Title:Frontiers in Copper-promoted C1-functionalization of Tetrahydroisoquinoline Using
Cross-dehydrogenative Coupling
Volume: 27
Issue: 14
Author(s): Rachana Upadhyay and Amit B. Patel*
Affiliation:
- Department of Chemistry, Government College Daman (Affiliated to Veer Narmad South Gujarat University), Daman (U.T.),
396210, India
Keywords:
C1-stereoselectivity, cross-dehydrogenative coupling, Csp3-H functionalization, copper catalyst, tetrahydroisoquinoline, compounds.
Abstract: The site-selective diversification of molecules is a pertinent unresolved issue within
the area of organic chemistry. The functionalization of Csp3-H has changed the landscape of synthetic
chemistry by enabling effective direct coupling of compounds and reducing chemical
waste by avoiding the usage of pre-functionalized compounds. The 1,2,3,4-
tetrahydroisoquinoline (THIQ), a molecule with potential bioactivity, has a stereoselective center
at the C1 position. However, there is still a fundamental problem with the C1-functionalization of
THIQs. To address this, transition metal-catalyzed cross-dehydrogenative coupling (CDC) has
evolved into an essential tool because such reactions can be carried out with enantio-, regio-, and
stereoselectivity. In particular, copper-promoted CDC reactions have undoubtedly made substantial
progress in THIQ chemistry as a selective protocol. The α-Csp3-H bond adjacent to the N-atom
of THIQs is activated using copper catalysts, followed by dehydrogenative coupling with various alkynyl,
alkane, and alkene groups to form the Csp-Csp3, Csp3-Csp3, and Csp3-Csp2 bonds and produce optically active
C1-substituted THIQs. The A3 coupling strategies also produce the endo-yne-THIQs with higher selectivity.
This critical discussion highlights all recent advancements (between 2010 and 2022) in CDC reactions to
THIQs with the substrate scope and plausible mechanistic routes. This study may be extremely useful to scientists
and researchers working on copper-promoted CDC.