Selective reductions. XIX. Rapid reaction of carboxylic acids with borane-tetrahydrofuran. Remarkably convenient procedure for the selective conversion of carboxylic acids to the corresponding alcohols in the presence of other functional groups

Abstract

Aliphatic and aromatic carboxylic acids are reduced rapidly and quantitatively to the corresponding alcohols by borane in tetrahydrofuran, either at 0°or 25°. Even sterically hindered acids, such as 1-adamantanecarboxylic acid, dicarboxylic acids, such as adipic acid, phenolic acids, and amino acids undergo facile and quantitative reduction with borane. Aliphatic carboxylic acids are reduced at faster rates than aromatic carboxylic acids. Unlike more conventional, very powerful reducing agents, such as lithium aluminum hydride, the mildness of the reagent, borane, permits the presence of other functional groups less susceptible to the reducing action of the reagent, groups such as ester, nitro, halogen, nitrile, keto, etc. The remarkable utility of this reagent for the selective reduction of carboxylic acids was confirmed by the selective conversion of adipic acid monoethyl ester to ethyl 6-hydroxyhexanoate and p-cyanobenzoic acid to p-cyanobenzyl alcohol in yields of 88 and 82%, respectively. This reaction provides a highly convenient synthetic procedure for the selective reduction of the carboxylic acid group where this is required in synthetic operations.

Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone

“…For example, methyl (S)-3-(oxiran-2-yl)propanoate (1a) has been employed for the synthesis of many compounds such as elicitor [1], Streptrubin B [2] or chiral β-3-substituted homopropargyl [3], thiobutyrolactone [4], γ-hydroxyesters [5], diol-γ or δ-lactones [6], keto-esters [7], (+/´)-4-alkanolides [8] (Figure 1). Classically, epoxides such as 1a are obtained from (S)-γ-hydroxymethyl-γ-butyrolactone (2H-HBO, 2), itself derived from glutamic acid (Scheme 1) [9][10][11][12][13][14][15][16][17][18][19], a natural amino acid that is produced by fermentation on a commercial scale [20]. Glutamic acid is first deaminated to give the intermediate (S)-γ-carboxy-γ-butyrolactone, which was first reported by Austin et al using nitrous acid [11].…”

“…Finally, the third and last route consists of a one-step reduction of the carboxylic acid into the alcohol in presence of borane-methylsulfide (BH3-Me2S) [3,17] or borane-THF [18]. It is noteworthy that the substitution of borane-methylsulfide by borane-THF to obviate odor problems on large scale [12,19] resulted in over-reduction to the lactol [16]. Although these three routes provide 2 in good yields, they either require two steps or use a carcinogenic reagent (i.e., BH3-Me2S).…”

“…Providing 2 in very good yield and high purity through a lipase-based mediated oxidation, this sustainable synthetic pathway has been studied further by our group as an alternative to the one involving L-glutamic acid to achieve the synthesis of epoxides (S)-1a and (S)-1b (Scheme 2). Classically, epoxides such as 1a are obtained from (S)-γ-hydroxymethyl-γ-butyrolactone (2H-HBO, 2), itself derived from glutamic acid (Scheme 1) [9][10][11][12][13][14][15][16][17][18][19], a natural amino acid that is produced by fermentation on a commercial scale [20]. Glutamic acid is first deaminated to give the intermediate (S)-γ-carboxy-γ-butyrolactone, which was first reported by Austin et al using nitrous acid [11].…”

Palladium-catalyzed cross-coupling of organic halides, alkenes and nucleophiles

“…Vinylic halides substituted at the a-position provided mixed results. 2-Iodo-1-hexene or a-iodostyrene both gave little or none of the desired products in the reaction with 1-heptene and morpholine (entries 21 and 22), while 2-bromopropene produced the desired product in high yields (entries [24][25][26][27]. However, in all of these cases with asubstituted halides, the nucleophile attacked exclusively at the less hindered end of the kallylpalladium species.…”

“…His results indicated that in some cases vinylic triflates give better yields than vinylic iodides. With this in mind, 2-methyl-1 -propenyl triflate was allowed to react with 1,5-hexadiene and several carbon nucleophiles (entries [26][27][28]. In all cases, the reactions led to a single product in moderate yield.…”