Catalytic Asymmetric Carbonylation of Prochiral Sulfonamides via C–H Desymmetrization

An
enantioselective oxidative C–H/N–H carbonylation
process was developed in this work. A bimetallic Pd/Cu-based catalyst
system was found to catalyze enantioselective C­(sp2)–H
carbonylation of prochiral arylsulfonamides via desymmetrization process
in the presence of mono-N-protected amino acid ligands. This reaction
provides a facile strategy to the stereoselective construction of
the lactam-type products, such as isoindoline-1-ones and isoquinoline-1-ones,
in good yields and enantioselectivities under balloon pressure with
the mixture of CO/O2. The reaction mechanism was rationalized
by using density functional theory (DFT) study.

本研究开发了一种对映选择性氧化型C–H/N–H羰基化反应体系。研究发现，在单N-保护氨基酸配体存在下，双金属钯/铜基催化体系可通过去对称化过程催化前手性芳基磺酰胺的对映选择性C(sp²)–H羰基化反应。该反应以CO/O₂混合气体为羰基源，在气球压力条件下即可顺利进行，能够以良好的收率和对映选择性实现异吲哚啉-1-酮、异喹啉-1-酮等内酰胺类产物的立体选择性构建。本研究通过密度泛函理论（Density Functional Theory, DFT）对该反应的机理进行了合理阐释。