Lit. seminar

Aerobic Catalytic Oxidative
Radical Reactions

Y. Tanaka (D2)
10. 5. 19

Use of Molecular Oxygen in Catalytic Cycle
Substrate

Product

Cat. ox.

Cat. red.

ByproductOxidant

Oxidant

Substrate

Product

Cat. ox.

Cat. red.

Catalytic one electron
donor/acceptor

ideal: O2
real: DDQ, CAN, etc…
O2

H2O

Contents
1. Cu-TEMPO catalyst system

2. Organic photo catalyst system

1. Cu-TEMPO catalyzed Aerobic Oxidation of Alcohols
1. Cu-TEMPO catalyst system

2. Organic photo catalyst system

Cu-TEMPO catalyzed Aerobic Oxidation of Alcohols

R-OH

CuCl (10 mol %), TEMPO (10 mol %)DMF, 25 ℃OR

HSemmelhack et al. J. Am. Chem. Soc. 1984, 106, 3376.

Proposed Reaction Mechanism by Semmelhack

Actual oxidant

O2 : Oxidize Cu(1)Semmelhack et al. J. Am. Chem. Soc. 1984, 106, 3376.

Proposed Reaction Mechanism by Sheldon

Actual oxidant

O2 : Oxidize TEMPOH

Sheldon et al. Org. Biomol. Chem. 2003, 1, 3232.

Verification of the Mechanism 1Cu(1) + TEMPO
Cu(1) + TEMPO
N2, rt, 24 hCu(2)Cu(2) + TEMPOH

TEMPO
Cu(1)

Verification of the Mechanism 2

Instantaneously occur in basic H2O (checked by the color)

Verification of the Mechanism 3

KIE
HammetCompared withother reactions

Kinetic isotope effectOH
D H
OH

catalytic under O2: kH/kD = 5.42

Cu-TEMPO+Stoichio. under N2: kH/kD = 5.77

OD

Verification of the Mechanism 3

Hammett plot

Verification of the Mechanism 3

R.D.S.

Verification of the Mechanism 3
cf. Galactose oxidase

Proposed Hydrogen Abstraction Mechanism

By analogy with galactose oxidase

Proposed Catalytic CycleFurther Improvement through Condition Optimization

Sheldon et al. Chem. Comm. 2003, 2414.

Other Examples of Cu-TEMPO Catalyzed Reactions

Vatele SYNLETT 2009, 13, 2143.

[Cat] = CuBr2
T = 60 ℃

Jiao et al. J. Am. Chem. Soc. 2010, 132, 28.

2. Organic Photo Catalyst System
1. Cu-TEMPO catalyst system

2. Organic photo catalyst system

Aerobic Photocatalytic Reactions

Floreancig et al.

Fukuzumi et al.

Fukuzumi et al.

Aerobic Oxidation of Toluene with Photo Catalyst

Conditions

33 mol %O2, CHCl3, 25 ℃
Fukuzumi et al. J. Am. Chem. Soc. 2003, 125, 12850.

Proposed Catalytic Cycle
LUMO
HOMO
LUMO

Photo catalyst

HOMO

LUMO
HOMO

Organic Photo Catalysts

3147561198210

Organic Photo Catalysts

One electron reduction potential of ground state

LUMO

LUMO

e−HOMOHOMO

cf. O2 + e−

O2: −0.72 eV

Organic Photo Catalysts

One electron reduction potential of singlet exited state
LUMO

e−LUMO
HOMO

HOMO

cf. DDQ: +0.56 V

Organic Photo Catalysts

Fluorescence life time

Fluorescence

Organic Photo Catalysts

Singlet exited energy E0red−E0red*
Nearly HOMO-LUMO gap
1 eV = ca. 1200/λ (nm-1) = 23 kcal/mol
1: 3.81 eV
λmax = 312 nm

8: 3.58 eV

10: 2.75 eV
λmax = 417nm

Organic Photo Catalysts

Quenching rate constants

Fluorescence

E0red vs Reactivity

1

50.1 eV difference: ca. 50 times faster reaction

798

346

11

210

Reaction with p-tolunitrile

rt

33 mol %E0red* = +3.17 V

254, 365, 405, 436, 546, 577, 579 nm

Mercury lamp throughacetophenone –methanol filter(>300 nm)

Reaction with Xylens

rtXenon lamp through UV cutoff filter (> 310 nm)

33 mol %Aerobic Photocatalytic Reactions

Floreancig et al.

Fukuzumi et al.

Fukuzumi et al.

Stichio. Reaction( )nStichio.

( )nProposed Reaction Mechanism

Floreancig et al. J. Am. Chem. Soc. 2001, 123, 3842.

Catalytic Reaction

Catalytic

Floreancig et al. Org. Lett. 2001, 3, 4123.

Condition Optimization

NMQ+

Substrate Scope

NMQ+Other Examples of This Type Reaction

Floreancig et al. Org. Lett. 2002, 4, 3443.