Aerobic oxidative desymmetrization of meso-diols with bifunctional amidoiridium catalysts bearing chiral N-sulfonyldiamine ligands

Article abstract of DOI:10.1016/j.tetlet.2013.12.103

Asymmetric aerobic oxidation of a range of meso- and prochiral diols with chiral bifunctional Ir catalysts is described. A high level of chiral discrimination ability of Cp^{a? -}Ir complexes derived from (S,S)-1,2-diphenylethylenediamine was successfully demonstrated by desymmetrization of secondary benzylic diols such as cis-indan-1,3-diol and cis-1,4-diphenylbutane-1,4-diol, providing the corresponding (R)-hydroxyl ketones with excellent chemo- and enantioselectivities. Enantiotopic group discrimination in oxidation of symmetrical primary 1,4- and 1,5-diols gave rise to chiral lactones with moderate ees under similar aerobic conditions.

Full text of DOI:10.1016/j.tetlet.2013.12.103

Tetrahedron Letters 55 (2014) 1188–1191
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aerobic oxidative desymmetrization of meso-diols with bifunctional
amidoiridium catalysts bearing chiral N-sulfonyldiamine ligands
⇑
Junki Moritani, Yasuharu Hasegawa, Yoshihito Kayaki, Takao Ikariya
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric aerobic oxidation of a range of meso- and prochiral diols with chiral bifunctional Ir catalysts
is described. A high level of chiral discrimination ability of Cp⁄Ir complexes derived from (S,S)-1,
2-diphenylethylenediamine was successfully demonstrated by desymmetrization of secondary benzylic
diols such as cis-indan-1,3-diol and cis-1,4-diphenylbutane-1,4-diol, providing the corresponding
(R)-hydroxyl ketones with excellent chemo- and enantioselectivities. Enantiotopic group discrimination
in oxidation of symmetrical primary 1,4- and 1,5-diols gave rise to chiral lactones with moderate ees
under similar aerobic conditions.
Received 9 November 2013
Revised 17 December 2013
Accepted 25 December 2013
Available online 3 January 2014
Keywords:
Aerobic oxidation
Bifunctional catalysts
Asymmetric desymmetrization
Meso-diols
Ó 2014 Elsevier Ltd. All rights reserved.
Lactonization
Oxidation of alcohols is a fundamental and useful transforma-
tion in synthetic organic chemistry. Most of the processes are
carried out by using stoichiometric or overstoichiometric oxidants,
resulting in the formation of undesirable waste materials.1 In
light of environmental sustainability and atom-economy, cata-
lytic dehydrogenative oxidation of alcohols using clean hydrogen
acceptors has been widely investigated to overcome some
drawbacks of the conventional methods using hazardous or
toxic reagents. After our original works on chiral bifunctional
of rac-secondary benzylic alcohols using molecular oxygen as an
oxidant. Thanks to the excellent enantiomer discrimination ability
of the chiral catalysts toward the racemic substrates, the unreacted
chiral alcohols were enantiomerically enriched (with a maximum
kf/ks ratio of >100) even at the ambient temperature under atmo-
spheric pressure of air without any additives; however, theoretical
yield of optically active products can never exceed a limit of 50%
while asymmetric hydrogenation of the corresponding ketones
can give optically active alcohols in 100% yield.
On the other hand, asymmetric desymmetrization of meso- or
prochiral molecules offers potentially useful access to chiral
compounds theoretically in 100% yield.6 Among them, various
enzymatic and chemical catalysts have been explored for the
desymmetrization of meso-diols through enantioselective acyla-
tion.7 Oxidative desymmetrization of meso-diols was also attain-
able in catalytic asymmetric hydrogen transfer reactions using
ketones as hydrogen acceptors. Ikariya and Noyori demonstrated
Ru(g
6-arene) complexes bearing chelating chiral amine ligands
including Tsdpen (N-(p-toluenesulfonyl)-1,2-diphenylethylenedi-
amine) as one of the most efficient catalysts for hydrogen transfer
reactions between secondary alcohols and ketones, isoelectronic
Cp⁄Rh and Cp⁄Ir (Cp⁄ = 1,2,3,4,5-pentamethylcyclopentadienyl)
variants have been also realized.2,3 During the interconversion be-
tween the amido and hydrido(amine) complexes based on the me-
tal/ligand bifunctionality as shown in Scheme 1, both chiral
catalysts efficiently promote asymmetric transfer hydrogenation
of aromatic ketones using 2-propanol as a hydrogen donor as well
as the reverse asymmetric oxidation of secondary alcohols using
acetone as a hydrogen acceptor.4
As an extensive study of this redox transformation, Rauchfuss
and we independently disclosed the reaction of hydrido(amine)
Ir complexes with molecular oxygen to give amido complexes
and water.5 We also reported that the chiral Cp⁄Ir complexes bear-
ing chiral diamines efficiently catalyze enantioselective oxidation
R
S
N
R
S
N
O
O
H
OH
O
O
M
O
O
M
C6H5
C6H5
C6H5
C6H5
N
N
H
H
H
OH
H
H
Ar
*
Ar
M
= Ru(arene), Cp*Ir
R = CH3, CF3, p-CH3C6H4, (CH3)5C6
⇑
Corresponding author. Tel.: +81 3 5734 2636; fax: +81 3 5734 2637.
E-mail address: tikariya@apc.titech.ac.jp (T. Ikariya).
Scheme 1. Interconversion between amido and hydrido-Ir complexes.
0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.12.103

J. Moritani et al. / Tetrahedron Letters 55 (2014) 1188–1191
1189
the corresponding hydroxy-enone in 70% yield and 96% ee as
shown in Scheme 2(a).4a Suzuki reported the related Ir-catalyzed
desymmetrization in which cyclic or acyclic secondary diols8 were
oxidized to hydroxyl ketones in good yields with high chemo- and
enantioselectivities of up to >99% ee, whereas primary meso-1,2-
cyclohexanedimethanol analogs afforded chiral lactones with up
to 81% ee (Scheme 2b).9
(a)
OH
OH
H
H
OH
O
Ru cat
+
+
acetone
H
H
O
OH
[diol] = 0.1 M
Ru cat: Ru[(S,S)-Tsdpen](η6-mesitylene)
70% yield
96% ee
Asymmetric aerobic oxidation via desymmetrization of meso-
diols is also possible with a chiral Pd-sparteine catalyst, which
has been developed independently by Sigman and Stoltz; however,
the scope of the reaction was limited to linear secondary 1,3- or
1,7-diols and 1,2,3,4-tetrahydronaphthalene-1,4-diol.10 Katsuki
et al. have developed Ru(salen) catalysts for the aerobic oxidation
of meso-diols to afford the corresponding hydroxyl ketones or lac-
tols as shown in Scheme 3.11 Herein, we disclose asymmetric
desymmetrization of secondary and primary symmetrical diols
via aerobic oxidation catalyzed by the well-defined bifunctional
Ir catalysts, Cp⁄Ir[(S,S)-Msdpen] (1a, Msdpen = N-(methanesulfo-
nyl)-1,2-diphenylethylenediamine) and Cp⁄Ir[(S,S)-Tsdpen] (1b).
Inspired by our earlier success with asymmetric oxidation of
1-phenylethanol derivatives,5 we initially examined the aerobic
asymmetric oxidation of acyclic meso-diols having secondary ben-
zylic alcohol groups as represented in Scheme 4, and the results are
listed in Table 1. The reactions using the amido–Ir complex, (S,S)-
1a, with a substrate/catalyst molar ratio (S/C) of 10 were con-
ducted in THF (0.1 M) under air (balloon) at 30 °C, according to
the reaction conditions reported in our previous work.5
(b)
Ir cat
O
OH
KOtBu, 10 equiv/Ir
+ 2
+ 2
CH2OH
CH2OH
acetone/CH2Cl2
30 °C, 24 h
O
O
S/C = 200
[diol] = 0.67 M
Ir cat: [Cp*IrCl2]2
97% yield
81% ee
NH
+
OH
Scheme 2. Oxidative desymmetrization of meso-diols with bifunctional catalysts.
OH
OH
OH
cat, air, hν
+ 1/2 O2
+ H2O
CHCl3, r.t.
O
n
2
–
7 d
n
n = 1
–
4
up to 99% yield
up to 93% ee
S/C = 25
cat: (NO)Ru-salen complexes
Scheme 3. Asymmetric oxidation of primary meso-diols.
A partial dehydrogenation of meso-1,4-diol (2a) was accom-
plished within 48 h to give a hydroxyl ketone in 70% yield with
90% ee (entry 1), and a trace amount of over-oxidation product,
diketone was observed. The reaction of 1,3-diol (2b) gave an
unsatisfactory result, the product yield being 31% even after the
96 h reaction, possibly due to its relatively strong chelating
interaction between two hydroxyl groups and the metal center
cat:
Ms
N
C6H5
Ir
C6H5
N
H
O
OH
OH OH
+ 1/2 O2
+ H2O
R
X
3a-f
* R
THF, 30 °C
S/C = 10, [diol] = 0.1 M, air 1 atm
Scheme 4. Asymmetric oxidation of secondary meso-diols.
R
* X * R
2a f
-
(entry 2). Asymmetric oxidation of meso-a,
a0-dimethyl-(1,4-ben-
zene)dimethanol (2c) proceeded smoothly, affording the desired
R-product in 62% yield with a high ee of 94% (entry 3).
The chiral Ir catalyst exhibited an excellent catalytic perfor-
mance in the oxidative desymmetrization of cyclic secondary
meso-diols. The oxidation of cis-indan-1,3-diol (2d) and 1,2,3,4-tet-
rahydronaphthalene-1,4-diol (2e) gave the corresponding oxida-
tion products, (R)-hydroxyl ketones (3d and 3e) with 95% and
that Ru[(S,S)-Tsdpen](g
6-mesitylene) promotes dehydrogenative
oxidation via desymmetrization of a secondary meso-diol to give
Table 1
Catalytic asymmetric aerobic oxidation of secondary meso-diols 2
Entry
Substrate
Product
Time (h)
48
% Conversiona
% Yielda,b
70 (1)
% eec
OH
O
C6H5
OH
C6H5
*
C6H5
C6H5
1
76
90 (+)
OH
2a
OH OH
3a
O
OH
2
3
96
48
40
68
31
90 (R)
94 (R)
C6H5
HO
C6H5
OH
C6H5
HO
C6H5
O
2b
3b
62 (4)
3c
O
2c
OH
4
48
99
99
95 (R)
OH
OH
3d
2d
(continued on next page)

1190
J. Moritani et al. / Tetrahedron Letters 55 (2014) 1188–1191
Table 1 (continued)
Entry
Substrate
OH
Product
Time (h)
48
% Conversiona
% Yielda,b
93 (2)
% eec
O
5
99
99 (R)
OH
OH
3e
2e
HO
O
6
96
46
40 (1)
85 (+)
*
HO
HO
3f
2f
a
Determined by 1H NMR analysis.
Yield of diketones is given in the parenthesis.
Determined by HPLC analysis.
b
c
l
g/ml).12,13 The reac-
O
significant anti-tubercular activity (MIC 50
cat
CH2OH
air, 1 atm
tion of a seven-membered diol (2f) gave a moderate yield (40%;
R
+ O2
+ 2 H2O
O
R*
5c
entry 6).14
THF
CH2OH
4a–e
C
H2
To expand the substrate scope and to improve the practicality of
the chiral amido complex, the aerobic oxidation of symmetrical
primary diols (4) to chiral lactones was also tested as outlined in
Scheme 5.15 In similar to the secondary diols, the outcome of the
reaction was influenced by the structure of substrates. When 2-
phenyl-1,3-propanediols (4a and 4b) were used as the prochiral
substrate, the reactions gave rise to only a trace or small amount
formation of hydroxyl aldehydes (5a and 5b) without providing
the corresponding lactols or lactones (Table 2 entries 1 and 2).
The oxidation of 3-phenyl-1,5-pentanediol (4c) with (S,S)-1b gave
a 6-membered (R)-lactone (5c) with only 25% ee in 30% yield (entry
3). The chiral catalyst differentiates the enantiotopic hydroxy
groups on the substrate to give d-hydroxyl aldehyde and the
subsequent formation of hemiacetal allows the oxidative lacton-
ization. Because of the facile latter process, the hydroxyl aldehyde
e
–
S/C = 10, [diol] = 0.1 M
- H2O
- H2O
OH
CHO
R*
R*
O
C
CH2OH
H2
5a 5b
,
Scheme 5. Asymmetric oxidation of symmetrical primary diols.
99% ees, respectively (entries 4 and 5). As notable applications of
the oxidation products, (R)-3e can be transformed to the antide-
pressant sertraline, and enantiomerically pure (S)-3e shows
Table 2
Catalytic asymmetric aerobic oxidation of symmetrical primary diols 4
Entry
1
Cat.
Substrate
C6H5
Product
Time (h)
24
% Conversiona
12
% Yielda
0
% eeb
––
C6H5
O
HO
OH
HO
1b
4a
5a
Et
Et
C6H5
OH
C6H5
O
HO
HO
2
3
1a
1b
48
24
35
38
8
––
4b
5b
C6H5
C6H5
HO
OH
30
25 (R)
4c
O
O
5c
O
O
OH
OH
4
5
1a
1b
24
70
77
64
72
34 (1R,6S)
50 (2S,3R)
4d
5d
O
CH2OH
CH2OH
120
O
5e
4e
a
Determined by 1H NMR analysis.
Determined by HPLC analysis.
b

J. Moritani et al. / Tetrahedron Letters 55 (2014) 1188–1191
1191
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yields. When the oxidation of cis-cyclohexane-1,2-dimethanol (4d)
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This work was supported by JSPS KAKENHI Grant Number
22225004 and 24350079, and partly supported by the GCOE
Program from the Ministry of Education, Culture, Sports, Science
and Technology of Japan.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
12.103.
References and notes
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