Stabilization of NaBH 4 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 11 B NMR spectrum of the NaOMe-stabilized NaBH4 solutions showed a minor quartet  due to monomethoxyborohydride (NaBH3 OMe) that persisted up to 18 h at 25 °C. We postulate that NaBH3 OMe 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.