报告题目： Development of transition-metal-catalyzed direct C-H amination reactions
报告人：Prof. Sukbok Chang
The direct amidation of C–H bonds to obtain nitrogen-containing heterocycles is a highly desirable reaction, because it will open the door to many new applications in chemical synthesis.1 Although tremendous progress has been made, current ability to prepare heterocycles via such direct C–H functionalization is limited.
We have developed a novel methodology that employs Ir-based catalysts and dioxazolone substrates to access short-lived Ir-nitrenoid complexes, which are key intermediates in the efficient construction of γ-lactams through direct C−H bond amidation.2 Stoichiometric studies with robust carbonylnitrene precursor, 1,4,2-dioxazol-5-ones, suggested that the insertion of C−H into metal-nitrenoid moiety is possible and mechanistic clues from the initial proof-of-concept studies further enabled the design of efficient and versatile catalysts that allows for the straightforward amidations of various sp3 C−H bonds with exceptional selectivity leading to lactam products. The power of this new method was demonstrated in the successful late-stage functionalization of bio-active molecules to produce molecules that are highly sought after for pharmaceutical and other applications in synthesis.
In case of sp2 C-H amination, while two mechanistic pathways (electrocyclization and electrophilic aromatic substitution) are mainly operative, an alternative mechanistic scaffold involving a spirocyclization step is elucidated, eventually inducing a skeletal rearrangement.3 Using the in situ generated metal imido intermedaites, we also developed a strategy of ligand participation for the Ir-catalyzed imido transfer into alkynes by employing [Cp*IrCl2]2 precatalyst and NaX salts (X = Cl or Br) as practical halide sources to furnish synthetically versatile Z-(halovinyl)lactams with excellent stereoselectivity.4
1. Park, Y.; Kim, Y.; Chang, S. Chem. Rev., 2017, 117, 9247–9301.
2. Hong, S. Y.; Park, Y.; Hwang, Y.; Kim, Y. B.; Baik, M.-H.; Chang, S. Science 2018, 359, 1016-1021.
3. Hwang, Y.; Park, Y.; Kim, Y. B.; Kim, D.; Chang, S. Angew. Chem., Int. Ed. 2018, 57, 13565-13569.
4. Hong, S.; Son, J.; Kim, D.; Chang, S. J. Am. Chem. Soc. 2018, 140, 12359-12363.
5. Kim, H.; Heo, J.; Kim, J.; Baik, M.-H.; Chang, S. J. Am. Chem. Soc. 2018, 140, 13350-13356.
6. Park, Y.; Chang, S. Nat. Catal. 2019, under revision.
Sukbok Chang教授是世界著名有机化学家，主要从事有机合成方法学研究,其科研成果主要集中于过渡金属催化的C-H键活化，用以形成新的C-C/C-O/C-N键,这些方法学主要用于一些有着重要活性的天然产物的全合成。现为KAIST化学院首席教授、韩国科学技术翰林院院士，国际著名催化杂志ACS Catalysis的副主编。