Carboxylic acids reduction, with sodium borohydride

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... 

Refluxing of 9-fluorenone-l-carboxylic acid with zinc dust and copper sulfate in aqueous potassium hydroxide for 2.5 hours afforded 9-fluorenol-1-carboxylic acid in 94% yield [1004]. Reduction with sodium borohydride in aqueous methanol at 0-25° converted 5-ketopiperidine-2-carboxylic acid to /ra j-5-hydroxypiperidine-2-carboxylic acid in 54-61% yield [1005], On the other hand, reduction of V-benzyloxycarbonyl-5-ketopiperidine-2-carboxylic acid gave 89% yield of V-benzyloxycarbonyl-cis-5-hydroxypiperidine-2-car-boxylic acid under the same conditions [1005],... 

The CD fragment 1s synthesized starting with resolved bicyclic acid 129. Sequential catalytic hydrogenation and reduction with sodium borohydride leads to the reduced hydroxy acid 1. The carboxylic acid function is then converted to the methyl ketone by treatment with methyl-lithium and the alcohol is converted to the mesylate. Elimination of the latter group with base leads to the conjugated olefin 133. Catalytic reduction followed by equilibration of the ketone in base leads to the saturated methyl ketone 134. Treatment of that intermediate with peracid leads to scission of the ketone by Bayer Villiger reaction to afford acetate 135. The t-butyl protecting... 

Furthermore unsaturated aldehydes can be obtained by the reaction of 12 with e. g. cyclohexane carboxylic acid chloride, subsequent alkaline cleavage of the remaining silyl grouping and reduction with sodium borohydride give 3-hydroxy-3-cyclohexyl-1,1-dimethoxypropane (54) which yields 3-cyclohexyl-acrolein (JJ)51 via acid treatment under dehydratation. 

Pictet-Spengler cyclization of L-tryptophan with formaldehyde afforded the monochiral carboxylic acids 20a,b, whereas cyclization with acetaldehyde yielded the diastereomeric carboxylic acids 21a,b (23). Acids 20a,b with a hydrogen at C-1 are enantiomers, but acids 21a,b are diaste-reomers the cis isomer 21a was the major reaction product when the cyclization of L-tryptophan with acetaldehyde was carried out in the presence of sulfuric acid. Direct removal of the carboxy group in these acids is difficult, but it can be accomplished in several steps dehydration of the amides prepared from the acids with phosphorus oxychloride affords nitriles, and the nitrile group can be removed by reduction with sodium borohydride in pyridine-ethanol (31). 

A ketone added to the aged solution is reduced effectively, but a carboxylic acid or ester is not reduced. This weak hydride donor is thus useful for the selective reduction of a keto acid to the corresponding hydroxy acid. Both intermolecular 2md intramolecular competition experiments with tetrakis-(N-dihydropyridyl)-aluminate showed that diaryl ketones are more reactive to this reagent than either dialkyl or aralkyl ketones. This relationship is the opposite of that found by H. C. Brown for reduction with sodium borohydride in isopropyl alcohol, where the order of reactivity is acetone > acetophenone > benzophenone. 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

The methyl substituent of 2-methyl-4,8-dihydrobenzo[l,2- 5,4-. ]dithiophene-4,8-dione 118 undergoes a number of synthetic transformations (Scheme 8), and is therefore a key intermediate for the preparation of a range of anthraquinone derivatives <1999BMC1025>. Thus, oxidation of 118 with chromium trioxide in acetic anhydride at low temperatures affords the diacetate intermediate 119 which is hydrolyzed with dilute sulfuric acid to yield the aldehyde 120. Direct oxidation of 118 to the carboxylic acid 121 proceeded in very low yield however, it can be produced efficiently by oxidation of aldehyde 120 using silver nitrate in dioxane. Reduction of aldehyde 120 with sodium borohydride in methanol gives a 90% yield of 2-hydroxymethyl derivative 122 which reacts with acetyl chloride or thionyl chloride to produce the 2-acetoxymethyl- and 2-chloromethyl-4,8-dihydrobenzo[l,2-A5,4-3 ]-dithiophene-4,8-diones 123 and 124, respectively. 

The carboxylic acid is then converted to its ester with ethanol in the presence of an acid. Carboxylic esters are not, in the normal course of events, reduced by sodium borohydride. The presence of an adjacent imine nitrogen apparently changes the resistance to that reagent. Thus, treatment of (71-7) with sodium borohydride leads to a selective reduction of the ester on the heterocyclic ring to an alcohol while leaving that on the benzene ring unaffected. There is thus obtained oxagrelate (71-8) [80]. 

We also found that ester functionality was compatible with this reduction sequence. Thus, treatment of the ester-lactone 81 with sodium borohydride and boron trifluoride etherate provided the tetrahydropyran 123 in 55% purified yield. Upon reaction with sodium hydroxide, 81 underwent simple ester hydrolysis to furnish the carboxylic acid 127 (see Table 3). 

Arenetellurolates, ethenetellurolates, and alkanetellurolates prepared by reduction of diorgano ditellurium compounds with sodium borohydride in ethanol, THF/ethanol, or DMSO add to acetylenes in regioselective and iran.y-stereoselcctive reactions to produce aryl ethenyl tellurium products either predominantly or exclusively as (Z)-isomers. The yields are almost always higher than 70%. In reactions with acetylenic aldehydes, ketones, carboxylic acids, and esters the arenetellurolate becomes bonded to the carbon atom in a [i-position to the carbonyl group. 

A large number of stable /e-organo tellurocarboxylates were prepared from tellurolates and aliphatic1,2 or aromatic2 carboxylic acid chlorides or aliphatic carboxylic acid anhydrides . The tellurolates were obtained by reduction of diorgano ditelluriums with sodium borohydride. 

The starting materials for the preparation of 1,3-benzotellurazoles are aromatic tellurium compounds that contain an amino functionality in an orv/to-position to the tellurium atom. The reduction of 2-benzeneazophenyl tellurium trichloride with sodium borohydride in ethanol generates 2-aminobenzenetellurol. This compound is acylated with carboxylic acid anhydrides and the acylaminobenzenetellurol cyclized by treatment with concentrated... 

Sodium borohydride is selective it usually does not react with carbonyl groups that are less reactive than ketones and aldehydes. For example, carboxylic acids and esters are unreactive toward borohydride reduction. Thus, sodium borohydride can reduce a ketone or an aldehyde in the presence of an acid or an ester. 

Selenocyanates produce selenols or diselenides upon either reduction (e g. with sodium borohydride) or hydrolysis (see Scheme 1). They undergo displacement of the cyanide ion by various nucleophiles and add to alkenes in a maimer similar to selenenyl halides (see equation 14), except that catalysis with Lewis acids is required in the case of unactivated alkenes. The selenocyanates are also popular reagents for the preparation of selenides from alcohols, and (8) from carboxylic acids, as indicated in Scheme 3. 

Reduction with concomitant A, Af -dialkylation is achieved by the action of potassium borohydride in the presense of carboxylic acids. Similarly, reduction of quinoxalines with sodium borohydride or sodium cyanoborohydride in the presence of benzyl chloroformate gives A -benzyloxycarbonyl- or /V,jV -bis(benzyloxycarbonyl)tetrahydro derivatives. ... 

Hydrogenation of acrylic acid esters with high enantioselectivity has usually been accomplished with difficulty. The enantioselective reduction of a,p-unsaturated carboxylates with sodium borohydride in the presence of cobalt-semicorrin complexes has been achieved in up to 96% ee (equation 14). The (Eland (Z)-isomers each afford products of opposite configuration, and the isolated double bonds remain un-touched. ... 

Hydroxymethylpyrazines may be prepared by reduction of carboxylic acid derivatives. Thus reduction of 2-amino-3-methoxycarbonylpyrazine with lithium aluminum hydride in tetrahydrofuran gave 2-amino-3-hydroxymethylpyrazine (1074, 1075) the imide from 23-dicarboxypyrazine (20) with sodium borohydride in tetrahydrofuran gave 2-carbamoyl-3-hydroxymethylpyrazine (21), and the methylcarbamoyl analogue was prepared similarly (1076). 

---