Olefinic alcohols reduction

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. 

Compounds 16 and 19 each deliver the expected six alcohols after reduction of the primarily formed hydroperoxide mixtures as a result of an oxygen attack on the trisubstituted A1 double bonds of these molecules. The ratio of tertiary/secondary hydroperoxides (or alcohols) is about 44 56, as has also been found with 1-methylcyclohexene (30)13S while open-chain olefins such as trimethylethylene (S3), 1,1-dimethyl-2-ethylethylene (id), 2,6-dimethyl-2-octene (39), myrcene (42), / -citronellol (45), linalool (48), and l,l-dimethyl-2-benzylethylene (51) give ratios of tertiary/secondary hydroperoxides between 54 46 and 60 40.104-1 7 7 1 79 The slight deviations from 1 1 ratios in all these cases are probably due to stereochemical rather than electronic effects exerted by the olefins on the reaction with oxygen. 

The discovery by the recent Nobel-laureate, Ryoji Noyori, of asymmetric hydrogenation of simple ketones to alcohols catalyzed by raras-RuCl2[(S)-binap][(S,S)-dpen] (binap = [l,l -binaphthalene-2,2/-diyl-bis(diphenylphosphane)] dpen = diphenylethylenediamine) is remarkable in several respects (91). The reaction is quantitative within hours, gives enantiomeric excesses (ee) up to 99%, shows high chemoselecti-vity for carbonyl over olefin reduction, and the substrate-to-catalyst ratio is >100,000. Moreover, the non-classical metal-ligand bifunctional catalytic cycle is mechanistically novel and involves heterolytic... 

The synthesis of the 1,6-linked ester was straightforward as outlined in Scheme 6. We were able to convert alcohol 23 to aldehyde 24 using Swern oxidation conditions. Wittig reaction was followed by olefin reduction and saponification to bring the sequence as far as 26. Esterification of 26 with olefin alcohol la, mediated by DCC, then afforded the target ester 27 in good overall yield (13). 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

The classification is unaffected by allylic, vinylic, or acetylenic unsaturation appearing in both starting material and product, or by increases or decreases in the length of carbon chains for example, the reactions t-BuOH - f-BuCOOH, PhCHaOH - PhCOOH, and PhCH=CHCH20H PhCH=CHCOOH would all be considered as preparations of carboxylic acids from alcohols. Conjugate reduction and alkylation of unsaturated ketones, aldehydes, esters, acids, and nitriles have been placed in category 74 (alkyls from olefins). 

The use of secondary alcohols as reductants for DODH was first reported by Elhnan, Bergman, and coworkers, who employed Re-carbonyl compounds, e.g., Re2(CO)io, as pre-catalysts under aerobic conditions (Scheme 16) [36]. Optimized conditions used the glycol substrate with the mono-alcohol as the solvent, e.g., 3-octanol, at 150-175°C, with 1-2.5 mol% Re2(CO)io and TsOH as a co-catalyst (2-5 mol%). Good yields of the olefin (50-84%) were obtained with representative glycols. The sy -3,4-decanediol was converted highly selectively to trans-3-decene, implicating a sy -eUmination process in the diol to olefin conversion (Scheme 17). Erythritol was converted moderately efficiently to 2,5-dihydrofuran (62% yield), presumably the result of initial 1,4-diol dehydration followed by DODH of the THF-diol intermediate. The nature of the active catalyst was unknown at the time, but was speculated to be an oxidized Re species. 

Terminal acetylenes are often used as precursors to the E- and Z-olefins. A typical synthesis is that reported by Schwarz and Waters (187) (Scheme 80). The alkali metal salt of the acetylene is coupled with an appropriate alkyl halide to give the acetylenic tetrahydropyranyl ether (444). Sodium in liquid ammonia reduction of the ether stereo-specifically affords.pure -olefins, which can be hydrolyzed to an alcohol and then acetylated. For Z-isomers, the protecting group must first be removed and the alcohol acetylated. Reduction over quinoline-poisoned... 

Enzyme-catalyzed hydrogenations have a long history as an alternative for stereoselective olefin reduction [12, 72). Selected illustrative examples of enzymatic olefin reductions are depicted below. In an elegant series of studies by scientists at Hoffmann-La Roche, it was found that baker s yeast effects the reduction of unsaturated ester 96 (Scheme 8.10) [73]. Unsaturated alcohol 99 was selectively transformed into lactone 100 by use of the fungus Geotrichum candidum. The optically pure substituted lactones, 98 and 100, were subsequently utilized in a synthesis of a-tocopherol (vitamin E 101) [74]. 

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

All lation. Thiophenes can be alkylated in the 2-position using alkyl halides, alcohols, and olefins. Choice of catalyst is important the weaker Friedel-Crafts catalysts, eg, ZnCl2 and SnCl, are preferred. It is often preferable to use the more readily accompHshed acylation reactions of thiophene to give the required alkyl derivatives on reduction. Alternatively, metalation or Grignard reactions, on halothiophenes or halomethylthiophenes, can be utilized. 

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