Reduction hydrodehalogenation

Alonso, F., Beletskaya, I.P. and Yus, M. (2002) Metal-mediated reductive hydrodehalogenation of organic halides. Chem. Rev. 102,4009 4091. 

Reduction. Hydrodehalogenation of ArX and a-bromo ketones is accomplished by heating the halides with Pd(OAc)2, PhyP and K2CO3 in an alcohol at 100°. Enol triflates are defunctionalized by the Pd-catalyzed reduction with HCOOH - BuyN in DMF. ... 

During their comparative study on the use of various dansition-metal-TPPTS catalysts under biphasic reaction conditions. Aria and coworkers [40] showed that a cobalt-TPPTS complex could be employed for the arylation of acrylate 18 with iodobenzene (13) (Scheme 10.21). However, the selectivity of this transformation is significantly reduced due to a competitive reductive hydrodehalogenation of electrophile 13. 

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

Hydrodehalogenations of chloro-, bromo-, and iodobenzene were carried out individually as well as in competitive reactions. When the reactions were carried out separately, the reduction of chlorobenzene closely paralleled that of bromobenzene, whereas the reduction of iodobenzene was slower. When they were allowed to react competitively, the reduction was highly selective, and the reaction was delayed, but iodobenzene reacted first followed by bromobenzene and then chlorobenzene. 

Atom Transfer Atom Transfer (AT) takes place typically in the case of d7 complexes, which abstract the halogen atom from RX. The radical formed combines then with a second metal [193, 194]. A classical example of this mechanism is the hydrodehalogenation with cyanocobaltates(II) (see Section 18.2.1) [8, 9], but an analogous pathway was suggested recently for the Co(II) corrin-catalyzed dechlorination of CC14 in the presence of S2 /cysteine as reductant (Eqs. (11)—(12))... 

In outer-sphere SET reductions (e.g., in electrochemical dehalogenations), hydrogen abstraction by R leads to the product RH (i.e., no step related to (ii) is required to occur). Process (ii) follows generally the activation of the substrate in the proposed hydrodehalogenation cycles, but we know also of opposite examples [77, 82, 106, 112],... 

The preparation of OPDA from CNA requires two different catalytic steps, i.e. dechlorination and reduction. Both of these reactions requires hydrogen and are catalyzed by Group VIII metals. Supported palladium is considered as one of the most active catalyst both for hydrodehalogenation [2,3] and reduction of the nitro group [2]. 

Surface reactions (1) and (2] have been widely used to prepare silica supported metal complex catalysts [6]. The stabilization of ionic forms of palladium was strurigly increased by the presence of -OLi moiety. Simultaneous presence of -OLi and (-D) Pd surface species resulted in a very active hydrodehalogenation and reduction catalyst. 

Electroreduction [5b] (with chiral quat as the supporting electrolyte) has been compared with chemical reduction (NaBH4) in the presence of chiral quats for ketone (up to 28% op) and imine (up to 22% op) reductions [57,58], The reduction (NaBH4) of a chiral a,p-enone prostaglandin intermediate in the presence of ephedra-derived catalysts led to the formation of the enol with 70% de [59]. Other reductions with lower asymmetric inductions are noted for ketone [lli,24h,24i,47e,60], imine [5b,57], and hydrodehalogenation of a cyclic a,a-dichlo-roamide [61],... 

The issue became one of selective reduction of the 1,3 diene moiety, and various conditions for 1,4 hydrogen addition were examined. Unfortunately, all of these failed. For 43, complex, difficult to purify mixtures of various reduction products were generated under various hydrogenation and dissolving metal conditions (Scheme 21).42 The amines 46 and 47 had the additional problem of the readily reducible alkenyl iodide segment. Indeed, exposure to hydride reagents led to quite facile hydrodehalogenation, with products such as 52. Thus, it became... 

Hydrodehalogenation. Unlike slurries of LiAlH4 in ethereal solvents, clear solutions of the hydride in THF reduce alkyl halides to the corresponding alkanes rapidly and often in practically quantitative yield.8 However at least 1 molar equiv. of LiA 1H4 per RX is required (equation I). The rate of reduction for the halides is I > Br>Cl. The effect of the structure on the rate is in the order n-butyl bromide >... 

Hydrodehalogenation. Triethylborane (10 mole %) can initiate reduction of organic halides, particularly iodides or bromides, by Bu3SnH even at —78°. Alkenyl iodides are also reduced under these conditions. Aryl halides require room temperature or higher. Yields are comparable to those obtained by radical initiators. 

Electrochemical methods for the reduction of halides have also been used in synthesis. For example, in the presence of chromium(II) salts as catalysts, deoxynucleosides have been prepared in DMF solutions with the use of a platinum electrode32. a-Halocarbonyl compounds have also been hydrodehalogenated in this way63,64. It should be noted, however, that this method is not always successful and significant problems have been reported in some instances65. 

Samarium iodide catalyzes the reduction of halides in damp THF120-122 and yields may be significantly improved if HMPA is added to the reaction mixture121,123. a-Halocarbonyl compounds are readily hydrodehalogenated by the use of this and similar methods124-126. Bis-cyclopentadiene complexes of samarium catalyze the reduction of benzylic and ally-lie halides via an organosamarium complex intermediate127-129. This reaction may be controlled so that monodeuteration occurs if the reaction is carried out under dry aprotic conditions followed by addition of D20 (equation 12). 

Polyhaloacetic acids and their partially hydrodehalogenated products represent a second important family of herbicide-/pesticide-derived substrates. In their review on the environmental applications of industrial electrochemistry, Juttner and co-authors (Juttner et al. 2000) documented the electroreductive dechlorination of dichloroacetic acid (a by-product of monochloroacetic acid), a way to recover the valuable compound and avoid wastes. The electrochemical reduction of polychloro- and polybromo-derivatives was performed by Korshin and Jensen (2001) on Cu and Au cathodes. Complete dehalogenation was obtained for all substrates, but for monochloroacetic acid. To overcome the intrinsic poor reactivity of the monochloro-derivative the photoelectrochemical properties of a p-doped SiC electrode were investigated (Schnabel et al. 2001) however, the dehalogenation stopped at monochloroacetic acid. 

Cheng, H., Scott, K. and Christensen, P.A. (2003c) Hydrodehalogenation of 2,4-dibromophenol by electrochemical reduction. J. Appl. Electrochem. 33, 893-899. 

Reformatsky-type reactions and reductions. Enolates generated from a-bromoketones by reaction with BiClj-Al in an aqueous medium condense with various aldehydes to give J-hydroxy ketones." A modification of reaction conditions (BiClj-NaBH ) and in the absence of aldehydes leads to hydrodehalogenation of the haloketones. ... 

Hydrodehalogenation. The reduction of a-bromo-P-alkoxy esters by BUjSnH-ELB... 

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