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Rhodium(III)-catalyzed amide-directed C-H activation and [4+2] cycloaddition for modular assembly of nitrogen heterocycles




Semakul, Natthawat, author
Rovis, Tomislav, advisor
Kennan, Alan, committee member
Shi, Yian, committee member
McCullagh, Martin, committee member
Kipper, Matt, committee member

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This dissertation describes the ligand and reaction developments by amide-directed rhodium(III)-catalyzed C(sp2)-H bond activation followed by amidoannulation with alkenes to form nitrogen-containing heterocycles. Chapter 1 details the ligand development for stereoselective synthesis of [4.1.0] dihydroisoquinolones through benzamidation of cyclopropenes mediated by Rh(III) catalysis. Quantum chemical calculations revealed the important role of heptamethylindenyl (Ind*) ligand and O-substituted ester of benzhydroxamate for achieving high diastereoselectivity in cyclopropene insertion. Efforts toward stereoselective synthesis of [4.1.0] dihydroisoquinolones have been also studied by streptavidin-based artificial metalloenzyme. Chapter 2 presents the stereoselective synthesis of [4.2.0] dihydroisoquinolones via the benzamidation of cyclobutenes. The transformation proved to have a broad substrate scope and functional group tolerance that generates the cyclobutane-fused azacycles with excellent diastereoselectivity. The artificial metalloenzymes can render this reaction asymmetric furnishing the dihydroisoquinolone products in moderate enantioselectivity. Chapter 3 communicates Rh(III)-catalyzed C-H activation and [4+2] annulation reaction of N-pivaloyloxy acrylamides with alkenes for an efficient synthesis of α,β-unsaturated-δ-lactams. This process offers a platform for the rapid assembly of a diverse set of delta-lactams from simple and abundant precursors. These lactams could serve as useful building blocks to access substituted piperidines.


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rhodium(III) catalysis
C-H activation


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