Preparation of TADOOH, a Hydroperoxide from TADDOL, and Use in Highly Enantioface- and Enantiomer-Differentiating Oxidations

Abstract

Replacement of one OH group in TADDOL (=α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol) by an OOH group gives a stable, crystalline chiral hydroperoxy alcohol TADOOH (={(4R,5R)-5-[(hydroperoxydiphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}diphenylmethanol) 3, the crystal structure of which resembles those of numerous other TADDOL derivatives (Fig. 2). The new hydroperoxide was tested as chiral oxidant in three types of reactions: the epoxidation of enones with base catalysis (Scheme 2), the sulfoxidation of methyl phenyl sulfide (Scheme 3), and the Baeyer-Villiger oxidation of bicyclic and tricyclic cyclobutanones, rac-10a – d with kinetic resolution (Scheme 4, Fig. 3, and Table). Products of up to 99% enantiomer puritiy were isolated (the highest values yet observed for oxidations with a chiral hydroperoxide!). Mechanistic models are proposed for the stereochemical courses of the three types of reactions (Schemes 5 and 6, and Fig. 4). Results of AM1 calculations of the relative transition-state energies for the anionic rearrangements of the exo Criegee adducts of TADOOH to the enantiomeric bicyclo[3.2.0]heptan-6-ones are in qualitative agreement with the observed relative rates (Table and Fig. 5).