Enantioselective Functionalization of Prochiral Diols via Chiral Spiroketals: Preparation of Optically Pure 2-Substituted 1,3-Propanediol Derivatives and Asymmetric Synthesis of Chroman Ring and Side Chain of α-Tocopherol

Article abstract of DOI:10.1021/ja00236a034

The enantioselective functionalization of a prochiral hydroxyl group in 2-substituted 1,3-propanediols (HOCH2CR¹R²CH2OH) is presented.The reaction of the bis(trimethylsilyl) derivative of the diol with l-menthone in the presence of trimethylsilyl trifluoromethanesulfonate selectively gave one of the diastereomers of the spiroketal in which the larger substituent (R¹) occupies an equatorial position.The equatorial spiroketal was treated with acetophenone enol trimethylsilyl ether in the presence of titanium tetrachloride to give the ring-cleavage product which was produced by the selective cleavage of the equatorial C-O bond.After a proper functionalization of the hydroxyl group, the chiral auxiliary was removed under basic conditions to give the optically pure (>95percent ee) derivatives 5. The stereoselective preparation of the axial spiroketal (R¹ = H, R² = Me) and its ring-cleavage are also described.The potentiality of the present method is demonstrated in an asymmetric synthesis of (2R,6R)-2,6,10-trimethylundecanol and (S)-6-benzyloxy-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-2-methanol which are key intermediates in the total synthesis of naturally occuring (2R,4'R,8'R)-α-tocopherol.