Nitrite-Catalyzed Stereoselective Bromocyclization to Access Tetrahydrofuran Scaffolds under Batch and Flow: An Economic and Sustainable Approach to Gram-Scale Total Synthesis of Posaconazole.

Abstract

A highly efficient and concise bromocyclization has been successfully achieved, in which chiral auxiliary-substituted 4-en-1-ol derivatives can be transformed to valuable THF scaffolds in an economic and green manner. Production was successfully scaled up under both batch and continuous flow processes. A distinctive feature of our synthetic approach is that water constitutes the primary byproduct. Notably, gram-scale total synthesis of posaconazole was successfully achieved, underscoring the industrial applicability and cost-effectiveness of this transformation.