Carboxylic acids, olefinic reduction

The electrochemical incorporation of CO2 into perfluoroalkyl derivatives has been explored in the case of (perfluoroalkyl)alkyl iodides and (perfluoroalkyl)alkenes, with an electrochemical system based on the use of consumable anodes combined with organometallic catalysis by nickel complexes. Iodide derivatives have been functionalized to the corresponding carboxylic acids by reductive carboxylation. Interesting and new results have been obtained from the fixation of CO2 into perfluoroalkyl olefins. Good yields of carboxylic acids could be reached by a carefull control of the reaction conditions and of the nature of the catalytic system. The main carboxylic acids are derived from the incorporation of carbon dioxide with a double bond migration and loss of one fluorine atom from the CF2 in a position of the double bond. 

The less hindered f/ans-olefins may be obtained by reduction with lithium or sodium metal in liquid ammonia or amine solvents (Birch reduction). This reagent, however, attacks most polar functional groups (except for carboxylic acids R.E.A. Dear, 1963 J. Fried, 1968), and their protection is necessary (see section 2.6). 

The carboxylic acid 150 (Scheme 10.15) was prepared from commercial (-)-carvone (68) via a chemoselective reduction of the terminal olefin using tris... 

The bis-DIOP complex HRh[(+)-DIOP]2 has been used under mild conditions for catalytic asymmetric hydrogenation of several prochiral olefinic carboxylic acids (273-275). Optical yields for reduction of N-acetamidoacrylic acid (56% ee) and atropic acid (37% ee) are much lower than those obtained using the mono-DIOP catalysts (10, II, 225). The rates in the bis-DIOP systems, however, are much slower, and the hydrogenations are complicated by slow formation of the cationic complex Rh(DIOP)2+ (271, 273, 274) through reaction of the starting hydride with protons from the substrate under H2 the cationic dihydride is maintained [cf. Eq. (25)] ... 

In a related study, the oxidation-reduction sequence was carried out in the presence of an olefin (Scheme 21). Two products were formed. The major product resulted from the net reduction of the carboxylic acid to an aldehyde. The minor product resulted from trapping of the radical anion intermediate generated from the reduction reaction by the olefin. It should be noted that, in the absence of a trapping group, the acid can be selectively reduced to the aldehyde without any over-reduction. Although not in the scope of this review, this is a very useful transformation in its own right [35]. At this time, the yields of the cyclized products from the cyclization reaction of the radical anion with the olefin remain low. 

The CD fragment 1s synthesized starting with resolved bicyclic acid 129. Sequential catalytic hydrogenation and reduction with sodium borohydride leads to the reduced hydroxy acid 1. The carboxylic acid function is then converted to the methyl ketone by treatment with methyl-lithium and the alcohol is converted to the mesylate. Elimination of the latter group with base leads to the conjugated olefin 133. Catalytic reduction followed by equilibration of the ketone in base leads to the saturated methyl ketone 134. Treatment of that intermediate with peracid leads to scission of the ketone by Bayer Villiger reaction to afford acetate 135. The t-butyl protecting... 

Oxidation of olefins 9-27 Oxidation of alkynes 9-65 Reductive condensation of aromatic carboxylic acids... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

A study of the photoaddition of formamide to olefins was undertaken with the aim of finding a new process for converting olefins to higher amides and possibly further to amines by reduction or by the use of the Hofmann rearrangement. Since hydrolysis of the amides to the corresponding carboxylic acids can be effected by standard procedures, this reaction provides a new process for carboxylation of olefins under mild conditions at room temperature. A similar reaction has been shown to take place in a thermal process, using peroxides as initiators (60). 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1,1-difluoro olefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a l,3-dichloro-2-propanol derivative and ethyl-... 

Lipstatin (58), comprised of a 3,5-dihydroxy-2-hexyl hexadeca-7,9-dienoic acid with cyclization of the hydroxy group at C-3 with the carboxylic acid to form a P-lactone and esterification of the hydroxy group at C-5 with a A-formyl leucine, was isolated from Streptomyces toxytricini. It inhibits gastric and pancreatic lipase and blocks intestinal absorption of lipids (40, 41). Reduction of the olefins led to the synthesis of tetrahydrolipstatin, which was approved in 1999 as Xenical (59) for the treatment of obesity (42-44). 

Hydrocarbon oxidations are also possible at Pt electrodes at elevated temperatures, for example, 250°C in phosphoric acid (92). For aliphatic hydrocarbons it is of some special interest that electrochemical oxidations all the way to CO2 and H2O or H can be achieved at Pt (61). Oxidation of olefins is also possible, but under some conditions, for example, at Pd, aldehydes are a product (62, 93). The fact that aliphatic hydrocarbons can be oxidized largely to CO2 plus H2O indicates that the intermediate stages in such multielectron oxidations must proceed successively on the electrode surface with a series of intermediates remaining chemisorbed, as otherwise aldehydes or carboxylic acids would appear in solution, which is not normally observed. Interesting attempts were made by Bruckenstein (94) to identify some of the intermediates by reductive desorption from porous electrodes into a mass spectrometer. 

Although the cross-reductive coupling between different activated olefins could also afford the formation of stereosiomeric (threo and erythro) products, no study has been reported so far. However, it was reported that acrylates gave almost predominantly the corresponding rrawj-unsaturated carboxylic acids (V) by reduction in the presence of butadiene [Eq. (5)] [55]. This reaction may be valuable from the aspect of stereoselective synthesis. 

The electrocarbojQ lation of (perfluoroalkyl)iodoalkene 2 (E/Z 90 10) under 1 atm of CO2 (Mg/Ni electrodes, Ni-bipy catalytic system) allowed the formation of unsaturated carboxylic acid 6 in 10% yield (E/Z 85 15) (eq. 2). Olefin 3, issued from the reduction of the halide function by protodehalogenation, was obtained in 30% together with 25% of unreacted starting material. 

T he reaction of ozone with olefins usually results in cleavage of the double bond and the formation of aldehydes, ketones, and/or carboxylic acids, depending upon the reaction conditions and the structures involved. For aldehydes, the intermediate ozonides are ordinarily treated with a mild reducing agent—for example, hydrogen or zinc—or subjected to neutral hydrolysis. Yields in excess of 70% are exceptional for the reduction methods, while hydrolysis gives considerably lower yields. 

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