Organocatalytic Aerobic Oxidation of α‐Fluoroalkyl Alcohols to Fluoroalkyl Ketones at Room Temperature

Abstract

Theo rganocatalytic aerobic oxidation of electron-deficient a-fluoroalkyl alcohols at room temperature is described. Ther esulting fluoroalkyl ketones are versatiles ynthetic intermediates for av ariety of fluorine-containingm olecules.T his otherwise difficult transformation has now been accomplished by the reactionofa-fluoroalkylalcohols with N-oxyl radicals,c atalytically generated from 9-azabicyclo[3.3.1]nonan-3-one N-oxyl/nitrogeno xide (keto-ABNO/NO x )a nd oxygeni na cetic acid (AcOH), affording the corresponding fluoroalkyl ketones in high yield. This operationally simple reaction can be performed under mild conditions,a nd was applied to aw ide range of alcohols( 20 examples), thus demonstrating ah igh functional group tolerance.M oreover, am odified one-pot protocol based on this method was able to convert an aldehyde to atrifluoromethyl ketone on ag ram scale.

Nitrosotetrazolium‐Catalyzed Aerobic Oxidation of Alcohols to the Corresponding Carbonyl Compounds

“…[1][2][3] In recent years, organocatalyst-mediated aerobic oxidation [4][5][6] has been successfully achieved using nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), 9-azabicyclo-[3.3.1]nonane-N-oxyl (ABNO), and 2-azaadamantane-N-oxyl (AZADO) with nitrogen oxides (H)NO x as cocatalysts. [7][8][9][10][11][12][13] We have recently developed mesoionic nitrosotetrazolium salt 1 through oxidation of mesoionic hydroxyamide 2 (Scheme 1). [14] Although nitroso compounds generally do not function as oxidation catalysts, a positively charged tetrazolium ring can render the nitroso group capable of acting as a mediator in the oxidation of alcohols.…”

Synthesis of a series of new ruthenium organometallic complexes derived from pyridine‐imine ligands and their catalytic activity in oxidation of secondary alcohols

“…These oxidations are often toxic and harmful to the environment, removal of traces of these reagents from the reaction mixture is costly and difficult. In recent years, considerable efforts have been devoted to the development of alcohol oxidation . For example, employing O 2 would be highly desirable to avoid toxic and hazardous stoichiometric oxidants.…”

Enhanced Structural Variety of Nonplanar <i>N</i>-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C–H Bonds

“…2-Hydroxy-3-(2,2,2-trifluoroethoxy)-3,7-bistrifluoromethy lisoindolin-1-one (21) According to the procedure B, the benzyl ether 19 (300 mg, 0.634 mmol) was converted into 21 (233 mg, 95% 2-Benzyloxy-3-methoxy-4-methyl-3-trif luoromethy lisoindolin-1-one (41) The mixture of iodide 40b (330 mg, 0.712 mmol), trimethylboroxine (0.299 mL, 2.14 mmol), Pd(OAc) 2 3-Hydroxy-7-iodo-2-(4-methoxybenzyloxy)-3-trif luorome thy lisoindolin-1-one (24a) and 4-Iodo Isomer (24b) According to the procedure described for the preparation of the alcohol 14a and b from phthalimide 13, the phthalimide 23 (6.60 g, 16.1 mmol) was converted into alcohol 24a (1.77 g, 23%) and 24b (1.74 g, 23%). Alcohol 24a: White powder; 13 (d, J=9.9 Hz, 1H), 3.81 (s, 3H) 3-Chloro-7-iodo-2-(4-methoxybenzyloxy)-3-trif luorome thylisoindolin-1-one (25) According to the procedure described for the preparation of the chloride 15 from alcohol 14a, the alcohol 24a (1.72 g, 3.59 mmol) was converted into chloride 25 (1.55 g, 87%). 7-Iodo-2-(4-methoxybenzyloxy)-3-(2-oxo-2-phenylethyl)-3-trifluoromethylisoindolin-1-one (26) According to the procedure described for the preparation of the phenylketone 8 from chloride 2, the chloride 25 (498 mg, 1.00 mmol) was converted into acetophenone 26 (464 mg, 80%).…”

“…As a part of our ongoing research program directed towards N-oxyl radical-catalyzed aerobic oxidations, [23][24][25] we applied the newly synthesized N-hydroxy precatalysts to the aerobic oxidation of benzylic C-H bonds. The results obtained are summarized in Table 1.…”