Diastereoselective Synthesis of α-Tocopherol: A New Concept for the Formation of Chromanols

Abstract

A diastereoselective synthesis of α-tocopherol 1 (93% de) was achieved via two key steps, (i) a highly diastereoselective Shi epoxidation of a trisubstituted alkene and (ii) an acid supported, “anti-Baldwin” epoxide ring opening under inversion of configuration leading to the 6-membered chromanol ring.

Catalytic, Enantioselective, Intramolecular Sulfenofunctionalization of Alkenes with Phenols

“…10 The difunctionalization of γ-substituted 2-allylphenol to afford chromans with stereocenters at both the 2- and 3-positions remains rare. 11 A recent example involves the stereocontrolled generation and intramolecular opening of a seleniranium ion by a phenolic hydroxyl group to form a 2-seleno-3-arylchroman (Scheme 3b). 12 The reaction proceeds via a DYKAT mechanism, since the seleniranium ion in question is not stable under the reaction conditions.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…Similar intramolecular processes have been catalyzed by caesium [594] and p-toluenesulfonic acid [595]. In one such intramolecular epoxide ring opening -a key step in the diastereoselective synthesis of a-tocopherol -anhydrous hydrochloric acid in ether/acetonitrile was chosen to promote the disfavored 6-endo-tet ring closure mode [596].…”

Synthesis of 2,2-Dialkyl Chromanes by Intramolecular Ullmann C–O Coupling Reactions toward the Total Synthesis of D-α-Tocopherol

“…12,13) Subsequently, researchers have focused on developing numerous different methodologies for the synthesis of chromanes. [14][15][16][17][18][19][20] However, we are currently interested in the application of Ullmann C-O coupling reactions to synthesize natural products containing cyclic ether. [21][22][23] This method could be used for the reaction with sterically hindered secondary alcohols using excess amounts of strongly coordinating monodentate ligands 23) (Chart 1).…”