Carboxylic acids, conjugated synthesis

Rueck, K, Kunz, H, Stereoselective conjugate addition of organoaluminum chlorides to a,(i-unsaturated carboxylic acid derivatives. Synthesis, 1018-1028, 1993. 

Polhni, G.P, Barco, A. and De Giuli, G. (1972) Tetramethylguanidine-catalysed addition of nitromethane to a, P-unsaturated carboxylic acid esters. Synthesis, 44-45 Alvarez, F.S. and Wren, D. (1973) Synthesis of ( )-deoxyprostaglandin Ei, and Fip and its 15P-epimers by conjugate addition of nitromethane to 2-(6 -carbomethoxyhexyl)-2-cyclopenten-l-one. Tetrahedron Letters, 569-572 Hewson, A.T. and MacPherson, D.T. (1983) Conjugate addition to the ethylene ketal of 2-carbomethoxy-2-cyclopentenone a synthesis of sarkomycin. Tetrahedron Letters, 24, 647-648 Naito, T., Honda, Y, Bhavakul, V. et al. (1997) Radical cyclization in heterocycle synthesis. II. Total synthesis of ( )-anantine and ( )-isoanantine. Chemical Pharmaceutical Bulletin, 45, 1932-1939. 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

The asymmetric synthesis of / -branched carboxylic acid derivatives was accomplished by conjugate addition of mixed organoaluminum reagents to optically active Arabinose-derived c -unsaturated A-acyloxazolidinones (Scheme 47). Efficient stereocontrol was achieved using different optically active bicyclic oxazolidinones, yielding (.R)- or ( -configured / -branched carboxylic acid derivatives.136a... 

Conjugate addition of RLi to simple alk-2-enoic acids provides a convenient synthesis of branched saturated carboxylic acids. ... 

A total synthesis of the title compound has been achieved. One of the key strategic elements involved the use of a furan ring as a surrogate for a carboxylic acid. This logic has been applied, on a model basis, to the synthesis of sialo and KDO conjugates. 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

Enantlomerically pure B-suhstituted carbonyl compounds serve as useful intermediates in the synthesis of many chiral organic compounds. The enantloselective synthesis of acyclic 0-substituted carboxylic acids has been reported by Meyers, Mukaiyama, and Koga. However, no effective, general method for the enantio-controlled preparation of P-substituted cycloalkanones was available prior to the investigations by the submitters. For example, poor enantloselectivity was observed in conjugate additions of organometallic... 

The homochiral f -branched carboxylic acids (13 or enf-13 Table 1) have been used for the synthesis of a variety of natural products21 such as California red scale pheromone,14 a-skytanthine,22 the southern com rootworm pheromone,15 and norpectinatone.16 Pure (5)-3-trichloromethylbutyric acid (a structural subunit of some sponge metabolites) was prepared via conjugate addition of ClaCMgCl to the chiral cro-tonate (16) followed by hydrolysis (Scheme S).23... 

The (diastereoselective) conjugate addition of silylcuprate reagents to a variety of chiral derivatives of a,(3-unsaturated carboxylic acids can be used to prepare optically active p-silyl esters.258 259 Best results are obtained with substrates of type (25). The (related) p-silyl ketones, which also constitute valuable building blocks for (acyclic) stereoselective synthesis, are now accessible in high ee via palladium-catalyzed enantioselective 1,4-disiiylation of a,p-unsaturated ketones (Scheme 76).260... 

---