Text

theses

ETD doctoral

The amide bond represents one of the most important functional motifs in chemistry and biology. However, despite the central role of amides as ubiquitous pharmacophores in medicinal chemistry and common intermediates in organic synthesis, transition-metal-catalyzed transformations of amides by N–C bond activation have remained largely unexplored. The major reason is that high activation energy is required for the N–C(O) bond scission due to nN→π*C=O conjugation (amide bond resonance of 15-20 kcal/mol in planar amides, ca. 40% double bond character). Our group has introduced a new generic mode of activation of amide bonds by geometric distortion, whereby metal insertion into an inert amide bond can proceed effectively if the classic Pauling’s amide bond resonance has been disrupted. During my Ph.D. research, we have successfully developed new classes of reactive amides as well as established previously unknown transition-metal-catalyzed transformations of amides and related electrophiles using ground-state-destabilization concept.

The focus of this thesis is on three major areas: (1) the use of amides as acyl electrophiles in palladium-catalyzed Suzuki-Miyaura acyl cross-coupling reactions; (2) the use of amides as aryl electrophiles in transition-metal-catalyzed aryl cross-coupling reactions; (3) the development of carboxylic acids as aryl electrophiles in transition-metal-catalyzed decarbonylative cross-coupling reactions by a redox-neutral manifold. Overall, these studies have demonstrated the potential of amides as acyl and aryl electrophiles and carboxylic acids as aryl electrophiles in catalytic cross-coupling reactions of broad synthetic interest.

ETD_11061

Ph.D.

Includes bibliographical references

doi:10.7282/t3-qdbj-gj67

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