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 (juglone) with butadienyl acetate catalyzed by the binaphthol-derived chiral titanium (BINOL-Ti) complex 1 proceeds in only 9% ee in the presence of molecular sieves (MS). Remarkably, however, this reaction proceeds in 76-96% ee with BINOL-Ti complex 1 freed from MS to provide the enrfo-adducts useful for the synthesis of anthracyclines and tetracyclines. The solid MS-free BINOL-Ti complex 1 is stable for months at —20 °C. Enhancements in endo selectivity and asymmetric induction are observed with the MS-free BINOL-Ti 1 also in the catalyzed D.—A. cycloaddition of methacrolein and glyoxylate with 1, 3-dienol ethers and esters. The glyoxylate adducts can be converted to the mevinolin (compactin) 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 amplification), depending simply on the mixing manner of (J?)-l with (S>1 or (±)-l.