1.2- Dibromocyclopropane

Turning to cyclic compounds we see that there are three not four stereoisomeric 1 2 dibromocyclopropanes Of these two are enantiomeric trans 1 2 dibromocyclo propanes The cis diastereomer is a meso form it has a plane of symmetry... 

The reaction of 1-ethoxycyclohexene with dibromocarbene gives less stable products which are difficult to process. The dibromocyclopropane (39)... 

Reaction of dibromocyclopropane (39) with hot quinoline gives 1-ethoxy-cyclohepta-l,3,5-triene (37) in 32% yield. Dihalocyclopropanes prepai ed from larger ring enol ethers do not react with hot pyridine but afford products with hot quinoline formed by transannular reactions. 

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

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)... 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

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... 

The l-chloro-2,2-dibromocyclopropanes 164 similarly undergo the nickel-carbonyl-induced ring-opening carbonylation with an amine or an alcohol to give the / ,y-unsaturated carboxylic acid derivatives 165 and the dicarboxylic acid ones 166 [84]. The mechanism described above appears to be operating this is supported by the four-component condensation to 167. (Scheme 61 and 62)... 

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... 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

Conjugated ketones and esters generally react with chloroform under basic conditions by Michael-type addition of the trichloromethyl anion to the C=C bond or by insertion of dichlorocarbene into the C=C bond, depending on the substitution pattern of the conjugated system (see Sections 6.4 and 7.3). The corresponding reaction with bromoform under basic conditions produces 1,1-dibromocyclopropanes. 

---