Immobilization of 2,4-cis-Diarylprolinol Silyl Ethers, Isothioureas, SPINOL-Derived Phosphoric Acids and Their Application in the Catalytic Enantioselective Synthesis in Batch and Flow

The main goal in this thesis has been to develop novel immobilization strategies leading to heterogenized catalysts with improved catalytic properties.

Firstly, a new family of polystyrene (PS)-supported cis-4-hydroxydiphenylprolinol derivatives has been prepared and evaluated in the tandem reaction between N-protected hydroxylamines and α,β-unsaturated aldehydes in batch and flow. The new immobilized catalysts compare favorably with previous, well-established catalysts, affording 5-hydroxyisoxazolidines as single diastereomers with high enantioselectivities and good yields.

Secondly, a PS-immobilized chiral isothiourea has been prepared and applied to the enantioselective acylative kinetic resolution of monoacylated BINOL(s) with inexpensive isobutyric anhydride in batch and flow. High selectivity and a remarkable stability of the catalytic system in the operation conditions have been recorded for unsubstituted BINOL. A continuous flow process has been implemented and operated with a 100 mmol (32.8 g) sample of racemic monoacetylated BINOL in a 84 hours experiment with a packed bed reactor containing 1 g (f = 0.37 mmol.g-1) of the functional resin.

Thirdly, we have used radical co-polymerization strategy to prepare a new family of PS-immobilized SPINOL-derived chiral phosphoric acids. The optimal immobilized species brings about the catalytic desymmetrization of 3,3-disubstituted oxetanes in excellent yields and enantioselectivities, exhibiting a very high recyclability. Finally, a continuous flow process has been implemented and operated for the sequential preparation of 17 diverse enantioenriched products.

In addition, the use of electricity as a green oxidant in combination with salts of abundant metals as catalysts has also been explored. We have thus developed a manganese/copper co-catalyzed electrochemical Wacker-Tsuji-type oxidation of aryl-substituted olefins, affording α-aryl ketones in moderate to excellent yields, with the advantages of avoidance of palladium as a catalyst and any external chemical oxidant, in an easily operated, cost-effective procedure.

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