Preparation of Polystyrene Beads with Dendritically Embedded TADDOL and Use in EnantioselectiveLewis Acid Catalysis

Abstract

A full account is given of the preparation and use of TADDOLates, which are dendritically incorporated in polystyrene beads (Scheme 1). A series of styryl-substituted TADDOLs with flexible, rigid, or dendritically branching spacers between the TADDOL core and the styryl groups (2–16 in number) has been prepared (5–7, 20, 21, 26 in Schemes 2–4 and Fig. 1–3). These were used as cross-linkers in styrene-suspension polymerization, leading to beads of ca. 400-μm diameter (Schemes 5 and 6, b). These, in turn, were loaded with titanate and used for the Lewis acid catalyzed addition of Et2Zn to PhCHO as a test reaction (Scheme 6). A comparison of the enantioselectivities and degrees of conversion (both up to 99%), obtained under standard conditions, shows that these polymer-incorporated Ti-TADDOLates are highly efficient catalysts for this process (Table 1). In view of the effort necessary to prepare the novel, immobilized catalysts, emphasis was laid upon their multiple use. The performance over 20 cycles of the test reaction was best with the polymer obtained from the TADDOL bearing four first-generation Fréchet branches with eight peripheral styryl groups (6, p-6, p-6⋅Ti(OiPr)2): the enantioselectivity (Fig. 4), the rate of reaction (Fig. 5), and the swelling factor (Fig. 6) were essentially unchanged after numerous operations carried out with the corresponding beads of 400-μm diameter and a degree of loading of 0.1 mmol TADDOLate/g polymer, with or without stirring (Fig. 7). The rate with the dendritically polymer-embedded Ti-TADDOLate (p-6⋅Ti(OiPr)2) was greater than that measured with the corresponding monomer, i.e., 6⋅Ti(OiPr)2 (Fig. 8). Possible interpretations of this phenomenon are proposed. A polymer-bound TADDOL, generated on a solid support (by Grignard addition to an immobilized tartrate ester ketal) did not perform well (Scheme 4 and Table 2). Also, when we prepared polystyrene beads by copolymerization of styrene, a zero-, first-, or second-generation dendritic cross-linker, and a mono-styryl-substituted TADDOL derivative, the performance in the test reaction did not rival that of the dendritically incorporated Ti-TADDOLate ((p-6⋅Ti(OiPr)2) (Scheme 7 and Fig. 10). Finally, we have applied the dendritically immobilized Cl2 and (TsO)2Ti-TADDOLate as chiral Lewis acid to preferentially prepare one enantiomer of the exo and the endo (3+2) cycloadduct, respectively, of diphenyl nitrone to 3-crotonoyl-1,3-oxazolidinone; in one of these reaction modes, we have observed an interesting conditioning of the catalyst: with an increasing number of application cycles, the amount of polymer-incorporated Lewis acid required to induce the same degree of enantioselectivity, decreased; the degrees of diastereo- and enantioselectivity were, again, comparable to those reported for homogeneous conditions (Fig. 9).