Carboxylic acids, reduction with

NBH, in the presence of carboxylic acids. Reduction with sodium cyanoborohydride gives reduction but no alkylation under similar conditions. The reduction of 5-nitroisoquinoline produced dihydroiso-quinoline (27) or tetrahydroisoquinoline (28) with NBH in acetic acid, depending on the solvent and temperatures employed. 

The partial hydrolysis of 4a with methanolic potassium hydroxide followed by selective carboxylic acid reduction with excess borane and treatment of the resulting monoalcohol with methanesulfonyl chloride affords methyl 4-0-methanesulfonyl-2,3-0-isopropylidene-L-threonate (43). Facile displacement of the mesylate with azide followed by ester hydrolysis and catalytic reduction to an amine provides 4-amino-4-deoxy-2,3-0-isopropylidene-L-threonic acid (44). Mild acidic deprotection and ion-exchange desalting of 44 yields (2i ,3 S)-4-amino-4-deoxy-L-threonic acid (45), which has been utilized for the preparation of anthopleurine 46, the alarm pheromone of the sea anemone Anthopleura elegantissima [4] (Scheme 11). 

Anion radical from anion of pyridine-4-carboxylic acid Reduction with solvated electrons/ Liquid NHj (flow system) EPR/ 213 H(2,6) 0.196 H(3,5) 0.196 N 0.551 ... 

REDUCTION OF CARBOXYLIC ACIDS Reduction With Lithium Aluminum Hydride Reduction with Diborane... 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

Curtius rearrangement of the heteroaroyl azides, obtained from the reaction of the carboxylic acid chlorides with sodium azide, provides a route to the amino-pyrroles and -indoles (e.g. B-70MI30504, B-77MI30506, 78CPB1054), which, because of the ease of synthesis of the carboxylic acids, is frequently preferable to reduction of the nitro compounds. 

Acylation. One of the most useful and important methods for preparations of alkylthiophenes is acylation. This is the reaction of carboxylic acids and carboxylic acid chlorides with thiophenes in the presence of a suitable catalyst and leads to 2-acylthiophenes in good yields (typically ca. 60-80% e.g. 23). Reduction of the ketone functionality by either a modified Wolff-Kishner procedure (8, 24) or with a mixed hydride, formed from aluminium trichloride and lithium aluminium hydride (25), yields the alkylthiophene (Figure 6). Alternatively, the ketone group can be alkylated, thereby giving access to 2-(r-alkyl)alkylthiophenes. 

The reaction of derivatives of 2-ethylamino-8-ethyl-7-pteridinone carboxylic acid (155) with sodium borohydride gave the corresponding 4,8-dihydropteridine153 (156). The original assignment of the 5,8-dihydro-structure153 was revised on the basis of NMR studies of the reduction products.154... 

Reactions of Nitriles Nitriles undergo acidic or basic hydrolysis to amides, which may be further hydrolyzed to carboxylic acids. Reduction of a nitrile by lithium aluminum hydride gives a primary amine, and the reaction with a Grignard reagent gives an imine that hydrolyzes to a ketone. 

For the structural optimization of the tricyclic triazolium salt 119 the cw-tricyclic lactam 126 was chosen as the precursor for the synthesis of the tetracyclic triazolium salt 127. The diastereo- and enantiopure y-lactam 126 was synthesized following a procedure reported by Ennis et al. (Scheme 32) (Ennis et al. 1996 Nieman and Ennis 2000). a-Tetralone (124) was a-alkylated with ethyl bromoacetate and subsequently hydrolyzed to the corresponding carboxylic acid. Condensation with (R)-phenylglycinol yielded the lactam 125 as a single stereoisomer. Stereoselective reduction, dehydration of the alcohol, and acid-catalyzed enamine hydrolysis provided the cis-tricyclic lactam 126. The one-pot procedure that had previously been successful in the synthe-... 

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