Deacylative Thiolation by Redox‐Neutral Aromatization‐Driven C−C Fragmentation of Ketones

Abstract

Herein we report the development of deacylative thiolation of diverse methyl ketones. The reaction is redox‐neutral, and heavy‐metal‐free, which provides a new way to introduce thioether groups site‐specifically to unactivated aliphatic positions. It also features excellent functional group tolerance and broad substrate scope, thus allowing late‐stage derivatization. The process benefits from efficient condensation between the activation reagent and ketone substrates, which triggers aromatization‐driven C−C fragmentation and rapid radical coupling with thiosulfonates. Experimental and computational mechanistic studies suggest the involvement of a radical chain pathway.

Photocatalytic Alkylation/Arylative Cyclization of N-Acrylamides of N-Heteroarenes and Arylamines with Dihydroquinazolinones from Unactivated Ketones

“…1 H NMR (500 MHz, CDCl 3 ) δ (ppm) = 8.67 (d,J = 8.2 Hz,1H),2H),3H),3H),3H), 7.02 (t, J = 7.6 Hz, 1H), 3.74−3.68 (m, 2H), 3.13−3.02 (m, 2H), 2.51 (dd, J = 14.1, 7.1 Hz, 1H), 2.03 (dd, J = 14.1, 5.3 Hz, 1H), 1.70 (s, 3H), 1.37−1.13 (m, 5H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ (ppm) = 173. 5,138.9,134.3,134.2,132.5,130.4,129.6,129.4,128.5,128.3,126.8(2),126.0,125.5,125.2,124.7,120.4,119.6,116.9,67.9(2),48.9,47.6,34.1,33.2,32.6,31.1;HRMS (ESI): m/z calc. for (C 29 H 28 N 1 O 2 ) [M + H] + : 422.2115; found: 422.2117; IR (ATR) (ν cm −1 ): 3077,2938,2865,1705,1617,1455,1398,1243,1155,990,757.…”

“…1 H NMR (500 MHz, CDCl 3 ) δ (ppm) = 8.39 (d, J = 7.4 Hz, 1H), 7.59−7.47 (m, 9H), 7.41 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.25−7.20 (m, 3H), 7.17 (t, J = 7.5 Hz, 1H), 6.86 (t, J = 7.7 Hz, 1H), 3.64−3.53 (m, 2H), 3.04−2.99 (m, 1H), 2.52−2.47 (m, 1H), 1.70 (s, 1H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ (ppm) = 172. 5,167.8,137.6,134.5,134.2,133.7,132.4,131.9,130.4,129.7,129.4,128.5,128.2,126.8,126.1,125.9,125.7,125.6,124.5,122.8,120.5,119.4,116.7,47.1,38.3,34.8,31.0;HRMS (ESI): m/z calc. for (C 33 H 24 N 2 O 3 Na 1 ) [M + Na] + : 519.1679; found: 519.1658; IR (ATR) (ν cm −1 ): 3070, 29453070, , 28673070, , 17823070, , 17223070, , 16183070, , 14593070, , 13993070, , 13403070, , 12703070, , 10983070, , 1042isoquinolin-6(5H)-one (3ba).…”

“…The spectroscopic data obtained were in agreement with the reported data for the compound 3mb. 9f 9,5]imidazo[2,1-a]isoquinolin-6(5H)-one (3nb). Green solid, Yield: 30 mg, 0.08 mmol, 40%, PE:EtOAc = 99:1, Melting Point: 123 °C.…”

“…Colorless liquid, Yield: 28 mg, 0.07 mmol, 35%, PE:EtOAc = 100:0 to 99:1. 1 H NMR (500 MHz, CDCl 3 ) δ (ppm) = 8.61 (d,J = 8.2 Hz,1H),7.96 (d,J = 8.2 Hz,1H),3H),7.39 (dt,J = 31.7,7.5 Hz,2H),7.15 (s,1H),2.49 (dd,J = 14.3,7.7 Hz,1H),1.98 (dd,J = 14.3,5.2 Hz, 1H), 1.66 (s, 3H), 1.47−1.40 (m, 3H), 1.22 (d,J = 4.6 Hz,2H), 1.00−0.90 (m, 3H), 0.84−0.76 (m, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ (ppm) = 172. 7,139.4,135.7,134.1,130.5 (q,J = 32.6 Hz),130.4,127.9,126.1,124.9,124.3,124.1 (q, J = 272.4 Hz), 124.1 (q, J = 3.9 Hz), 124.0 (q, J = 3.9 Hz), 121.0, 117.1, 104.8, 49.2, 35.1, 34.6, 33.1, 31.4, 26.1(3); 19 F NMR (471 MHz, CDCl 3 ) δ (ppm) = −62.56.…”

“…3 Encouraged by earlier reports on a UV-light-mediated Norrish type I reaction of aliphatic ketones, 4 the recent trend on devising safe and convenient techniques for radical α-C−C bond cleavage of ketones has become quintessential for catalytic C−C bond functionalization. 5,6 Particularly, unstrained ketone-derived proaromatic synthons have emerged as excellent redox-responsive alkyl radical precursors, upon aromatization-driven thermal 5 or photochemical C−C cleavage. 6 In this vein, relying on the flourishing visible-light photocatalysis, 7 Zhu et al demonstrated the reactivity profile of proaromatic dihydroquinazolinones in catalytic hydroalkylation of electron-deficient alkenes (Scheme 1a).…”