Azidobenziodazolones as Azido Sources for the Enantioselective Copper-Catalyzed Azidation of N-Unprotected 3-Trifluoromethylated Oxindoles

Abstract

Both azido (N 3 ) and trifluoromethyl (CF 3 ) groups are key moieties of numerous valuable molecules that are extensively applied in drug discovery, chemical biology, and synthetic chemistry. However, the asymmetric construction of chiral quaternary stereocenters bearing both N 3 and CF 3 groups is still unexplored. Herein, we report a kind of bench-stable and easily adjustable benziodazolone-based azidating reagents. These reagents were used to achieve an enantioselective copper-catalyzed azidation of N-unprotected 3-trifluoromethylated oxindoles to provide diverse enantioenriched 3-N 3 -3-CF 3 oxindoles.

Copper-Catalyzed/Hypervalent Iodine-Mediated Functionalization of Unactivated Compounds

“…After the copper-assisted single-electron oxidation, cations L and LI were produced, promoting the final intramolecular nucleophilic attack to the reaction products. Concerning the direct functionalization of C(sp 3 )-H bond, Deng and co-workers reported an enantioselective azidation of N-unprotected 3-trifluoromethyl oxindoles (Scheme 100) [138]. The reaction conditions involve Cu(CH 3 CN) 4 PF 6 as catalyst, benziodazolone-based azidating reagent, and bis-oxazoline ligand XLIX.…”

Mn-electrocatalytic oxidative C(sp3)–H azidation of 2-oxindoles and β-keto esters and azidation–cyclization of tryptamines

“…The pursuit of efficient and widely applicable electrocatalytic C(sp 3 )–H azidation is still highly desirable. With the continued interest in the synthesis of aliphatic azides, 17 herein, we present a general protocol for producing tertiary azides by Mn-electrocatalytic oxidative C(sp 3 )–H azidation of 2-oxindoles, 3 a ,18 β-keto esters 3 a , b ,2 c , d and azidation–cyclization of trypamines, 19 all of which serve as prevalent structural motifs in various natural products and pharmacologically active molecules. Furthermore, the first instance of enantioselective electrocatalytic C(sp 3 )–H azidation was achieved by the catalysis of the chiral Jacobsen catalyst, 20 with the ee values reaching up to 43% (Scheme 1b).…”

Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles

“…Among these, hypervalent iodine-based azidating reagents were often selected as the azido sources 60 – 66 due to their advantages of mild properties and high selectivity. In previous research, benziodazolone-based azidating reagents were identified as efficient azido transfer reagents that could significantly improve reaction outcomes by adjusting the substituents 64 . In continuation of our interest in hypervalent iodine chemistry 64 – 69 , we report herein an efficient enantioselective copper-catalyzed azidation/click cascade reaction of N -propargyl-β-ketoamides and azidobenziodazolone 1d .…”

“…In previous research, benziodazolone-based azidating reagents were identified as efficient azido transfer reagents that could significantly improve reaction outcomes by adjusting the substituents 64 . In continuation of our interest in hypervalent iodine chemistry 64 – 69 , we report herein an efficient enantioselective copper-catalyzed azidation/click cascade reaction of N -propargyl-β-ketoamides and azidobenziodazolone 1d . This method demonstrates broad substrate scope, easy operation, and mild reaction conditions.…”