Cyclopropanes dichloro

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). 

Phenyltnhalomethylmercunals, reaction with olefins to form dichloro-cyclopropanes, 46,100 Phenylurea, 46, 72 Phosgene, 46, 98... 

Cyclopropylchlorocarbene [20] has been generated by UV photolysis (A = 335 nm) of cyclopropylchlorodiazirine [21] frozen in a nitrogen matrix at 12 K (Ho et al., 1989). IR and UV spectra of [20] have been recorded. The reaction of [20] with HCl resulted in the formation of (dichloromethyl)-cyclopropane [22], and annealing of the matrix gave (dicyclopropyl)dichloro-ethene [23]. Subsequent irradiation (A = 450 nm) of the carbene [20] led to its isomerization to 1-chlorocyclobutene [24], which was partialy destroyed to give ethene and chloroacetylene. Ab initio calculations predict the existence of two carbene conformers, but attempts to distinguish them in IR or UV spectra were unsuccessful. 

A striking example for the preferred formation of the thermodynamically less stable cyclopropane is furnished by the homoallylie halides 37, which are cyclopro-panated with high c/s-selectivity in the presence of copper chelate 3891 The cyclopropane can easily be converted into cw-permethric acid. In contrast, the direct synthesis of permethric esters by cyclopropanation of l,l-dichloro-4-methyl-l,3-pentadiene using the same catalyst produces the frans-permethric ester (trans-39) preferentially in a similar fashion, mainly trans-chrysanthemic ester (trans-40) was obtained when starting with 2,5-dimethyl-2,4-hexadiene 92). 

The change in selectivity is not credited to the catalyst alone In general, the bulkier the alkyl residue of the diazoacetate is, the more of the m-permethric acid ester results 77). Alternatively, cyclopropanation of 2,5-dimethyl-2,4-hexadiene instead of l,l-dichloro-4-methyl-l,3-pentadiene leads to a preference for the thermodynamically favored trans-chrysanthemic add ester for most eatalyst/alkyl diazoacetate combinations77 . The reasons for these discrepandes are not yet clear, the interplay between steric, electronic and lipophilic factors is considered to determine the stereochemical outcome of an individual reaction77 . This seems to be true also for the cyclopropanation of isoprene with different combinations of alkyl diazoacetates and rhodium catalysts77 . 

Electrochemical reduction of a variety of polyhalogenated alkanes has been undertaken. Stepwise dechlorination of gem-dichloro- and gem-trichloroalkanes occurs. Dichloromethane can be reduced in the presence of an olefin to form a cyclopropane [25], and... 

The geminal dihalogenated cyclopropane derivatives 83a and 83b were lithiated by Vlaar and Klumpp . 7,7-Dichloro- (83a) and 7,7-dibromonorcarane (83b) were reacted with four equivalents of LiDBB in diethyl ether and several reaction conditions were examined by the authors such as reaction temperatures, the influence of different coordinating additives as well as various methods (Scheme 31). The achieved maximum yield for the geminal dilithium compound 84 was 55% (from 83b). Side-products, like the 1,2-dilithioethane derivative 85, the dilithiated dicyclohexylacetylene 86 or 1,3-dilithium compound 87, were observed in different quantities, sensitively depending on the reaction conditions. Also, carbenoid intermediates were formed as verified by trapping reactions (deuteriolysis). 

Phase transfer-catalyzed reactions have recently been employed to dehydro-halogenate gem-dihalocyclopropanes [156, 157]. Thus, 1-methylene-2-vinylcyclo-propane has been prepared from l,l-dichloro-2-ethyl-3-methylcyclopropane in 60 % yield. Under the reactipn conditions (solid KOH, DMSO in the presence of dibenzo-18-crown-6, 100-130 °C) further transformations may take place, however. For example, monoalkylated cyclopropanes have been converted to mixtures of acyclic enynes and conjugated trienes. And 7,7-dichloronorcarane is converted to toluene under these conditions. 

One of the classical papers in this area is Neureiter s discovery of the vinyl-cyclopropane to cyclopentene rearrangement [185]. This important process was first observed on a l,l-dichloro-2-vinylcyclopropane derivative, which on heating yielded a chlorocyclopentadiene, presumably by the loss of hydrochloric acid from the initially formed 4,4-dichlorocyclopentene. 

The yields of these thermal processes are low, however, especially if they are employed for the preparation of a specific target molecule. For example, the pyrolysis of l,l-dichloro-2,2-dimethyl-cyclopropane furnishes a product mixture (total yield 63 %) which contains the diene XVI in 24 % yield only. 

Ring expansion reactions are much better known and sulfolene substrates have received considerable investigation. Cyclopropanation with dichlorocarbene affords 6,6-dichloro-3-thiabicyclo[3.1.0]hexane 3,3-dioxides which may readily be ring enlarged by base or acid treatment. Base treatment, especially with LDA, cleanly affords 2//-thiopyran dioxides hydrochloric acid does likewise, but less cleanly, while hydrobromic acid treatment causes a more complex set of reactions leading to thiopyranones containing bromine in which the sulfur has been reduced. The intermediacy of thiopyrylium oxides has been invoked to rationalize the observations (Scheme 27) (81JOC4502). 

I-Butene 4.4-Dichloro-4-fluoro-l-phenyl- ElOa. Ill [(1-OH-alkyl) — cyclopropane + HF]... 

Perfluorocyclopropene reacts readily with sodium methoxide at low temperature [22] (equation 19) Slow addition of sodium methoxide to 1,2 dichloro-3,3-di fluorocyclopropane yields initially l-chloro-2-methoxy-3,3-difluorocyclopro pane Further addition of methanol produces probably a ketal Opening of the cyclopropane ring gives an ortho ester that undergoes facile hydrolysis during the workup to form (Z)-methyl 2-fluoro-3-chloroacrylate [23] (equation 20) A per-fluorocyclobutene dimer is also very reactive and undergoes an easy SN2 displacement on treatment with ethanol [24] (equation 21)... 

Although many recent improvements in the preparation of the Simmons Smith reagent might be helpful23 24, the authors of this chapter would recommend one to consider an alternative two-step cyclopropanation procedure, which includes cycloaddition of dichloro- or dibromocarbene to methylenecycloalkane25 followed by reductive dehalo-genation (equation l)26. The first reaction is usually carried under phase transfer conditions and presents a very simple and efficient procedure. Reduction of gem-dihalocyclopropanes with lithium in tert-butanol or with sodium in liquid ammonia usually proceeds without complications and with high yield. 

Recently, it was found that the triangular skeleton can be easily destroyed in reactions which most likely include an electron transfer step. For example, the reduction of gem-dichloro[3]triangulane 66 with lithium in f-butanol (which is the standard method for the synthesis of cyclopropanes) unexpectedly gave 50% of unsaturated hydrocarbon (equation 45)88. An even more complex mixture of hydrogenolysis products was obtained in the reduction of dichloride 67. ... 

Dihalocyclopropanes containing all possible combinations of halogens have been synthesized. From the vantage point of the synthetic chemist, dibromo- and dichloro-cyclopropanes elicit the most useful and fascinating chemistry, and therefore this discussion will be centered around the formation and transformations of these two groups of compounds. For the sake of completeness, dihalocyclopropenes have been discussed where appropriate. To emphasize the synthetic potential, separate subsections are devoted to certain topics, e.g. formation of heterocycles. 

Dihalocydopropanes readily undergo reductive dehalogenation under a variety of conditions. Suitable choice of reagents and reaction conditions will allow the synthesis of monohalocyclopropanes or the parent cyclopropanes.19 " The ease of reduction follows the expected order I > Br > Cl > F. In general, complete reduction of dibromo and dichloro compounds is accomplished by alkali metal in alcohol,99-102 liquid ammonia103 or tetrahydrofuran (equations 28 and 29).104 The dihalocydopropanes can be reduced conveniently with LAH (equation 30).105 LAH reduction is particularly suited for difluoro compounds which are resistant to dissolving metal reductions.19 106 It is noteworthy that the sequence of dihalocar-bene addition to an alkene followed by the reduction of the dihalocyclopropyl compounds (equation 31) provides a convenient and powerful alternative to Simmons-Smith cyclopropanation, which is not always reliable. 

Not much is known about the opening of dihalocyclopropanes by Lewis acids beyond reports on the reaction of dibromo- and dichloro-cyclopropanes with aromatic hydrocarbons under the influence of AlCb or FeCb leading to indenes.229"231... 

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