Catalytic, Enantioselective Aldol Additions with Methyl and Ethyl Acetate OSilyl Enolates: A Chiral Tridentate Chelate as a Ligand for Titanium(1V)

Asymmetric catalysis of the Mukaiyama aldol reaction has been reported with complexes derived from Al, B, Sn(II), and Ti(IV).l The levels of asymmetric induction for the addition of propionate-, isobutyrate-, and acetate-derived silyl thioketene acetals to aldehydes parallel those obtained with chiral-auxiliarybased methodologies.2 However, silyl ketene acetals derived from 0-alkyl acetates uniformly provide aldolates possessing lower levels of asymmetric induction. We have initiated a study aimed at thedesign and synthesisof chiralTi(1V) complexes that catalyze the enantioselective Mukaiyama aldol of 0-trimethylsilyl, 0methyl, and 0-ethyl ketene acetals with aldehydes. We report herein a catalyst that consists of a tridentate ligand derived from 3, Ti(O'Pr)d, and 3,5-di-tert-butylsalicylic acid.3 This catalyst (2-5 mol %) furnishes aldol adducts in good yields and high levels of asymmetric induction (88-97'31 ee). The design of ligands for catalysts for the Mukaiyama aldol addition have primarily included bidentate chelates derived from optically active diols,la,k diamines,lbj amino acids,lH,hJ and tartrates.lf-g Enantioselective reaction processes utilizing chiral Ti(1V) complexes have proven to be some of the most powerful transformations available to the synthetic ~ h e m i s t . ~ However, the propensity of Ti(1V) complexes to form multinuclear aggregates results in complex dynamic equilibria that can render mechanistic and structural analysis difficult. We have investigated complexes prepared from Ti(O'Pr)4 and tridentate ligands derived from 2-amino-2'-hydroxy1 ,l'-binaphthy1 (1) (Scheme 1). This amino alcohol serves as a useful scaffold for the construction of multidentate ligands for Ti(IV) and possesses several salient features: (1) facile synthesis; (2) easy derivatization of the amine; and, consequently, (3) amenability to incremental variations in the overall electronics and sterics of the metal-ligand complex.s In addition, we anticipated that tridentate ligands derived from 1 would generate well-defined