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Scheme 4. SCS Pd-pincer catalysed cross-coupling of vinyl epoxide with phenylboronic acid to afford branched (2.13) and linear (2.14) alcohols.

The palladium catalysed cross-coupling of boronic acids with unsaturated substitutes (Sizuki-Miyuara coupling) is an extremely important synthetic tool,57 with specific examples of coupling to vinyl epoxides using Pd(II) having been previously reported.58 To evaluate the effect of creating a catalytically active nanostructure, a small molecule analogue of 2.09 was also synthesised, 2.12.57, 58 The catalytic activity of 2.09 and 2.12 were compared for the coupling reaction described in

Scheme 4. Reagents were added simultaneously to the catalyst solution at 2 mol% and the mixture was agitated at 25 °C (Note: for the micellar system it was not necessary to pre-form the micelles in water and the order of reagent addition did not affect the catalysis significantly). Samples from both reactions were removed at set times and analysed by 1H NMR spectroscopy in D2O and CDCl3 for 2.09 and 2.12

respectively in order to follow the reaction kinetics (an example 1H NMR spectrum showing how conversion was determined is discussed later, Figure 49).

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Figure 44. Conversion vs. time data for catalysis by 2.12 at 2 mol %, showing the distribution of products and the total conversion.

The reaction times of the benchmark catalyst, 2.12 (at 2 mol %) in THF (Figure 44), were similar to previous literature, where 16 hours in THF gave 84 % yield.58Figure 44 also shows that the product distribution remains constant throughout the reaction 1 : 2 : 11 (2.14Z : 2.13 : 2.14E), with the linear E alkene (2.14E) being the most favoured. Again this is similar to the previous literature which showed a 11 : 1 ratio of linear to branched for a similar pincer ligand.58 The data indicated the new SCS pincer complex 2.12 catalyses this Suzuki–Miyaura effectively and performs comparably to other pincer catalysts.

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Figure 45. Conversion vs. time data for catalysis by 2.09 at 2 mol %, showing the distribution of products and the total conversion (2.13 + 2.14E + 2.14Z).

The self-assembled structures of polymer 2.09 in water (also at 2 mol%) catalysed the reaction approximately 100 times quicker than 2.12 in organic solvents (Figure 45 and Figure 44). Figure 45 also shows that the ratio of product distribution remains constant throughout the reaction (1 : 6 : 7) (2.14Z : 2.13 : 2.14E), for catalysis by 2.09 but that the selectivity toward the linear 2.14Eis diminished. This was also seen for Uozumi’s nanoreactors which had a selectivity of 1 : 1 for the linear vs. branched products (the E/Z selectivity was not mentioned). This suggests that the product distribution can possibly be altered by performing the reaction in a confined environment. However, for a similar coupling reaction using allylic alcohol and boronic esters, it has been shown that more protic environments lead to enhanced selectivity towards branched alcohols over the linear product,59 therefore the difference here could also be due to the reaction environment (aqueous vs. organic). Another interesting comparison between the kinetics of 2.09 and 2.10 is

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related to the reaction profile. By simple inspection 2.09 appears to show a first order kinetic profile whereas 2.10 appears to be zero order (with respect to reactant concentration). Typically, zero order reactions occur when the rate limiting step is during the catalytic cycle (i.e. the catalyst is effectively saturated with reactants). In the case of 2.09 this rate limiting step must have changed which causes both an increase in overall reaction rate and a shift to first order kinetics. Further investigation is needed for a more detailed understanding of the change in kinetic profiles and this is discussed later in relation to the recycling experiments. Due to the poor solubility of PAA in chloroform separation of reactants and polymer supported catalyst was achieved by simple extraction with CDCl3. After 3 extractions with

CDCl3 no product could be observed in the water phase by 1H NMR spectroscopy,

indicating complete extraction. For the reaction with 2.09 at 2 mol % 100 % conversion was reached in less than 20 minutes, isolated yields were quantitative (measured by 1H NMR using DMF as an internal standard) and the products could be characterised after extraction without the need for further purification (Figure 46).

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Scheme 5. Reaction protocol for catalysis by 2.09 in water. CDCl3

Micelles + product product Micelles

Shake Separate

Starting materials +

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Figure 46.1H NMR spectrum of the crude products 2.13 and 2.14 after extraction with CDCl3.

Control reactions in water using 2.10 (a PAA-pincer amphiphile which self- assembled but without Pd complexation) or 2.12 (which was insoluble in water) under the same conditions showed no product formation after 24 hours. This result indicates that the nanostructures must be capable of sequestering the hydrophobic substrates and also have the active Pd-pincer complex to promote effective catalysis in water. The dramatic rate increase observed in the self-assembled system 2.09

compared to the small molecule reactions in organic solvents can be attributed to an increase in local concentration around the catalyst, driven by the hydrophobic concentrator effect.6, 11-13 This increase of rate compared to the previously reported nanoreactor vesicle system,60 is attributed to an increase in nanoreactor surface area due to a reduced particle radius of the spherical or cylindrical micelles compared to vesicles, as well as the orientation in active site location; here the active site is facing inward towards the hydrophobic domain which creates a more hydrophobic local

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environment (Figure 27). The dramatic rate increase for catalysis by 2.09 in water allows for this coupling reaction to be performed in minutes rather than hours. However, as Pd is expensive and the synthesis of pincer ligands is often time consuming it might be more desirable to perform the reactions at lower loadings rather than in shorter time scales.

2.2.6 Catalytic activity at different polymer concentrations (and Pd