DABCO-promoted reaction sequence of β-nitro alcohols and α-oxoaldehydes: construction of diverse tetrahydrofurans and total synthesis of (+)-bruguierol B

Abstract

A DABCO-promoted highly efficient reaction sequence has been developed. Under mild conditions, β-nitro alcohols (chiral/achiral or cyclic/acyclic) reacted smoothly with α-oxoaldehydes through a sequential Henry reaction, HNO₂ elimination, and intramolecular hemiketalization to form the functionalized hemiketal intermediates. These intermediates serve as oxocarbenium ion precursors, reacting with external or internal nucleophiles diastereoselectively to afford diverse tetrahydrofuran derivatives, including dihydrofuran-3-one, benzoxa[3.2.1]octane, furo[3,2-b]furan, and hexahydrobenzofuranol scaffolds. Notably, this strategy enabled the first total synthesis of (+)-bruguierol B.