2640
A. Itoh et al.
LETTER
Table 2 Aerobic Photooxidation for Various Alcohol Substrates
Br2
Br
RCH2OH
LiBr
hν
LiBr (0.3 equiv), hν (400 W)
RCHOH
O2-balloon
13
substrate
(50 mg)
product
EtOAc (5 mL)
Yield (%)a
82
O2
Entry Substrate
1
t (h) Product
HBr
6
O
OH
10
O
O
OH
1
10
RCHOH
14
2
4
2
3
15
2
75
83
O
OH
O
RCO2H
OH
RCHOH
9
9
15
3
5
O
OH
Scheme 2 Possible path of the aerobic photooxidation of alcohols
OH
References
(1) Comprehensive Organic Transformations: A Guide to
Functional Group Preparations; Larock, R. C., Ed.; Wiley-
VCH: New York, 1999.
6
4
5
89
O
OH
(2) Itoh, A.; Hashimoto, S.; Kodama, T.; Masaki, Y. Synlett
2005, 2107.
OH
Cl
7
Cl
(3) Regarding photooxidation with alkali metal halides, the
conversion of CO to CO2 and H2 to H2O in the presence of
hydrogen exposed to over 200 nm of ultraviolet light has
been previously reported, see: Ryabchuk, V. Catal. Today
2000, 58, 89.
8
5
6
9
82
O
OH
(4) (a) For direct oxidations of alcohols to carboxylic acid
without photoirradiation, see ref. 1. See also: (b) Zhao, M.;
Li, J.; Song, Z.; Desmond, R.; Tschaen, D. M.; Grabowski,
E. J. J.; Reider, P. J. Tetrahedron Lett. 1998, 39, 5323.
(c) Zhao, M.; Li, J.; Mano, E.; Song, Z.; Tschaen, D. M.;
Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1999, 64,
2564. (d) Ji, H.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
Tetrahedron Lett. 2002, 43, 7179. (e) Yasuda, K.; Ley, S. V.
J. Chem. Soc., Perkin Trans. 1 2002, 1024.
(5) We believe an effective wavelength of light is 365 nm.
(6) When using primary alcohol as substrate, a typical procedure
follows: a solution (5 mL) of the substrate (50 mg) and LiBr
(0.3 equiv) in dry EtOAc was stirred and irradiated at r.t.
with a 400 W high-pressure mercury lamp externally for the
indicated time. The reaction mixture was concentrated under
reduced pressure, and 1% NaOH aq solution was added. The
aqueous solution was washed with Et2O, and then acidified
with 2 N HCl aq solution, which was extracted with Et2O.
The organic layer was washed with brine and dried over
Na2SO4, and concentrated under reduced pressure. The
product was pure without further purification.
9
10
24
20b
OH
O
24
12
a All yields are for pure, isolated products.
b A total yield of 59% of 11 was recovered.
even after 24 hours reaction time when using 4-tert-butyl-
cyclohexanol (11, entry 6).
The reaction mechanism has not been clearly understood;
however, we present here a supposed mechanism
(Scheme 2). In Scheme 2 is shown a path of this oxida-
tion, which is postulated by considering both the necessity
of the catalytic amount of LiBr and of molecular oxygen
in this reaction. The pale yellow coloration of the suspen-
sion suggests that bromine is generated in situ from lithi-
um bromide under UV irradiation.6 We believe that the
radical species 13 is generated by abstraction of a hydro-
gen radical with a bromo radical, formed under irradiation
from bromine. The radical species traps molecular oxygen
to afford peroxy radical species 14, which subsequently
transforms to a carboxylic acid via hydroperoxide 15.
When using secondary alcohol as substrate, a typical
procedure follows: a solution (5 mL) of the substrate (50 mg)
and LiBr (0.3 equiv) in dry EtOAc was stirred and irradiated
at r.t. with a 400 W high-pressure mercury lamp externally
for the indicated time. The reaction mixture was
concentrated under reduced pressure, and 1% NaOH aq
solution was added. The aqueous solution was washed with
Et2O and the organic layer was concentrated, and the residue
was purified by preparative TLC. The aqueous layer was
then acidified with 2 N HCl aq solution and extracted with
Et2O the same as in the former cases.
This new form of oxidation reaction is interesting in keep-
ing with the notion of green chemistry due to non-use of
heavy metals, waste reduction, use of molecular oxygen,
inexpensive acquisition of reagents, and possible solvent
recovery.
(7) Catalytic bromine oxidized 1 to 2 in 59% yield under similar
conditions.
Synlett 2005, No. 17, 2639–2640 © Thieme Stuttgart · New York
Itoh, Akichika
