Professor and Director Sukbok Chang
Korea Advanced Institute of Science & Technology (KAIST) and Institute for Basic Science (IBS)
Title: Stereoselective Amidation of Unsaturated Compounds: Transposed Pathways and Synthetic Applications
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Abstract: Synthetic methods for constructing enantioenriched lactams are highly valuable given their ubiquity in bioactive compounds, most notably in antibiotics such as penicillins and carbapenems. An intramolecular formal hydroamidation of -unsaturated carbonyl compounds may offer a promising means to access this important chemical space, yet it remains limited due to the regioselectivity issue arising from the difficulty associated with the formation of strained four-membered rings. To address these issues, we have developed a NiH-catalysed approach utilizing readily accessible alkenyl dioxazolone derivatives. The reaction turned out to surpass conventional NiH mechanism through an unprecedented pathway initiated by prior N-activation, enabling proximal C–N bond formation with excellent regioselectivity, irrespective of substituent electronic properties. We also explored a Ni-catalyzed formal hydroamidation of α,β-unsaturated carbonyl compounds, yielding valuable chiral β-amino acid derivatives (up to >99:1 e.r.) using dioxazolones as a robust amino source. Furthermore, we recently developed a base-mediated, stereoretentive decarboxylative amidation of carboxylic acids under transition-metal-free and ambient conditions. This method effectively converts primary, secondary and tertiary carboxylic acids into α-chiral amines, providing straightforward access to this crucial pharmacophore.
Keywords: Transition metal catalysis, C-H amidation, hydroamidation, nitrenoid intermediacy