Dibromocyclopropanes carbonylation

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)... 

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)... 

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-... 

Carbonylation of geminal dibromocyclopropanes, in the presence of primary amines in DMF, yields cyclopropylamides908 which, in some cases, undergo ring opening under the reaction conditions909. 

The effectiveness in carbonylations of Ni(CO)4 is well documented, as well as its toxicity. Substitutes for this catalyst are therefore of much interest, and [Ni(CN)(CO)J], generated in situ from Ni(CN)2, CO and aqueous NaOH under phase transfer conditions, fulfills this role in many cases394. Under these conditions (1 atm CO), several types of organic halides are carbonylated, including allyl halides394, benzyl chlorides (with lanthanide salts)395, aryl iodides396, vinyl bromides397 and dibromocyclopropanes (equation 199)398. 

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... 

Work on other halides is much more limited. Gera-dibromocyclopropanes give modest yields of alkoxycarbonylation with alkoxide bases419. Aryl iodides may be carbonylated by catalytic mixtures of Fe(CO)5-Co2(CO)8 predominantly to the carboxylic acids or predominantly to the benzophenones, depending upon conditions420. 

The catalytic pair Ni(CN)2/Bu4N Br readily catalyzes the biphasic carbonyla-tion of a-haloalkynes [144, 145] and allenyl halides [145]. The first reaction results in a mixture of allenic monoacids and unsaturated diacids, whereas allenyl halides transform to allenic acids with high regioselectivity. The carbonylation of gem-dibromocyclopropanes under PTC conditions is catalyzed by Ni" and Co" salts. The reaction gives the corresponding cyclopropanecarboxylic acids in fair yields [146]. 

Reductive carbonylation of 1,1-dibromocyclopropanes with tetracarbonylnickel in dimethyl-formamide in the presence of a nucleophile is a powerful method for direct introduction of carboxylic acid functions to cyclopropanes. Nucleophiles, such as alcohols, amines, and silylamines, are particularly reactive and give cyclopropyl esters and amides, respectively, in reasonable to good yields, e.g. formation of 5 and... 

A plausible mechanism for the reaction includes several organometallic species that are sensitive to reactive moieties elsewhere in the molecule. If a chloro, chloromethyl, or mesyloxymethyl substituent is attached vicinal to the 1,1 -dibromo moiety, efficient ring opening occurs prior to carbonylation and P,y- and y, -unsaturated acid derivatives are formed. Reductive carbonylation has also been achieved with 1,1-dibromocyclopropanes using an excess of pentacarbonyliron in dimethylformamide with added methanol or sodium methoxide, or cobalt(II) chloride and nickel(ll) cyanide under phase-transfer conditions in a carbon monoxide atmosphere. However, the yield of cyclopropanecarboxylic acid derivatives is low, and when pentacarbonyliron is used the amount of monobromides is fairly high. ... 

R2 = O). Under acetylation conditions the amide obtained cyclized to the imide 292 (R = Ac). One carbonyl group of the corresponding alcohol 292 (R = H) was selectively reduced, and after removal of the chiral auxiliary, the chiral lactone 291 (R = H) was obtained. A rapid route to racemic 291 (R = H) consists in the reductive carbonylation of the dibromocyclopropane 293 (from dibromocarbene and prenol) with tetracarbonylnickel in dimethylform-amide, when up to 73% of the lactone 291 (R = H) can be obtained. 

Research trends of the last few years highlight applications to more involved systems either from the substrate/product side or from the catalyst side. Furthermore, a deeper insight into underlying mechanism is intended. Thus, reductive carbonylation of dibromocyclopropanes was performed in toluene/5 M KOH with syngas (CO/H2, 3 1) at elevated temperature (90 °C) using a mixture of CoCl2, KCN, and Ni(CN)2 for the metal catalyst and PEG-400 as PT catalyst which was much more efficient than a quaternary ammonium catalyst [81]. l,l-Dibromo-2-phenylcydopropane furnished a 72% yield of 2-phenylcydopropanecarboxylic add (1 1 cis/trans mixture). 

Seebach has described in detail the alternative preparation of cyclobutanones via oxaspiropentane intermediates/ 1-Bromo-l-lithiocyclopropanes react with ketones or aldehydes to give bromohydrins (259) which are readily converted via oxaspiro-pentanes (260) to cyclobutanones. A variety of examples are described. Overall yields vary somewhat with substitution pattern, but can be as high as 90% in the most favourable cases. A variation of the sequence is the conversion of the dibromocyclo-propane into its 1-bromo-l-thiomethyl derivative before lithiation and reaction with a carbonyl partner. As dibromocyclopropanes are readily available from the addition of dibromocarbene to olefins, this sequence affords a useful method of annelat-ing cyclobutanones to olefins, and is complementary to the Trost secoalkylation procedure. 

The insertion of a carbonyl group in between the 5/7 -hybridized carbon atoms of an alkene can be accomplished through the formation of cyclopropanone thioacetals from the appropriate epoxide or dibromocyclopropane and treatment of these compounds with aqueous trifiuoroacetic acid (Scheme 16), ... 

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