Sodium borohydride-trifluoroacetic acid reduction

The Gribble reduction of diaryl ketones refers to the sodium borohydride-trifluoroacetic acid (NaBHVTFA) reduction of diaryl ketones (1) to diarylmethanes (2).1 The reaction is very general and is applicable to the reduction of diarylmethanols (3) and triarylmethanols (4) to the respective diarylmethanes (2) and triarylmethanes (5).2... 

Gribble GW, Leese RM, Evans BE (1977) Reactions of Sodium Borohydride in Acidic Media IV. Reduction of Diarylmethanols and Triarylmethanols in Trifluoroacetic Acid. Synthesis 172... 

G. W. Gribble, W. J. Kelly, and S. E. Emery. Reactions of sodium borohydride in acidic media VII. Reduction of diaryl ketones in trifluoroacetic acid. Synthesis, 1978, 763. 

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

Catalytic reduction of folic acid to 5,6,7,8-tetrahydrofolic acid (225) proceeds fast in trifluoroacetic acid (66HCA875), but a modified method using chemical reductants leads with sodium dithionite to 7,8-dihydrofolic acid (224). Further treatment with sodium borohydride gives (225) which has been converted into 5-formyl-(6i ,S)-5,6,7,8-tetrahydro-L-folic acid (leucovorin) (226) by reaction with methyl formate (equation 70) (80HCA2554). 

On heating with sodium borohydride in glacial acetic acid. 5//-dibenz[/t,/ azepine (5) undergoes sequential acylation and reduction to yield 5-ethyl-5/7-dibcnz[A,/ ]azepine (8, R = Et).192 Similarly, reduction in trifluoroacetic acid produces the trifluoroethyl derivative 8 (R = CF3CH2 61% mp 69-70 C).193... 

Reduction of the ketone carbonyl of cis-1, 2,3,4,4a,9b-hexahydro-8-hydroxydi-benzofuran-3-one with trifluoroacetic acid and triethylsilane at 0° produces a mixture of the a- and /3-isomers of the C3 alcohol with an u / ratio of 1 4 (Eq. 211).394 This result can be compared with the isomer ratio of 100 1 that results when sodium borohydride is used as the reducing agent.394 The same cis pair of alcohol isomers is formed in 77% combined yield, but in a reversed ratio of a /3 = 4 1, when the less saturated tetrahydrodibenzofuran analog is used as the substrate (Eq. 212).394... 

Reduction of carbonyl to methylene in aromatic ketones was also achieved by (dane prepared from lithium aluminum hydride and aluminum chloride [770], by soditim borohydride in triiluoroacetic acid [841 with triethylsilane in trifluoroacetic acid [555, 777], with sodium in refluxing ethanol [842], with zinc in hydrochloric acid [843] and with hydrogen iodide and phosphorus [227], geiibrally in good to high yields. 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

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... 

Methylcryptaustoline iodide (14) was synthesized from phenylacetic acid 47 by Elliott (39) as shown in Scheme 7. Nitration of 47 to the 6-nitro compound 48 and reduction with sodium borohydride afforded lactone 49. Reduction of the aromatic nitro group with iron powder in acetic acid gave ami-nolactone 50, which was converted to tetracyclic lactam 51 with trifluoroacetic acid in dichloromethane. Reduction of the lactam by a borane-THF complex followed by treatment with methyl iodide afforded ( )-0-methylcryptaustoline iodide (14). 

Lithium aluminium hydride has also been used for the reduction of nitriles to amines a recommended procedure involves the slow addition of the nitrile to at least one molar proportion of the reducing agent in a cooled ethereal solution.205 The reduction of nitriles is also effected by the use of sodium trifluoro-acetoxyborohydride (from sodium borohydride and trifluoroacetic acid) in tetrahydrofuran solution.206... 

Deoxygenation of naphthalene-1,4-endoxides. A new method for conversion of these Diels-Alder adducts of benzynes with furanes to naphthalenes consists in reduction with sodium borohydride in trifluoroacetic acid.5 Excess acid is used when the substrate bears methyl groups at the bridgeheads. Substrates lacking such groups tend to undergo acid-catalyzed rearrangement to naphthols, but are reduced satisfactorily with THF as solvent and a limited amount of acid. 

The first McCasland s pseudo-sugar, pseudo-a-DL-talopyranose (P) was synthesized from 4-acetoxy-2,3-dihydroxy-5-oxo-cyclohexanecarboxylic acid (6) as follows [13]. Reduction of the oxo acid 6 with sodium borohydride and subsequent esterification with methanol and trifluoroacetic acid, followed by acetylation gave methyl (1, 2, 3, 4/5)-2, 3, 4, 5-tetraacetoxycyclohexanecarboxylate (7). Hydrogenation of 7 with lithium aluminium hydride and successive acetylation yielded pseudo-a-DL-talopyranose pentaacetate (8). Hydrolysis of 8 in ethanolic hydrochloric acid gave pseudo-a-DL-talopyranose 9 in 23% overall yield from 6 [1] (Scheme 6). 

A McMurry coupling of (176, X = O Y = /3H) provides ( )-9,ll-dehydroesterone methyl ether [1670-49-1] (177) in 56% yield. 9,11-Dehydroestrone methyl ether (177) can be converted to estrone methyl ether by stereoselective reduction of the C —double bond with triethji silane in trifluoroacetic acid. In turn, estrone methyl ether can be converted to estradiol methyl ether by sodium borohydride reduction of the C17 ketone (199,200). 

Sodium borohydride or sodium borohydride and trifluoroacetic acid reduce 5- or 6-sub-stituted quinoxalines to the 1,2,3,4-tetrahydro compounds 1.2,3,4-tetrahydroquinoxaline is also formed in the reduction of quinoxaline with bis(trifluoroacetoxy)boranc-tetrahydrofuran. The sodium borohydride reduction of 2,3-dimethylquinoxaline 1,4-dioxide in alcohols affords c 3-2,3-dimethyl-l,2,3,4-tetrahydroquinoxaline as the predominant product and identical to that obtained from the reduction of 2,3-dimethylquinoxaline with lithium aluminum hydride. ... 

Sodium borohydride and trifluoroacetic acid (TFA) reduce 2-aryl-l,3-dioxoIanes to hydroxy ethers. Zinc borohydride, with TMS-Cl as its acidic partner, has proven to be effective in the reductive cleavage of a variety of acetals. MOM ethers are reduced to methyl ethers in good yield (equation 13). Cyclohexene is hydroborated under these conditions, indicating that diborane may be present. 

Borohydride reduction of indole (198) in the presence of trifluoroacetic acid (TFA) gave the indoline 201 without alkylation but in low yield. The yield of 201 can be increased when carried out with sodium cyanoborohy-dride in acetic acid at 15°C. This eliminates the isolation of any /V-alkyl indolines. ... 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Treatment of 3-(l-benzyloxymethylcyclopropyl)propanoic acid with various mercury(II) salts such as nitrate, trifluoroacetate and perchlorate gave the lactones 25A and 25B in 35-86% yield after aqueous potassium bromide workup. A number of related cyclopropanecarboxylic esters were reacted in the same fashion to give bromomercurio-substituted lactones 26 and 27/28 from which the mercury was removed by reduction with sodium borohydride. ... 

The sample is desorbed from the XAD-8 column with 0. IN sodium hydroxide, which immediately is removed by passage of the base eluate through a hydrogen-saturated cation-exchange column connected in series with the XAD-8 column. Most of the trifluoroacetic acid and water are removed from the sample by vacuum rotary evaporation of the sample to a moist residue. Lastly, the sample is diluted to 20 mL in distilled water and freeze-dried. The sodium borohydride reduction product is readily soluble in water, methanol, tetrahydrofuran, dimethylsulfoxide, and dioxane. 

The reduction of pteridines to 5,6,7,8-tetrahydropteridines almost certainly proceeds via 7,8-dihydropteridine intermediates. In the case of pteridine itself the use of sodium borohydride in tetrahydrofuran and trifluoroacetic acid results in the formation of a separable mixture of 1,2,3,4- and 5,6,7,8-tetrahydropteridine in yields of 38 and 58%, respectively.232 If lithium aluminum hydride in diethyl ether is used, only the 5,6,7,8-product is obtained (58 %).181,233... 

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