Olefin dibromo

Dibromo adducts have been used for many years for purifying olefins. Reduction with zinc or iodide has been the traditional way of regenerating the olefin, although occasionally other reagents, ferrous chloride, for example, have been employed. Zinc is usually effective and may be used in acetic acid in favorable cases. Milder conditions are necessary if sensitive groups are present (ref. 185, p. 51). A well known application of the protective function... 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

The addition proceeds most smoothly with highly functionalized (more polar) steroids as seen in examples by Bernstein and others. The polar reaction conditions pose solubility problems for lipophilic androstane, cholestane and pregnane derivatives. Improved yields can be obtained in some cases by using dimethyl sulfoxide or t-butanol " as solvents and by using sodium A-bromobenzenesulfonamide or l,3-dibromo-5,5-dimethyl hydantoin (available from Arapahoe Chemicals) as a source of positive bromine. The addition of bromo acetate and bromo formate to steroid olefins has been studied to a limited extent. ... 

Additions of the halogen fluorides to unsaturated steroids [62, 95, 96, 97, 98, 99] and carbohydrates [62, 75] are well known Typical reagent combinations include l,3-dibromo-5,5-dimethylhydantoin (DBH) or the Af-halosuccinimides with hydrogen fluoride Reversal of the expected regiochemistry can be observed with certain steroidal olefins [JOO, 101] (equation 7)... 

The stereochemistry of addition reactions of Br2 to olefins is difficult to control. For example, the reaction of ( )-stilbene (1) with Br2 in CH2CI2 gives a 84 16 mixture of meso- (2) and rac-l,2-dibromo-l,2-diphenylethane (3) in 98%... 

Another instructive example is provided by a series of a-phenyl-a,P-dibromo-phosphonates 170, 171, 172. While the phosphonate dianion 170 fragments instantaneously at room temperature with formation of the POf ion (see also Sect. 4.1.3), the analogous reaction of the phosphonic monoester anion 171 leading to methyl metaphosphate 151 requires more drastic conditions and is at least 1000 times slower the diester 172 is essentially stable under the reaction conditions described for 171 addition of triethylamine leads to slow demethylation H0). The behavior of 171 contrasts with that of simple (3-haloalkylphosphonic monoesters which merely eliminate HHal on treatment with bases94. Thus it is the possibility of formation of a phenyl-conjugated double bond which supports the fragmentation of 171 to olefin + 151. 

Low intensity ultrasound has also been applied to the Simmons-Smith cyclopropanation of olefins with zinc-diiodomethane (237). This reaction normally will not occur without activation of mossy Zn with I2 or Li, and was difficult to scale-up due to delayed initiation. Yields upon sonication are nearly quantitative, activation of the Zn is unnecessary, and no delayed exotherms are observed. In reactions with another class of organic dihalides, ultrasonic irradiation of Zn with a,a -dibromo-o-xylene has proved a facile way to generate an o-xylylene-like species [Eq. (49)],... 

When zinc and a,a -dibromo-o-xylene are irradiated with ultrasonic waves at room temperature, synthetically useful quantities of the reactive intermediate, o xylylene, are generated which can be treated in situ with activated olefins to give good yields of cycloaddition products(30). Chew and Ferrier used this methodolgy to generate a-xylylene for the synthesis of optically pure functionalized hexahydroanthracenes(31). The reaction with lithium takes a different course(19). Rather than generate the -xylylene intermediate, ionic species are produced. The two fates of a, a -dibromo-o-xylene are presented in the scheme below ... 

Syntheses of the 1,2- and the 3,4-dihydrodiols of MBA via Methods II and IV have been described (74). The 1,2- and 3,4-diol dibenzoates of 1,2,3,4-tetrahydro-MBA prepared from MBA via the Li/-NH reduction route were readily separable by crystallization. Introduction of the olefinic bond into the 1,2-position of the 3,4-diol dibenzoate by the usual bromination-dehydrobromination procedure was complicated by the greater facility of bromination by NBS on the methyl group than the 1-position. This problem was solved (Figure 14) by allowing bromination to proceed to the dibromo stage, followed by selective reduction of the bromomethyl group with NaBH in diglyme. The monobromo derivative underwent dehydrobromination... 

The power of the HR-MAS method for on-resin analysis has been further underscored in the development of new linkers. Without this method, only indirect analytical data after removal from the resin was available. Direct assessment of the resin-bound linker greatly facilitated the introduction of a 4,5-dibromo octane- 1,8-diol linker that was converted into an octane-1,8-diol linker cleavable by olefin metathesis at the end of the synthesis.6 The disappearance and reappearance of the olefinic protons as well as the growing oligosaccharide chain was clearly visible in the H spectrum (Fig. 8.7).7... 

The electrochemical reduction of 2,2-dibromo-l,3-diones in the presence of various olefins (styrene, indene) affords the [3 + 2] cycloadducts, 2,3-dihydrofuran derivatives in moderate to good yields (37-94%) (Scheme 84) [124]. 

The ozonolysis reaction, followed by reductive workup with sulfur dioxide, as described in Part A of the present procedure, illustrates a general method which has been developed for the preparation of acetals. Application of the procedure is illustrated by conversion of the following olefins in alcoholic solution to the corresponding acetals (1) l-chloro-4-(o-nitrophenyl)-2-butene to o-nitrophenylacetaldehyde dimethyl acetal in 84% yield (2) l,4-dibromo-2-butene tobromoacetaldehyde dimethyl acetal in 67% yield (3) 3-butenoic acid to malonaldehydic acid diethyl acetal ethyl ester in 61% yield (4) cyclopentadiene to malonaldehyde bis(diethyl acetal) in 48% yield and (5)... 

Reduction of the 19-tosylates (28) and (30) with lithium aluminium hydride gave the 5,10-methano-compound (29) and the alcohol (31) respectively. Vicinal dibromo-steroids are converted readily into olefins when treated with silver salts in the presence of amines. Diaxial bromohydrins are converted into the epoxides under these conditions. 

Several acetylenic derivatives are prepared by dehydrohalogenation of vicinal dibromo compounds, which are obtained by adding bromine to olefinic compounds. 

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). 

Skattebol [12], on the other hand, could not detect such carbene intermediates by their addition product (spiropentanes) to olefins using gem-dibromo-cyclopropanes derived from noncyclic olefins. 

Elimination of HBr from meso-l,2-dibromo-l,2-diphenylethane gave c -2-bromostil-bene, while the ( + ) or (-) isomer gave the trans olefin. This stereospecific result, which... 

A full account5 describes the enantioselective carbonyl-ene reaction of glyoxylate esters catalyzed by a binaphthol-derived chiral titanium complex that is potentially useful for the asymmetric synthesis of a-hydroxy esters of biological and synthetic importance.6 The present procedure is applicable to a variety of 1,1-disubstituted olefins to provide ene products in extremely high enantiomeric purity by the judicious choice of the dichloro or dibromo chiral catalyst (see Table). In certain glyoxylate-ene reactions involving removal of a methyl hydrogen, the dichloro catalyst... 

Treatment of 12A ,3 R -2,3-dibromo-3-methylpcntanc with Zn gives (Z)-3-methyl-2-pentene as the only product. What is the stereochemistry of die reduction Based on this result could the reaction of a trails olefin with Bi 2 and then Zn be used as a way to convert trails olefins to cis olefins ... 

The bromonium ion tribromide salt of 3390,91 (as well as the triflate salt92) transfers Br2 to other olefins by irreversible reactions forming dibromo derivatives. 

Bromonium ion is generated by reactions of both erythro (38) and threo 2-bromo-1,2-diphenylethane with hydrogen bromide95 (in 1,2-dichloroethane and in chloroform) as illustrated by Scheme 15. Stilbene (39) and the 1,2-dibromo derivative are the main reaction products. Product distribution and kinetic investigations on the bromination of stilbenes clearly confirm the reversibility of the bromonium/bromide formation in bromination of olefins, through an olefin/bromine CT complex. 

Furthermore, in the addition of bromine to 44 (in 1,2-dichloroethane, chloroform or carbon tetrachloride, see Scheme 19) to obtain the trans dibromo derivative99 (47), which is found to be in two main conformers100, the formation of the bromonium ion (46) from 5//-dibenz[ >,/]azepine-5-carbonyl chloride (44) is a reversible step. The formation of the bromonium ion (46) follows the association of reagents in the CT complex (45). 49 reacts with hydrogen bromide through the protonated 48, forming" both the dibromo derivative 47 and the olefin 44. The bromonium ion (46) is the probable intermediate... 

Y may also be the leaving group in the monomolecular formation of substituted carbocations (60), to yield the saturated derivative 63 (and 63 may equal 62, if Z = Y), as usually indicated in Sjyl reactions. If Z = E = Br, in the dibromo derivative 63, the cation 60 has the same form as that obtained by the bromination of olefins. 

Another annellation reaction starts from a,a -dibromo-o-xylene, an activated olefin and zinc.63 This reaction, according to the authors proceeds by a Diels-Alder cycloaddition via the o-xylylene (Scheme 15.10), and was employed in carbohydrate chemistry to prepare anthracyclinones analogues.64 No reaction occurs without sonication. Instead of a cycloaddition, another explanation can be postulated, consisting first of addition of a mono-organozinc reagent to the activated olefin, followed by alkylation of the resulting enolate by the second benzylic bromide. 

Beside NXS, other effective electrophiles are -butylhypochlorite (combined with BF3)498, elementary chlorine (with SF4-HF)499 and KBr03 (with aqueous HF)500. A recent breakthrough in this area is the application of SiF4 (combined with Ar,Ar -dibromo-5,5 -dimethylhydantoin, DBDMH) for bromofluorination of olefins in a highly regio-, stereo-and chemoselective manner501,502. 

Electrochemical cyclopropanation of alkenes occurs using dibromomethanes at a sacrificial zinc electrode in a CH2C12/DMF mixture with a one compartment cell (equation 65). Yields using more than twenty isolated and conjugated olefins were generally good (30 to 70%)98. Benzal halides give only poor yields in the same reaction, but 2,2-dibromo-propane leads to the equivalent gem-dimethylcyclopropanes in fair yields. The method represents a useful alternative to other methods of cyclopropanation of olefins such as the Simmons-Smith reaction. 

---