Dibromocarbene, reactions

A mixture of 0.20 mol of the adduct from cyclooctene and dibromocarbene (note 1) and 250 ml of dry diethyl ether was cooled to -65°C. A solution of 0.23 mol of ethyllithium (note 2) in 200 ml of diethyl ether (see Chapter II, Exp. 1) was added in 15 min with cooling between -60 and -50°C. The reaction was very exothermic (note 3). After the addition the cooling bath was removed and the temperature was allowed to rise to about -10°C and the reaction mixture was poured into 200 ml of ice-water. The aqueous layer was extracted twice with diethyl ether. After drying, the solvent was removed in a water-pump vacuum and the remaining liquid was distilled through a 40-cm Vigreux column. 1,2-Cyclononadiene, b.p. 62°C/22 mmHg, 1.5059, was obtained in 86 yield. 

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 1-ethoxycyclohexene with dibromocarbene gives less stable products which are difficult to process. The dibromocyclopropane (39)... 

A-Homo-estra-l 0),2,4c[-triene-4,ll-dione (45) by solvolysis of the l-keto dibromocarbene adduct (43a).A mixture of monoadduct (43a 0.25 g) and silver perchlorate (0.3 g) in aqueous acetone (1 4, 30 ml) is heated under reflux for 30 min. The reaction mixture is filtered to remove the precipi-... 

A-Homo-estra- Q>),2,Aa-triene-4, l-dione (45) from the l-ketal mono-dibromocarbene adduct (43b). A solution of monoadduct 17-ketal (43b 0.46 g) and dry pyridine (20 ml) is heated at reflux for 2 hr. After cooling the reaction mixture, the pyridine hydrobromide (0.1 g) is removed by filtration and the filtrate is concentrated under reduced pressure. The resultant gum is dissolved in ether and washed successively with water, ice-cold 4 N hydrochloric acid, water, 5% aqueous sodium bicarbonate solution, water, saturated salt solution and dried over anhydrous magnesium sulfate. Evaporation of the solvent at reduced pressure gives 3-bromo-4-methoxy-A-homo-estra-2,4,5(10)-trien-17-one (44 0.22 g) mp 158-162° after crystallization from ether. 

The use of sodium tribromoacetate as the dibromocarbene precursor has been investigated and found to provide the Ciamician-Dennstedt product in higher yield than the traditional alkoxide/alcohol reaction conditions. Deprotonation of bromoform with sodium ethoxide in ethanol and reaction of the resultant carbene with 6 provides quinoline 9 in 9% yield thermolysis of sodium tribromoacetate in the presence of 6 furnishes 9 in 20% yield (Scheme 8.3.3). 

Dibromocarbene CBr2 has been formed in inert matrices by two different procedures. The reaction of CBr4 with lithium atoms in an argon matrix as well as the irradiation (with vacuum UV light) of a matrix containing tribromomethane HCBrs led to the appearance in the IR spectra of two bands of CBt2 at 595 and 641 cm . These absorptions were assigned, respectively, to the symmetrical and asymmetrical C—Br stretches. 

Similarly, the ratio of dibromocarbene addition to CBr. substitution in the reaction of propyl bromide with tribromomethyl can be varied between 92 1 and 1 91, depending on whether a small and accessible quat or a bulky anion-activating quat is used (Dehmlow and... 

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 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. 

The properties of carbenes are also expected to depend very greatly on the electronic characteristics of substituents bound to the divalent carbon. For example, many carbenes with heteroatomic elements attached directly to the central carbon are calculated to have single ground states (Mueller et al., 1981). The early, pioneering work on the stereochemistry of the reaction of carbenes with olefins was done with dibromocarbene (Skell and Garner,... 

A related series of reactions derives from dibromocarbene adducts of olefins as in Eq. 28 32,33). Metal-halogen exchange at very low temperature produces the... 

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]. 

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. 

Cyclohexadiene, generated by the reaction of MeLi with the dibromide formed from cyclopentene and dibromocarbene, is so reactive as to add to styrene and 1,3-butadiene [19]. Hexahydronaphthalene 22 was formed by thermolysis of 21 and 21 via diradical 23 [20]. 

Alternative procedures for the generation of dichlorocarbene and dibromocarbene under phase-transfer catalysed conditions are also available. Where the reactive substrate is labile under basic conditions, the thermal decomposition of solid sodium trichloroacetate or bromoacetate under neutral conditions in an organic solvent is a valuable procedure [10-12], The decarboxylation is aided by the addition of a quaternary ammonium salt, which not only promotes dissolution of the trihaloacetate anion in the organic solvent, but also stabilizes the trihalomethyl anion. Under optimum reaction conditions, only a catalytic amount of the quaternary ammonium salt is required, as a large amount of the catalyst causes the rapid generation of the dichlorocarbene with resultant side reactions. 

Phase-transfer catalysed reaction of dibromocarbene generated from sodium tribromoacetate... 

Cycloocta-2,5-diene yields the mono adduct with dimethylvinylidene carbene ( 19%) [156]. With dichloro- and dibromocarbene, the syn- and cmh-bis-adducts are obtained in a ratio which favours the syn-isomer [55, 104] whereas, with bromochlorocarbene, the mono-adduct is reported to be the major product (55%) with only 9% of the bis-adduct [142]. In contrast, cyclo-octatetraene is converted into the mono-, syn-1,2 5,6-bis-, tris-, and tetra-adduct with dichlorocarbene depending on the reaction conditions [4, 17, 25, 55] and the 1,2 5,6-bis-adduct with... 

The tropone ring of cyclohepta[c]thiophen-6-one reacts preferentially at the C=C bond, instead of at the carbonyl group, with both dichloro- and dibromocarbene to give mono- and bis-adducts in relatively low yields (5-40%) [60]. Benzoquinones produce anfi-bis-insertion adducts in their reaction with chloroform (95%), or bromoform (57%), under basic conditions [29]. 

The reaction of 2- and 4-hydroxyadamantane-l-carboxylic esters with dibromo-carbene produces the corresponding 2- and 4-bromo derivatives (10-20%). Slow hydrolysis of the ester groups may also occur under the basic conditions. l-Acetyl-4-hydroxyadamantane yields 4-bromoadamantane-l -carboxylic acid (37%), as a result of a concomitant reaction with dibromocarbene and a haloform-type reaction [8]. 

Methylisoquinol-l-one behaves as an enamine with dichlorocarbene to produce the dichlorocyclopropane derivative (83%). The corresponding reaction with dibromocarbene produces a thermally labile compound, which is assumed to have an analogous structure. Rearrangement of the dichloro compound under basic conditions leads to the isoindole derivative (96%), whereas controlled thermolysis... 

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. 

Reaction of norbornane trithiolane (24) with both dichloro- and dibromocarbene afforded the trithiocarbonate (94), which upon further reaction with the dihalocarbene yielded the corresponding dithiocarbonate <90JOC1146>. The mechanism of formation of (94) from (24) is postulated to proceed by addition of the carbene to S-2 of the trithiolane, followed by a ring-expansion reduction sequence as outlined in Scheme 22. 

Acylation of limonene at the disubstituted double bond is favoured by a factor of 2.3 over reaction at the trisubstituted double bond using acetyl hexachloroan-timonate. Mixed alkylcuprate alkylation of tricarbonylcyclohexadienyliron salts has been used to synthesize the a-phellandrene tricarbonyliron complex. Dichlorocarbene addition to limonene in the presence of 1,4-diazabicy-clo[2,2,2]octane is almost 100% stereoselective at the trisubstituted double bond (no yield given) (cf. Vol. 6, p. 31) in contrast to dibromocarbene addition to carvone (Vol. 7, p. 34), dichlorocarbene addition to the carveols is not regio-specific. ... 

The double dibromocarbene adduct 120 obtained from 119 was shown to be predominantly the anti-form 73), and its reaction with (—)-sparteine-methyllithium reagent at —10 °C was reported to yield a mixture of 121 a of D2 symmetry, [a]D + 24.4° (hexane), and a small amount of the meso-form 122a, [a]D 0°. Both these isomers... 

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). 

Smaller cyclic olefins react with dibromocarbene to give the gem-dibromo-bicyclic systems, but these have not been reported to give allenes on reaction with methyl- or n-butyllithium. One possible reason may be the severe ring strain of cyclic allenes with less than seven carbon atoms. For example, Moore and Ward [14] found that 7,7-dibromobicyclo[4.1.0]heptane reacts with methyllithium to give bicyclic carbene intermediates which can be trapped with olefins (Eq. 4). 

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