Abstract
Catalytic C–H activation and hydroamination represent two important strategies for eco-friendly chemical synthesis with high atom efficiency and reduced waste production. Combining both C–H activation and hydroamination in a cascade process, preferably with a single catalyst, would allow rapid access to valuable nitrogen-containing molecules from readily available building blocks. Here we report a single metal catalyst-based approach for N-heterocycle construction by tandem C–H functionalization and alkene hydroamination. A simple catalyst system of cationic rhodium(I) precursor and phosphine ligand promotes redox-neutral [4+2] annulation between N–H aromatic ketimines and internal alkynes to form multi-substituted 3,4-dihydroisoquinolines (DHIQs) in high chemoselectivity over competing annulation processes, exclusive cis-diastereoselectivity, and distinct regioselectivity for alkyne addition. This study demonstrates the potential of tandem C–H activation and alkene hydrofunctionalization as a general strategy for modular and atom-efficient assembly of six-membered heterocycles with multiple chirality centres.
Highlights
Catalytic C–H activation and hydroamination represent two important strategies for eco-friendly chemical synthesis with high atom efficiency and reduced waste production
Transition metal-mediated C–H bond activation has been increasingly explored in catalytic construction of heterocycles that involve tandem formation of carbon–carbon and carbon–heteroatom bonds[1,2,3,4,5,6,7,8]
A major strategy for such catalytic heterocycles synthesis via C–H activation is the intermolecular coupling between aromatic compounds and alkynes to form six-membered benzoheterocycles (Fig. 1a)
Summary
Catalytic C–H activation and hydroamination represent two important strategies for eco-friendly chemical synthesis with high atom efficiency and reduced waste production. Redox-neutral [4 þ 2] annulations with aromatic compounds and alkynes would provide direct access to partially saturated benzoheterocycles in 100% atom efficiency and forms up to two new chirality centres (Fig. 1a) This strategy was only demonstrated in a single report in 2013 by Sun, Wang and coworkers[35], who developed a Re(I)–Mg(II) bimetallic catalyst for benzamide/alkyne coupling to synthesize 3,4-dihydroisoquinolinones with controlled cis- or trans-diastereoselectivity (Fig. 1c). This redox-neutral [4 þ 2] annulation featured a ring-closure step of Mg-catalysed intramolecular alkene addition by the amide N–H bond, which represents an example of main group metal-catalysed alkene hydroamination[36]. Synthetic utility of target DHIQ products are demonstrated with several stoichiometric and catalytic transformations including diastereoselective hydride reduction and Rh(III)-mediated regioselective C–H functionalizations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
