Chelating Group Enabled Palladium‐Catalyzed Regiodivergent Carbonylative Synthesis of 2,3‐Dihydroquinolin‐4(1H)‐ones

Abstract

An ew procedure on palladium-catalyzedc arbonylative cyclization of N-(2-pyridyl)sulfonyl (N-SO 2 Py)-2iodoanilines with terminal alkenes has been developed for the rapid construction of dihydroquinolin-4(1H)-ones caffolds. Enabled by the chelatingg roup and using benzene-1,3,5-triyl triformate (TFBen) as the CO source, both aromatic and aliphatic alkenes were smoothly transformed into the corresponding 2,3-dihydroquinolin-4(1H)-ones in good yields with excellent regioselectivities. Notably,t he reaction of aromatic alkenes produces 2-aryl-2,3-dihydroquinolin-4(1H)-ones, while 3-alkyl-2,3-dihydroquinolin-4(1H)-ones were obtained when aliphatic alkenes were used. This protocol has been appliedi nt he synthesiso f antitumora gent A as well. Scheme3.Removal of the N-SO 2 Py directing group. Scheme4.Synthesis of the antitumoragent A. Scheme5.Preliminarymechanistic studies. Scheme6.Plausible mechanism.

TFBen (Benzene‐1,3,5‐triyl triformate): A Powerful and Versatile CO Surrogate

“…[40] The dihydroquinolin-4(1H)-one scaffolds can be readily synthesized by palladium-catalyzed carbonylative cyclization of N-(2-pyridyl)sulfonyl (N-SO 2 Py)-2-iodoanilines with terminal alkenes using TFBen as the CO source (Scheme 23). [43] The presence of the N-SO 2 Py directing group is considered to stabilize the key Pd(II) intermediate and promote the formation of the target products, and it could be easily removed with excess zinc powder and THF/NH 4 Cl. Noteworthy is that regiodivergence with respect to aromatic alkenes and aliphatic alkenes is observed, which is possibly effected by the electronic effect of substituents on alkenes.…”

Additive-Controlled Divergent Synthesis of Indole and 4H-Benzo[d][1,3]oxazine Derivatives: Palladium-Catalyzed Carbonylative Cyclization of 2-Alkynylanilines and Benzyl Chlorides

“…11 However, carbonylative cyclization of 2-alkynylanilines to access 4Hbenzo [d][1,3]oxazine derivatives has been less studied. Herein, we report a palladium-catalyzed carbonylative cyclization of 2alkynylanilines and benzyl chlorides with TFBen 13 as the CO source for the construction of indole and 4H-benzo [d][1,3]oxazine scaffolds (Scheme 2c). Notably, the reaction using AlCl 3 as the additive afforded indoles, while 4H-benzo [d]- [1,3]oxazines were produced when AcOH was added.…”

“…The product was obtained as a yellow solid (0.82 g, 85%); mp 87.5−88.1 °C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.59−7.57 (m, 2H), 7.44−7.36 (m, 4H), 7.18 (td, J = 8.0, 1.5 Hz, 1H), 6.79−6.74 (m, 2H), 4.31 (s, 2H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 147.9, 132.2, 131. 5, 129.8, 128.5, 128.3, 123.4, 118.0, 114.4, 107.9, 94.8, 86.0. 2-(p-Tolylethynyl)aniline (1b).…”

“…The was obtained as a yellow solid (0.803 g, 72%); mp 104.1−105.5 °C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.48 (d, J = 8.8 Hz, 2H), 7.37 (dd, J = 7.8, 1.2 Hz, 1H), 7.16−7.12 (m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.74−6.71 (m, 2H), 4.27 (s, 2H), 3.83 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 159. 6, 147.7, 133.0, 132.1, 129.5, 118.0, 115.5, 114.3, 114.1, 108.4, 94.7, 84.5, 55.4. 2-((4-Fluorophenyl)ethynyl)aniline (1e).…”

“…The product was obtained as a yellow solid (0.876 g, 83%); mp 90.4−92.1 °C. 1 H NMR (400 MHz, CDCl 3 ) δ 7.54−7.50 (m, 2H), 7.39 (d, J = 8.1 Hz, 1H), 7.19− 7.15 (m, 1H), 7.06 (t, J = 8.7 Hz, 2H), 6.77−6.73 (m, 2H), 4.28 (s, 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 162.5 (d, J = 249.5 Hz), 147.9, 133.4 (d, J = 8.3 Hz), 132.2, 129.9, 119.5 (d,J = 3.4 Hz),118.1,115.7 (d,J = 22.1 Hz),114.5,107.8,93.7,85.7. 2-((4-Bromophenyl)ethynyl)aniline (1f). Petroleum ether and ethyl acetate (20:1) were used as eluents.…”