Electrophilic cyclopropanes reaction with carbon nucleophiles

Reaction of electrophilic cyclopropanes with carbon nucleophiles. 534... 

The stabilization of chloromethoxycarbene (234) was intensively studied. It is formed from diazirine (233) in a first order reaction with fi/2 = 34h at 20 C. It reacts either as a nucleophile, adding to electron poor alkenes like acrylonitrile with cyclopropanation, or as an electrophile, giving diphenylcyclopropenone with the electron rich diphenylacetylene. In the absence of reaction partners (234) decomposes to carbon monoxide and methyl chloride (78TL1931, 1935). 

It is supposed that the nickel enolate intermediate 157 reacts with electrophiles rather than with protons. The successful use of trimethylsilyl-sub-stituted amines (Scheme 57) permits a new carbon-carbon bond to be formed between 157 and electrophiles such as benzaldehyde and ethyl acrylate. The adduct 158 is obtained stereoselectively only by mixing nickel tetracarbonyl, the gem-dibromocyclopropane 150, dimethyl (trimethylsilyl) amine, and an electrophile [82]. gem-Functionalization on a cyclopropane ring carbon atom is attained in this four-component coupling reaction. Phenyl trimethyl silylsulfide serves as an excellent nucleophile to yield the thiol ester, which is in sharp contrast to the formation of a complicated product mixture starting from thiols instead of the silylsulfide [81]. (Scheme 58)... 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Yet another kind of alkene addition is the reaction of a carbenewith an alkene to yield a cyclopropane. A carbene, R2 - is a neutral molecule containing a divalent carbon with only six electrons in its valence shell. It is therefore highly reactive and IS generated only as a reaction intermediate, rather than as an isolable molecule. Because theyhe electron-deficient, carbenes behave as electrophiles and react with nucleophilic C=C bonds. The reaction occurs in a single step without intermediates. 

If compound II is electrophilic, the involvement of the 7 carbon of VI now becomes clear. Thus, the sodium hydride generated anion V may be imagined as attacking nucleophilically carbon C-2 of activated cyclopropane II. The resulting anion is precisely the proposed phosphorous ylide postulated as structure VII by our previous fragmentation analysis. What follows then is an intramolecular Wittig reaction with the departure of triphenylphosphine oxide that was predicted by the atom budget procedure (see Scheme 17.2). 

Solvolysis of electrophilic cyclopropanes with alcohols and phenols readily occurs as illustrated by the following examples of equations 166-168. It is worthwhile to note that methanolysis at 126 °C of ( + )-( ) methyl l-cyano-2-phenylcyclopropanecarboxylate (495) gives rise to (— )-(S)-methyl 2-cyano-4-methoxy-4-phenylbutanoate (496), indicating that the nucleophilic substitution reaction at the benzylic carbon of the cyclopropane proceeds with essentially complete inversion of configuration (equation 169). ... 

Diethyl cyclopropane-1,1-dicarboxylate underwent a nucleophilic ring-opening reaction with disodium tetracarbonylferrate in which one of the carbon monoxide ligands acted as a C-nucleo-phile. The intermediate iron complex reacted with electrophiles such as protons or iodomethane to give y-oxopropanedioates. ... 

Cyclopropanes can undergo attack by electrophiles with either inversion or retention of configuration at the carbon to which the electrophile becomes attached. The stereochemistry at this center, plus the fact that the nucleophile enters with inversion in nearly all cases, can best be accounted for by an intermediate, corner-substituted cyclopropane for many ring-opening reactions. In some cases a direct, single step process may compete with this mechanism. The possibility of an edge-substituted cyclopropane as a reaction intermediate under special circumstances cannot be ruled out at present. 

The information provided is all you need to write a mechanism. First, because you know the structure of methylene, you can see that it can be generated by breaking the C—N bond of diazomethane. Second, because methylene has an empty orbital, it is an electrophile and, therefore, will react with ethene (a nucleophile). Now, the question is. What nucleophile reacts with the other sp carbon of the alkene Because you know that cyclopropane is the product of the reaction, you also know that the nucleophile must be the lone-pair electrons of methylene. 

Carbenes are uncharged reactive intermediates of general formula CR2, in which carbon atom has a sextet of electrons. Depending on the nature of substituents R, they can behave as electrophilic or nucleophilic species, able to enter a variety of synthetically useful reactions. Perhaps the most important reaction of electrophilic carbenes is addition to C=C double bond giving cyclopropanes. Many electrophilic carbenes can be generated via the base-induced a-elimination process—abstraction of a proton from a carbon atom, connected with a halogen, followed by departure of the halogen anion from the initially formed a-halocarbanion (eq. 101). 

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