Copper Catalysts for Aerobic Oxidation of Alcohols - Transition Metal Catalysis in Aerobic Alcohol Oxidation - page 58

Organic ligands produce a steric environment at the metal center and
thereby increase the chemoselectivity in the oxidation reaction. These
compounds catalyze the aerobic oxidation of alcohols in the absence of
TEMPO or other nitroxyl radicals. Aerobic alcohol oxidation employing a
copper( I ) salt and pyridine or phen was first reported in 1977. 99 The copper-
phen complex has been reported to oxidize benzylic and allylic alcohols in
the presence 2 equiv. of base at elevated temperature in benzene. The system
required 2 equiv. of copper complex for optimum conversion and therefore
was not considered catalytic. Sakharov and Skibida reported a novel catalytic
system based on copper complexes of phen that exhibited better activity in
non-aqueous solvents, as determined by kinetic studies. 100
Mark´ and co-workers reinvestigated the copper-phen system and im-
proved the eciency of the system remarkably by using substituted hydra-
zines as reducing agents. 101-106 In 1996, Mark´ and co-workers reported the
aerobic oxidation of alcohols using CuCl (5 mol%), phen (5 mol%), di-tert-
butylazodicarboxylate hydrazine (DBADH 2 ) (5 mol%) and 2 equiv. of K 2 CO 3
in toluene at 70-90 1C. 101 The catalytic system was ecient for a number of
alcohols with high tolerance of other functional groups. However, the
catalytic system required 2 equiv. of K 2 CO 3 and was not ecient for the
oxidation of primary aliphatic alcohols. Under the basic reaction conditions,
alcohols containing a-stereogenic centers were oxidized without racemiza-
tion. It was proposed that the insoluble K 2 CO 3 acted as a heterogeneous base
in the catalytic reaction. When fluorobenzene was used instead of toluene, a
catalytic amount of base was needed. 103 Further investigation revealed that
the use of DMAP or NMI in the catalytic system improved its eciency to
such an extent that conversion of aliphatic alcohols such as 1-decanol was
increased markedly in the homogeneous phase (Figure 2.25). 105
Based on several mechanistic studies and probable roles of the additives, a
mechanistic proposal was put forward (Figure 2.25b). Initially, the copper( I )-
hydrazide complex (I) is oxidized to a peroxo-bridged copper( II )-hydrazide
species (II). Homolytic O-O bond cleavage of the peroxide intermediate
forms a copper( II )-oxyl radical species, which then abstracts a hydrogen
atom from the coordinated hydrazide to form intermediate III. Reaction of
III with alcohol affords a copper-alkoxide species (IV). Intramolecular
hydride transfer to DBAD and subsequent dissociation of the aldehyde
regenerate the copper( I ) catalyst. The mechanistic pathway of the intra-
molecular oxidation of coordinated alcoholate bears a similarity to that
proposed for GO and Cu-TEMPO system.
Mark´ and co-workers' copper catalyst in combination with a diazo re-
agent and triphenylphosphine has been applied to a domino one-pot
oxidation-olefination process. The method was applied to a variety of alco-
hols, including alcohols bearing a-stereogenic centers. 107 A catalytic system
composed of both bpy and phen in equimolar proportions in a CuCl-DBAD-
K 2 CO 3 system was effective in the aerobic oxidation of allylic and propargylic
alcohols with high yields. 108 The same strategy has also been employed in
the aerobic oxidation of 2,3-allenols to 1,2-allenic ketones. 109

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