On the Mechanisms of Enantioselective Reactions Using α,α,α′,α′ ‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol(TADDOL)‐Derived Titanates: Differences between <i>C</i>₂‐ and <i>C</i>₁‐symmetrical TADDOLs – facts, implications and generalizations

Abstract The titanates derived from α,α,α′,α′‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (TADDOLs, prepared from tartrate) act as catalysts for enantioselective additions of dialkylzinc compounds to aldehydes. For the standard reaction chosen for this investigation of the mechanism, the addition of diethylzinc to benzaldehyde, there is very little change of selectivity with different aryl substituents on the TADDOLate ligands ( Tables 2–4 , examples). With 0.02 to 0.2 equiv. of the chiral titanates, selectivities above 90% are observed only in the presence of excess tetraisopropyl titanate! According to NMR measurements ( Fig. 2 ), the chiral bicyclic titanate and the achiral titanate do not react to give new species under these conditions. From experiments with different stoichiometries of the components, and with different achiral or chiral OR groups on the Ti‐atom of the seven‐membered ring titanate, it is concluded ( i ) that a single chiral titanate is involved in the product‐forming step, ( ii ) that the bulky TADDOLate ligand renders the Ti‐center catalytically more active than that of (i‐PrO) 4 Ti, due to fast dynamics of ligand exchange on the sterically hindered Ti‐center ( Table 5, Fig. 3 ), and ( iii ) that the role of excess (i‐PrO) 4 Ti is to remove – by ligand exchange – the product alkoxides (R*O) from the catalytically active Ti‐center ( Scheme 4, Table 6 ). Three new crystal structures of TADDOL derivatives (two clathrates with secondary amines, and a dimethyl ether) have been determined by X‐ray diffraction ( Figs. 5–7 ), and are compared with those previously reported. The distances between the C(aryl) 2 O oxygen atoms in the C 2 ‐ and C 1 ‐symmetrical structures vary from 2.58 to 2.94 Å, depending upon the conformation of their dioxolane rings and the presence or absence of an intramolecular H‐bond ( Fig. 8 ). A single‐crystal X‐ray structure of a spiro‐titanate, with two TADDOLate ligands on the Ti‐atom, is described ( Fig. 9 ); it contains six different seven‐membered titanate‐ring conformations in the asymmetric unit ( Fig. 10 ), which suggests a highly flexible solution structure. The structures of Ti TADDOLate complexes are compared with those of C 2 ‐symmetrical Ru, Rh, and Pd disphosphine chelates ( Table 7 ). A common topological model is presented for all nucleophilic additions to aldehydes involving Ti TADDOLates ( Si attack with ( R , R )‐derivatives, relative topicity unlike; Fig. 11 ). Possible structures of complexes containing bidentate substrates for Ti TADDOLate‐mediated ene reactions and cycloadditions are proposed ( Fig. 12 ). A simple six‐membered ring chair‐type arrangement of the atoms involved can be used to describe the result of TADDOLate‐mediated nucleophilic additions to aldehydes and ketones, with Ti, Zr, Mg, or Al bearing the chiral ligand ( Scheme 6 ). A proposal is also made for the geometry of the intermediate responsible for enantioselective hydrogenation of N ‐(acetylamino)cinnamate catalyzed by Rh complexes containing C 2 ‐symmetrical diphosphines ( Fig. 13 ).