ASYMMETRIC CATALYSIS OF DIELS-ALDER CYCLOADDITIONS BY AN MS-FREE BINAPHTHOL-TITANIUM COMPLEX - DRAMATIC EFFECT OF MS, LINEAR VS POSITIVE NONLINEAR RELATIONSHIP, AND SYNTHETIC APPLICATIONS

Asymmetric Diels-Alder (D.-A.) reaction of 5-hydroxynaphthoquinone (ju glone) with butadienyl acetate catalyzed by the binaphthol-derived chi ral titanium (BINOL-Ti) complex 1 proceeds in only 9% ee in the presen ce of molecular sieves (MS). Remarkably, however, this reaction procee ds in 76-96% ee with BINOL-Ti complex 1 freed from MS to provide the e ndo-adducts useful for the synthesis of anthracyclines and tetracyclin es. The solid MS-free BINOL-Ti complex 1 is stable for months at -20 d egrees C, Enhancements in endo selectivity and asymmetric induction ar e observed with the MS-free BINOL-Ti 1 also in the catalyzed D.-A. cyc loaddition of methacrolein and glyoxylate with 1,3-dienol ethers and e sters. The glyoxylate adducts can be converted to the mevinolin (compa ctin) intermediates. Surprisingly, the MS-free complex 1 exhibits not only a linear relationship between the ee's of BINOL-Ti 1 and the D.-A . products but also a positive nonlinear effect (asymmetric amplificat ion), depending simply on the mixing manner of (R)-1 with (S)-1 or (+/ -)-1.