Alkene reaction with dichlorocarbene

The reactive intermediates under some conditions may be the carbenoid a-haloalkyllithium compounds or carbene-lithium halide complexes.158 In the case of the trichloromethyllithium to dichlorocarbene conversion, the equilibrium lies heavily to the side of trichloromethyllithium at — 100°C.159 The addition reaction with alkenes seems to involve dichlorocarbene, however, since the pattern of reactivity toward different alkenes is identical to that observed for the free carbene in the gas phase.160... 

Compared with the classical procedures, which employ chloroform and dry potassium /ert-butoxide, Makosza s method is several magnitudes superior, in spite of the normally recognized requirements that the dichlorocarbene should be produced under totally anhydrous conditions. Several early reports of the reactions of dichlorocarbene, generated by Makosza s procedure, led to suggestions that the activity of the carbene was considerably greater than that of the classically produced carbenes. This assumption was based on the overall higher yields of dichlorocyclopropanes derived from the reaction with alkenes, and upon the observation that weakly activated alkenes reacted with Makosza carbenes, but not with the classically produced carbenes. A consideration of the mechanism of formation of the carbenes under phase-transfer catalytic conditions exposes the fallacies in the assumptions. 

Figure 5.5 Dichlorocarbene generation, and reaction with alkenes.

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

Alkynes tend to be much less reactive than alkenes. For example, 1,2-diphenylethyne produces only 23% of the dichlorocyclopropene from its reaction with dichlorocarbene, compared with 96% of the dichlorocyclopropane obtained from rrans-stilbene under analogous conditions [4]. Conjugated eneynes react preferentially at the C=C bond with dihalocarbenes [18-20, 22, 38] and with dimethylvinylidene carbene [158],... 

Addition of carbenes to Jt-electron excessive aromatic compounds, or those which possess a high degree of bond fixation, is well established. Dihalocarbenes react with naphthalenes with ring expansion to produce benztropylium systems (Scheme 7.8). Loss of hydrogen halide from the initially formed product leads to an alkene which reacts with a second equivalent of the carbene to yield the spirocyclopropyl derivatives in high yield (>95%) [14, 50]. Insertion into the alkyl side chain (see Section 7.2) also occurs, but to a lesser extent [14]. Not unexpectedly, dichlorocarbene adds to phenanthrenes across the 9,10-bond [9, 10, 14], but it is remarkable that the three possible isomeric spiro compounds could be isolated (in an overall yield of 0.05% ) from the corresponding reaction with toluene [14]. 

This dominance of sulfur in the reactions with electrophiles is well brought out in the addition of carbenes to the-two monocycles. Tire allylic sulfide (5,6-dihydro-2jF/- thiopyran) only affords the products of reaction at sulfur, while the vinylic sulfide (3,4-dihydro-2f/-thiopyran), in which the alkene is a little more nucleophilic due to the small interaction with the heteroatom, shows dichotomous behaviour. Dichlorocarbene affords the cyclopropane product (78) in 70% yield, but the stabilized ylide (76) is produced from bismethoxycar-bonylmethylide and (75). In fact it is possible that the initial reaction with dichlorocarbene is reaction at sulfur and subsequent rearrangement of this less stabilized ylide. Schemes 6 and 7 illustrate the results and proposed mechanisms (77JOC3365,64JOC2211). 

A number of cheletropic reactions also appear to be anomalous, including the best known of all cheletropic reactions, the stereospecific insertion of a carbene into a double bond, as in the reaction of dichlorocarbene 2.173 with alkenes. Here we have a reaction involving only four electrons, which is known to be suprafacial on the alkene, preserving the geometry of the substituents in the starting alkenes in the cyclopropanes 2.174 and 2.175. Furthermore, the [2+2] reaction takes place even with a diene, which could. undergo an allowed [4+2] reaction, but chooses not to. 

A carbene, RjC , is a neutral molecule containing a divalent carbon with only six valence electrons. Carbenes are highly reactive toward alkenes, adding to give cyclopropanes, Dichlorocarbene adds to alkenes to give 1,1- dichlorocyclopropanes, Nonhalogenated cyclopropanes are best prepared by treatment of the alkene with CH l2 and zinc-copper alloy—the Simmons-Smith reaction. 

Further studies showed that using a combination of sonication and phase-transfer catalyst (PTC) the rate and yield of the reaction of alkene with dichlorocarbene which resulted from chloroform and sodium hydroxide pellets in situ could be improved efficiently [40], Compared with the results reported by Regen [41 ] where sonication alone was used, they found that mechanical stirring was not necessary under high-power sonication. Other findings included the fact that the ratio of NaOHialkene could be decreased from 10 1 to 3 1 and the reaction period could be shortened from 5 h to 10—15 min in the presence ofO. 1-0.05% PTC. 

A similar method was used to generate dibromocarbene using a combination of sonication and PTC for the reaction of alkene with dibromocarbene formed from bromoform and solid sodium hydroxide in situ [42], Compared with the preparation of dichlorocarbene, however [39], the amount of PTC required had to be increased 10-fold. The combination of the effect of sonication and PTC was significant in that the presence of PTC allowed a shortening of the reaction period to 20-30 min and an increase in yield to 96% compared with 3 h and 40-50% using sonication alone. 

Chlorofluorocarbene is an electrophilic species whose reactivity and selectivity is between those of difluoro- and dichlorocarbene. It reacts with alkenes to give 1-chloro-l-fluorocyclopropanes, often in good yield these reactions are stereospecific and stereoselective (the isomers with the chlorine cis or endo to the alkyl group or the second ring, respectively, predominate, see Houben-Weyl, Vol. E19b, p 1493). 

Of the many methods used for dichlorocyclopropanation of alkenes, the formation of dichlorocarbene from chloroform and base/phase-transfer catalyst and its subsequent reaction with an alkene is strongly recommended. In fact, since inception this method has been the most frequently used for the preparation of 1,1-dichlorocyclopropanes. ... 

Determination of the optimal conditions for the reaction of dibromocarbene with alkenes is more difficult than for the corresponding reaction of dichlorocarbene. This is due to the high reactivity of dibromocarbene which enters into other competitive reactions, particularly hydrolysis under the conditions of phase-transfer catalysis and, in the case of alkenes of low reactivity, its precursor bromoform forms products of free radical reactions if the reaction system is not protected from air and oxygen and from light. These processes have been studied and are described in detail in Houben-Weyl, Vol.E19b, pp 1609-1612. 

The dibromocyclopropanes are frequently preferred to their less reactive dichlorides, although the latter are often prepared in higher yields from dichlorocarbene additions to alkenes. Di-fluorocyclopropanes are not useful precursors to cyclopropylidenes with reactions leading to alkylated cyclopropenes and alkynes. ... 

High yields are obtained in the reaction of dichlorocarbene with alkenes in the presence of this catalyst ... 

M kosza et al. have confirmed the strong catalytic effect of trialkylamines in the generation of dichlorocarbene and also of dibromocarbene. Actually, di-bromocarbene generated by catalysis with trialkylamines adds to 1-alkenes, a reaction that is not observed with dibromocarbene generated with tetraalkyl-ammonium halide catalysts. The authors have presented indirect evidence that dichlorocarbene reacts with a trialkylamine to form a basic salt that abstracts a proton from chloroform ... 

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]. 

First ionization potentials of representative acyclic alkenes have been shown to correlate with log rei (alkene relative reactivities) for the reactions with dichlorocarbene, nitrosyl chloride, and osmium tetroxide. Each reaction gives a single line of correlation, which includes all alkenes studied, regardless of the degree of substitution. 

If dichlorocarbene is generated in the presence of an alkene, addition to the double bond occurs and a dichlorocyclopropane is formed. As the reaction of dichlorocarbene with ds-2-pentene demonstrates, the addition is stereospecific, meaning that only a single stereoisomer is formed as product. Starting from a cis alkene, for instance, only cis-disubstituted cyclopropane is produced starting from a trans alkene, only trans-disubstituted cyclopropane is produced. 

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