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

Abstract

Dedicated to Professor Barry M. Trost on the occasion of his 60th birthday 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-mm diameter (Schemes 5 and 6, b). These, in turn, were loaded with titanate and used for the Lewis acid catalyzed addition of Et 2 Zn 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 Fre¬chet branches with eight peripheral styryl groups (6, p-6, p-6 ¥ Ti(O i Pr) 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-mm 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(O i Pr) 2 ) was greater than that measured with the corresponding monomer, i.e., 6 ¥ Ti(O i Pr) 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-styrylsubstituted TADDOL derivative, the performance in the test reaction did not rival that of the dendritically incorporated Ti-TADDOLate ((p-6 ¥ Ti(O i Pr) 2 ) (Scheme 7 and Fig. 10). Finally, we have applied the dendritically immobilized Cl 2 and (TsO) 2 Ti-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).

Cheap and Long‐Life Reusable Polymer for Asymmetric Organozinc Catalysis Based on Camphor‐Derived Hydroxyamides

“…The obtained results show the high stability of these hydroxyamide‐grafted polymers because 6b could be easily recovered, recycled, and reused in, at least, 20 sequential applications with practically constant both enantioselectivity (96–97% of R isomer) and chemical yield (95–98%). This high reproducibility is similar to the ones achieved for certain titanium catalysts in the same reaction, which is especially noticeable by taking into account the acidic treatment used for the reaction quenching in our case, and as it was expected by us on the basis of the chemical robustness of the used hydroxyamide ligands toward such treatment.…”

“…For this purpose, we decided to graft 2 onto polystyrene (PS), on the basis of the known good swollen properties of this polymer by the action of several organic solvents used in organozinc reactions (i.e., toluene). The polymer swelling factor is a key parameter in catalyst heterogenization because a good swelling factor reduces the undesired diffusion effect produced by the heterogenization . For grafting 2 onto PS, we prepared 4 as a conveniently functionalized analogue of 2 .…”

“…Although the recorded enantioselectivities are somewhat lower than those achieved with standard catalysts, the hydroxyamide‐supported polymeric system demonstrated a remarkable recyclability, allowing 20 consecutive uses (more cycles were not tested), including 20 consecutive catalyst quenching and polymer washing and drying, which is not the common case in most of the recyclable organozinc‐based catalysts. Therefore, it is worthwhile to investigate this strategy in other asymmetric reactions involving zinc catalysts, as well as the use of dendritically cross‐linked polymers or nanosized matrixes to reduce the observed negative diffusion effect on the reaction rates.…”

Dendrons and dendritic catalysts immobilized on solid support: Synthesis and dendritic effects in catalysis

“…11 To keep this presentation concise, we have excluded a number of heterogeneous dendritic catalysts obtained via the polymerization and crosslinking of homogeneous dendritic catalysts or ligands prepared a priori in solution. 12,13 …”

Chiral Porous TADDOL-Embedded Organic Polymers for Asymmetric Diethylzinc Addition to Aldehydes

“…3135 Heterogeneous TADDOL catalysts can be prepared by immobilizing TADDOL to resins, 33 highly porous silica gel, 34 or by copolymerizing TADDOL derivatives with styrene, 35 but only a few of them exhibit satisfactory enantioselectivity. Asymmetric diethylzinc addition to aldehydes is important for preparing chiral alcohols.…”