The reduction of vicinal dihalides

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 

It is not possible to use zinc for reductive debromination in the presence of (x-halo ketones and for transformations involving these intermediates, sodium iodide has been used. ° In some instances, e.g. 5,6-dihalo-3-ketones, iodide does not always give a completely halogen-free product, and zinc does not give clean debromination. The use of chromous chloride has proved advantageous in such cases and is the reagent of choice for vicinal dichlorides, which are inert to iodide  

The ability of chromous ion to efficiently reduce a-halo ketone impurities may be the reason for superior results. 

Lithium aluminum hydride has also been shown to reduce vicinal dibromides to olefins efficiently, but the scope is limited by the reactivity of this reagent towards many functional groups. 

The stereochemistry of formation and rearrangement of vicinal dihaUdes has been elucidated, chiefly by Barton s group. Trans diaxial addition occurs but the product may then equilibrate with the more stable 

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Similar kinetics are exhibited by the reduction of vicinal dihalides by Cr(II) , which proceeds 10-40 times faster than that of the allylic halides. Such activation by a second halogen atom suggests a neighbouring group effect, viz. 

Casanova and Rogers [59] as well as Fry [69] postulate that the reduction of vicinal dihalides is a concerted process in which both carbon-halogen bonds are partially cleaved as a carbon-carbon double bond starts to form. Nonelectrochemical evidence [70] suggests that a vicinal dihalide undergoes one-electron reduction to a radical anion, which loses the first halide ion to form a neutral radical, after which the neutral radical accepts an electron to become a carbanion that eliminates the second halide ion to yield an olefin. From a study of the behavior of meso- and c/,/-l,2-dibromo-l,2-diphenylethane, Fawell and coworkers [71,72] concluded that the reduction of vicinal dihalides is a stepwise process. Andrieux and coworkers [73] have examined the reductive elimination of vicinal dibromides at carbon in MeCN. 

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. ... 

Two examples illustrating this approach, will be discussed one is the electrochemical reduction of vicinal dihalides leading to the corresponding olefins and the second (me is the electrcx emical reducricn of carixm dioxide. In both cases, two advantages are expected from chemical (inner-sphere) catalysis over redox (outer-sphere) catalysis, namely the enhancement of efficiency for catalysts having the same standard potential and better opportunities to achieve selective reactions. 

The interrelation among homovalent and ambivalent reactions on the five-atom pericycles (equations 3 and 4) was described and given a similar but more complex nomenclature reflecting their lower symmetry. Homovalent pericycles include the amine oxide eliminations in Scheme 1 and the sulfoxide-sulfenate rearrangement in Scheme 2, with the shells in boldface as in Figure 1. For the ambivalent reactions of equation (4) the ambivalent atom X is often not carbon, as seen in Scheme 3 for a metal reduction of vicinal dihalides (which may not be pericyclic) Scheme 3 has an unchanging shell of only one bond. The cycloaddition of sulfur dioxide to dienes in Scheme 4 is another with a three-bond shell. Numerous examples were quoted, again many not confirmed as pericyclic. ... 

The reductive elimination of vicinal dihalides has been accomplished by using many reagents, including the use of aqueous media.16 An interesting method is the reductive elimination of vicinal dihalides by an electrochemical method using vitamin Bi2 in a water-in-oil microemulsion (Eq. 6.8).17... 

Reduction is probably stepwise when 0 = 90°. (The plot in fact resembles very closely in form the familiar Karplus plot of the magnitude of vicinal proton-proton coupling constants as a function of 0 48>. The half-wave potentials of 43 and 44 are representative the half-wave potential of a related monohalide (45) is given for reference 46>. These investigators did not examine the products of electrochemical reduction of the vicinal dihalides which they studied. If reduction is concerted, the products should... 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

This chapter surveys the reduction of saturated alkyl halides to alkanes. Reductive -eliminations of vicinal dihalides to alkenes are also described briefly. Reduction of vinyl and aryl halides is covered in this volume. Chapter 4.5 hydrogenolysis of allyl and benzyl halides is covered in this volume. Chapter 4.7, and reduction of a-halo-substituted carbonyl compounds CX—CO to carbonyl compounds CH—CO is covered in this volume. Chapter 4.8. 

Sodium borohydride, a representative borohydride reagent, behaves as an effective source of nucleophilic hydride in an aprotic polar solvent, such as DMSO, sulfolane, HMPA, DMF or diglyme, and is used for the reduction of alkyl halides. As shown in Table 3, primary and secondary iodides, bromides and chlorides are converted to hydrocarbons at temperatures between 25 and 100 C using sodium borohydride. Vicinal dihalides, such as 1,2-dibromooctane, are smoothly converted to the corresponding saturated hydrocarbons, in contrast to the reductions using LiAlH4 or low-valent metal salts, which predominantly afford alkenes. 

The mechanism is shown in Scheme 10 and involves reductive elimination of bromide anions to give quinodimethane intermediates (19) that polymerize. In the case of o-quinodimethane, their intermediacy has been proved by trapping via Diels-Alder reaction with a reactive maleic anhydride derivative [63, 64]. The second elimination step is analogous to the cathodic eliinination of vicinal dihalides, which is known to give tra s-alkenes [65]. 

There is on the other hand a great deal of evidence showing that the electrochemical reduction of 1,2-dihalides to olefins can occur via a concerted pathway, i.e., via a transition state (39) in which both carbon-halogen bonds are partially broken and the carbon-carbon double bond is partially formed. An important, indeed critical, point of evidence supporting the conclusion that reduction is concerted lies in the remarkable ease with which vicinal dihalides are reduced. For example, the half-wave potentials of ethyl bromide and 1,2-dibromoethane are -2.08 V and -1.52 V (vs. s.c.e.), respectively 15 >46) those of ethyl iodide and /J-chloroethyl iodide are -1.6 V and -0.9 V, respectively 47). These very large differences must reflect the lower energy of delocalized transition state 39 relative to the transition state for reduction of an alkyl monohalide. 

Open-chain vicinal dihalides are apparently reduced conceitedly via a conformation in which the two halogen atoms are anti to each other. This conclusion is based upon the fact that meso isomers of structures 47 ait generally more easily reduced than the dl isomers, presumably because steric repulsions are less for meso than for dl in the transition state for electron transfer. The stereochemistry of the products of reduction of simple open chain vicinal di-... 

Cathodic elimination can remove a variety of vicinal nucleophiles (X = Br [140], Cl [141], S-C6H5 [142], or oxalate [143]) to form a double bond. Controlled potential cathodic reduction allows the selective elimination of vic-dihalides depending on the degree of alkylation [144]. Chemically, these reductions are more limited in scope they can be conducted with 1 in DMF, with Zn, Mg, or Cr + [145]. 

Vic -dihalides exhibit a single 2e polarographic wave, while nonvicinal ( >3) dibromides normally are reduced in two separate 2e transfers. The reduction potential of the dihalides is more positive (A E +0,4 to +0,7 V) than that of the monohalides 3,6>321 3221. A plot of the half-wave potentials of 21 vicinal dibromides versus the dihedral angle,, between the two C-Br bonds exhibits maxima (most positiveE t j2) for y = 180 0 (anti-periplanar conformation) and i/) = 0°... 

Olefin inversion via epoxides is reported by two groups of workers. One sequence involves epoxidation with peracid, which occurs with retention of stereochemistry, followed by deoxygenation with hexamethyldisilane and potassium methoxide in HMPT at 65 °C. The alternative procedure utilizes reaction of the episode with triphenylphosphine dihalides to give vicinal dihalides. Zinc reduction of the dihalides is specifically trans, and thus the sequence epoxidation-bromination-reduction gives overall inversion of olefin configuration. ... 

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