Catalytic aerobic oxidation of diols under photo-irradiation: Highly efficient synthesis of lactols

Article abstract of DOI:10.1016/S0040-4039(02)00605-6

Aerobic oxidation of 1, n- and 1,ω-diols with (ON)Ru(salen) 1 as the catalyst was found to give the corresponding lactols in almost quantitative yields. Furthermore, in the oxidation of 2,2-dimethylalkane-1,ω-diols, less sterically hindered ω-alcohols were found to be preferentially oxidized when (ON)Ru(salen) 6 was used as the catalyst. n-Decanol was preferentially oxidized in the presence of 2,2-dimethylpropanol also by using 6 as the catalyst.

Full text of DOI:10.1016/S0040-4039(02)00605-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3481–3484
Catalytic aerobic oxidation of diols under photo-irradiation:
highly efficient synthesis of lactols
Atsushi Miyata, Mizuki Furukawa, Ryo Irie and Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33 CREST, JST (Japan Science and
Technology) Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Received 25 February 2002; accepted 22 March 2002
Abstract—Aerobic oxidation of 1,n- and 1,v-diols with (ON)Ru(salen) 1 as the catalyst was found to give the corresponding
lactols in almost quantitative yields. Furthermore, in the oxidation of 2,2-dimethylalkane-1,v-diols, less sterically hindered
v-alcohols were found to be preferentially oxidized when (ON)Ru(salen) 6 was used as the catalyst. n-Decanol was preferentially
oxidized in the presence of 2,2-dimethylpropanol also by using 6 as the catalyst. © 2002 Elsevier Science Ltd. All rights reserved.
We recently reported chemoselective aerobic oxidation
of primary alcohols to the corresponding aldehydes1–3
with (ON)Ru(salen) 1 as the catalyst in the presence of
secondary alcohol, under photo-irradiation (Scheme 1).
On the other hand, 1,n-diols are ordinary synthetic
precursors of lactols that occur in many natural prod-
ucts as subunits and also serve as useful intermediates
for organic synthesis. Nevertheless, conventional oxida-
tion of 1,n-diols often give lactones, over-oxidation
products of lactols,4 together with the desired lactols
except for several reactions.5 We expected that
(ON)Ru(salen)-catalyzed aerobic oxidation of 1,n-diols
would give the corresponding lactols preferentially,
because the lactols are secondary alcohols and should
H
OH
O
1, hν, air, rt
quantitative
OH
O
NO
0%
N
O
N
O
Ru
t-Bu
Bu-t
Cl
Bu-t
t-Bu
1
1
oxidation
R
OH
OH
H
O
n
O
n
O
n
oxidation
OH
R
R
H
O
R
oxidation
R= H
O
O
n
n
H
OH
Scheme 1.
Keywords: Ru(salen); aerobic oxidation; oxygen; diol; lactol; photo-irradiation.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00605-6

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A. Miyata et al. / Tetrahedron Letters 43 (2002) 3481–3484
not suffer over-oxidation (Scheme 1). It was, however,
considered that the product would be a 1,v-dial, when
the starting material is a 1,v-diol (R=H) and the
resulting lactol is equilibrated with a hydroxy aldehyde.
because 1-octanol was preferentially consumed and the
ratio of neopentyl alcohol in unreacted alcohols became
large. This suggested that complex 6 could differentiate
n-octanol and neopentyl alcohol efficiently at the initial
stage of the reaction. Thus, it was expected that high
regioselectivity would be realized, if 2,2-dimethylated
1,n-diols are used as substrates.
With these expectations in mind, we first examined
aerobic oxidation of 1,v-diols by using (ON)Ru(salen)
1 as the catalyst (Scheme 2). Indeed, butane-1,4-diol
and pentane-1,5-diol were oxidized to the correspond-
ing lactols, accompanied with a small amount of dials.
On the other hand, oxidation of hexane-1,6-diol gave
1,6-hexanedial exclusively, suggesting that the seven-
membered lactol intermediate was equilibrated with
6-hydroxyhexanal. Formation of a trace amount (<1%)
of lactones was detected in these reactions.
Along this line, oxidation of 2,2-dimethyl-1,4-butane-
diol and 2,2-dimethyl-1,5-pentanediol was next exam-
ined (Scheme 6). Although oxidation with complexes 4
and 5 showed modest selectivity, the oxidation with
complex 6 showed high regioselectivity as expected
[A:B=22:1 (n=1), 15:1 (n=2)].
Typical experimental procedures are exemplified by the
oxidation of hexane-1,5-diol with complex 1 and by the
oxidation of 2,2-dimethylpentane-1,5-diol with complex
6.
We also examined oxidation of 1,n-diols under the
same conditions (Scheme 3). As expected from the
previous results, the primary alcohols were oxidized
exclusively to give mixtures of the corresponding trans-
and cis-lactols, and oxidation of the secondary alcohols
was not observed.
Hexane-1,5-diol (11.8 mg, 0.1 mmol) was weighed into
a round-bottomed flask (Pyrex) followed by addition of
1-bromonaphthalene (0.1 mmol) as an internal stan-
dard and diethyl ether (1 ml). An aliquot was taken out
of the flask and concentrated, and then submitted to 1H
NMR (400 MHz) analysis to adjust the molar ratio of
the components. To the solution was added 1 (1.4 mg,
2 mmol) and the mixture was stirred under air for 24 h
under irradiation with a halogen lamp (15 V, 150 W) at
room temperature. The reaction mixture was concen-
trated under slightly reduced pressure and analyzed by
1H NMR to calculate the yield of the lactols. The
formation of 5-oxohexan-1-ol was not observed.
This aerobic oxidation has been considered to proceed
through a coordinatively unsaturated Ru(IV) species 2
to which alcohol is coordinated and oxidized to the
corresponding carbonyl compound (Scheme 4). Upon
the coordination, primary alcohols suffer less steric
repulsion with the axial methyl group than secondary
alcohols and are oxidized selectively.1
Naturally, the oncoming alcohol is considered to direct
their alkyl moiety away from the axial methyl group.
Therefore, when the Ru(salen) carries a bulky sub-
stituent at C3 and C3%, oxidation of primary alcohols is
expected to become slower, as the alkyl moiety of the
alcohols becomes bulkier. Thus, we examined oxidation
of a 1:1 mixture of 1-octanol and neopentyl alcohol by
using complexes 1, 4, and 5 as the catalyst (Scheme 5).
The differentiation of non- and b-branched alcohols
with 1 was unsatisfactory. As expected, the reaction
with 4 bearing a bulky 2-phenylnaphthyl group at C3
and C3% showed better selectivity (A:B=9:1) but the
reaction was slow. However, chemical yield of the
aldehyde was considerably improved without severely
vitiating the selectivity when complex 5 bearing a
triphenylsilyl group at C3 and C3% was used as the
2,2-Dimethylpentane-1,5-diol (13.2 mg, 0.1 mmol) and
pentamethylbenzene (14.8 mg, 0.1 mmol, an internal
standard) were dissolved in CDCl3 (1 ml). An aliquot
1
was taken out of the flask and submitted to H NMR
(400 MHz) analysis to adjust the molar ratio of the
components. To the solution was added complex 6 (6.0
mg, 5 mmol) and the mixture was stirred under air for
1 (2 mol%), hν, rt
OH
OH
n
O
n
air,ether
OH
n= 1: 81%
n= 2: 95%
catalyst.
Use
of
complex
6
bearing
1,2-
diphenylethylenediamine as its diamine unit further
improved the selectivity (A:B=18:1) at the point of 24
h. The selectivity decreased with the reaction time
Scheme 3.
H
1 (2 mol%), hν, rt
HO
O
OH
+
OH
O
n
O
n
n
air,ether
H
A
B
n= 1: A: 86%, B: 5%
n= 2: A: 95%, B: 5%
n= 3: A: <1%, B: 99%
Scheme 2.

A. Miyata et al. / Tetrahedron Letters 43 (2002) 3481–3484
R1
R2
OH
3483
R1
R2
axial
R1
N
R2
N
O
-
O2
O2
hν
OH
RuIV
N
O
N
RuIII
N
O
N
RuIV
1
1
-
·NO
k
O
O
O
O
Cl
Cl
Cl
2
R1≠ H, R2= H; k: fast
R1≠ H, R2≠ H; k: slow
R
axial
OH
R-OH
R'
N
N
N
N
RuIV
RuIV
O
O
O
O
R
Cl
Cl
R
R'
Scheme 4.
H
A
O
OH
catalyst (2 mol%), hν, air
O
OH
CDCl3, rt
B
H
1: A: 64%, B: 38% (24 h)
4: A: 9%, B: 1% (24 h)
5: A : 29%, B: 5% (24 h)
6: A: 36%, B: 2%, (24 h)a)
Cl
N
O
N
Ru
NOO
6: A: 72%, B: 9%, (96 h)a)
Ph Ph
a) Five mol% of catalyst was used.
4
Ph
N
Ph
N
Cl
Cl
N
O
N
Ru
Ru
t-Bu
O
NOO
Bu-t
t-Bu
NOO
Bu-t
TPS
TPS
TPS
TPS
6
5
Scheme 5.
Scheme 6.

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A. Miyata et al. / Tetrahedron Letters 43 (2002) 3481–3484
36 h under irradiation with a halogen-lamp at room
temperature. H NMR analysis demonstrated that the
diol was completely consumed and lactols (A and B)
were formed in the ratio of 15:1. No formation of
lactone was detected.
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1
In conclusion, we were able to demonstrate that well-
designed (ON)Ru(salen) complexes catalyzed regiose-
lective oxidation of diols to the corresponding lactols
under aerobic conditions. Further study is under way in
our laboratory.
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