Amide Formation via Ni-Catalyzed Reductive Coupling Reactions with Isocyanates

Identifier:  TDX:2800

Handle: https://hdl.handle.net/20.500.11797/TDX2800

Authors:  Serrano Robledo, Eloísa Sofía

Abstract:
Recently, cross-electrophile couplings have become powerful alternatives to classical cross-coupling reactions that are based on nucleophile/electrophile regimes. Starting from readily available building blocks, reductive couplings are practical and mild protocols that circumvent the use of moisture and air-sensitive organometallic species. The ubiquity of amides in biologically relevant molecules such as peptides, agrochemicals and pharmaceuticals, as well as in polymers, continually prompts the design of novel methods for amide synthesis. This Doctoral Thesis focuses on the development of novel nickel-catalyzed reductive protocols for the synthesis of amides using isocyanates as the amide synthon. Specifically, we have discovered a novel protocol for the synthesis of aliphatic amides from primary, secondary and tertiary alkyl bromides in combination with aryl and alkyl isocyanates. A methodology for the highly diastereoselective hydroamidation of alkynes with isocyanates to afford acrylamides has been developed, with alkyl bromides used as in situ and mild hydride sources. Finally, efforts towards the regiodivergent retentive and chain-walking amidation of unactivated acyclic secondary alkyl bromides are discussed. The transformations developed herein are characterized by their mild conditions, wide substrate scope and excellent chemo- and regioselectivity, and constitute novel methods for the formation of amides via metal-catalyzed C—C bond formation.