Dihalocarbenes, cyclopropanation

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

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... 

Although the C=C bond of allyl alcohols is frequently less susceptible to reaction with dihalocarbenes, insertion of the carbene into the C=C bond invariably occurs (Table 7.4) to the exclusion of reaction at the hydroxyl group (see Section 7.5) [98]. A complex mixture of products is obtained from the reaction of dichlorocarbene with allyl alcohol, but the cyclopropane can be obtained in high overall yield (>70%) via... 

Vinyl acetate fails to react with dihalocarbenes, but reacts with the trihalo-methyl anion precursor to produce the l,l,l-trihalo-2-acetoxypropane [33, 166-168], In contrast, where the a-position is substituted by an alkyl group, normal cyclopropanation occurs. Cyclic enol acetates behave in a similar fashion to the enol ethers [12, 88], e.g. bicyclo[3,2,l]oct-2-enyl acetate and its 3-isomer... 

Ab initio and RRKM calculations indicate that the reactions of C, CH, and (H2C ) with acetylene occur with no barrier." Laser flash photolysis of the cyclopropanes (69) and (70) was used to generate the corresponding dihalocarbenes. The absolute rate constant for the formation of a pyridine ylide from Br2C was (4-11) x 10 lmoP s. The rates of additions of these carbenes to alkenes were measured by competition with pyridine ylide formation and the reactivity of BrClC was found to resemble that of Br2C rather than CI2C . 

Dihalocarbenes generated under phase transfer catalysis add to vinylic tellurides to give the corresponding gem-dihaloarylteUuro cyclopropanes. ... 

Although the gem-dihalocyclopropanes are fairly stable compounds, they can participate — as has been shown in the above sections — in quite a number of chemical transformations. Several reactions between dihalocarbenes and alkenes have been described in which no dihalocyclopropane formation could be observed that these intermediates might have been produced was only inferred from the type of products finally isolated. A typical process of this type is the e/ufo-addition of dihalocarbenes to norbomene and norbomadiene as discussed above. Comparable rearrangements have been observed, when dichlorocarbene additions either lead to aromatic products or when they cycloadd to rather inert aromatic systems. In the latter case a ring-enlargement takes place. A reaction related to the concerted opening of two cyclopropane rings in a bicyclopropyl system as discussed above takes place when dichlorocarbene is added to spiro[2.4]hepta-4,6-diene [227]. 

Reactions of carbanions, anions of weak organic acids (e.g., indole or carbazole), and dihalocarbenes may be carried out in liquid-liquid systems, in which concentrated aqueous sodium hydroxide is the aqueous phase. The term phase transfer catalysis is mechanistically incorrect these are often referred to as catalytic two-phase systems. Numerous reactions of carbanions including alkylation, nitroarylation, addition, the Darzens condensation, cyclopropanation, and also a variety of reactions of dihalocarbenes are conveniently carried out in this way. 

The production of buta-1,3-dienes (37) by reaction of 1,2-diarylcyclopropenes with dihalocarbenes is thought to involve electrophilic attack of the carbene to give a dipolar intermediate (38).51 The addition of carbene to CO and H2C=0 has been studied by MNDO calculations.52 Photolysis of diethyl diazomalonate in a CO matrix at low temperature gave rise to ketenes by immediate trapping of the postulated carbene (39).53 The major products of reaction between dichlorocarbene and cyclone were CO and the gem-dichloro species (40).54 The predominance of this pathway over formation of the dichlorooxirane or the cyclopropane is attributed to the aromatic nature of the carbonyl ylide and its twist geometry. 

Fluorinated dihalocarbenes have been used as central synthons in the synthesis of fluorinated aromatics from cyclopentadienes.62 The reaction proceeds via a fluorinated fused bicyclic cyclopropane, which upon heating undergoes a ring opening to achieve the ring expansion of the second cycle. 

Attack by dihalocarbenes on diphenyltropone 522a (Scheme 137) leads to mono- and bis-cyclopropanation [525,526 77BSF(2)571]. With dichloro-carbene, bis(carbethoxy) (522b) and dimethyl derivatives give mono- or bishomotropones, respectively. 

The addition of dihalocarbenes to double bonds occurs stereospecifically to give cyclopropane derivatives [68J. The reaction appears to have electrophilic character even though the electronic state of the carbene is uncertain (cf. p. 341). Again the direction of attack on the double bond is subject to steric control. The diene (2) for example, reacts with di-bromocarbene to give first the 2ct,3[Pg.294]

Since dihalocarbenes are electrophiles, they readily react with double bonds to afford cyclopropanes, forming two new carbon-carbon bonds. 

Although the reaction of dihalocarbenes with alkenes gives good yields of halogenated cyclopropanes, this is not usually the case with methylene, tCH2, the simplest carbene. Methylene is readily formed by heating diazomethane, CH2N2, which decomposes and loses N2, but the reaction of CH2 with alkenes often affords a complex mixture of products. Thus, this reaction cannot be reliably used for cyclopropane synthesis. 

Tor a review of the use of phenyl(trihalomethyl)mercury compounds as dihalocarbene or dihalocarbenoid precursors, see Seyferth, D. Acc. Chem. Res. 1972, 5, 65. For a review of the synthesis of cyclopropanes with the use of organomercury reagents, see Larock, R.C. Organomercurcury Compounds in Organic Synthesis, Springer, NY, 1985, pp. 341-380. 

The cyclopropanation of alkenes with dihalocarbenes, CX2 or CX X, except for CF2, can be efficiently executed by the PTC procedures (CHX3/strong aqueous base/catalyst), which are well-documented in books and reviews . The dichloro- and dibromo-carbene additions by the PTC procedure have successfully been applied for many alkenes, conjugated polyolefins and allenes. Satisfactory results are also reported for the reactions of sterically hindered olefins as well as electronically deactivated olefins, which frequently... 

Gem-dihalocyclopropanes are readily prepared from the corresponding dihalocarbenes or dihalocarbenoids. Conversion of these compounds to cyclopropanes containing a deuterium label at a stereochemically defined site is relatively straightforward. Both... 

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... 

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