Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

Abstract

This report describes a highly enantioselective oxidative sp3 C–H arylation of N-aryltetrahydroisoquinolines (THIQs) through a dual catalysis platform. The combination of the photoredox catalyst, [Ir(ppy)2(dtbbpy)]PF6, and chiral copper catalysts provide a mild and highly effective sp3 C–H asymmetric arylation of THIQs.

Metal-supported and -assisted stereoselective cooperative photoredox catalysis

“…The coupling with the corresponding boronic acid 42 leads to the desired product 43. 74 It is noteworthy that the reaction without the iridium catalyst was already described in 2008 by Baslé and Li. The product with hydrogen atoms for the substituents R 1 and R 2 was obtained in yields up to 75% and 44% ee.…”

“…73 A complementary study of the functionalization of N-aryltetrahydroisoquinoline 39 was accomplished by the same group in 2016 (Scheme 17). 74 The THIQ 39 was arylated via a stereoselective photoredox catalysis by also including [Ir( ppy) 2 (dtbbpy)]PF 6 as a photosensitizer and a combination of copper(I) bromide and the chiral PhPyBox ligand as catalysts. The arylated THIQs 43 were obtained in yields of up to 85% and with ee values of up to 90%.…”

“…(1.0 mol%), Cu salt (10.0 mol%), TBHP (2.00 equiv. ), PhPyBox (12.0 mol%), DCE, 4°C, Ar, visible light, 48 h 74. Scheme 16 Asymmetric alkynylation of tetrahydroisoquinoline (THIQ) via photoredox catalysis, overview (top) and mechanism (bottom).…”

Visible-Light-Promoted Asymmetric Catalysis by Chiral Complexes of First-Row Transition Metals

“…A chiral PhPyBox ligand was utilized for asymmetric induction and provided moderate enantioselectivities (up to 68% ee). 32…”

Stereoinduktion in der Metallaphotoredoxkatalyse

“…Die Produktbildung in Abwesenheit von Licht oder Ir III ist vermutlich auf die Cu‐eigene SET‐Chemie zurückführbar. Die Arylierung von N ‐Aryl‐1,2,3,4‐tetrahydroisochinolinen mit Arylboronsäuren wurde mit einem ähnlichen Verfahren erreicht, jedoch mit moderater Enantioselektivität (26–80 % ee ) [32] …”