Gem-dibromocyclopropane

An Arbuzov reaction between gem-dibromocyclopropanes yields phosphonate esters (55) accompanied by debrominated compounds successful reaction requires the presence of traces of water (and is thus not the normal Arbuzov reaction) which, by studies with D2O, has been shown to supply the a-proton of (56), Normal Arbuzov reactions, using ethyl diphenyl phosphite, have been used to prepare a phosphonate isostere of B-D-arabinose-1,5-diphosphate. ... 

Direct attachment of a functional group to the carbon atoms of the cyclopropane ring is fairly difficult. gem-Dibromocyclopropanes are readily available through the addition of dibromocarbene to olefinic compounds. Their synthetic versatility is reviewed in a previous volume of this series [77]. Substitution of the bromide with the aid of nucleophilic organometallics to form a new carbon-carbon bond has been investigated [78]. 

Metal carbonyls in a low oxidation state are able to induce the carbonylative transformation. Reductive carbonylation of the gem-dibromocyclopropanes 150 is realized by treatment with nickeltetracarbonyl in an alkanol to give the alkyl cyclopropanecarboxylates 151 with reduction of another bromide [79], Amines, phenol, and imidazole can also be used instead of alcohols. (Scheme 53)... 

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)... 

The carbonylation reaction of the gem-dibromocyclopropanes 159 bearing the chloromethyl group leads via ring-opening to the 7, d-unsaturated carboxylic... 

Reduction of gem-dibromocyclopropanes has been achieved by a variety of reducting agents to give either monobromocyclopropanes or cyclopropanes,... 

The presence of trialkyl phosphite 198 in the above mentioned reduction of the gem-dibromocyclopropanes 150 with dialkyl phosphonate and triethylamine alters the reaction course. Dialkyl cyclopropanephosphonates 199 are produced via reductive phosphonation [104]. Trialkyl phosphite participates in the carbon-phosphorous bond formation. It is supported by the exclusive formation of diisopropyl cyclopropylphosphonate in the phosphonation reaction with diethyl phosphonate and triisopropyl phosphite. (Scheme 74)... 

Vanadium compounds in a low oxidation state are known to be effective for inducing one-electron reduction. The highly stereoselective monodebromination of gem-dibromocyclopropanes proceeds with the help of a low-valent vanadium species generated from vanadium(III) chloride and zinc in dimethoxyethane in cooperation with diethyl phosphonate or triethyl phosphite... 

One-electron reduction of organic halides is convenient for generating radicals. gem-Dibromocyclopropanes are reduced by such a system [77]. Using an excess of M0H2CP2, stereoselective debromination is successful, possibly because of... 

Cathodic reduction of bicyclic gem-dibromocyclopropane in the presence of chlorotrimethylsilane provides the exo-silylated isomer selectively. With a sacrificial Mg anode the current efficiency can be increased by sonication as the anode acts additionally as a chemical reducing agent [358]. The 2e reduction of (5 )-(+)-l-bromo-l-carboxy-2,2-diphenylcyclopropane showed that the stereoselectivity at a Hg cathode was strongly determined by the supporting electrolyte cation. With NH4+, a preferential retention of configuration was observed, which increased with a more negative reduction potential. By contrast, a R4N+ cation gives rise to a major inversion, which increases with the bulkiness... 

The gem-dibromocyclopropanes are treated with an etheral solution of either methyllithiura or n-butyllithium at 0° to — 80°C. Methyllithium is preferable to /2-butyllithium because occasionally difficulties are encountered in completely separating the n-butyl bromide from the allene product. 

Doering and LaFlamme [10b] were the first to report that sodium and magnesium metal are capable of converting substituted gem-dibromocyclo-propanes to allenes in varying yield. However, it was found that sodium reacts best in the form of a high surface dispersion on alumina. At a later date, Moore and Ward [11a] and then Skattebol [12] reported that methyllithium or n-butyl-lithium reacts with gem-dibromocyclopropanes to give allenes in high yield. The related dichloro compounds were found to be inert to methyllithium but reacted slowly with -butyllithium. Several examples of the preparation of allenes from gem-dibromocyclopropanes are shown in Table I. 

The preparation and dehalogenation of gem-dibromocyclopropanes to give allenes can be carried out in one step by the reaction an excess of olefins with... 

Treatment of gem-dibromocyclopropane 34 with Bu3ZnLi from —85 to 0°C generates 1-butylcyclopropylzinc 36 via the 1,2-migration of the zincate carbenoid 35 (equation 27)24. Subsequent Pd°-catalyzed cross-coupling reactions afford cyclopropane... 

No other dibromocarbene adduct has probably been used in more subsequent reactions than that of benzvalene. Besides the allene producing reaction shown, Christl and his students have described dozens of transformations of this versatile gem-dibromocyclopropane, among them practically all reaction-types discussed in the different chapters of this review [92],... 

A number of gem-dibromocyclopropane derivatives has been reacted with aromatic compounds in the presence of aluminum chloride or ferric chloride providing indenes in yields up to 80%. To rationalize this interesting anellation process it has been proposed that the cyclopropyl cation formed under the influence of the Lewis acid collapses to an allylic ion, which then functions as the alkylating agent [179],... 

When gem-dibromocyclopropanes are heated with alcoholic potash, cyclopropanone acetals and propargylic ethers are obtained.42 The mechanism was discussed. 

Werstiuk, N. H. Roy, C. D. Simple and efficient synthesis of bromine-substituted 1,3-dienes and 1,3,5-cydoheptatriene by vacuum pyrolysis of gem-dibromocyclopropanes. Tetrahedron Lett. 2001, 42, 3255-3258. 

Disubstitution of a gem-dibromocyclopropane synthesis of 1-butyl 1,2-diphenylcyclopropane (Structure S))81... 

C/s-selective alkylation of a gem-dibromocyclopropane via a zincate carbenoid synthesis of r-1 -acetyl-1 -ethyl-f-2-phenylcyclopropane (Structure IS)8 ... 

An illustration of this divergent reactivity can be observed in BanwelTs use of gem-dibromocyclopropane 7 to construct an intermediate used in an approach to the Amaryllidaceae alkaloids (Scheme 4.2).9 When 7 was heated in the absence of Lewis acid, allyl bromide 8 was produced in quantitative yield via thermal ring opening of the cyclopropane and subsequent trapping of the resultant cation by free bromide in... 

In many instances, however, solvolysis of a halocyclopropane is deliberately accomplished in order to install an essential vinyl halide or hindered olefin. In 2000, Murphy and coworkers performed a silver ion-mediated ring expansion of gem-dibromocyclopropane 18 in wet acetone to afford the allylic alcohol 19 in 82% yield (Scheme 4.5).16 Under these conditions the desired cyclononene product was obtained as an inseparable mixture of E- and Z-isomers (7 93). Interestingly, two sets of peaks observed in the1H NMR spectrum indicated that the Z-isomer existed as two separate conformers at room temperature. This intermediate was subsequently used in Murphy s approach to the radical-based preparation of tricyclic indoles. 

The silver(I)-mediated ring opening of halocyclopropanes has been used to construct complex frameworks through the inter- and intramolecular trapping of cationic intermediates with heteronucleophiles. An obvious extension of this work is the involvement of carbon-based nucleophiles to form new carbon-carbon bonds. In 1996, Kostikov and coworkers reported the participation of aromatic solvents in the capture of halocyclopropane-derived allyl cations even in the absence of silver(I).30 However, this early example of intermolecular attack by a carbon nucleophile is one of very few such reports. In the same year, Gassman et al. reported cationic cyclizations of gem-dibromocyclopropanes tethered to remote diene moieties (Scheme 4.16).31... 

Despite the toxicity of volatile metal carbonyls, particularly Ni(CO)4, several useful transformations have been developed employing these reagents. Monocarbonylation of gem-dibromocyclopropanes may be accomplished with Ni(CO)4 in the presence of alcohols, amines or (less successfully) thiols, to afford cyclopropane carboxylic esters, amides or thioesters, respectively (equation 202)400. Silylamine or silylsulfide reagents may take the place of amines or thiols401. The intermediacy of a nickel enolate in the carbonylations is... 

Reduction of bromides. gem-Dibromocyclopropanes and g m-dibromoalkenes are reduced to the monobromides by (C,H50)2P(0)H and N(CiHdv Under these conditions gem-bromochlorocyclopropancs are reduced to chlorocyclopropanes.- l,l-Dibromo-2-tri-methylsilyloxycyclopropanes or a-bromo-a, 3-enones are reduced in this way to [3,7-cnones. Other examples indicate that only activated halogen atoms are subject to this reduction. 

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