Dibromocarbene, preparation

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. 

Levisalles and co-workers have prepared A-homo-5a-cholestan-4-one by the dibromocarbene procedure starting with 3-methoxy-5a-cholest-2-ene. Wieland and Anner have converted 19-mesyloxy-A -3-keto steroids into... 

Potassium /-butoxide is prepared by dissolving potassium metal in t-butanol followed by removal of the excess of -butanol by distillation under reduced pressure. The resultant cake is powdered and used directly in the dibromocarbene additions. 

The, g 7M-dibroniodihydrocyclopropa[r]isoqiiinolines 8 (R = H, Cl), prepared by addition of dibromocarbene to the corresponding 2-acctyl-l-phcnyl-l,2-dihydroisoquinolines, in the presence of silvcr(I) trifluoioacetate, undergo rearrangement to the 5/f-2-bcnzazepines 9, albeit in poor yields.3... 

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)... 

Some other ring expansions involving the intramolecular amino Claisen rearrangement of vinylarylaziridine [ 123], the Diels-Alder reaction of indoles with acetylene derivative [124-127] and the dibromocarbene insertion into quinoline enol ethers [ 128] have been used to prepare 1-benzazepines. On the other hand, treatment of 3-chloro-3-phenyl-l,2,3,4,5,6-hexahydro-l-benz-azocin-2-ones with piperidine causes a ring contraction to give 2-phenyl-2-(l-piperidinylcarbonyl)-2,3,4,5-tetrahydro-l//-l-bcnzazepines in an excellent yield [23]. 

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],... 

The other possible linear vinylallene vinylog, 1,2,4,6-heptatetraene (22), has been prepared by the DMS route from the mono dibromocarbene adduct to 1,3,5-hexa-triene, 210 [78], practically simultaneously with the methyl derivative 211 [79] and several higher alkylated derivatives of 22, 214 (Scheme 5.31) [80],... 

The next higher homologs of 28-30 have all been prepared without difficulty as shown in Scheme 5.37. Single and double addition of dibromocarbene to 1,5-hexa-diene (biallyl) (240) leads to the adducts 241 and 242, respectively, which on methyl-lithium treatment are debrominated/rearranged to 32 and 34 in the usual way [43, 96, 97]. 

The cycloadditions of 1-substituted 1,2-cyclohexadienes and among them their dimerization are of interest because of the position selectivity. Does the reaction occur at the substituted or the unsubstituted ethylene subunit For that question to be answered, 1-methyl- (74), 1-phenyl- (75), 1-cyclopropyl- (76), l-(3-phenylpropyl)-(77) and l-trimethylsilyl-l,2-cyclohexadiene (79) were generated from the corresponding 1-substituted 6,6-dibromobicyclo[3.1.0]hexanes with methyllithium. Several of these dibromides are thermolabile, which particularly applies to the phenyl (93) [76] and the cydopropyl derivative [70], In those cases, it is advisable or necessary to prepare the dibromide in situ, that is, the dibromocarbene is liberated from tetrabro-momethane with methyllithium at -60 °C in the presence of the respective cyclopen-tene. Without workup, from the thus formed 6,6-dibromobicyclo[3.1.0]hexane, the 1,2-cyclohexadiene is then generated by addition of methyllithium at -30°C. 

The DMS method has not been employed yet for the generation of 117 and 123, since the dibromocarbene adducts of norbomadiene and norbornene rearrange under the usual conditions for the preparation [89]. However, they could be synthesized at -60 °C by taking advantage of tetrabromomethane and methyllithium as a source of the carbene [90] and could prove stable enough to serve as precursors of 117 and 123. On the other hand, the adducts of bromofluorocarbene to norborna-diene and norbornene having the fluorine atom in a cis-orientation should be isol-able at room temperature and hence be usable as stable precursors of 117 and 123. These variations ofthe DMS method were published on the occasion ofthe preparation of cycloadducts of l-oxa-2,3-cyclohexadiene (351) (Section 6.3.6) [35, 91], 1,2,4-cyclohexatriene (162) and 3d2-lJ-f-naphthalene (221) (Section 6.3.4) [35, 92],... 

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. 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

The ketone (48) can be obtained by Dieckmann cyclization, but this reaction failed for other isomers of (48) (72JCS(Pl)885). Friedel-Crafts cyclization has been used to obtain the N-tosyl ketone (49) (72JCS(Pl)2l3). Ring expansion reactions based on dibromocarbene additions have also been used to prepare benzo derivatives (72JCS(Pl)889). 

Although many recent improvements in the preparation of the Simmons Smith reagent might be helpful23 24, the authors of this chapter would recommend one to consider an alternative two-step cyclopropanation procedure, which includes cycloaddition of dichloro- or dibromocarbene to methylenecycloalkane25 followed by reductive dehalo-genation (equation l)26. The first reaction is usually carried under phase transfer conditions and presents a very simple and efficient procedure. Reduction of gem-dihalocyclopropanes with lithium in tert-butanol or with sodium in liquid ammonia usually proceeds without complications and with high yield. 

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... 

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>. 

Dibromocarbene.2 1-Bromobenzocyclobutene can be prepared conveniently by reaction of cycloheptatriene with dibromocarbene generated from bromoform with base in the presence of 18-crown-6. No reaction occurs in the absence of the crown ether. 

Prepared by the reaction of the corresponding alkene with dibromocarbene generated from CHBr3... 

While the nucleophilic addition of 1-lithio-l-bromocyclopropanes to ketones gave oxaspiropentanes, precursors of 1-donor substited vinylcyclopropane derivatives vide supra, Sect. 4.5, Eq. (28)), addition of n-BuLi at low temperature to 1,1-di-bromocyclopropane 199 (prepared in 75 % yield from the addition of dibromocarbene... 

Since dibromocarbene is more susceptible to hydrolysis than dichlorocarbene, dibro-mocarbene addition by the PTC method often gives the expected adducts in lower yields than those of the dichlorocarbene addition. Use of excess tribromomethane , execution of the reaction at ambient or lower temperature and addition of a small amount of alcohol have been recommended to improve the yields. Diiodocarbene has also been generated by PTC procedures and has been added to alkenes . However, the CHl3/r-BuOK method appears to be superior . It has also been pointed out that the Cl2 adducts are sometimes rather unstable when they are prepared by the PTC method, probably due to contamination of some sensitive byproducts . 

Again, much efficiency was gained by switching from alkoxy to siloxycyclopropanes . Dibromocarbene addition to silyl enol ethers generates cyclopropanes which open to a-bromo a,j5-unsaturated carbonyl compounds on thermolysis or treatment with acid in methanol (equation 137) . It has been shown that this homologation process also works for siloxycyclopropanes obtained by addition of other carbenoids (equation and that it is useful for terpene preparation . ... 

In an effort to expand the available synthetic tools for the preparation of various metacyclophanes and pyridinophanes, C.B. Reese and co-workers prepared [6](2,4)pyridinophane derivatives by treating 4,5,6,7,8,9-hexahydro-1H-cyclo-octa[it>]pyrrole with dichloro- and dibromocarbene respectively. The dihalocarbenes predominantly inserted into the most substituted (more electron rich) double bond of the pyrrole ring in modest to poor yields. 

---