1.2- Dibromoethane ester

Dibromoethane, 1-bromononane (98%), 4-chlorobenzoic acid methyl ester (99%), and Fe(acac)3 (99.9%) were purchased from Aldrich Chemical Co. and used as received. 

Certain esters have often been employed in attempts to confer organ selectivity to molecules possessing carboxyl functions. Thus, for example, treatment of piperidinecarboxylic acid 76 with N-hydroxysuccinimide and DCC affords the ester 77. In a convergent synthesis, the anion from diphenylacetonitrile (78) is alkylated with dibromoethane to afford the bromide 79. Alkylation of the piperidine derivative 77 with that halide 79 gives the anti-diarrheal agent difenoximide (80). The same sequence starting with the phenoxyethyl ester 81 gives fetoxylate (82). 

Alkylisoselenocyanates 339 are also used in the synthesis of 2-methylidene-l,3-selenazolidine derivatives <06T3344>. Nucleophilic addition of the carbanion derived from malononitrile 347 to 339 leads to an intermediate kcten-A, -acetal 348, which reacts with 2-haloacetate ester and 1,2-dibromoethane to provide l,3-selenazolidin-4-ones 350 and 1,3-selenazolidines 352, respectively. 

RCu(CN)ZnI.u These new copper reagents are prepared by reaction of primary or secondary iodides with zinc that has been activated with 1,2-dibromoethane and chlorotrimethylsilane. The resulting organozinc compounds are then allowed to react with the THF-soluble CuCN-2LiCl (equation I). Because of the mild conditions, these new reagents can be prepared from iodides containing keto, ester, and nitrile groups. 

Reaction of malonic esters with 1,2-dibromoethane and 1,3-dibromopropane under liquiddiquid two-phase conditions produces the cyclopropane- and cyclobutane- 1,1 -dicarboxyl ic esters, which can be hydrolysed under the basic conditions (6.2.24.C) [e.g. 75, 109] and decarboxylated to give the monocarboxylic acid [e.g. 109]. 

A sequence starting with methylenebis[phosphonic acid] tetraester carbanions, and consisting of alkylation with an appropriate 3-substituted-propyl halide, side-chain modification, and cyclization, ultimately affords the tetraalkyl esters of cyclopropane-1,l-bis[phosphonic acid], and from which the free acid has been obtained.The reaction between 1,2-dibromoethane and ethyl (diethoxyphosphinyl) acetate or ethyl... 

The addition of LiCl to zinc dust (activated with 1,2-dibromoethane plus TMSCl) has a dramatic effect on the reaction rates. The reaction is successful with iodo-heterocycles and some activated bromo-compounds, such as the furan ester shown below. 

Bromine source. Some ester enolates form a-bromoesters instead of the bro-moethylated products on reaction with 1,2-dibromoethane. 

The failure to obtain an ester of (2-bromoethyl)phosphonic acid from trimethyl phosphite and 1,2-dibromoethane is due partly to competitive reaction between the evolved methyl bromide and the phosphite and partly to debromination. On the other hand, the use of higher trialkyl phosphites is more successful, although it still becomes necessary... 

Only a trace ofp-tolyl phenyl ketone was formed when the simple thiol ester 35a was treated with phenylboronic acid in the presence of Nal under similar reaction conditions. Although less efficient than the intramolecular system, intermolecular alkylative activation was also feasible. For example, 35b was transformed into undecyl phenyl ketone (48%) when treated with PhB(OH)2 and 1,4-dibromobutane in the presence of 6 mol% of34,30% Nal, and 4.1 equiv of K2CO3 in DMF at 90 °C for 18 h. Use of 1,2-dibromoethane and 1-bromo-hexane in place of 1,4-dibromobutane did not promote this reaction. 

Analogous treatment of the unsaturated ester 207 using 1,1-dibromoethane in this case cleanly produced the dihydropyran 208 in high yield on a gram scale (Scheme 2.73) [41bj. Cydic enol ether 208 was then efficiently advanced to a spiroacetal, which corresponds to the core structure of the bioactive polyketide spirofungin A. 

A soln. of startg. benzyl bromide in THF added slowly to cut zinc foil activated with 1,2-dibromoethane at 0°, after stirring for 2-3 h at 5° the soln. added to CuCN and LiCl in THF at —70°, warmed to —20° for 5 min, re-cooled to —70°, a soln. of allyl bromide in THF added, the mixture warmed slowly to 0°, and worked up after 5 min - product. Y 96%. The method is mild, and formation of 1,2-diarylalkane crosscoupling products minimal functional groups such as esters, nitriles, halides, and ketones are tolerated. F.e. and electrophiles s. S.C. Berk et al., J. Org. Chem. 53, 5789-91 (1988). 

Enolates of ketones and esters can he brominated hy treatment with bromine (eq 20), as can the anions of terminal alkynes. The high reactivity of bromine, however, is sometimes a problem milder sources of electrophihc bromine (such as 1,2-dibromoethane) are occasionally used in its place. 

---