Copper-Mediated Fluoroalkylation of Aryl Iodides Enables Facile Access to Diverse Fluorinated Compounds: The Important Role of the (2-Pyridyl)sulfonyl Group

Abstract

The (2-pyridyl)sulfonyl group was found to be a multifunctional group in the preparation of structurally diverse fluorinated products. It not only facilitates the copper-mediated (or catalyzed) cross-coupling reaction between α-fluoro sulfone 4a and aryl iodides, but also enables further transformations of the coupling products 2.

Radical (2-pyridylsulfonyl)difluoromethylation of terminal alkenes with iododifluoromethyl 2-pyridyl sulfone

“…Firstly, we tried several radical initiators and found that Cu, Pd(PPh 3 ) 4 and Na 2 S 2 O 4 were not efficient in initiating this reaction ( Table 1, entries 1-4). Then we conducted these reactions with equal molar amounts of Et 3 B/air as the radical initiating system [13], and found that the reactions afforded the corresponding radical atom-transfer products 3a in 29-70% yields in different solvents ( Table 1, entries [5][6][7][8][9][10][11][12][13][14][15]. Regarding the amount of Et 3 B, the reaction with 0.1 equiv of Et 3 B performed better than that with 1.0 equiv ( Table 1, entry 16).…”

“…13 C NMR (125 MHz, CDCl 3 ) d 151.9, 150.9, 138.3, 128.8, 126.4, 124.0 (t, J = 290.9 Hz), 40.8 (t, J = 18.6 Hz), 40.2, 31. 8,29.61,29.60,29.59,29.58,29.56,29.5 (d,J = 2.1 Hz),29.44,29.33,29.29,29.28,28.4,22.6,21 4.2.5. 5,pentan-1-ol (3d) 1 H NMR (400 MHz, CDCl 3 ) d 8.83 (d,J = 4.4,1H),8.14 (d,J = 7.9 Hz,1H),8.03 (td,J = 7.8,1.7 Hz,1H),7.67 (ddd,J = 7.6,4.7,1.1 Hz,1H),1H),1H),1H),2H), 2.20 (s, 1H), 2.02- 1.98 (m, 2H).…”

“…In particular, 2-PySO 2 CF 2 H was found to act as a novel and efficient gemdifluoroolefination reagent for preparing gem-difluoroalkenes from both aldehydes and ketones via a Julia-Kocienski protocol [7]. Furthermore, the (2-pyridyl)sulfonyl group exhibited versatile chemical behaviors in fluoroalkylation reactions [8]. Moreover, fluoroalkyl 2-pyridyl sulfones (2-PySO 2 R f ) are important potential precursors for fluorinated sulfinate salts by depyridination [9], which have recently emerged as promising reagents for the direct incorporation of fluoroalkyl groups onto heteroaromatic systems by a formal C-H functionalization through a radical addition process [10].…”

“…F NMR (376 MHz, CDCl 3 ) d À100.34 (ddd,J = 229.9, 26.5, 9.7 Hz, 1F), À101.93 (ddd, J = 230.0, 24.6, 10.5 Hz, 1F). 13 C NMR (125 MHz, CDCl 3 ) d 178 8, . 151.5, 150.9, 138.5, 128.9, 126.4, 123.7 (t, J = 290.9 Hz), 40.7 (t, J = 18.7 Hz), 39.1, 32.6, 24.5, 19.5.…”

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

“…Im Allgemeinen werden für nucleophile Fluormethylierungen Elektrophile mit Fluormethidäquivalenten eingesetzt, die durch elektronenziehende Gruppen stabilisiert sind und aus Pränucleophilen wie Fluorbis(phenylsulfonyl)methan (FBSM) oder a-Fluor(phenylsulfonyl)methan (FSM) durch Deprotonierung gebildet werden. [197] Enantiomerenangereicherte a-monofluormethylierte Amine wurden durch phasentransferkatalysierte enantioselektive Mannich-Reaktion mit FBSM synthetisiert. [191] Da ein chirales Auxiliar verwendet wird, muss die chirale Verbindung in stçchiometrischer Menge eingesetzt werden, aber die Reaktion kann mit > 99:1 Seitenselektivität durchgeführt werden.…”