Dibromocyclopropane derivative

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],... 

Of the many catalysts which were investigated, benzo-15-crown-5 and tetramethylam-monium chloride favor cyclopropanation (1), though in the latter case long reaction times are required to reach satisfactory yields, while tetraphenylarsonium chloride promotes alkylation (2) . Evidently, the optimum conditions for cyclopropanation of any particular allylic bromide must be determined in each case, e.g. allyl bromide and bromoform (1 1.1) with ben-zyltriethylammonium chloride as catalyst gave l,l-dibromo-2-bromomethylcyclopropane as the main product 3-bromocyclohexene afforded a 1,1-dibromocyclopropane derivative in a high yield, in the presence of all catalysts listed in Table 28 except for tetraphenylarsonium chloride. On the other hand, if type 1 and 3 products only are formed, they may easily be separated by distillation. 

Reactions of organic anions. Part LXVIIL An improved method of synthesizing dibromocyclopropane derivatives in a catalytic two-phase system M. Makosza and M. Fedorynski, Rocz. Chem. 50, 2223 (1976)... 

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)... 

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)... 

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). 

In another series of experiments involving tricyclic dibromocyclopropanes Warner and co-workers have studied the behavior of a propellane derivative towards methyllithium either in the presence or absence of trapping agents. Whereas in the former case a dimer is produced, with diphenylisobenzofuran (DPIBF) two adducts are obtained in a 2 1 ratio in 24% yield [85]. 

In yet another tropone synthesis Skattebol has shown that dibromocyclopropanes carrying a phenolether function react to 1 l-oxa-tricyclo[5.5.0.07,9]undecatrienes when treated with methyllithium. The strained polycyclic intermediate is converted into a 2-alkenyltropone derivative when heated to about 200 °C [137]. 

When the carbene or carbenoid resulting from a dihalocyclopropane is unable to rearrange to the al-lene due to steric or other factors, insertion or addition reactions characteristic of carbenes take place. Thus dibromonorcarane on reaction with methyllithium gives a bicyclobutane derivative by insertion of the carbene into a 0-C—H bond (equation 57).178 Allene formation is sterically unfavorable in this case. Similarly, dibromotetramethylcyclopropane gives l,2,2-trimethylbicyclo[1.1.0]butane instead of tetra-methylallene (equation 58).179 181 An example involving a tricyclic dibromocyclopropane is given in equation (59).182... 

Dibromocyclopropanes with vicinal chloromethoxy or mesyloxymethyl substituents undergo [Ni(CO)4]-induced ring opening-carbonylation in the presence of alcohol or amine, leading to y.S-un-saturated carboxylic acid derivatives selectively via intermediate nickel enolates (equation 115).262 Di-... 

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... 

Dibromocyclopropane-cw-l,2-diacetic acid (82) is debrominated to the corresponding cyclopropane derivative over Raney Ni in the presence of alkali and to the... 

The propadienyl-steroid (273) has also been obtained, but in lower yields, either by dibromocarbene addition to the 17-methylene derivative, followed by methyl-lithium fragmentation of the mixture of dibromocyclopropanes, or by treatment of 17a-ethynyl-17jS-hydroxy-steroid with lithium aluminium hydride in the presence of aluminium trichloride. ... 

Treatment of em-dibromocyclopropanes with one equivalent of alkyllithium at low temperature generates 1-bromocyclopropyllithiums, which have proved to be very versatile intermediates for the synthesis of various cyclopropyl derivatives. Thus, the reactions of the bromolithium compounds with disulfides ketones, alkyl ha-lides , methyleneammonium salts and trimethylsilyl chloride provide the corresponding 1-bromocyclopropyl derivatives (equation 124). A neighbouring ether... 

Displacement reactions on 1,1-disubstituted cyclopropanes have been used to prepare other cyclopropanone equivalents. The most readily available 1,1-disubstituted cyclopropanes are geminal dihalo derivatives prepared by the addition of dihalocarbenes to olefins. Unfortunately, these materials do not undergo direct displacement easily and therefore do not provide a general route to other cyclopropanone derivatives. Solvolysis usually leads to ring-opened products, although dibromocyclopropanes with a barrier to... 

Gem-dibromocyclopropanes can be converted into synthetically useful cyclopropanone equivalents by a process consisting of lithium-halogen exchange followed by reaction of lithiocyclopropane (113) with dimethyl disulfide (Scheme 43) . The resulting bromo-methylthio derivative (114) undergoes a variety of substitution reactions. Methanolysis gives S,0-dimethylketal (115) which can be converted into l,l bis(methyl-thio)cyclopropane (116) with methyl mercaptan in trifluoroacetic acid. Reaction of 114 with other nucleophiles provides the derivatives shown in Scheme 44 . The sulfur-... 

Moore, W. R., Ward, H. R. Reactions of gem-dibromocyclopropanes with alkyllithium reagents. Formation of allenes, spiropentanes, and a derivative of bicyclopropylidene. J. Org. Chem. 1960, 25, 2073. 

A recent article by Swenton et al.I04 reported deuterium incorporation via the reduction of halides with a zinc-copper couple. They found that freshly prepared zinc-copper couple in dry ether solvents with heavy water as the deuterium source effects clean reduction of dibromocyclopropanes to their monobromo derivatives. In a second system, they104 found that dichloroketene adducts underwent clean reduction to the corresponding cyclobutanones... 

Derivation Reduction of dibromocyclopropane with zinc dust. 

As the bromines in 1,1-dibromocyclopropanes are more reactive than the chlorines in the corresponding 1,1-dichloro derivatives, 1,1-dibromocyclopropanes are attractive intermediates in organic synthesis. The most convenient method for the preparation of 1,1-dibromocyclopropanes consists of the addition of dibromocarbene (carbenoid) to an alkene. The mechanistic details of this process have been less thoroughly investigated than dichlorocyclopropanation of alkenes, but both reactions are similar in many respects. 

Conversion of 1,1-Dibromocyclopropanes to Cyclopropanecarboxylic Acid Derivatives General Procedure ... 

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