Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction of Esters and Lactones at Room Temperature without Solvent-Induced Loss of Hydride

Rapid reaction of NaBH₄ with MeOH precludes its use as a solvent for large-scale ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %) stabilizes NaBH₄ solutions in methanol at 25 °C and permits the use of these solutions for the reduction of esters to alcohols. The generality of this reduction method was demonstrated using 22 esters including esters of naturally occurring chiral γ-butyrolactone containing dicarboxylic acids. This method permits the chemoselective reductions of esters in the presence of cyano and nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical and chemical yields. Lactones, aliphatic esters, aromatic esters containing electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than aryl esters containing electron-donating groups. The ¹¹B NMR spectrum of the NaOMe-stabilized NaBH₄ solutions showed a minor quartet due to monomethoxyborohydride (NaBH₃OMe) that persisted up to 18 h at 25 °C. We postulate that NaBH₃OMe is probably the active reducing agent. In support of this hypothesis, the activation barrier for hydride transfer from BH₃(OMe)^- onto benzoic acid methyl ester was calculated as 18.3 kcal/mol.