Preparation and Structural Analysis of Several New α,α,α′,α′‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (TADDOL's) and TADDOL analogs, their evaluation as titanium ligands in the enantioselective addition of methyltitanium and diethylzinc reagents to benzaldehyde, and refinement of the mechanistic hypothesis

Abstract

AbstractPreparation and screening of twenty new ligands, all analogs of α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL), for the Ti‐catalyzed asymmetric addition of methyltri(isopropoxy)titanium and diethylzinc to benzaldehyde are described. These ligands have the dioxolane ring of the TADDOL's replaced by cyclobutane, cyclopentane, cyclohexene, cyclohexane, bicyclo[2.2.1]heptene and ‐heptane and bicyclo[2.2.2]octene and ‐octane moieties; several have H‐atoms or alkyl groups in place of the aryl groups, and nine of them have C2 symmetry. X‐Ray crystallography and molecular mechanics are used to analyze the structure of the ligands, and two structural features appear to correlate with selectivity: (i) the torsion angle for the chelating O‐atom and the ortho‐C‐atom of the axial Ph group (a small, ca. 19°, angle is optimum, Fig.8) and (ii) the “degree of perpendicularity” of the axial Ph group (Fig. 9). Competition experiments indicate that TADDOL 1a catalyzes both the methyltitanium and diethylzinc additions ≥ 50 times faster than the related dioxolane analogs 12a, 12c, and 12e (Scheme 7), indicating that both axial and equatorial aryl groups (see Footnote 6) are necessary for ligand‐accelerated catalysis of these reactions. A refined mechanistic hypothesis is presented (Fig. 10) to explain the selectivities observed for these new ligands. Our analysis suggests that a combination of structural features appear necessary for good catalytic efficiency and high selectivity. These features, especially the rather subtle conformational effects, appear to be optimized (among the ligands tested) in the TADDOL's.