Pyrrole acetic acid derivatives in Lewis base catalyzed enantioselective formal [4+2] cycloadditions
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This thesis describes the use of C(1) ammonium enolate chemistry with Lewis base isothiourea catalysis in Michael addition-lactonization/lactamization between 2-pyrrolyl acetic acid derivatives and various Michael acceptors. Chapter 2 proved the principle that amino esters protected as benzophenone Schiff base could be α-functionalized using Lewis base catalysis. Chapter 3 described the use of 2-pyrrolyl acetic acid in enantioselective Michael addition-lactonization with CCl3 enone. After in situ ring-opening, a range of 30 diesters and diamides in up to 98% yield, >95:5 dr and >99:1 er. Further demonstration of the synthetic utility of these ring-opening derivatives was achieved with an intramolecular Friedel-Crafts acylation utilizing the electron-rich nature of pyrrole to afforded dihydroindolizinone derivatives in up to 90% yield with no erosion in stereoselectivity. Chapter 4 described the use of either α,β-unsaturated trifluoromethyl ketones or α-keto-β,γ-unsaturated esters with 2-pyrrolyl acetic acid to synthesize tetrahydroindolizine derivatives in one-pot, with up to 98% yield, >95:5 dr and >99:1 er. Chapter 5 described the synthesis of dihydropyridinones from chalcone-derived N-Ts ketimine and unsaturated cyclic sulfonamide derived from saccharin in up to 97% yield, >95:5 dr and >99:1 er. Chapter 6 described the synthesis of tetrasubstituted pyridines using a variety of unsaturated ketimines bearing esters with DHPB catalyst in up to 66% yield. Further derivatization was demonstrated via transforming 2-pivaloyloxy group into 2-OTs group in a two-step process, enabling the Pd-catalyzed cross coupling and reduction.
Thesis, PhD Doctor of Philosophy
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