Dichlorocarbene precursors

Dichlorocarbene cannot be isolated, but it can be produced in the presence of an alkene with which it rapidly reacts. The best dichlorocarbene precursor is the anion C13C , which easily eliminates a chloride ion. This anion is obtained from C13CH and fairly strong bases like potassium ferf-butoxide (KO-ferf-Bu), KOH or NaOH. The deprotonation of C13CH is run very efficiently with a solution of KO-terf-Bu in THF. Alternatively, when a concentrated aqueous solution of NaOH or KOH is vigorously stirred with a chloroform solution of the alkene (which is not miscible with the first) there is only moderate conversion into the corre-... 

R = H, alkyl, OH, O-alkyl, CO2H, NO2, Cl, Br, I R = H, alkyl dichlorocarbene precursor CHCI3, CI3CCO2H, CI3CCHO, CI3CNO2 ... 

Deoxygenation of pyridine N-oxide. Schweizer and O Neill showed that dichlorocarbene generated from a large excess of phenyl(trichloromethyl)mercury deoxygenates pyridine N-oxide to pyridine. The reaction was slow but the yield better than obtained with other dichlorocarbene precursors. 

An interesting new method of synthesis of carbonimidoyl dichlorides involves the addition of dichlorocarbene to aliphatic carbodiimides. Thus, reaction of phenyl(bromodichloromethyl)mercury (LXV) (the dichlorocarbene precursor) with diisopropylcarbodiimide produces isopropyl-carbonimidoyl dichloride (LXVI) in 63% yield... 

Before our studies, high temperatures (>600°C) had usually been used to generate dichlorocarbene in the gas phase. Based on trapping experiments we have shown that the trihalomethyl mercury derivatives RHgCHals, which were successfully used earlier as sources of dihalocarbenes in solution (Seyferth, 1972), are also convenient precursors of carbenes in the gas phase (Mal tsev etaL, 1971a,b). 

Section D illustrates formation of carbenes from halides by a-elimination. The carbene precursors are formed either by deprotonation (Entries 14 and 17) or halogen-metal exchange (Entries 15 and 16). The carbene additions can take place at low temperature. Entry 17 is an example of generation of dichlorocarbene from chloroform under phase transfer conditions. 

Tochtermann reported the addition of dichlorocarbene to the racemic glycal 52, whose cyclopropyl-allyl rearrangement leads to the 2//-pyran. The synthesis of the optically pure (+)-(2S,3R,7S) and (-)-(2f ,3S,7f )-glycal precursors has also been achieved. As pointed out, optically pure glycals are versatile precursors for carbohydrate synthesis <00EJO1741>. 

The inertness of [10.8]betweenanene toward dichlorocarbene was the first reaction 54a) observed which distinguishes between (Z)[10.8] precursor and ( )[10.8] isomer, and this distinction was further observed in the [8.8]series of compounds 54b). 

The 7,7-dihalobicycloheptene route appears easily adaptable to the synthesis of 6n 5 atom cyclopropa[c]heteroarenes 61 as the three-membered ring is suitably located and the requisite precursors—the dichlorocarbene addition products of, for example, 2,5-dihydrofuran—are easily accessible. Unfortunately, treatment of halides 59 with r-BuOK fails to provide any evidence for sought after 61. Dehydrochlorination does occur but the strained 1,3-bridged cyclopropenes 60 ring expand to carbene or add a nucleophile faster than rearrangement and loss of a second molar equivalent of HCl. The precise outcome of these reactions is very dependent upon the nature of the ring system as the detailed studies show . ... 

Dichlorocarbene is a typical singlet ground-state carbene which is commonly used for cydopropanation reactions, since it gives satisfactory yields in many cases, but in general, carbene synthesis implies a metal catalyst (usually copper) together with a diazo compound as the carbene precursor. In (he particular case of the O -H insertion reaction, sulfur dioxide has been reported as being an efficient catalyst for the insertion of carbalkoxycarbenes generated from diazoesters. 

The addition of a carbene or benzyne to a sulfide, and to a lesser extent to an amine, provides a direct route to ylides. Enormous progress has been realized with this approach, mainly as a result of the efforts of Ando and Doyle. Most noteworthy amongst examples using benzyne is die squalene synthesis reported by Ollis, in which the sulfide (55) was transformed by a 3,2-rearrangement into the squalene precursor (58) and eventually into squalene itself (Scheme The stereospecific rearrangement of cjco-methylenecyclohexane derivatives discovered by Evans employed dichlorocarbene, generated under phase transfer conditions (Scheme 15). ... 

Haloform test. A modification of a test devised by Fujiwara permits detection of fluoroform, chloroform, bromoform, or iodoform or of any precursor of a haloform or of a dihalocarbene. A few drops of a mixture suspected of containing a haloform or a precursor is added to a mixture of 3 ml. of 10% sodium hydroxide and 2 ml. of pyridine. If the mixture turns pink to bright blue-red within one or two minutes of vigorous shaking at room temperature, a haloform is present. If the color change occurs not at room temperature but when the solution is heated on the steam bath for one minute, a precursor of a haloform or a dichlorocarbene is indicated. The intensity of the color is proportional to the concentration of haloform or of precursor. 

Dichlorocarbene usually undergoes addition to the double bond of enynes in the case of poly-enynes the more substituted double bond reacts faster. Which double bond is attacked also depends on the type of the substituents. Using excess carbene precursor, dichlorocarbene can also undergo addition to the triple bond. The products thus formed are hydrolyzed into cyclo-propenones, either under the reaction conditions or during the workup of the reaction mixture. In separate instances, exclusive addition of dichlorocarbene to the triple bond of enyne was observed (Houben-Weyl, Vol.4/3, pp 172-175 and Vol.E19b, ppl543-1544). 

The enamine structure, which is formed in situ (by means of the trichloromethyl anion, the precursor of dichlorocarbene), may undergo further addition of dichlorocarbene. The reaction of A -methylpyridinium iodide with chloroform under phase-transfer catalytic conditions exemplifies this case, forming 16 and 17 (see Houben-Weyl, Vol. E19b, p 1557). 

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. ... 

The synthesis of still higher benzocyclopropene homologs by the dichlorocarbene route was unsuccessful. Thus, when the precursor of l//-cyclopropa[/t]anthracene was treated with base under the usual conditions, only 1-chloromethyl- (5a) or 1-rm-butoxymethylanthracenc (5b) in a ratio as a function of the base concentration were isolated. Similarly, twofold dehydrochlorination of the precursor, which should lead to 3,8-dihydrocyclopropa[h]anthracene, gave only 1-methylanthracene (6), and the analogous elimination in the cyclopropa[a]anthracene series afforded no cycloproparene. " ... 

Bis(trichloromethyl)mercury has been prepared in the same way it has been used as a precursor of dichlorocarbene. In this case temperatures of 170-190° are required and the yields of dichlorocyclopropanes obtained are around 25%.2... 

Precursor of difluorocarbene [before references]. In a study of the behavior of cholesterol to dihalocarbenes, a Syntex group6 found that dichlorocarbene does not add to the somewhat unreactive double bond of cholesterol but that the less bulky difluorocarbene, generated from sodium chlorodifluoroacetate, does add to give a difluorocyclopropane which was assigned the 5/3,6/3-orientation mainly on the basis... 

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 above cases, dichlorocarbene was generated from chloroform under liquid-liquid phase transfer catalytic conditions. Alternatively, sodium trichloroac-etate was also used as the precursor of dichlorocarbene as shown by the 6 -> 7 transformation (Scheme 3)[16, 18]. 

Dichlorocarbene, generated in situ from an organomercury precursor, phenyl(bromo, dichloromethyl)mercuiy (Seyferth reagent), adds to polybutadiene in a similar maimer [56]. The reactions take place under homogeneous conditions. They can be carried out aal% solutions of the polymer in benzene, using 10-20% mol excess of the reagent. 

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