Copper Catalysts for Aerobic Oxidation of Alcohols - Transition Metal Catalysis in Aerobic Alcohol Oxidation - page 43

4Cu(II) + 4Cu(I) + 4

4

Step 1:

N
O

N
O

d n 4 r 4 n g | 0

Step 2:

2H +

2

+ 2 RCH 2 OH 2 + 2 RCHO +

N
O

N
OH

Step 3:

2H + 2 + 2 + 4

N
OH

N
O

N
O

4H +

4Cu(I) O 2 4Cu(II) + 2H 2 O

Step 4: + +

Overall Reaction:

2H 2 O

2RCH 2 OH + O 2 2RCHO +

Figure 2.3 Mechanism of the aerobic oxidation of primary alcohols by CuCl-
TEMPO catalyst proposed by Semmelhack et al.

oxidation of primary alcohols to aldehydes and is reduced to hydroxylamine.
Then a rapid comproportionation reaction between hydroxylamine (TEMPO-
H) and nitrosonium cation gives rise to nitroxyl radical (TEMPO) species
essentially required for the catalytic cycle. The copper( I ) ion is simul-
taneously oxidized to copper( II )byO 2 . TEMPO, being a stable radical, pre-
vents the aldehydes from further oxidation to acids.
Following this work, a combination of TEMPO (2 mol%) and mixed Mn( II )-
Cu( II ) nitrate (2 mol%) catalytic system was reported by Minisci and co-
workers for the aerobic oxidation of primary and secondary alcohols in acetic
acid under mild conditions with excellent yields of the oxidized products. 23 A
macrocyclic tetrafunctional nitroxyl radical (E in Figure 2.2) was also em-
ployed in the mixed metal nitrate catalysis. 24 Although the exact role of
Mn( II ) nitrate remained unclear, an oxoammonium cation was proposed as
the active oxidant formed via disproportionation of TEMPO to oxoammo-
nium and TEMPO-H. Then the metal ion oxidized TEMPO-H to TEMPO in
the presence of dioxygen.
Oxoammonium cations have been reported earlier to exhibit the oxidation
of simple aliphatic alcohols 25-27 and a Cope-like cyclic elimination of the
nitrosonium-alcoholate adduct in the transition state has been proposed. 28
In Semmelhack et al.'s procedure, however, aliphatic alcohols were not
oxidized to aldehydes. This prompted Sheldon and co-workers to reinvesti-
gate the mechanism. In 2003, they reported a detailed mechanistic study on
the CuCl-TEMPO-catalyzed oxidation of benzyl alcohol. On the basis of
results from stoichiometric oxidations with TEMPO, kinetic isotope effects
and Hammett correlation studies, they proposed a copper-mediated
dehydrogenation mechanism rather than the oxoammonium mechanism of
Semmelhack et al. 29 The formation of a copper( II )-piperidinoxyl complex via

.