Dibromocarbenes

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. 

The syn stereochemistry of dibromocarbene cycloaddition was demonstrated in experiments using as- and trans-2 butene Give the structure of the product obtained from addition of dibromocarbene to each alkene... 

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

Entries 1 and 2 in Scheme 2.9 are typical of concerted syn addition to alkene double bonds. On treatment with peroxyacetic acid, the Z-alkene affords the cis-oxirane, whereas the -alkene affords only the iraws-oxirane. Similarly, addition of dibromocarbene to Z-2-butene yields exclusively l,l-dibromo-cw-2,3-dimethylcyclopropane, whereas only 1,1-dibromo-/ra 5-2,3-dimethylcyclopropane is formed from -2-butene. There are also numerous stereospecific anti additions. Entiy 3 shows the anti stereochemistry typical of bromination of simple alkenes. 

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)... 

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. 

Treatment of dibromocarbene adduct (43) (Rji, = O) with aqueous methanol containing silver nitrate or perchlorate gives A-homo-estra-1 (10), 2,4a-triene-4,17-dione (45) in 21 % overall yield from the enol ether (42). The exact pathway is not known, but the first step may be formation of a bromo-homo-dienone facilitated by the methoxyl group, which then undergoes further loss of hydrogen bromide involving shift of a double bond by enolization. ... 

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. 

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. 

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. 

Dibenzoy loxy-7 a, 8a-methylen-5a,8a-androstan-6a-ol, 113 Dibromocarbene, 366, 367, 372 1,4-Dichloro-2-butyne, 68 Dichlorocarbene, 364 9a,l 1 -Dichloroandrosta-1,4-diene-3,17-dione, 150... 

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). 

The cyclopropane derivative 1, formed by the addition of dibromocarbene to 4-ethoxy-l-tosyl-1,2-dihydroquinoline, in refluxing pyridine undergoes ring expansion and aromatization to the 1/f-l-benzazepine 2.168... 

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... 

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. 

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