Stereocontrolled Synthesis of 1,3‐Substituted 2‐Oxabicyclo[3.1.0]hexanes as Ring‐Constrained Tetrahydrofuranosyl C‐Glycosides

Abstract

AbstractHerein, we describe the stereocontrolled synthesis of 2,3‐α‐methano 2‐substituted‐5‐(S)‐hydroxymethyl tetrahydrofurans, (formally 1,3‐disubstituted 2‐oxabicyclo[3.1.0]hexanes), using a TFA‐mediated destannylative cyclopropanation reaction, starting from commercially available 4‐(S)‐hydroxymethyl‐butyrolactone. A variety of chiral aryl, alkynyl and heterocyclic anomeric substituents were prepared in good to excellent yields. Facile derivatizations of these versatile compounds provide a series of anomerically functionalized chiral non‐racemic 2,3‐α‐methano tetrahydrofurans as potential substrates for heteroatom mediated ring opening reactions of potential interest in medicinal chemistry. Acid‐promoted methanolysis of a phenyl C‐glycoside analogue resulted in cleavage of the cyclopropane ring and formation of (1S,4S,6R)‐6‐methyl‐1‐phenyl‐2,7‐dioxabicyclo[2.2.1]heptane, a novel dioxabicyclo ketal and its oxocarbenium ion mediated oligomers.