Adding Aliphatic C–H Bond Oxidations to Synthesis

Abstract

Oxidations of aliphatic C–H bonds, known since the 1800s, have only recently been considered for use in organic synthesis.

Site-selective C–H arylation of primary aliphatic amines enabled by a catalytic transient directing group

“…Furthermore, the primary amines with a cyclic alkyl group reacted smoothly in this catalytic system (2j and 2k). Although many successful examples for functionalizing unactivated secondary sp 3 C−H bonds have been reported with the installation of a mono-or bidentate directing group on the substrates [5][6][7][8][9][10][11][12][13][14][15] , direct functionalization of these bonds remains a great challenge with carbonyl compounds using a transient directing group 37 and free aliphatic amines 23,30,31 , presumably due to the inherent steric hindrance. In this catalytic system, substrate 1l with cyclic methylene C−H bonds provided the γ-arylated product 2l in 23% yield, while arylation of noncyclic secondary C−H bonds was not realized.…”

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

“…The oxygenation of the benzylic C-H bonds in 36a was investigated using 5 mol% of the N-hydroxy precatalyst, 1 mol% of Co(OAc) 2 , and 1 mol% of Mn(OAc) 3 ·2H 2 O in CH 3 CN under an atmosphere of O 2 (1 atm) at 60°C. When 1 was used as a control catalyst, ketone 37a was obtained in 92% yield after 12 h (entry 1).…”

“…2-Benzyloxy-3-(2,2,2-trifluoroethoxy)-3,7-bistrifluoromethy lisoindolin-1-one (19) According to the procedure described for the preparation of the trifluoromehyl compound 18 from iodide 16, the iodide 17 (444 mg, 0.837 mmol) was converted into trifluoromethyl compound 19 (346 mg, 87%). 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%).…”

“…[1][2][3] In the context of green chemistry, the use of molecular oxygen (O 2 ) for this conversion has recently attracted much attention, as it minimizes both the use of potentially hazardous oxidants and the generation of byproducts. However, C-H oxidations using O 2 are challenging, as the formation of reactive oxygen species from triplet O 2 is kinetically unfavorable.…”

Computational Insight into the Mechanism of Alkane Hydroxylation by Non-heme Fe(PyTACN) Iron Complexes. Effects of the Substrate and Solvent

“…[3][4][5][6] Furthermore, alkane C-H oxidation reactions find major interest in current organic synthesis. 7,8 Particularly interesting are C-H oxidation processes mediated by iron based species that occur with retention of the configuration at the hydroxylated carbon.…”