The Reaction of Dichlorocarbene With Olefins

Although phase transfer catalysis is a many faceted technique, it was the observation that dichlorocarbene could be generated in a two-phase aqueous-organic system in which sodium hydroxide was used as base that first captured the attention of the organic chemical community. Both Starks [1,2] and Makosza [3] reported the di-chlorocyclopropanation of cyclohexene in the late 1960 s. The reaction was conducted as shown in equation 2.1. 

The convenience and potential of this method was immediately apparent and its disclosure was followed by numerous examples and extensions. The method was of particular interest because previous methods used to generate dichlorocarbene all required rigorous exclusion of moisture. Among these methods are treatment of chloroform with potassium -butoxide in pentane, pyrolysis of anhydrous sodium trichloroacetate, and the thermal decomposition of phenyl(bromodichloromethyl)-mercury. 

The availability of 1,1-dichlorocyclopropanes by phase transfer processes combined with reduction methods such as sodium in ethanol, lithium in r-butanol [4], or sodium in liquid ammonia [5] provides a high yield two-step alternative to the Simmons-Smith reaction (Eq. 2.2). 

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Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

The Reaction of Dichlorocarbene With Olefins Table 2.1 (continued)... 

The reactions of dichlorocarbene with phosphorus ylides result in the corresponding olefins and phosphines.66-68 In the reaction of dichlorocarbene generated in situ with tributyl- and triphenylmethylenephosphoranes or triphenylethylidenephosphorane, the olefin yield increases as the nucleo-philicity of phosphorus ylide increases. According to,67 the reaction starts from the electrophilic attack of carbene at the a-C atom of phosphorus ylide. Then the intermediately formed betaine (28) (Scheme 14) decomposes to eliminate the phosphine molecule and form dichloroolefin (29). 

Kobrich0 has presented evidence that the reaction of trichloromethyllithium with olefins is stereospecific and that it probably does not proceed through prior decomposition to dichlorocarbene. He suggests a cyclic transition state in which lithium chloride is present. Tribromomethyllithium has been prepared in high yield from the reaction of tetrabromomethane and phenyllithium or n-butyllithium.7... 

The reaction of carbenes with olefins to form cyclopropyl derivatives has been used to modify elastomers. Pinazzi and Levesque and Berentsvich et al. found that carbene addition had a significant influence on the properties of polydienes. Thermogravimetric analysis (TGA), flammability and oil resistance in NR and dichlorocarbene modified styrene butadiene rubber (DCSBR) blends were investigated by thermogravimetrie analysis as a funetion of different composition. The TGA plots confirmed the better thermal stability and flame resistance of DCSBR as well as its blends with NR. The amount of DCSBR in the blend significantly affected the properties of blends. 

The reactions of dichlorocarbene with a variety of olefinic and acetylenic substrates have been discussed in Chap. 2. We wish now to turn our attention to the reactions of this species with a number of other substrates which either are non-olefmic or contain double bonds which do not constitute the major reactive function. The substrates considered here are alcohols, imines, amines, amides, thioethers, and hydrocarbons. With the exception of the latter, all of these species appear to react by initial coordination of the electrophilic carbene with a Lewis basic site. Subsequent reactions attributable to differences in the basic function or involvement with other reactive sites lead to differences in the chemistry of each substrate, and each is therefore considered separately. 

You will become familiar with selected cycloadditions that lead to four-, five-, or six-membered rings in Chapter 12. Two more cycloadditions, which are also oxidations, will be examined in Chapter 14, which deals with oxidations and reductions the ozonol-ysis reaction can be found in Section 14.3.2 (as well as in Section 12.5.5) and the cis-vic dihydroxylation with 0s04 can be found in Section 14.3.2. Here we discuss only the addition of dichlorocarbene to olefins as an example of a cis addition of the cycloaddition type (Figure 3.11). 

Polymerization. Monomers. The cyclopropane type monomers are prepared either by addition of the dichlorocarbene or by the Simmons-Smith reaction on the corresponding olefins. Most of these compounds have been described. Spiropentane is prepared by the Applequist method (I, 2), by the reaction of zinc with C(CH2Br)4 in alcohol in the presence of ethylenediaminetetraacetic acid (EDTA). This hydrocarbon is purified until a single NMR signal is obtained at t = 9.28. 

Quaternary alkylammonium salts, tertiary amines, and crown ethers have all been utilized as catalysts in the reaction of hydroxide with chloroform to yield dichlorocarbene. The most commonly utilized catalyst has been benzyltriethylammonium chloride (see Sect. 1.7) but other quaternary ammonium chloride catalysts have proved effective. Cetyltrimethylammonium chloride and tricaprylmethylammonium chloride (Aliquat 336) have both been used effectively in the cyclopropanation of simple alkenes. The use of Z e a-hydroxyethyltrialkylammonium hydroxides as phase transfer catalysts results in increased regioselectivity in the addition of dichlorocarbene to olefins [12]. Crown ethers such as dibenzo and dicyclohexyl-18-crown-6 have both been utilized in place of quaternary ammonium compounds. 18-Crown-6 has also been used as a catalyst in the phase transfer thermal decomposition of sodium trichloroacetate to yield dichlorocarbene [13]. 

Direct evidence for the existence of dichlorocarbene, by trapping with a suitable substrate, was obtained by Doering and Hoffmann in 1954. Dichlorocarbene was shown to add in a characteristic manner to the double bond of cyclohexene to give dichloronorcarane (1) in 59% yield similar adducts were obtained with other olefins. Bromo-form imderwent an analogous reaction in the presence of olefins to give... 

The generation of dichlorocarbene for addition to olefins has been realized by the use of chloroform and alkali metal alk-oxides4 6 (preferably potassium feri-butoxide), sodium trichloro-acetate,6 butyllithium and bromotrichloromethane,7 and the reaction of an ester of trichloracetic acid with an alkali metal alkoxide.2,8 The latter method, which is here illustrated by the preparation of 2-oxa-7,7-dichloronorcarane, generally gives higher yields of adducts. 

Dichlorocarbene is the reactive intermediate formed by the reaction of alkali on chloroform, and typically it adds to olefins to give 1,1-dichlorocyclo-propanes. The PTC procedure for the generation of dichlorocarbene is particularly useful and is illustrated by its reaction with cyclohexene to form (38) (Expt 7.15). The mechanism is formulated below and probably involves the reaction of the quaternary ammonium hydroxide with chloroform at the phase boundary, and dissolution into the organic phase of the quaternary ammonium derivative of the trichloromethyl anion (41). This species breaks down to form dichlorocarbene and the quaternary ammonium chloride. The latter returns to the aqueous phase to maintain the cycle of events, while the dichlorocarbene reacts rapidly with the cyclohexene in the organic phase. 

Dichlorocarbene. Polish chemists have reported a new method for generation of dichlorocarbene (or a carbenoid species) it involves the reaction of an olefin with chloroform in the presence of a 50 % aqueous NaOH solution and a catalytic amount of benzyl-triethylammonium chloride. For example, dichloronorcarane was obtained from cyclohexene in this way in 72% yield. In the absence of the catalyst, a yield of only 0.5% has been reported.2... 

Kinetic studies of the reaction of phenyl(bromodichloromethyl)mercury with olefins show that dichlorocarbene is liberated as a free species. Moreover, the fact that the reaction is insensitive to the effect of substituents in the phenyl group suggests that the extrusion process proceeds in a concerted process through a cyclic transition state, 5a or 5b.7c... 

The effect of substituents other than alkyl on the reactivity of olefins has received little attention so far. The variation with n in the compounds (CH j)3Si(CH2) CH=CH2 of the dipole moment , the rates of reaction with ethyl diazoacetate (CuSO -catalyzed) , and the rates of dichlorocarbene addition are listed in Table 22. The maximum at = 1 reflects the opposite effects of bonding from the double bond to silicon and of the inductive effect... 

Excellent regioselectivity is observed in the reaction of 3-methyl-2,6-heptadien-l-ol with dichlorocarbene generated in the presence of benzyl-2-hydroxyethyldimethyl-ammonium hydroxide as phase transfer catalyst. Dichlorocarbene adds, in this case, exclusively to the trisubstituted double bond bearing the hydroxymethyl function rather than to the terminal double bond (see Eq. 2.38). The results of dichlorocyclo-propanation of several allylic olefin systems are recorded in Table 2.9. 

Systematic studies of the dicyclopropanation of olefinic sugars have been published [194], Dichlorocarbene, generated under phase-transfer catalysis reacts with 2,3-unsaturated pyranosides, such as 161 to yield a single isomer of the expected cyclopropane 162 (Scheme 55). A typical procedure is given in Section IE. The reaction is also possible with an enol... 

A comparison of olefin reactivities toward CeHjHgCBrCt in benzene at 80° with the reactivities of the same olefins toward sodium trichloroacetate in 1,2-dimethoxy-ethane at 80° established near identity of the relative reactivities toward both reagents, a result which favors the interpretation that both reactions involve free dichlorocarbene as an intermediate. Of practical significance is the fact that yields are consistently higher by the mercurial route. Thus the latter route proved effective as applied to olefins of low reactivity toward dihalocarbenes generated by other procedures. Examples are formulated ... 

Precursor of dichlorocarbene. Treatment of chloral with potassium /-butoxide at about 0° leads to dichlorocarbene, as shown by the reaction with an olefin.1... 

In the presence of more conventional bases carbene production is supressed. The decomposition of the chlorodifluoromethyl anion has been shown to be reversible and the yield of difluorocyclopropane is increased by increasing the alkene concentration. Epoxides upon treatment with dichlorocarbene afford cyclopropanes stereospecific-ally. The reaction proceeds by stereospecific deoxygenation of the epoxide to give olefin (41) which is subsequently trapped by the carbene. 

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