Mild Two-Step Conversion of Primary Amides to Alcohols by Reduction of Acylimidodicarbonates with Sodium Borohydride

Abstract

Di-tert-butyl acylimidodicarbonates, prepared from primary amides with two equivalents of di-tert-butyl dicarbonate under catalysis by 4-dimethylaminopyridine, readily undergo selective reductive cleavage of their acyl CO-N bonds by NaBH₄ to provide the corresponding alcohols in high yields.

Key words

alcohols - amides - cleavage - reductions - sodium borohydride

References

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9

Typical Reduction Procedure: A solution of 2c (732 mg, 2 mmol) in abs EtOH (12 mL) was treated with an excess of NaBH₄ (151 mg, 4 mmol) in one batch. After 20 h, when all starting material had been consumed (TLC monitoring), acetone (1 mL) was added, whereupon after 1 h the solvent was evaporated. The obtained foam was dissolved in Et₂O/H₂O, the aqueous phase backwashed once with Et₂O and the combined extracts dried (Na₂SO₄). After evaporation the mixture was purified by chromatography on silica gel (eluent: Et₂O/CH₂Cl₂ 1:15). HNBoc₂ eluted first, followed by pure 3c (298 mg, 97%); mp 91-92 °C; it was recrystallized from Et₂O/light petroleum.