Carboxylic acids, esters reductive coupling

Reduction. Carboxylic acids, esters, amides, and nitriles are reduced very rapidly by Sm and hydrochloric acid. Ytterbium may be used instead of samarium. The reduction of a-halocarbonyl compounds and the pinacol coupling with Sm in an aprotic system (MejSiCl-Nai/MeCN) are as efficient as those mediated by Sml2. 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

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... 

Carboxy terminal amino acid or peptide thiols are prepared from various p-amino alcohols by conversion into a thioacetate (R2NHCHR1CH2SAc) via a tosylate followed by saponification.Several methods have been used to prepare N-terminal peptide thiols, the most common procedure is the coupling of (acetylsulfanyl)- or (benzoylsulfanyl)alkanoic acids or add chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 16 Other synthetic methods include deprotection of (trit-ylsulfanyl)alkanoyl peptides, 1718 alkaline treatment of the thiolactones from protected a-sulfanyl acids, 19 and preparation of P-sulfanylamides (HSCH2CHR1NHCOR2, retro-thior-phan derivatives) from N-protected amino acids by reaction of P-amine disulfides with carboxylic acid derivatives, followed by reduction. 20,21 In many cases, the amino acid or peptide thiols are synthesized as the disulfides and reduced to the corresponding thiols by the addition of dithiothreitol prior to use. 

Sulopenem (CP-70429 see Tables 1 and 7) has been prepared via this reaction as the key step (G=0/C=S reductive coupling). The total synthesis utilizes L-aspartic acid to generate the chiral precursor 78 of the C-2 side chain, a modified chiron 76 (X = C1) to improve the preparation of the trithiocarbonate intermediate 79, a chemoselective oxalofluoride-based azetidinone N-acylation to give 80 (a procedure that avoids sulfoxide O-acylation), and mild final deprotection conditions of hydroxyl and carboxyl functions. In particular, the chloroallyl ester 81 has been selected, owing to its smooth cleavage by a palladium-mediated transesterification procedure (Scheme 42) <1992JOC4352>. 

This chapter is concerned with the cathodic reduction of carboxylic acids and their derivatives, that is, esters, amides, anhydrides, acyl halides, hydrazides, nitriles, and corresponding thio derivatives. Cyclic derivatives of substituted carboxylic and polycarboxylic acids, such as lactones, lactams, imides, and anhydrides, are also included. Only those transformations in which the functional group itself is involved are discussed. Reductive coupling of carboxylic acids and derivatives is covered in Chapter 22, and there is some overlap with reduction of heterocycles in Chapter 18. 

Cysteamine was used to couple redox-active carboxylalkyl-4,4 -bipyridinium salts to the gold surface . The nonordered monolayer assembly was then transformed into a densely packed monolayer with 1-hexadecanethiol and cyclic voltammetry of the surface bound viologen was performed. The electron transfer rate constants to the bipyridinium sites depended on the alkyl chain length Abridging the redox site to the electrode. Electron transfer rate constants followed the Marcus theory. Cysteic-acid-active ester monolayers chemisorbed on gold were used to electrode-immobilize the protein glutathione reductase, then a bipyridinium carboxylic acid was condensed onto the enzyme in the presence of urea to wire the protein towards electrochemical reduction (Figure 6.26). 

Trost chose to exemplify the utility of organopalladium coupling reactions for carbon-carbon bond formation by use of this process for the ring closure step in a synthesis of 1 (Scheme 1.9) To this end, monoprotected diol 31 was oxidized and chain extended to form the a,p-unsaturated ester 32. Reduction to the allylic alcohol followed by acetylation and desilylation gave 33 in 53% overall yield from 31. Carboxylic acid 35 was then obtained via a two-step sequence from bromo ester 34 (84%) by alkylation with methyl... 

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