Open AccessHighly Enantioselective Oxidation of Nonactivated Aliphatic C–H Bonds with Hydrogen Peroxide Catalyzed by Manganese Complexes
Author(s) -
Michela Milan,
Massimo Bietti,
Miguel Costas
Publication year - 2017
Publication title -
acs central science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.893
H-Index - 76
eISSN - 2374-7951
pISSN - 2374-7943
DOI - 10.1021/acscentsci.6b00368
Subject(s) - enantioselective synthesis , catalysis , chemistry , hydrogen peroxide , desymmetrization , manganese , regioselectivity , steric effects , stereoselectivity , peroxide , yield (engineering) , medicinal chemistry , organic chemistry , combinatorial chemistry , materials science , metallurgy
Monosubstituted cycloalkanes undergo regio- and enantioselective aliphatic C-H oxidation with H 2 O 2 catalyzed by biologically inspired manganese catalysts. The reaction furnishes the corresponding ketones resulting from oxidation at C3 and C4 methylenic sites (K 3 and K 4 , respectively) leading to a chiral desymmetrization that proceeds with remarkable enantioselectivity (64% ee) but modest regioselectivity at C3 (K 3 /K 4 ≈ 2) for tert -butylcyclohexane, and with up to 96% ee and exquisite regioselectity toward C3 (up to K 3 /K 4 > 99) when N -cyclohexylalkanamides are employed as substrates. Efficient H 2 O 2 activation, high yield, and highly enantioselective C-H oxidation rely on the synergistic cooperation of a sterically bulky manganese catalyst and an oxidatively robust alkanoic acid. This represents the first example of nonenzymatic highly enantioselective oxidation of nonactivated methylenic sites. Furthermore, the principles of catalyst design disclosed in this work constitute a unique platform for further development of stereoselective C-H oxidation reactions.