Research

The functionalization of carbon–hydrogen bonds offers an attractive step-economical entry into valuable organic intermediates from simple precursors containing hydrocarbon fragments. The current research of our group mainly focuses on the development of various transition-metal-catalyzed methods for the functionalization of non-activated C(sp³)–H and C(sp²)–H bonds.

The reactions that we recently developed allow the formation of C(sp²)–C(spⁿ) bonds from simple C(sp²)–X/C(spⁿ)–H precursors (X = leaving group; n = 2, 3) using palladium catalysts. A variety of valuable carbocycles and heterocycles are generated through these methods.

Review: Acc. Chem. Res. 2017, 50, 1114.

Leading papers: Angew. Chem. Int. Ed. 2003, 42, 5736; J. Am. Chem. Soc. 2008, 130, 15157; J. Am. Chem. Soc. 2010, 132, 10706; Angew. Chem. Int. Ed. 2012, 51, 10399; Angew. Chem. Int. Ed. 2016, 55, 2805; Angew. Chem. Int. Ed. 2017, 56, 7218; Angew. Chem. Int. Ed. 2018, 57, 12131; ACS Catal. 2023, 13, 12563.

Recently, we harnessed the 1,4-Pd shift mechanism to reach more distant C(sp³)–H bonds and create rings that would be challenging to make through the direct reaction.

Leading papers: Org. Lett. 2019, 21, 1434; Angew. Chem. Int. Ed. 2019, 58, 14625; J. Am. Chem. Soc. 2020, 142, 15355; Angew. Chem. Int. Ed. 2020, 59, 18980; Angew. Chem. Int. Ed.2022, e202116101.

We are developing enantioselective C(sp³)–H and C(sp²)–H activation reactions using various types of chiral catalysts (ancillary ligand, base, bifunctional ligand). These methods allow access to enantioenriched molecules containing stereogenic centers or axes, with potential applications in medicinal chemistry or chiroptical devices.

Review: Chem. Eur. J.  2021, 27, 1231.

Leading papers: ACS Catal. 2015, 5, 4300; Angew. Chem. Int. Ed. 2017, 56, 7218; Chem. Sci.  2017, 8, 1344; Angew. Chem. Int. Ed. 2018, 57, 1394; J. Am. Chem. Soc. 2020, 142, 2161;Angew. Chem. Int. Ed. 2021, 60, 5136; Angew. Chem. Int. Ed. 2021, 60, 7245; Nat. Chem.2023, 15, 872.

C–H activation-based strategies allow to streamline the synthesis of bioactive natural products using simpler precursors. Using such strategies, we recently synthesized:

- aeruginosins (e. g., aeruginosin 298A), cyanotoxins isolated from various blue-green algae;
- lycorine alkaloids, originated from Amaryllidaceae plants (e. g., g-lycorane);
- (nor)illudalane sesquiterpenes (e. g., puraquinonic acid and russujaponol F), isolated from various species of higher fungi;
- pentacyclic dithiodiketopiperazines (e. g., epicoccin G and rostratin A), isolated from various types of fungi;
- prenylated chalcones (e. g., indidene C), isolated from Southeastern Asian plants.

Review: Angew. Chem. Int. Ed. 2020, 59, 17798.

Leading papers: Angew. Chem. Int. Ed. 2015, 54, 4919; Org. Lett.2018, 20, 772; Org. Lett. 2019, 21, 812; J. Am. Chem. Soc. 2019, 141, 15779.

We are also interested in the development of new C–H amination methods. In particular, we recently reported a new dioxazolone reagent for directed iridium-catalyzed C(sp³)–H amidations. This reagent combines good reactivity and safety profile, and furnishes an easily cleavable amide. These C–H amination methods lead to valuable 1,2-aminoalcohols and 1,2-diamines.

Leading papers: Angew. Chem. Int. Ed.2021, 60, 22948; Angew. Chem. Int. Ed.2023, e202309263.