Dibromocarbene, synthesis

Isonitnle synthesis from pnmary amines and dichlorocarbene or dibromocarbene... 

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. 

An ingenious approach to the synthesis of steroids incorporating a tropone A ring has been developed by Birch and co-workers. Addition of dibromocarbene to 3-methoxyestra-2,5(10)-dien-17-one 17-ethylene ketal (42) gives a monodibromocarbene adduct formulated as (43) accompanied by a minor amount of a bisadduct. This confirms earlier observations that electrophilic halocarbenes add mainly to 2,3- or 2,5-dihydroanisoles at the double bond bearing the methoxyl group. 

Birch s procedure for tropone synthesis appears to be widely applicable to 2,3- or 2,5-dihydroanisole derivatives which are readily obtained by reduction of appropriate aromatic methyl ethers by alcoholic metal-ammonia solutions. " Additional functional groups reactive to dibromocarbene or sensitive to base such as double bonds, ketones and esters would need to be protected or introduced subsequent to the expansion steps. 

Gem-dibromospiropentane (620), obtained by the reaction of MCP with dibromocarbene, was used in the synthesis of BCP (3) (Scheme 90) [6a]. The reaction of the intermediate vinylidenecyclopropane 621 with a large excess of Simmons-Smith reagent gave exclusively BCP (3), but using modified Simmons-Smith procedures the [3]-triangulane (247) was also obtained in small yield (Scheme 91) [165],... 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

The rational synthesis of 3,8-methano[ 1 ljannulenone 12 started from 2-meth-oxy-l,4,5,8-tetrahydronaphthalene 25 which on reaction with dibromocarbene provided the bis-adduct 26. 

Our approach to the synthesis of model compounds, suited for the generation of carbenes, which are bound to the bridgehead of a strained bicyclic system, used the facile synthesis of [n.l.ljpropellanes, which we developed some years ago. Starting from substituted allyl chlorides 35, dibromocarbene addi-... 

Generally, cycloproylallenes are prepared by the same methods as employed for the synthesis of other allenic hydrocarbons. Thus, cyclopropylallene (17) itself has been obtained from vinylcyclopropane (139) via its dibromocarbene adduct 140 using the DMS method (Scheme 5.19) [54],... 

Since the yield of 161 is only 20%, the overall yields of the cycloadducts with reference to 1,3-cyclopentadiene are rather modest. Therefore, it was tested whether or not 6,6-dibromobicyclo[3.1.0]hex-2-ene (168) is after all stable enough to serve as progenitor of 162. To that end, dibromocarbene was generated from tetrabromo-methane by methyllithium [90] at -60 °C in the presence of 1,3-cyclopentadiene. Low-temperature NMR spectra revealed that 168 remains intact in the solution up to 0 °C. On the basis of this observation, a one-pot procedure was developed for the synthesis of the trapping products of 162 from 1,3-cyclopentadiene. As illustrated in Scheme 6.37, 168 was prepared at -60 °C, then an allenophile and methyllithium in succession were added to the mixture at -30 °C. In this way, the adducts of 162 to... 

Because of the yield of only 16% in the synthesis of 239, the overall yields of cycloadducts with reference to indene according to Scheme 6.54 are rather low, however. A substantial improvement was achieved by the development of a one-pot procedure, which starts from indene and takes advantage of its dibromocarbene adduct (254) (Scheme 6.55). This was prepared at -60 °C with tetrabromomethane and MeLi as source for the carbene and remained unchanged in solution up to temperatures around 0 °C [92]. If an activated alkene and MeLi were added sequentially to such a solution at -30 C, cydoadducts of 221 were isolated in a number of cases in relatively good yields. In Scheme 6.55, this procedure is illustrated by the example of 1,3-cyclopentadiene, which furnished the [4 + 2]-cydoadducts 255 and 256, both as a mixture with endo exo= 2 1, in the ratio of 8 1 in 23% yield with reference to indene [67]. Analogously, the products from 221 and styrene, 1,3-butadiene [92] and 2,3-dimethylbutadiene [66], namely the compounds 240, 241, 246-249 and 250-253, were obtained in yields of 40, 24 and 25%, respectively, by means of the one-pot procedure from indene. 

In practice, the synthesis of compound 13 was carried out according to Scheme 4.15, in which the "dibromocarbene" was substituted for "methylene" in order to exert better control of the reaction and thus giving the monoadduct as the predominant reaction product [31]. Although this meant an extra step in the synthetic sequence, the great selectivity and the excellent yields obtained compensated this "deviation" from the original retrosynthetic scheme. 

Elimination reactions of this type can be useful in synthesis for the formation of carbon-carbon bonds. For example, if dibromocarbene is generated in the presence of an alkene, it will react by cycloaddition to give a cyclopropane derivative ... 

Intramolecular alkylation of a lithiated species has been exploited in the synthesis of [1.1.0]- and [1. l.l]-propellanes (equation 45).143-145 In what appears to be a related reaction, the bis(dibromocarbene) adduct (11) on treatment with methyllithium undergoes a ring closure by 1,6-elimination, presumably via a four-center transition state, to give (12 equation 46), which was subsequently converted to a bis(ho-mobenzene).146... 

Cyclic allenes have been obtained in high yields, as illustrated by the synthesis of 1,2-cyclononadiene from the dibromocarbene adduct of the readily available cyclooctene (equation 51).138 The smallest stable cyclic allene known to date is (14) it was prepared from the dibromocyclopropane (13) in high yield.139 A small amount of the tricyclic compound (15) was also obtained (equation 52). The cyclic allene (14) did not undergo dimerization even on prolonged standing at ambient temperatures. In contrast, the unsubstituted analog was detected only at -60 °C by H NMR. It should also be noted that cyclohexa-1,2-diene was generated by the reaction of methyllithium on dibromobicyclo[3.1.0]hexane and trapped as the Diels-Alder adduct.160... 

This process has found occasional use in the synthesis of heterocycles. The major product resulting from the reaction of MeLi on the dibromocarbene adduct (51) is the tetrahydrofuran (52), as shown in equation (105).189 In a novel approach to the synthesis of spiroacetal pheromones, caibene insertion into an acetal C—H bond was studied (equation 106).252 Unfortunately, the reaction proceeds in low yield and the approach is further hampered by the lack of stereocontrol in the ring opening of the cyclopropane. Carbene insertions into N—H and C—H bonds adjacent to nitrogen have been shown to give azabicyclo systems, as shown in equations (107) and (108).188... 

The reaction of 2-methyl-3-trimethylsilyloxy-2//-5,6-dihydropyran with dibromocarbene (Equation 42) to give 4-bromo-2-methyl-6,7-dihydrooxepin-3(2//)-one and catalytic reduction of the latter (H2-Pd/C) to corresponding oxepanone should be mentioned. An analogous transformation is used to prepare an intermediate in the synthesis of zoapatanol <1994TL3085>. 

As the bromines in 1,1-dibromocyclopropanes are more reactive than the chlorines in the corresponding 1,1-dichloro derivatives, 1,1-dibromocyclopropanes are attractive intermediates in organic synthesis. The most convenient method for the preparation of 1,1-dibromocyclopropanes consists of the addition of dibromocarbene (carbenoid) to an alkene. The mechanistic details of this process have been less thoroughly investigated than dichlorocyclopropanation of alkenes, but both reactions are similar in many respects. 

The preparation of mono- and diadducts 5 and 6, respectively, of dibromocarbene with cyclo-hexa-1,4-diene is described. The synthesis of the diadduct encounters difficulties in its isolation, due to the formation of an emulsion and polymeric products. Such problems occur occasionally if an alkene is allowed to react with bromoform under phase-transfer catalysis conditions. 

The synthesis of metacyclophanes 4 was accomplished by thermolysis (ring expansion with elimination of hydrogen bromide and water) during vacuum distillation of the labile crude dibromocarbene adduct 3. ... 

A new synthesis of hotrienol (100) starts with the addition of dibromocarbene to isoprene. The dibromocyclopropane was reduced (BU3S11H) and the monobromide 101 submitted to a Grignard reaction with methacrolein the... 

The first synthesis of this class of monocyclic diallenes has been reported by Sondheimer and co-workers (59, 60). They treated the dibromocarbene adduct 35 with (-)-sparteine-CH3Li complex at -10°C to obtain 36 (D2 symmetry), m.p. 113-116°C, [a] D +24.4°, together with the optically inactive meso 37 (C2h symmetry) m.p. 86-87.5°C. X-ray crystallographic data (61) have become available which show that the only isolable isomer of 1,2,6,7-cyclodecatetraene, m.p. 36°C (62), a lower homolog of 37 (X=H2), has a center of symmetry, indicating that this is a meso compound with C2h symmetry. 

Isonitrile synthesis from primary amines and dichlorocarbene (from chloroform) or dibromocarbene (see 1st edition). 

As with the synthesis of chlorophenols, methods are available for bromophenols from non-aromatic precursors. The substituted cyclopentadienone shown reacts with dibromocarbene to give a substituted 3-bromophenol (ref.20). 

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