The Concept of Multicatalysis in Aerobic Oxidation of Alcohols - Transition Metal Catalysis in Aerobic Alcohol Oxidation - page 175

NAD + Fe II Fe III Fe II Fe III

S FMNH 2 CoQ H 2 O

Cyt b Cyt c1

Fe II

Cyt c Cyt a

Fe II

NADH
+ H +

Fe III Fe III

FMN

P CoQH 2 O 2

Scheme 7.2 Electron transport chain in mitochondria.

remains challenging because of the high energy barrier associated with this
step. As a result, several drawbacks are still associated with these processes
including high pressure (O 2 or air), temperature or catalyst loading as well as
the use of costly and/or toxic additives. 3,5
Nature has elaborated a clever and complex system to make these trans-
formations mild and selective. Electrons go through several redox systems
(the electron transport chain of mitochondria) from substrate S to oxygen as
illustrated in Scheme 7.2. Initially, the coenzyme NAD + dehydrogenates the
substrate (i.e. alcohol) and electrons are successively accepted by the flavin
mononucleotide (FMN) and ubiquinone (CoQ) cofactors which are acting as
electron-transfer mediators (ETM). Finally, electrons go through various
cytochrome complexes (Cyt) to reduce molecular oxygen to water in presence
of protons. 6
By analogy, the development of a biomimetic multicatalytic systems in-
cluding transition metal catalyst as dehydrogenation agent, hydroquinone as
ETM and metalloporphyrins as oxygen-activating agent should be possible.
In 1987, the feasibility of this approach was demonstrated by the B¨ckvall's
group. 7 Mild and selective 1,4-diacetoxylation of diene 1 was accomplished
by using a three-component catalytic system of Pd II -hydroquinone-
Co II (TPP) 3 (Equation 7.1).

Ph

Pd(OAc) 2 (5 mol %)
hydroquinone (5 mol %)
Co II (TPP) (5 mol %)

N N

Ph

Ph Co

(7.1) AcO OAc

N N

LiOAc (1.1 equiv)
hexane-AcOH 2:1
25 °C, O 2 (1 atm), 18 h

1 2

89%
trans/cis 9:1

Ph

Co II (TPP) 3

Both the hydroquinone (as an ETM) and the metal-macrocyclic complex,
Co II (TPP) 3 (as oxygen-activating agent), were essential to lower the energy
barrier for the reoxidation of Pd 0 to Pd II (Scheme 7.3). An overview of bio-
mimetic catalytic oxidation of organic substrates can be found in the ex-
cellent review by Piera and B¨ckvall. 8
It is possible to use such a biomimetic approach for the oxidation of
alcohols in the presence of low-valent ruthenium complexes known to
dehydrogenate alcohols. 9

Benzyl alcohol (4) in the presence of