Ethers, vinyl cyclopropanation

For cyclopropanation of very electron-rich alkenes such as vinyl ethers copper(II) trifluoroacetate, copper(II) hexafluoroacetylacetonate or rhodium(II) acetate are the catalysts of choice. Copper trifluoroacetate catalysed cyclopropanation of vinyldia-zomethane with dihydropyran gives the corresponding vinyl cyclopropane adduct in low yield (equation 17). In contrast, catalytic decomposition of phenyldiazomethane in the presence of various vinyl ethers results in high-yield phenylcyclopropane formation (equations 18 and 19)27. 

The reaction accommodates halides, esters, ethers, nitriles, cyclopropanes, epoxides, alcohols and nitio groups. Even carbohydrates can be used.492-494 However, vinylic halides afford aldehydes and ketones... 

In analogy to the preparation of the cyclopropanone hemiacetal 3 (vide supra, Eq. (1)7), reductive cyclization of the piperidide of 3-chloropropionic acid 193 with sodium in ether in the presence of ClSiMe3, gave the 1-piperidino-l-trimethylsilyloxy-cyclopropane 194 a which was converted to the cyclopropanol 194 b upon treatment with methanolic tetrabutylammonium fluoride. Both 194 a and 194 b can be used for the ready generation of cyclopropane derivatives thus the silyl ether 194a could be reacted directly with the vinylic Grignard reagents 195 to provide the vinyl cyclopropane derivative 196, (Eq. (61)128). 

As discussed in Sect. 2, a-selanylalkyllithiums, generated from selenoacetals, can react with various electrophilic reagents, i. e. chloromethyl isopropyl ether for the synthesis of la-hydroxy vitamin D analogues [25] and with propargylic chloride derivatives for the preparation of alkynols [26]. A synthesis of vinyl-cyclopropane derivatives from l,4-dichloro-but-2-ene was achieved with trans stereoselectivity (>93%) in 68-89% yield. This one-pot cyclization, via an intramolecular allylic substitution, required the presence of two equivalents of u-BuLi [26] (Scheme 23). 

The [3-1-2] methylenecyclopentane annulation of [(trimethylsilyl)methylene]-cyclopropane dicarboxylates with unactivated and electron-rich alkenes (vinyl ether, vinyl thioether, or vinyl silyl ether) are efficiently photocatalyzed by butyl disulfide or bis(tributyltin) [78]. 

Ring opening at low temperature (20°C) occurred with l,2-dichloro-3,3-dimethylcyclopropene (S). This compound, which is stable in solution, was prepared from l-bromo-l,2,2-trichloro-3,3-dimethylcyclopropane with methyllithium in diethyl ether at — 78 °C, followed by warming to 0°C. The cyclopropene 5 could either be isolated in moderate yield, or directly reacted (15 min to 2h) with electron-rich or electron-poor alkenes. Thus, l-chloro-l-(l-chloro-vinyl)cyclopropanes 6 were obtained via the chloro(2,2-dimethyl-l-chlorovinyl)carbene. 

This is rather an unexpected result, since sulfur is a weaker electron donor than oxygen and consequently vinyl sulfides should react slower compared to vinyl ethers if cyclopropanation is considered as a straightforward reaction of dichlorocarbene with an alkene double bond. Therefore, the formation of 2-alkyl(or aryl)sulfanyl-l,l-dichlorocyclopropanes is a multistep process, which starts with the generation of sulfonium ylides via the attack of carbene on the sulfur atom of the vinyl sulfide. The ylide thus formed undergoes 1,3-rearrangement and cyclization or reacts with another molecule of vinyl sulfide and then cyclizes. ... 

If the leaving group of the substrate, like in allyl ethers, vinyl epoxides and vinyl cyclopropanes, is sufficiently basic to deprotonate the conjugate acid of the nucleophile then no additional base has to be added, thus broadening the scope and simplicity of this method. 

The intramolecular reaction of vinyl-cyclopropanes tethered to alkenes 206 yielding fused bicyclic products 207 has also been applied to the [5-f2-l-l] cycloaddition (Scheme 92) (164). However, in this case, a low partial pressure of CO was found to be effective. Substrates with sulfonamides, ethers, and germinal diesters tethers were effective in the cycloaddition. In addition, substitutions on either the olefin component or the VCP component were also tolerated yielding 5-8 fused ring products with high diastereoselectivity. The ElZ olefin geometry... 

Further examples of cyclopolymerization have been cited. Divinyl ether gives polymers containing bicyclic units. The polymerizations of 1,4-divinylbenzene and 1,3,5-trivinylbcnzene have been investigated. Ring-opening radical polymerizations for derivatives of vinyl cyclopropane have been described... 

A number of inhalation anesthetics have been introduced to clinical practice, some of which are Hsted in Table 1. AH agents introduced after 1950, except ethyl vinyl ether, contain fluorine. Agents such as ether, chloroform, trichloroethylene (Tdlene), cyclopropane, and fluoroxene (Fluoromar), which were once used, have been displaced by the newer fluorinated anesthetics. 

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Photolysis of the sulphinyl-3H-pyrazole 587 in ether or methylene chloride leads to the formation of a relatively stable carbene 588 that can be identified by physical methods. When the irradiation is performed in ethyl vinyl ether or in furan, the expected cyclopropanes are formed smoothly and stereospecifically683 (equation 374). 

Stabilised sulphur ylides react with alkenylcarbene complexes to form a mixture of different products depending on the reaction conditions. However, at -40 °C the reaction results in the formation of almost equimolecular amounts of vinyl ethers and diastereomeric cyclopropane derivatives. These cyclopropane products are derived from a formal [2C+1S] cycloaddition reaction and the mechanism that explains its formation implies an initial 1,4-addition to form a zwitterionic intermediate followed by cyclisation. Oxidation of the formed complex renders the final products [30] (Scheme 8). 

ETHYLENE GLYCOL ETHYL MERCAPTAN DIMETHYL SULPHIDE ETHYL AMINE DIMETHYL AMIDE MONOETHANOLAMINE ETHYLENEDIAMINE ACRYLONITRILE PROPADIENE METHYL ACETYLENE ACROLEIN ACRYLIC ACID VINYL FORMATE ALLYL CHLORIDE 1 2 3-TRICHLOROPROPANE PROPIONITRILE CYCLOPROPANE PROPYLENE 1 2-DICHLOROPROPANE ACETONE ALLYL ALCOHOL PROPIONALDEHYDE PROPYLENE OXIDE VINYL METHYL ETHER PROPIONIC ACID ETHYL FORMATE METHYL ACETATE PROPYL CHLORIDE ISOPROPYL CHLORIDE PROPANE... 

Copper(II) triflate has also been used for the carbenoid cyclopropanation reaction of simple olefins like cyclohexene, 2-methylpropene, cis- or rran.y-2-butene and norbomene with vinyldiazomethane 2 26,27). Although the yields were low (20-38 %), this catalyst is far superior to other copper salts and chelates except for copper(II) hexafluoroacetylaeetonate [Cu(hfacac)2], which exhibits similar efficiency. However, highly nucleophilic vinyl ethers, such as dihydropyran and dihydrofuran cannot be cyclopropanated as they rapidly polymerize on contact with Cu(OTf)2. With these substrates, copper(II) trifluoroacetate or copper(II) hexafluoroacetylaeetonate have to be used. The vinylcyclopropanation is stereospecific with cis- and rra s-2-butene. The 7-vinylbicyclo[4.1.0]heptanes formed from cyclohexene are obtained with the same exo/endo ratio in both the Cu(OTf)2 and Cu(hfacac)2 catalyzed reaction. The... 

As for cyclopropanation of alkenes with aryldiazomethanes, there seems to be only one report of a successful reaction with a group 9 transition metal catalyst Rh2(OAc)4 promotes phenylcyclopropane formation with phenyldiazomethane, but satisfactory yields are obtained only with vinyl ethers 4S) (Scheme 2). Cis- and trans-stilbene as well as benzalazine represent by-products of these reactions, and Rh2(OAc)4 has to be used in an unusually high concentration because the azine inhibits its catalytic activity. With most monosubstituted alkenes of Scheme 2, a preference for the Z-cyclopropane is observed similarly, -selectivity in cyclopropanation of cyclopentene is found. These selectivities are the exact opposite to those obtained in reactions of ethyl diazoacetate with the same olefins 45). Furthermore, they are temperature-dependent for example, the cisjtrcms ratio for l-ethoxy-2-phenylcyclopropane increases with decreasing temperature. 

Apart from these findings, the limited application of ZnCl2 (cyclopropanation of some cyclic 1,3-dienes, isoprene and ethyl vinyl ether 4S-49)) and copper(II) acetyl-acetonate (cyclopropanation of enamines 50)) still stand alone. 

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