Carboxylic acids, from ketenes

Alcohols and carboxylic acids from ketene dihalides via trialkylboranes... 

Yamamoto and Ishihara et al. have revealed that acidic protons in the optically active binaphthol (BINOL) or BINOL monomethyl ether are activated by coordination of SnCU to form a Lewis acid-assisted chiral Bronsted add (LBA) (43) and can be used a s a chiral proton source f or the synthesis of chiral ketones or carboxylic acids from silyl enol ethers or ketene bis (trialky Isilyl) acetals [44]. The chiral LBA system is also effective in the catalytic version with 5-10 mol% of the optically active BINOL monomethyl ether and SnCU in the presence of 2,6-dimethylphenol as a stoichiometric proton source (Scheme 10.22). Further details and backgrounds of the reactions using LBA are reviewed in the first edition of this series [12]. 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

Amides prepared from carboxylic acids and primary amines using azolides obtained from acid chloride/imidazolea) or ketene/imidazole systems.b)... 

Flash vacuum pyrolysis of methyl imidazol-2-yl carboxylate 290 at 750°C gave 20% yield of 268 via the corresponding ketene 291. Similar pyrolysis of methyl imidazol-l-yl carboxylate 292 gave 20% of a 1 1 2 mixture of compounds 267,268, and 296. This fact can be rationalized by the pathway depicted in Scheme 71. Ketenes 291 and 295 may be intermediates formed from 293 and 294, respectively. They are products of rearrangement of 292. Similar pyrolysis of 4-imidazole carboxylic acid anilide performed at 800°C gave 267 in 20% yield (86JOC306). 

Monoalkyl ethers of (R,R) 1,2-bis[3,5-bis(trifluoromethyl)phenyl]ethanediol, 24, have been examined for the enantioselective protonation of silyl enol ethers and ketene disilyl acetals in the presence of SnCU (Scheme 12.21) [25]. The corresponding ketones and carboxylic acids have been isolated in quantitative yield. High enantioselectivities have been observed for the protonation of trimethylsilyl enol ethers derived from aromatic ketones and ketene bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids. 

Photosynthesis of azo-dyestuffs has been reported to be effected by the irradiation of o-quinone diazides. The reaction proceeds via the contraction of the diazide CCXV to the cyclic ketene CCXVI which adds water to form the eyclopentadiene carboxylic acid CCXYII. The latter couples with unchanged CCXV (obtained from 2-amino-l-phenol-4-sulfonic acid) to form the azo-dyestuff CCXVTII.270 Similarly, V-heterocyclic azo-dyestuffs, e.g., CCXX is obtained by the photolysis of CCXIX.275... 

Chiral hydroxy carboxylic acids The chiral acetals 2, available from (2R, 4R)-pentanediol (12,375-378), couple with ketene f-butyl f-butyldimethylsiiyl acetal (3) in the presence of TiCl4 (0.5 equiv.) to give adducts that are hydrolyzed by TFA-H20 to 4 and 5. The mixture is converted on oxidation and p-elimination into essentially pure (3R)-p-hydroxy carboxylic acids (6). 

Manufacture. Ketenes can be considered the internal anhydrides of the corresponding carboxylic acids, and as such can be made by removing a molecule of water from these acids, either direcdy or indirecdy. Numerous methods to convert a carboxylic acid or derivative to the corresponding ketene have been described (1—4). 

Thioketenes can be prepared in several ways, from carboxylic acid chlorides by thionation with phosphorus pentasulfide [1314-80-3], P2S5, from ketene dithioacetals by p-elimination, from 1,2,3-thiadiazoles with flash pyrolysis, and from alkynyl sulfides (thioacetylenes). The dimerization of thioketenes to 2,4-bis(alkylidene)-l,3-dithietane compounds occurs quickly. They can be cleaved back pyrolytically (63). For a review see Reference 18. 

The pH-rate profiles of the enol of l-indene-3-carboxylic acid and of its ketene precursor, formed from either l-diazo-2( 1 //jnaphthalenone or 2-diazo-l(2//)naphthalenone by photochemical deazotization and Wolff rearrangement, are shown in Fig. 5.36 The first and second acidity constants of the diol, p = 1.9 and p aE = 8.3, are evident from the downward curvature of log (k /s-1) at these pH values. The photo-Wolff rearrangement of diazonaphthoquinones is the active principle of Novolak photoresists. 

In connection with these results, and as an extension of their studies toward the reactivity of new bicyclic mesoionic compounds and their usefulness in the synthesis of condensed heterocycles, they further reported the stereoselective synthesis of spiro-(3-lactams 153, 154 (Scheme 36) by reactions of imines with mesoionic compounds or ketenes generated from A-acyl-thiozolidine-2-carboxylic acids 152 [110]. 

Recently, they have synthesized enantiomerically pure 1,3-thiazolidine-derived spiro-(3-lactams [111] (Scheme 37) using Staudinger ketene-imine reaction starting from optically active lV-boc-1,3- thiazolidine-2-carboxylic acid derivatives and imines, thus confirming the generality of the earlier reported 1,3-thiazolidine-derived spiro-(3-lactams. 

The cyclic ketenes were generated from /V-acy 1-1,3-thiazolidine-2-carboxylic acids by means of Mukaiyama s reagent. The same reaction generated enantio-merically pure 1,3-thiazolidine-derived spiro-p-lactams, using optically active /V-A rt-butoxycarbonyl-1,3-thiazolidine-2-carboxylic acid derivatives as precursors of the asymmetrical chiral cyclic ketenes (7< r/-butoxy carbonyl Boc) [101]. 

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