l-Proline moieties bound to a thermoresponsive polymer
nanoreactor efficiently directed the asymmetric aldol reaction in
water with excellent yields and enantioselectivity (ee). The reactions
were efficient at higher temperatures in direct contrast to the low
yields and ee values found when the reaction was carried out in a
DMF/water mixture due to the location of the l-proline moieties
within the hydrophobic pocket inside the core of the nanoreactors.
This ideal environment formed for catalysis allows control over the
water content as well as enhancing interactions between the carboxylic
acid of l-proline and the aldehyde substrate. The nanoreactors
were disassembled to fully water-soluble polymers by lowering the
temperature to below the lower critical solution temperature (LCST)
of the polymer, resulting in precipitation of the product in near
pure form. The product was isolated by centrifugation and the polymer/water
solution reused in additional catalytic cycles by heating the polymer
above its LCST and thus reforming the nanoreactors. Although a small
decrease in yield after five cycles was observed, the selectivity
(anti/syn ratio and ee) remained high.
Six novel functional monomers: 4-(4-vinylphenyl)pyridine (M1), 4′-vinylbiphenyl-4-ol (M2), N,N-dimethyl-4′-vinylbiphenyl-3-amine (M3), (4′-vinylbiphenyl-4-yl)methanol (M4), 4′-vinylbiphenyl-4-carboxylic acid (M5) and 4-hydroxy-5-methyl-4′-vinylbiphenyl-3-carboxylic acid (M6), were examined for their ability to imprint theophylline (1). Using a molecular modelling-NMR titration approach, M2 and M6 were predicted to give rise to the most specific molecularly imprinted polymers (MIPs). Rebinding analysis suggests that no imprinting effect resulted from the polymerisation of monomers M1, M5 and M6, but modest to good levels of imprinting were evident from monomers M2, M3 and M4 with IF values ranging from 1.1 (MIPM3, 20 mg) to 45 (MIPM2, 10 mg). The selective recognition of 1 varied as a function of polymer mass used. At low polymer loadings MIPM2 gave the very high IF of 45, reducing to IF = 4.1–2.3 at 20–40 mg polymer loading. With monomer M2, microwave synthesised MIP (MW-MIPM2) was examined. The MW-MIPM2 displayed lower specific rebinding than its conventionally produced counterpart (MIPM2) with IF values ranging from 1.6–2.3 (cf., MIPM2 IF 2.3–45), but significantly higher levels of rebinding with 25–52% of 1 rebound from a 0.080 mM CH3CN solution of 1 (cf., MIPM2 5–25%). MW-MIPM2 displayed a lower BET surface area than MIPM2 (185 m(2) g(−1)vs. 240 m(2) g(−1)), and lower surface (zeta) potential (−13.1 ± 8.22 mV vs. −31.4 ± 4.84 mV). Freundlich isotherm analysis revealed that MW-MIPM2 possessed higher affinity binding sites for 1 than MIPM2 with Kd values of 1.38 and 2.31 respectively. In addition, MW-MIPM2 also exhibits a higher number of binding sites (NT) compared to MW-NIPM2 (0.72 and 0.41 mg g(−1), respectively). In specificity studies using caffeine (2), MIPM2 displayed a two-fold preference for rebinding of 1 and MW-MIPM2 a five-fold preference for 1 over 2. The quantity of 2 bound in both cases was consistent with non-specific binding events. In competitive rebinding experiments, increased discrimination in favour of 1 over 2 was observed.
Carrying out organic reactions in water-based nanoreactors represents a ‘green’ method for the preparation of organic compounds. This process eliminates the need for solvents, thus reducing the effect of high volumes of solvent on the environment. In this work, we demonstrate a successful Heck cross-coupling reaction, one of the most used approaches to form C–C bonds using a palladium catalyst, in a miniemulsion. The miniemulsion droplet sizes were small (25 to 42 nm), and the reactions resulted in high conversions of three different products with high trans stereoisomers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.