Dihalocarbenes cycloadditions

The reaction of dihalocarbenes with isoprene yields exclusively the 1,2- (or 3,4-) addition product, eg, dichlorocarbene CI2C and isoprene react to give l,l-dichloro-2-methyl-2-vinylcyclopropane (63). The evidence for the presence of any 1,4 or much 3,4 addition is inconclusive (64). The cycloaddition reaction of l,l-dichloro-2,2-difluoroethylene to isoprene yields 1,2- and 3,4-cycloaddition products in a ratio of 5.4 1 (65). The main product is l,l-dichloro-2,2-difluoro-3-isopropenylcyclobutane, and the side product is l,l-dichloro-2,2-difluoro-3-methyl-3-vinylcyclobutane. When the dichlorocarbene is generated from CHCl plus aqueous base with a tertiary amine as a phase-transfer catalyst, the addition has a high selectivity that increases (for a series of diolefins) with a decrease in activity (66) (see Catalysis, phase-TRANSFEr). For isoprene, both mono-(l,2-) and diadducts (1,2- and 3,4-) could be obtained in various ratios depending on which amine is used. 

The cycloaddition reactions of dihalocarbenes (CF2, CCI2, CBr2) with pairs of alkenes have also been studied ... 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives ([1 -f 2]-cycloaddition). Many derivatives of carbene (e.g., PhCH, ROCH) ° and Me2C=C, and C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes, " and with carbalkoxycarbenes (generated from diazoacetic esters). Alkylcarbenes (HCR) have been added to alkenes, but more often these rearrange to give alkenes (p. 252). The carbene can be generated in any of the ways normally used (p. 249). However, most reactions in which a cyclopropane is formed by treatment of an alkene with a carbene precursor do not actually involve free carbene... 

Independently Volpin17 synthesized diphenyl cyclopropenone from diphenyl-acetylene and dibromo carbene (CHBr3/K-tert.-butoxide). This reaction principle of (2 + 1) cycloaddition of dihalocarbenes or appropriate carbene sources ( caibenoids ) to acetylenic triple bonds followed by hydrolysis was developed to a general synthesis... 

When generated in the presence of an alkene, dihalocarbenes undergo cycloaddition to the double bond to give dihalocyclopropanes. 

In addition to acyclic and monocyclic enamines, bicyclic and tricyclic enamines also undergo cycloaddition with dihalocarbenes. Endocyclic enamines , such as pyrrole and indole, add dichforocarbene and the adducts rapidly undergo ring cleavage to afford 3-chloropyridine and 3-chloroquinoline, respectively, in moderate yields (c/. Section 4.7.3.9).75-77... 

Reaction of dihalocarbenes with alkenes, [1 +2] cycloaddition, is the method of choice for the preparation of 1,1-dihalocyclopropanes. The reaction proceeds stereospecifically preserving the configuration of the alkene in the products. These observations allow the conclusion to be made that the dihalocarbene reacts in the singlet state with alkenes. Experimental data (relative activities of alkenes, selectivity indices as well as theoretical calculations indicate that dihalocarbenes are electrophilic species. This means that they react readily with electron-rich (nucleophilic) alkenes. Dihalocarbenes may also react with electron-poor alkenes, but at a much slower rate. In the case of alkenes with a fairly unreactive double bond, dihalocarbene may also attack other sites of the alkene molecule, e.g. insert into a C-H bond. The selectivity (reactivity) of dihalocarbenes depends on the temperature at 20 C typical dihalocarbenes can be arranged in the order given, with respect to their selectivities versus reactivities (Houben-Weyl, Vol. El9b, p 1598). 

Besides methylene and dihalocarbenes, carbonyl-substituted carbenes or their equivalents, particularly diazo esters, are the most important building blocks for the synthesis of cyclopropanes via [2 + 1] cycloadditions. This is because... 

Many other examples, in particular reactions of dihalocarbenes obtained by phase-transfer catalyzed a-elimination of the corresponding trihalomethane derivatives, confirm the stereospecificity of these cycloadditions. This is also valid for most cyclopropanations performed with dibromomethylene obtained from phenyl(tribromomethyl)mercury (Seyferth reagent2, see Vol. IV/3, p 179), however, a few exceptions have been reported3. 

Difluorocarbene is the only dihalocarbene, which, being generated via PT-catalyzed a-elimination from chlorodifluoromethane in a two-phase system does not enter the cycloaddition reaction to alkenes. This is because of the instability of the chlorodifluoro-methyl anion, which due to its very short lifetime cannot be transferred from the interfacial region, where it is formed, into the organic phase. Therefore, difluorocarbene is generated in the interfacial region and undergoes fast hydrolysis. 

Calculations of energy barriers and heats of the cycloaddition reaction have shown that the selectivity of carbenes (found at ambient temperature) is linearly related with their stability [44]. This conclusion in the spirit of the conventional activity-selectivity relationship does not, however, explain the experimental data referring to entropy control of the dichlorocarbene addition to alkenes [55], to the temperature-dependent selectivity of dihalocarbenes [56, 57] or to the zero or even negative activation energies for a number of cycloaddition reactions of carbenes [58, 59]. 

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