, with iodobenzene proceeded smoothly under aerobic condition without exclusion of water. Up to 1.7 x 10(6) TON as well as 1.2 x 10(5) TOF were achieved.     

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch-Sosnovsky Reaction

Kharasch and Sosnovsky reported the allylic oxidation of alkenes to give racemic allylic benzoates. This could be achieved efficiently using a tert-butyl perester as the oxidant, in the presence of a copper or cobalt salt. The use of C(2)-symmetric bis(oxazoline) ligands in the presence of copper(I) triflate with cyclic olefinic substrates gave the first synthetically useful asymmetric variant. The enantioselective control was good (up to 84 % ee) although yields were variable. In all cases the facial preference of the newly formed C-O bond was the same giving an S configuration at the allylic stereocenter. Lower stereocontrol was observed for large-ring alkenes and substantially reduced enantioselectivities were found with open-chain alkenes. This reaction has been further screened using a variety bis(oxazoline) and proline-derived ligands, which give a direct correlation between the chirality of the ligand and the enantioselectivity obtained. Individual substrates were found to be extremely sensitive to both the ligand structure and copper salt used as well as the presence of additives such as zinc, hydrazine, and molecular sieves.     

Enantioselective epoxidation of terminal alkenes to (R)- and (S)-epoxides by engineered cytochromes P450 BM-3

Cytochrome P450 BM-3 from Bacillus megaterium was engineered for enantioselective epoxidation of simple terminal alkenes. Screening saturation mutagenesis libraries, in which mutations were introduced in the active site of an engineered P450, followed by recombination of beneficial mutations generated two P450 BM-3 variants that convert a range of terminal alkenes to either (R)- or (S)-epoxide (up to 83 % ee) with high catalytic turnovers (up to 1370) and high epoxidation selectivities (up to 95 %). A biocatalytic system using E. coli lysates containing P450 variants as the epoxidation catalysts and in vitro NADPH regeneration by the alcohol dehydrogenase from Thermoanaerobium brockii generates each of the epoxide enantiomers, without additional cofactor.     

Cationic carbohydroxylation of alkenes and alkynes using the cation pool method

The reactions of an N-acyliminium ion pool with alkenes and alkynes gave gamma-amino alcohols and beta-amino carbonyl compounds, respectively, after treatment with H(2)O/Et(3)N. The present reaction serves as an efficient method for cationic carbohydroxylation of alkenes and alkynes. When vinyltrimethylsilane was used as an alkene, the reaction was highly diastereoselective and served as an access to an enantiomerically pure alpha-silyl-gamma-amino alcohol. [reaction: see text]     

Mechanism of migration of the trimethylsilyl group during reactions of methoxy[(trimethylsilyl)ethoxy]carbene with N-phenylmaleimide and C(60).

A novel migration of the trimethylsilyl group during reaction of methoxy[(trimethylsilyl)ethoxy]carbene with N-phenylmaleimide (NPM) and with C(60), reported earlier, was examined by means of deuterium labeling of the carbene. For the NPM case it was found that the CD(2)CH(2)SiMe(3) group, initially bound to oxygen, became the CH(2)CD(2)SiMe(3) group bound to carbon in the end product. Not only had the trimethylsilylethyl group moved from oxygen to carbon, but the TMS group had also migrated 1,2 along the ethyl chain. For the C(60) case, complete scrambling of the CD(2) group was observed, strongly implying the involvement of a silacyclopropane carbocation responsible for product formation. The labeling study supports the mechanism that was tentatively advanced earlier for addition to NPM and one of the possibilities suggested for addition to C(60).     

Osmium-catalyzed dihydroxylation of alkenes by H2O2 in room temperature ionic liquid co-catalyzed by VO(acac)2 or MeReO3

Room temperature ionic liquid [bmim]PF₆ was used to immobilize a bimetallic catalytic system for H₂O₂-based dihydroxylation of alkenes. Osmium tetroxide was used as the substrate-selective catalyst with either VO(acac)₂ or MeReO₃ as co-catalyst. The latter serve as an electron transfer mediator (ETM) and activates H₂O₂. For an increased efficiency N-methylmorpholine is required as an additional ETM in most cases. A range of alkenes were dihydroxylated using this robust bimetallic system and it was demonstrated that for some of the alkenes the catalytic system can be recycled and used up to five times.