Carboxylic acids, from acyl alkenes

The reaction between carbonium ions and carbon monoxide affording oxocarbonium ions (acyl cations) is a key step in the well-known Koch reaction for making carboxylic acids from alkenes, carbon monoxide and water ... 

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... 

The Koch-Haaf reaction397 for the preparation of carboxylic acids from alkenes uses formic acid or carbon monoxide in strongly acidic solutions. The reaction between carbocations and carbon monoxide affording oxo-carbenium ions (acyl cations) is a... 

As with carboxylic acids obtained by palladium hydroxycarbonylation, their derivatives esters, amides, anhydrides and acyl halides are synthesized from alkenes, CO and HX (X = OR, NR2 etc.). The Pd-catalyzed methoxycarbonylation is one of the most studied reactions among this type of catalyzed carbonylations and has been reviewed and included in reports of homogeneous catalysis.625, 26 The methoxycarbonylation has been applied to many different substrates to obtain intermediates in organic syntheses as well as specific products. For instance, the reaction has been applied for methoxycarbonylation of alkynes666 Highly efficient homogeneous Pd cationic catalysts have been reported and the methoxycarbonylation of alkynes has been used to develop economically attractive and environmentally benign process for the production of methyl... 

In fluorosulfonic acid the anodic oxidation of cyclohexane in the presence of different acids (RCO2H) leads to a single product with a rearranged carbon skeleton, a 1-acyl-2-methyl-1-cyclopentene (1) in 50 to 60% yield (Eq. 2) [7, 8]. Also other alkanes have been converted at a smooth platinum anode into the corresponding a,-unsaturated ketones in 42 to 71% yield (Table 1) [8, 9]. Product formation is proposed to occur by oxidation of the hydrocarbon to a carbocation (Eq. 1 and Scheme 1) that rearranges and gets deprotonated to an alkene, which subsequently reacts with an acylium cation from the carboxylic acid to afford the a-unsaturated ketone (1) (Eq. 2) [8-10]. In the absence of acetic acid, for example, in fluorosulfonic acid/sodium... 

It was determined that carbon nucleophiles derived from carbon acids with p/fa > 22 or so are sufficiently reactive to combine with the diene ligand rapidly at —78°C to produce an anionic intermediate (Scheme 25). With a few exceptions, the regioselectivity favors formation of the homoallyl anionic complex from addition at C-2, by kinetic control. This intermediate can be quenched with protons to give the terminal alkene, or can react with excess CO to produce an acyl iron intermediate. Following the recipes of Collman s reaction, the acyl iron intermediate can lead to methyl ketones, aldehydes, or carboxylic acids. The processes are illustrated with the 1,3-cyclohexadiene complex (Scheme 25). ... 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

The construction of the naturally derived narbomycin and tylosin-aglycones by Masamune and coworkers employ identical methodology for seco-acid formation. In each case, Peterson alkenation of a functionalized al hyde (not shown) and the silyl ketones (96 R = SiMes Scheme 36) or (99 Scheme 37) efficiently introduced the required ( )-a,3-unsaturation. Silyl ketone formation is accomplished in each case through cuprate acylation by an activated carboxylic acid derivative. Formation of an acid chloride was not possible in the sensitive tylosin-aglycone intermediate however, selective acylation of the silylcuprate proceeded at the pyridyl thiol ester moiety of (98) and not with the r-butyl thiol ester. In a related investigation, (97), an advanced intermediate for 6-deoxyerythronolide B, was obtained from (95) via addition of lithium diethylcuprate to the acid chloride (84% yield). In all the above cases, no addition was observed at the r-butyl thiol ester. 

Azetidin-2-ones are more reactive than y- and <5-lactams because of ring strain. This is true for the alkaline fission to give salts of / amino carboxylic acids, as well as for the acid-catalysed hydrolysis to fi-carboxyethylammonium salts. Starting from alkenes and chlorosulfonyl isocyanate, a stereocontrolled synthesis of / -amino carboxylic acids can be realized. Ammonia and amines react with azetidin-2-ones, also with ring-opening, to produce / -amino carboxylic amides. Hence they are acylated by azetidin-2-ones ... 

The cyclocondensation of 4-alkoxy-l,l,l-trichloro-3-alken-2-ones with hydroxyl-amine using toluene as solvent is more efficient under the action of microwave irradiation than using the classical method (the average time ratio for the two methods is 1 160) [49]. Katritzky et al. have demonstrated the applicability of microwaves to the synthesis of a variety of 2-oxazolines from readily available N-acylbenzotriazoles and 2-amino-2-methyl-l-propanol under mild conditions (80 °C) with short reaction times (12 min). Use of N-acyl benzotriazoles also avoids some complications in microwave reactions, for example dimerization or the exclusive formation of amides from carboxylic acids [50]. 

The reactions of lipids represent many reactions that we have studied in previous chapters, especially reactions of carboxylic acids, alkenes, and alcohols. Ester hydrolysis (e.g., saponification) liberates fatty acids and glycerol from triacylg-lycerols. The carboxylic acid group of a fatty acid can be reduced, converted to an activated acyl derivative such as an acyl chloride, or converted to an ester or amide. Alkene functional groups... 

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