Study On Reduction System Of NaBH₄/Me₂SO₄/B(OMe)₃

Reductions of hydroxy-substituted aromatic carboxylic acids have found utility in synthesis of pharmaceutical intermediates and other functional materials, however, there is no convenient reduction method. In this paper, reductions of hydroxy-substituted aromatic carboxylic acids are investigated with a novel reduction systerm: NaBH₄/Me₂SO₄/B(OMe)₃. And borane solution prepared in situ from NaBH₄/Me₂SO₄ and CBS catalyst is used for asymmetric reductions of prochiral ketones.Borane solution is generated in situ by the reaction of NaBH₄ with Me₂SO₄ in THF. There is no residual NaBH₄ in the solution by ¹¹B-NMR. Effect of amount of trimethyl borate and NaBH₄/Me₂SO₄ is investigated using 4-hydroxybenzoic acid as model substrate. The optimum ratio for reduction of 4-hydroxybenzoic acid is obtained as follow: NaBH₄/Me₂SO₄/B(OMe)₃/4-hydroxybenzoic acid=2/2/2/1. As for salicylic acid, it only needs 1 equivalence of B(OMe)₃ because hydroxyl is ortho to carboxyl. So the optimum ratio for reduction of salicylic acid is NaBH₄/Me₂SO₄/B(OMe)₃/salicylic acid =2/2/1.1/1. Having established the optimum condition, the method is applied to a number of hydroxy-substituted aromatic acids with isolated yield of 74-98%. The effect of substituted groups is that electron-donating groups accelerate the reaction, while electron-withdrawing groups slow the reaction, and aliphatic carboxylic acids are more easily reduced by borane than aromatic carboxylic acids. The systerm NaBH₄/Me₂SO₄/B(OMe)₃ is successfully applied in the one-step reduction of hydroxy-substituted aromatic carboxylic acids after the hydroxyl is protected in situ by trimethyl borate. Then the mechanism for reduction of hydroxy-substituted aromatic carboxylic acids is discussed.The asymmetric reduction of prochiral ketones is investigated using the borane prepared in situ from NaBH₄/Me₂SO₄ and CBS catalyst. The optimum condition which is obtained using acetophenone as model substrate is NaBH₄/Me₂SO₄/CBS/ketones=0.7/0.7/0.1/1. A number of ketones are studied under optimum condition with the yield of 80-99% and the enantiomeric excess of 93-99%.