Polymeric bimetallic catalyst-promoted in-water dehydrative alkylation of ammonia and amines with alcohols

Article abstract of DOI:10.1055/s-0033-1338797

A dehydrative alkylation with three kinds of Ir/B heterobimetallic polymeric catalysts in water is reported. The polymeric heterobimetallic catalysts were readily prepared by ionic convolution of a poly(catechol borate) and iridium complexes. The N-alkylation of ammonia and amines with alcohols, as alkylating agents, was carried out with a heterogeneous catalyst (1 mol% Ir) at 100 °C without the use of organic solvents under aerobic and aqueous conditions to afford the corresponding alkylated amines in high yield. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1338797

SPECIAL TOPIC
▌2093
special topic
Polymeric Bimetallic Catalyst-Promoted In-Water Dehydrative Alkylation of
Ammonia and Amines with Alcohols
Dehydrative Alkylation of Ammonia and Amines with Alcohols
Yoichi M. A. Yamada,*a Hidetoshi Ohta,a Yoshinari Yuyama,a Yasuhiro Uozumi*a,b
a
RIKEN Center for Sustainable Resource Science, Green Nanocatalysis Research Team, Wako, Saitama 351-0198, Japan
Fax +81(48)4671423; E-mail: ymayamada@riken.jp
b
Institute for Molecular Science (IMS), Okazaki, Aichi 444-8787, Japan
E-mail: uo@ims.ac.jp
Received: 19.02.2013; Accepted after revision: 14.04.2013
complexation, affording insoluble polymer-metal com-
Abstract: A dehydrative alkylation with three kinds of Ir/B hetero-
posites.10 We had an interest in the bimetallic complex-
bimetallic polymeric catalysts in water is reported. The polymeric
ation of dicationic iridium species and catechol borate
heterobimetallic catalysts were readily prepared by ionic convolu-
tion of a poly(catechol borate) and iridium complexes. The N-alkyl-
polymer species for constructing heterobimetallic multi-
ation of ammonia and amines with alcohols, as alkylating agents, functional catalysts;11,12 iridium species could work as a
was carried out with a heterogeneous catalyst (1 mol% Ir) at 100 °C
without the use of organic solvents under aerobic and aqueous con-
ditions to afford the corresponding alkylated amines in high yield.
cross-linker of borate polymers as well as a catalytic spe-
cies. Catechol borate polymer species should be not only
a main-chain polymer backbone but also a Brønsted base.
Herein, we report the full detail of the preparation of sev-
Key words: dehydrative alkylation, polymeric boron iridium cata-
lyst, amines, ammonia, alcohols
eral novel convoluted polymeric heterobimetallic cata-
lysts for the hydrogen-transfer dehydrative N-alkylation
of amines with alcohols in water.13 Aqueous ammonia and
amines were readily alkylated with alcohols in water un-
der aerobic conditions.
The dehydrative alkylation of amines and ammonia is an
important reaction for organic syntheses although the de-
hydration in water is a paradox under equilibrium condi-
tions, known as water paradox.1 Enzymes promote such
reactions with extremely high efficiency; for instance, N-
methyltransferases are enzymes for methylation of termi-
nal amines to form N-methylated amines under aqueous
conditions.2 Therefore, development of N-methyltransfer-
ase-inspired polymeric metal catalysts for the dehydration
system has attracted interest:3 Especially, a hydrogen-
transfer dehydrative N-alkylation of amines with alcohols
under aqueous conditions provides a fundamental and
straightforward synthetic route for the preparation of ni-
trogen-containing bioactive compounds as well as phar-
maceutical molecules, and agrochemicals.4,5 Alcohols can
be utilized as alkylating agents in place of harmful and
toxic alkyl halides in the conversion. Several reports have
been shown as pioneering studies on the N-alkylation of
amines with alcohols by a use of homogeneous catalysts
in organic solvents and/or water.6,7 Recently, Madsen,
Milstein, Williams, Fujita, and Yamaguchi and their co-
workers reported the interesting alkylation reactions of
amines with alcohols in water by utilizing homogeneous
catalysts.8 In contrast, the catalytic system of this reaction
under aqueous and heterogeneous9 catalytic conditions
still remains a major challenge.
Poly(spiroborate)iridium catalysts 3, 3′, and 3′′ were syn-
thesized as follows. A linear catechol borate polymer 1
was prepared from 1,2-dimethoxybenzene (4) and dodec-
anedioyl dichloride (5) in four steps (see experimental
section).14 Polymer 1 is a white powder soluble in DMSO,
DMF, MeOH, MeCN, DME, THF, and acetone. The
11B{1H} NMR spectrum of 1 in DMSO-d6 showed a broad
singlet peak at 14.7 ppm that was assigned to a catechol
borate moiety.15 Self-assembly of the borate polymer and
three kinds of iridium species was carried out by our
convolution method in accordance with Danjo and
Yamaguchi’s process by which D3-symmetric tris(spiro-
borate)cyclophane-Ir complex was prepared.16 Thus,
when the ionic convolution of 1 and Cp*Ir(κ2-CO3)(IPr)17
(2) (brownish orange) was performed in DME–MeCN at
50 °C for 24 hours, a polymeric metal composite 3 precip-
itated out. It is hardly soluble in H2O, MeOH, MeCN,
DME, THF, Et2O, acetone, toluene, and hexane. Also,
polymeric metal conposites 3′ and 3′′ were prepared from
Cp*Ir(κ2-CO3)(IMes) (2′) and Cp*Ir(κ2-CO3) (2′′) under
similar conditions, respectively (Scheme 1). In the ATR-IR
spectra of 3, 3′, and 3′′, the absorption peaks correspond-
ing to the hydroxy group in 1 and the carbonate group in
2, 2′, and 2′′ were not observed (Figure 1). The results
suggested that the Ir-borate complexes 3, 3′, and 3′′ were
readily formed. The XPS spectra of 3, 3′, and 3′′ showed
five characteristic peaks attributed to C, B, O, N, and Ir
(Table 1). The B 1s binding energy in the case of 3, 3′, and
3′′ was 192.2, 191.9, and 191.9 eV, respectively. These
values were close to that of the tetravalent ate 1·NEt3 com-
plex (192.4 eV) and was lower than that of the trivalent 118
(193.0 eV). The results indicated that tetravalent borate
We have reported a novel protocol for the preparation of
highly active and reusable polymer-supported catalysts
from soluble linear polymer having multiple ligand
groups and metal species through the coordinate or ionic
SYNTHESIS 2013, 45, 2093–2100
Advanced online publication: 29.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338797; Art ID: SS-2013-C0144-ST
© Georg Thieme Verlag Stuttgart · New York

2094
Y. M. A. Yamada et al.
SPECIAL TOPIC
O
O
O
Cp*Ir(κ2-CO3)(IPr) (2)
O
O
O
10
B–
• [Cp*Ir2+(IPr)]n
10
B
O
DME, MeCN, 50 °C, 24 h
HO
n
2n
1
1
PB-Cp*Ir(IPr) (3)
O
O
B–
Cp*Ir(κ2-CO3)(IMes) (2')
10
• [Cp*Ir2+(IMes)]n
O
DME, MeCN, 50 °C, 24 h
O
2n
PB-Cp*Ir(IMes) (3')
O
O
O
Cp*Ir(κ2-CO3) (2'')
10
B–
• [Cp*Ir2+
]
n
1
O
DME, MeCN, 50 °C, 24 h
2n
PB-Cp*Ir (3'')
O
O
O
10
B–
N
N
N
N
IPr =
IMes =
••
••
O
+NHEt3
n
1•NEt3
Scheme 1 Preparation of poly(spiroborate)iridium catalysts PB-Cp*Ir(IPr) (3), PB-Cp*Ir(IMes) (3′), and PB-Cp*Ir (3′′)
anion species had formed in all cases. The Ir 4f7/2 binding With the convoluted polymeric heterobimetallic catalysts
energy in 3, 3′, and 3′′ was 62.7, 62.2, and 61.9 eV, re- 3, 3′, and 3′′ in hand, we concentrated on the survey of the
spectively. These energy values were assigned as two- hydrogen-transfer dehydrative alkylation of aniline (9a)
valent iridium species. ICP-AES analysis of 3, 3′, and 3′′ with benzyl alcohol (10a) in water by using the catalysts
revealed that the loading ratio of Ir was 12.06, 12.98, and 3, 3′, and 3′′ in water (Table 2). When the reaction of an-
16.57 wt%, respectively. These results clearly indicated iline (9a) with benzyl alcohol (10a) (1.0 mol equiv) was
that the precipitates 3, 3′, and 3′′ comprised anionic spi- carried out with 3 (1 mol% Ir) and NaHCO3 (1 mol%) in
roborate polymer species and dicationic Ir2+ species. The water at 100 °C for 24 hours, N-benzylaniline (11a) was
results were also supported by elemental analysis of 3, 3′, obtained in 72% yield with the formation of N-benzyli-
and 3′′.
deneaniline (12a) in 13% (Table 2, entry 1). In contrast,
Figure 1 ATR-IR spectra of 1, 2, 2′, 2′′, 3, 3′, and 3′′: x axis, wavelength (cm–1); y axis, absorbance.
Synthesis 2013, 45, 2093–2100 © Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Dehydrative Alkylation of Ammonia and Amines with Alcohols
2095
(entry 6). The catalyst 3 was collected by decantation,
where 95% of the Ir species was recovered (ICP-AES
analysis).19 The recovered catalyst was reused twice with-
out loss of activity to afford 11f in 87% (2nd use) and 87%
yield (3rd use), respectively (entries 7–8). Substituted
benzylic alcohols were also suitable alkylating agents for
this reaction. The alkylation of 9a with 2-methylbenzyl, 4-
methoxybenzyl, 3,5-dimethoxybenzyl, and 4-chloroben-
zyl alcohols 10b–e afforded the corresponding N-alkylat-
ed amines 11g–j in 78–86% yields (entries 9–12). The
reaction of 9f with a less reactive aliphatic alcohol 10f
proceeded smoothly to give an octylated amine 11k in
86% yield (entry 13). When the reaction of an aliphatic
primary amine 9g was carried out in pH 4 standard buffer
aqueous solution under microwave conditions at 150 °C
in a sealed tube, the alkylation proceeded to give triben-
zylamine (11l) in 83% yield (entry 14).20 The alkylation of
an aliphatic secondary amine 9h also afforded 11l in 83%
yield (entry 15). An alicyclic amine 9i was also reacted
under similar microwave conditions to give N-benzylmor-
pholine (11m) in 83% yield. N-Benzyl 4-piperidinemeth-
anol (11n), a substrate for the preparation of an
Alzheimer’s disease drug Aricept (donepezil hydrochlo-
ride),21 was obtained from 4-piperidinemethanol (9j) in
61% yield (entry 17).
Table 1 Binding Energy in XPS Spectra of 3, 3′, 3′′, 1·NEt3, and
1·DMFa
Binding energy (eV)
Ir 4f7/2
B 1s
C 1s
N 1s
O 1s
3
62.7
62.2
61.9
–
192.2
191.9
191.9
192.4
193.0
285.0
285.0
285.0
285.0
285.0
401.4
401.5
–
532.4
532.9
532.5
532.7
533.7
3′
3′′
1·NEt3
1·DMF
402.6
402.0
–
a The binding energies were referred to 285.0 eV of a C 1s peak.
the catalysts 3′ and 3′′ gave 11a in 63% and <1%, respec-
tively (entries 2 and 3). When the reaction of 9a with 1.2
mol equivalents of 10a was performed with 3 in the ab-
sence of NaHCO3, the reaction proceeded smoothly to
give 11a in 87% yield with 6% of 12a (entry 4).
Table 2 Dehydrative N-Alkylation of Aniline (9a) with Benzyl
Alcohol (10a) in Water Promoted by Boron-Iridium Heterobimetallic
Polymeric Catalysts 3, 3′, and 3′′a
Ph
CH2Ph
N
PhNH2
H
As shown in Table 3, entries 14–17, for the alkylation of
aliphatic and alicyclic amines, the reaction was performed
in pH 4 aqueous solution to give the corresponding prod-
ucts in high yield. Table 4 shows the effect of buffer with
a variety of pH values in the alkylation. Thus, the reaction
of 9i with 10a under basic conditions (pH 7.41–12.83)
gave 11m in 29–48% yields (Table 4, entries 1–4). In con-
trast, when the alkylation under mild acidic conditions
(pH 3.26–6.86) was carried out under otherwise similar
conditions, the reaction proceeded to afford 11m in 64–
83% yields (entries 5–9). Especially, pH 4.02 buffer con-
ditions provided the best yield (83%) of 11m (entry 8).
The reaction under strong acidic conditions (pH 1.70)
gave 11m in 36% yield (entry 9). Under mild acidic con-
ditions, an aldehyde, a reaction intermediate (see Scheme
2), could be activated by the weak acid to facilitate the
condensation with an amine and thus to form an imine
readily.
11a
9a
+
catalyst (1 mol% Ir)
H2O, 100 °C, 24 h
+
CHPh
HO CH2Ph
Ph
N
10a
12a
Entry
Catalyst
10a (mol
equiv)
11a Yield
12aYield
(%)b
(%)b
1c
2c
3c
4
3
1.0
1.0
1.0
1.2
72
13
13
2
3′
3′′
3
63
<1
87 (85)
6
a Reaction conditions: 9a (0.5 mmol), 10a (0.5–0.6 mmol), 3 (3′ or
3′′) (1 mol% Ir) in H2O (0.5 mL) at 100 °C for 24 h under aerobic con-
ditions.
b Determined by GC analysis using biphenyl as an internal standard;
the isolated yield is given in parentheses.
c In the presence of 1 mol% NaHCO3.
Moreover, the catalyst 3 was used in the reaction of aque-
ous ammonia as a substrate (Table 5). Aqueous ammonia
is less reactive than other amines although it is a funda-
mental substrate for organic transformations. The in-
water alkylation of ammonia with alcohols is challenging
and important as shown in the pioneering works:
Yamaguchi and Fujita reported the in-water reaction of
aqueous ammonia with alcohols by homogeneous cata-
lysts.8c Milstein described the reaction of gaseous NH3
(7.5 atm) and alcohols with a homogeneous ruthenium
complex in aqueous toluene.8b Beller22 and Vogt23 report-
ed amination of liquid ammonia with alcohols in organic
solvents. Gratifyingly, the alkylation of aqueous NH3 with
benzyl alcohol (10a) proceeded in the presence of the het-
erogeneous catalyst 3 (1 mol% Ir) in pH 4 standard buffer
Since the catalyst 3 exhibited higher catalytic activity, the
alkylation of a variety of amines was carried out by using
alcohols as the alkylating reagents in water (Table 3). In
all entries, the reaction was carried out in water without
employing additional bases under aerobic conditions.
Thus, the reaction of aniline (9a) with benzyl alcohol
(10a) proceeded to afford N-benzylaniline (11a) in 85%
yield as described in Table 2, entry 4. The reaction of elec-
tron-sufficient (Table 3, entries 2 and 3) and electron-
deficient (entries 4 and 5) anilines 9b–e with 10a was carried
out to give the corresponding N-alkylated anilines 11b–e
in 63–93% yields. Alkylation of 1-naphthylamine (9f)
with 10a gave the N-benzylated amine 11f in 89% yield
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2093–2100

2096
Y. M. A. Yamada et al.
SPECIAL TOPIC
Table 3 Dehydrative N-Alkylation of Amines with Alcohols in Water Promoted by 3a
3 (1 mol% Ir)
+
HO R3
10
NR1R2R3
R1R2NH
H2O, 100–150 °C
9
11
(1.2 mol equiv)
Entry
Amine 9
Alcohol 10
Product 11
Yield (%)b
1
2
PhNH2 (9a)
PhCH2OH (10a)
PhNHCH2Ph (11a)
85
80
63
92
93
89
87
87
79
78
2-MeC6H4NH2 (9b)
10a
2-MeC6H4NHCH2Ph (11b)
4-MeOC6H4NHCH2Ph (11c)
4-O2NC6H4NHCH2Ph (11d)
3-ClC6H4NHCH2Ph (11e)
1-naphthNHCH2Ph (11f)
11f
3
4-MeOC6H4NH2 (9c)
10a
4
4-O2NC6H4NH2 (9d)
10a
5
3-ClC6H4NH2 (9e)
10a
6
1-naphthNH2 (9f)
10a
7c
8d
9
9f
10a
9f
10a
11f
9a
2-MeC6H4CH2OH (10b)
4-MeOC6H4CH2OH (10c)
3,5-(MeO)2C6H3CH2OH (10d)
4-ClC6H4CH2OH (10e)
C8H17OH (10f)
10a
PhNHCH2C6H4-2-Me (11g)
PhNHCH2C6H4-4-OMe (11h)
10
11
12
13
14e,f
15e
9a
9a
PhNHCH2C6H3-3,5-(OMe)2 (11i)
PhNHCH2C6H4-4-Cl (11j)
1-naphthNHC8H17 (11k)
N(CH2Ph)3 (11l)
83
86
86
83
83
9a
9f
PhCH2NH2 (9g)
(PhCH2)2NH (9h)
10a
11l
Ph
O
NH
O
N
16e
17e
10a
10a
83
61
(9i)
(11m)
HO
HO
Ph
NH
N
(9j)
(11n)
a All reactions were carried out using 9 (0.5 mmol), 10 (0.6 mmol), and 3 (1 mol% Ir) in H2O (0.5 mL) at 100 °C for 24 h under aerobic
conditions.
b Isolated yield.
c Catalyst 3 was used a 2nd time.
d Catalyst 3 was used a 3rd time.
e Condition: 150 °C, microwave in pH 4 buffer aqueous solution in a sealed tube.
f Amount of 10a used: 2.5 mmol.
aqueous solution at 150 °C under microwave conditions
to afford tribenzylamine (11l) in 84% yield (Table 5, entry
1). The reaction with both electron-sufficient and -defi-
cient (4-methoxy, 4-chloro, 4-trifluoromethyl, 4-methyl,
3,5-dimethoxy) benzylic alcohols was also carried out un-
der similar conditions to afford the corresponding triben-
zylic amines 11o–s in 57–93% yields (entries 2–6).
R2
HO
R2
O
A
B
R1
NH2
[Ir]
[H–Ir]
C
O
O
O
O
B–
B
O
O
O
O
H
water
R2
R1
R1
One plausible working model for the alkylation of amines
with alcohols could be as shown in Scheme 2 in accor-
dance with the reported reaction pathways.7,8 Thus, an al-
cohol A is dehydrogenated by Ir species and deprotonated
by a borate moiety as a Brønsted base to give an aldehyde
N
R2
N
D
H
E
Scheme 2 A working model of dehydrative alkylation of amines
with alcohols
Synthesis 2013, 45, 2093–2100
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Dehydrative Alkylation of Ammonia and Amines with Alcohols
2097
3' (1 mol% Ir)
Table 4 Effect of Buffer Solution in the Reaction of 9i with 10a (Ta-
N
Ph
H
ble 3, Entry 16)a
Ph
N
Ph
11a
(88%)
+
+
Ph
NaHCO3 (1 mol%)
H2O, 100 °C
24 h, air
H
11a
12a (5%)
Entry Buffer solution
pH
11m
Yield (%)b
O
Ph
NH2
Ph
9a (2%)
1
2
aq 0.1 M NaOH
12.83
10.00
9.14
7.41
6.86
5.14
4.52
4.02
3.26
1.70
29
30
48
31
64
79
65
83
72
36
H
(2%)
carbonate pH std soln
Scheme 3 Equilibrium investigation
3
tetraborate pH std soln
4
phosphate pH std soln
In conclusion, we have described the full detail of the de-
velopment of convoluted polymeric novel heterobimetal-
lic iridium boron catalysts. The polymeric Ir–B bimetallic
catalyst promoted the in-water alkylation of amines, in
particular aqueous ammonia, with alcohols without the
use of organic solvents under aerobic conditions to meet
green chemical requirements.
5
phosphate pH std equimolal soln
0.2 M AcOH/0.2M NaOAc (8.8:41.2)
0.2 M AcOH/0.2M NaOAc (25.5:24.5)
phthalate pH std soln
6
7
8
9
0.1 M glycine/0.1 M HCl (50:22)
oxalate pH std soln
10
All manipulations involving air- and moisture-sensitive compounds
were performed under N2 or argon atmosphere. Reagents and sol-
vents were obtained from commercial suppliers and used without
further purification, unless otherwise noted. Anhyd THF, Et2O,
CH2Cl2, and DMF were purchased from Wako Pure Chemical In-
dustries, Ltd. and purified by passage through activated Al2O3 under
positive N2 pressure as described by Grubbs et al.24 Anhyd DME
and MeCN were purchased from Kanto Chem. Co., Inc. H2O was
deionized with a Millipore system as a Milli-Q grade. Melting
points were measured using an FP900 Thermo System (Metler-
Toledo International, Inc.). 1H NMR (500 MHz), 13C{1H} NMR (126
MHz), and 11B{1H} NMR (160 MHz) spectra were recorded on a
a Reaction conditions: 9i (0.5 mmol), 10a (0.6 mmol), and 3 (1 mol%
Ir) in buffer solution (0.5 mL) at 150 °C, microwave in a sealed tube.
b Determined by GC analysis using dodecane as an internal standard.
Table 5 Dehydrative N-Alkylation of Ammonia in Watera
3 (1 mol% Ir)
NH3
NR3
+
HO
R
(aqueous)
pH 4 buffer
microwave, 150 °C
1
Entry ROH (10)
Product 11 Yield (%)b
JEOL JNM ECA-500 spectrometer. The H NMR chemical shifts
are reported relative to TMS (0.00 ppm) or residual protiated sol-
vent (2.50 ppm for DMSO-d6, 5.32 ppm for CD2Cl2). The 13C{1H}
NMR chemical shifts are reported relative to CDCl3 (77.0 ppm),
CD2Cl2 (54.0 ppm), or DMSO-d6 (39.5 ppm). The 11B{1H} NMR
chemical shifts are reported relative to BF3·OEt2 in CDCl3 (0.00
ppm) as an external standard. Elemental analyses were performed
on a Yanaco CHN Corder MT-6 elemental analyzer by the chemical
analysis team in RIKEN. Inductively coupled plasma atomic emis-
sion spectrometry (ICP-AES) was performed on a Shimadzu ICPS-
8100 equipment by the chemical analysis team in RIKEN. Matrix-
assisted laser desorption ionization time-of-flight mass spectrome-
try (MALDI-TOF mass) was performed on an Applied Biosys-
tems/MDS SCIEX 4800 spectrometer using dithranol (DIT) as a
matrix. The GC-MS analysis was conducted using an Agilent
7860A/JEOL JMS-T100GC equipped with a capillary column (DB-
Wax, 0.25 mm i.d. × 30 m or HP-1, 0.32 mm i.d. × 30 m). FT-IR
spectra were recorded on a JASCO FT/IR-4100 spectrometer
equipped with an ATR device (ZnSe crystal). XPS spectra were re-
corded on an ESCALA 250 (Thermo Fisher Scientific K.K.) by the
cooperative support team in RIKEN. The Microwave reactions
were performed with CEM Discover system. pH was measured with
a SK-620PH pH meter (Sato Keiryouki Mfg. Co. Ltd.). TLC analy-
sis was performed on Merck silica gel 60 F254 and Wako NH2 silica
gel 60 F254 plates. Column chromatography was carried out on silica
gel [Wakogel C-200 and Kanto Silica Gel 60 (spherical) NH2]. The
following abbreviations are used for assignments: Cp* = η5-penta-
methylcyclopentadienyl, IPr = N,N′-bis(2,6-diisopropylphenyl)im-
idazol-2-ylidene, IMes = N,N′-bis(2,4,6-trimethylphenyl)imidazol-
2-ylidene.
1
PhCH2OH (10a)
4-MeOC6H4CH2OH (10c)
11l
84
76
93
95
68
57
2
11o
11p
11q
11r
11s
3
4-ClC6H4CH2OH (10e)
4 c
5
4-F3CC6H4CH2OH (10g)
4-MeC6H4CH2OH (10h)
3,5-(MeO)2C6H3CH2OH (10d)
6
a All reactions were carried out using 9 (0.5 mmol), 10 (3.4 mmol),
and 3 (1 mol% Ir) in pH 4 buffer aqueous solution (0.5 mL) at 150 °C
for 24 h under aerobic microwave conditions in a sealed tube.
b Isolated yield.
c Reaction time: 48 h.
B, which undergoes dehydrative imine formation with an
amine C to afford an imine D. The imine D was converted
by H–Ir and the boronic acid moiety to give a desired
amine E with reproduction of Ir and the borate species.
The working model is supported by the following results:
As shown in Table 2, the intermediate imine D was ob-
tained as 12a in the reaction of 9a and 10a. As shown in
Scheme 3, the reaction of 11a with 3′ under similar con-
ditions in Table 2 afforded the imine 12a (= D) in 5%, the
substrate 9a (= C) in 2%, and benzaldehyde (= B) in 2%.
1,12-Bis(3,4-dimethoxyphenyl)dodecane-1,12-dione (6)
To a suspension of 1,2-dimethoxybenzene (4; 16.6 g, 120 mmol)
and AlCl3 (17.6 g, 132 mmol) in CH2Cl2 (150 mL) at 0 °C under N2
was added a solution of dodecanedioyl dichloride (5; 16.0 g, 60
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2093–2100

2098
Y. M. A. Yamada et al.
SPECIAL TOPIC
mmol) in CH2Cl2 (50 mL). The reaction mixture was stirred under
reflux for 24 h under N2. After cooling to 0 °C, the mixture was
quenched with aq 3 M HCl (100 mL). The mixture was extracted
with CH2Cl2 (3 × 60 mL), and the combined organic layers were
washed with H2O (2 × 100 mL), dried (MgSO4), filtered, and con-
centrated. The crude product was recrystallized from toluene (100
mL) to give the diketone 6 as a colorless solid (23.4 g, 49.7 mmol,
83%); mp 95–96 °C.
1H NMR (500 MHz, CDCl3): δ = 7.59 (dd, J = 8.4, 2.0 Hz, 2 H),
7.54 (d, J = 2.0 Hz, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 3.95 (s, 6 H),
3.94 (s, 6 H), 2.92 (t, J = 7.5 Hz, 4 H), 1.72 (quint, J = 7.5 Hz, 4 H),
1.40–1.30 (m, 12 H).
IR (ATR, ZnSe): 3224 cm–1 (OH).
1H NMR (500 MHz, anhyd DMSO-d6): δ = 7.95 (s, 1 H, DMF), 7.84
(br s, 1 H, OH), 6.60–6.24 (m, 6 H), 2.89 (s, 3 H, DMF), 2.73 (s, 3
H, DMF), 2.40–2.35 (m, 4 H), 1.53–1.40 (m, 4 H), 1.30–1.16 (m, 16
H).
13C{1H} NMR (126 MHz, anhyd DMSO-d6): δ = 162.3 (DMF),
151.5, 149.5, 144.9, 143.0, 133.1, 118.8, 116.4, 115.6, 115.4, 108.0,
106.84, 106.79, 35.8 (DMF), 35.4, 34.5, 31.7, 31.2, 30.8 (DMF),
29.2, 29.09, 29.07, 29.00, 28.98, 28.9, 28.7, 28.6.
11B{1H} NMR (160 MHz, anhyd DMSO-d6): δ = 14.7.
Anal. Calcd for C24H31BO4·1.5C3H7NO: C, 67.92; H, 8.30; N, 4.17.
Found: C, 67.90; H, 8.42; N, 3.91.
13C{1H} NMR (126 MHz, CDCl3): δ = 199.3, 153.0, 149.0, 130.3,
122.7, 110.1, 109.9, 56.0, 55.9, 38.1, 29.5, 29.42, 29.39, 24.7.
MALDI-TOF MS (DIT): m/z = 509 [M + K]+, 493 [M + Na]+.
Poly(triethylammonium catechol borate) (1·NEt3)
Et3N (0.648 g, 6.4 mmol) was added to a solution of 1·DMF (0.598
g, 1.28 mmol of B) in anhyd DMF (13 mL) at 23 °C under argon.
The reaction mixture was stirred at 23 °C for 3 h under argon, then
concentrated to dryness. The resulting solid was washed with anhyd
MeCN (3 × 26 mL) and dried under reduced pressure to give the bo-
rate salt 1·NEt3 as a colorless solid (0.426 g, 0.860 mmol, 67%).
Anal. Calcd for C28H38O6: C, 71.46; H, 8.14. Found: C, 71.38; H,
8.26.
1,12-Bis(3,4-dimethoxyphenyl)dodecane (7)
To a solution of 6 (42.1 g, 89.5 mmol) in CH2Cl2 (180 mL) and tri-
fluoroacetic acid (125 mL) at 0 °C was added Et3SiH (52.1 g, 448
mmol). The reaction mixture was stirred at 23 °C for 24 h, then neu-
tralized with aq NaHCO3 at 0 °C. The mixture was extracted with
CH2Cl2 (3 × 90 mL) and the combined organic layers were dried
(MgSO4), filtered, and concentrated. The crude product was puri-
fied by silica gel column chromatography (CHCl3), and washed
with MeOH (90 mL) to give the product as a colorless solid (34.9 g,
78.9 mmol, 88%); mp 86–88 °C.
1H NMR (500 MHz, DMSO-d6): δ = 6.72–6.00 (br m, 6 H), 3.06 (br
s, 6 H), 2.39 (br s, 4 H), 1.72–0.81 (br m, 29 H).
13C{1H} NMR (126 MHz, DMSO-d6): δ = 151.5, 149.5, 131.0,
116.4, 107.9, 106.7, 45.8, 35.4, 31.8, 29.19, 29.17, 29.1, 28.8, 8.7.
11B{1H} NMR (160 MHz, DMSO-d6): δ = 14.7.
Anal. Calcd for C30H46BNO4: C, 72.72; H, 9.36; N, 2.83. Found: C,
72.34; H, 9.47; N, 2.85.
1H NMR (500 MHz, CDCl3): δ = 6.79–6.77 (m, 2 H), 6.72–6.70 (m,
4 H), 3.87 (s, 6 H), 3.85 (s, 6 H), 2.54 (t, J = 7.5 Hz, 4 H), 1.59
(quint, J = 7.5 Hz, 4 H), 1.35–1.23 (m, 16 H).
13C{1H} NMR (126 MHz, CDCl3): δ = 148.6, 146.9, 135.6, 120.0,
111.7, 111.0, 55.8, 55.7, 35.5, 31.7, 29.61, 29.57, 29.5, 29.3.
Cp*Ir(κ2-CO3)(IPr) (2)
A mixture of 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride
(0.425 g, 1.0 mmol), [Cp*IrCl2]2 (0.398 g, 0.5 mmol), and K2CO3
(0.484 g, 3.5 mmol) in anhyd THF (8 mL)–CH2Cl2 (2 mL) was
stirred at 24 °C for 10 h under N2. The resulting suspension was
stirred at 60 °C for 24 h under N2, then concentrated to dryness. Af-
ter the addition of CH2Cl2 (10 mL) to the residue, the resulting sus-
pension was filtered through Celite. The filtrate was concentrated to
dryness to give the iridium complex 2 as a brownish orange solid
(0.748 g, 0.963 mmol, 96%).
MALDI-TOF MS (DIT): m/z = 442 [M+].
Anal. Calcd for C28H42O4: C, 75.98; H, 9.56. Found: C, 75.88; H,
9.68.
1,12-Bis(3,4-dihydroxyphenyl)dodecane (8)
To a solution of 7 (5.533 g, 12.5 mmol) in CH2Cl2 (100 mL) at 0 °C
under N2 was added a solution of BBr3 (1.0 M in CH2Cl2, 100 mL,
100 mmol). The reaction mixture was stirred at 22 °C for 24 h under
N2, then cooled to 0 °C. The mixture was quenched with H2O (300
mL). The resulting solid was collected by suction filtration, washed
with H2O (2 × 150 mL), and dried under reduced pressure. The
crude product was purified by silica gel column chromatography
(CHCl3–MeOH, 9:1) to give the biscatechol 8 as a colorless solid
(3.85 g, 10.0 mmol, 80%); mp 131–133 °C.
1H NMR (500 MHz, DMSO-d6): δ = 8.61 (br s, 4 H, OH), 6.60 (d,
J = 8.0 Hz, 2 H), 6.54 (d, J = 1.5 Hz, 2 H), 6.39 (dd, J = 8.0, 2.5 Hz,
2 H), 2.37 (t, J = 7.7 Hz, 4 H), 1.49–1.44 (m, 4 H), 1.28–1.19 (m, 16
H).
IR (ATR, ZnSe): 1659 cm–1 (CO2).
1H NMR (500 MHz, CD2Cl2): δ = 7.43 (t, J = 8.0 Hz, 2 H), 7.33 (d,
J = 8.0 Hz, 4 H), 7.09 (s, 2 H), 2.99–2.94 (m, 4 H), 1.45 (d, J = 7.0
Hz, 12 H), 1.21 (s, 15 H), 1.06 (d, J = 6.0 Hz, 12 H).
13C{1H} NMR (126 MHz, CD2Cl2): δ = 168.1, 165.9, 138.1, 130.1,
126.4, 124.2, 87.2, 29.0, 27.2, 23.5, 9.4.
Anal. Calcd for C38H51IrN2O3·H2O: C, 57.48; H, 6.73; N, 3.53.
Found: C, 57.40; H, 6.54; N, 3.57.
PB-Cp*Ir(IPr)-MeCN Adduct (3·2MeCN)
A solution of Cp*Ir(κ2-CO3)(IPr) (2; 39 mg, 0.05 mmol) in anhyd
MeCN (2 mL) was added to a solution of 1·DMF adduct (0.10 mmol
of B, 47 mg) in anhyd DME (2 mL) at 50 °C at 1500 rpm under N2.
The resulting suspension was stirred at 50 °C for 24 h under N2. Af-
ter removal of the solvent, the residue was washed with anhyd DME
and anhyd MeCN (4 × 4 mL each) and dried under reduced pressure
(0.1 Torr) for 12 h to give the adduct 3·2MeCN as a dark brown sol-
id (52 mg, 0.627 mmol Ir/g, 65%).
13C{1H} NMR (126 MHz, DMSO-d6): δ = 144.9, 143.0, 133.1,
118.8, 115.6, 115.3, 34.5, 31.3, 29.084, 29.075, 29.0, 28.7.
MALDI-TOF MS (DIT): m/z = 409 [M + Na]+.
Anal. Calcd for C24H34O4: C, 74.58; H, 8.87. Found: C, 74.52; H,
9.00.
Anal. Calcd for C85H111B2IrN2O8·2MeCN·H2O: C, 66.69; H, 7.48;
N, 3.50; Ir, 11.99. Found: C, 66.34; H, 7.48; N, 3.29; Ir, 12.06.
Poly(catechol borate)-DMF Adduct (1·DMF)
To a mixture of 8 (1.93 g, 5.0 mmol) and boric acid (0.309 g, 5.0
mmol) was added anhyd DMF (50 mL) under argon. The reaction
mixture was stirred at 40 °C for 24 h under reduced pressure (12
Torr), then concentrated to dryness. The resulting solid was washed
with anhyd Et2O (3 × 100 mL) under argon and dried under reduced
pressure (0.1 Torr) for 12 h to give the 1·DMF adduct as a colorless
solid (1.11 g, 2.37 mmol of B, 47%).
PB-Cp*Ir(IMes)-MeCN Adduct (3′·2MeCN)
A solution of Cp*Ir(κ2-CO3)(IMes) (2′; 35 mg, 0.05 mmol) in anhyd
MeCN (2 mL) was added to a solution of 1·DMF adduct (0.10 mmol
of B, 47 mg) in anhyd DME (2 mL) at 50 °C at 1500 rpm under N2.
The resulting suspension was stirred at 50 °C for 24 h under N2. Af-
ter removal of the solvent, the residue was washed with anhyd DME
Synthesis 2013, 45, 2093–2100
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Dehydrative Alkylation of Ammonia and Amines with Alcohols
2099
and anhyd MeCN (4 × 4 mL each) and dried under reduced pressure
(0.1 Torr) for 12 h to give the adduct 3′·2MeCN as a dark brown
solid (47 mg, 0.675 mmol Ir/g, 62%).
(3) For reviews, see: (a) Organic Synthesis in Water; Grieco, P.
A., Ed.; Blackie Academic and Professional: London, 1998.
(b) Li, C.-J. Chem. Rev. 1993, 93, 2023. (c) Ishihara, K.
Tetrahedron 2009, 65, 1085.
Anal. Calcd for C79H99B2IrN2O8·2MeCN·H2O: C, 65.65; H, 7.10;
N, 3.69; Ir, 12.66. Found: C, 65.48; H, 7.11; N, 3.77; Ir, 12.98.
(4) For a review, see: Nicolaou, K. C.; Snyder, S. A. Classics in
Total Synthesis II; Wiley-VCH: Weinheim, 2003.
(5) For reviews, see: (a) Fujita, K.; Yamaguchi, R. Synlett 2005,
560. (b) Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M.
J. Adv. Synth. Catal. 2007, 349, 1555. (c) Guillena, G.;
Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2007, 46,
2358. (d) Nixon, T. D.; Whittlesey, M. K. J.; Williams, M. J.
Dalton Trans. 2009, 753. (e) Dobereiner, G. E.; Crabtree, R.
H. Chem. Rev. 2010, 110, 681. (f) Guillena, G.; Ramón, D.
J.; Yus, M. Chem. Rev. 2010, 110, 1611. (g) Watson, A. J.
A.; Williams, J. M. J. Science 2010, 329, 635. (h) Crabtree,
R. H. Organometallics 2011, 30, 17.
PB-Cp*Ir (3′′)
A solution of Cp*Ir(κ2-CO3) (2′′; 19 mg, 0.05 mmol) in anhyd
MeCN (2 mL) was added to a solution of 1·DMF adduct (0.10 mmol
of B, 47 mg) in anhyd DME (2 mL) at 50 °C at 1500 rpm under N2.
The resulting suspension was stirred at 50 °C for 24 h under N2. Af-
ter removal of the solvent, the residue was washed with anhyd DME
and anhyd MeCN (4 × 4 mL each) and dried under reduced pressure
(0.1 Torr) for 12 h to give PB-Cp*Ir (3′′) as a pale brown solid (37
mg, 0.862 mmol Ir/g, 65%).
Anal. Calcd for C58H75B2IrO8·H2O: C, 61.54; H, 6.86; Ir, 16.98.
Found: C, 61.68; H, 6.94; Ir, 16.57.
(6) For reactions using Ir catalysts, see: (a) Fujita, K.;
Yamamoto, K.; Yamaguchi, R. Org. Lett. 2002, 4, 2691.
(b) Cami-Kobeci, G.; Slatford, P. A.; Whittlesey, M. K.;
Williams, J. M. J. Bioorg. Med. Chem. Lett. 2005, 15, 535.
(c) Eary, C. T.; Clausen, D. Tetrahedron Lett. 2006, 47,
6899. (d) Prades, A.; Corberán, R.; Poyatos, M.; Peris, E.
Chem. Eur. J. 2008, 14, 11474. (e) Aramoto, H.; Obora, Y.;
Ishii, Y. J. Org. Chem. 2009, 74, 628. (f) Chang, Y.-H.; Fu,
C.-F.; Liu, Y.-H.; Peng, S.-M.; Chen, J.-T.; Liu, S.-T. Dalton
Trans. 2009, 861. (g) Blank, B.; Michlik, S.; Kempe, R.
Chem. Eur. J. 2009, 15, 3790. (h) Liu, S.; Rebros, M.;
Stephens, G.; Marr, A. C. Chem. Commun. 2009, 2308.
(7) For reactions using Ru, Rh, and Pt catalysts, see:
(a) Watanabe, Y.; Tsuji, Y.; Ohsugi, Y. Tetrahedron Lett.
1981, 22, 2667. (b) Murahashi, S.-I.; Kondo, K.; Hakata, T.
Tetrahedron Lett. 1982, 23, 229. (c) Arcelli, A.; Khai, B. T.;
Porzi, G. J. Organomet. Chem. 1982, 235, 93. (d) Watanabe,
Y.; Tsuji, Y.; Ige, H.; Ohsugi, Y.; Ohta, T. J. Org. Chem.
1984, 49, 3359. (e) Marsella, J. A. J. Org. Chem. 1987, 52,
467. (f) Watanabe, Y.; Morisaki, Y.; Kondo, T.; Mitsudo,
T.-a. J. Org. Chem. 1996, 61, 4214. (g) Abbenhuis, R. A. T.
M.; Boersma, J.; van Koten, G. J. Org. Chem. 1998, 63,
4282. (h) Bitsi, G.; Schleiffer, E.; Antoni, F.; Jenner, G.
J. Organomet. Chem. 1989, 373, 343. (i) Del Zotto, A.;
Baratta, W.; Sandri, M.; Verardo, G.; Rigo, P. Eur. J. Inorg.
Chem. 2004, 524. (j) Tillack, A.; Hollmann, D.; Michalik,
D.; Beller, M. Tetrahedron Lett. 2006, 47, 8881. (k) Hamid,
M. H. S. A.; Allen, C. L.; Lamb, G. W.; Maxwell, A. C.;
Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J. J. Am.
Chem. Soc. 2009, 131, 1766.
Dehydrative Alkylation of Amines with Alcohols in Water;
General Procedure
The appropriate amine 9 (0.5 mmol), the respective alcohol 10 (0.6
mmol), PB-Cp*Ir(IPr) (3; 1 mol% Ir), and H2O (0.5 mL) were
mixed in a vial tube at 23 °C under air. The vial was sealed with a
screw cap, and the reaction mixture was stirred at 100 °C for 24 h.
After cooling to 23 °C, the mixture was extracted with Et2O or
EtOAc (3 × 2 mL) and the combined organic layers were concen-
trated. The crude product was purified by column chromatography
over silica gel eluting with hexane–EtOAc (98:2 to 85:15) to afford
the corresponding N-alkylated amine 11a–n (Table 3, see also SI).
Dehydrative Alkylation of Ammonia with Alcohols in Phthalate
pH Standard Solution; General Procedure
Aq ammonia (28%, 0.5 mmol), the appropriate alcohol 10 (3.4
mmol), the catalyst 3 (1 mol% Ir), and the phthalate pH standard so-
lution (0.5 mL, pH 4.01) were mixed in a microwave vial tube at
23 °C under air. The vial was sealed with a cap, and the reaction
mixture was stirred at 150 °C for 24 h in a microwave reactor (25–
32 W). After cooling to 23 °C, aq NaOH (0.1 M, 1 mL) was added
to the mixture and extracted with EtOAc (3 × 2 mL). The combined
organic layers were concentrated. The crude product was purified
by column chromatography over silica gel eluting with hexane–
EtOAc (98:2 to 9:1) or CHCl3 to afford the corresponding N-alkyl-
ated amine 11l,o–s (Table 5, see also SI).
Acknowledgment
We acknowledge the partial financial support extended by JSPS
(Grant-in-Aid for Scientific Research, no. 24550126), MEXT (Sci-
ence Research on Priority Areas, no. 460), JST (ACT-C, and
CREST Projects), and METI/NEDO (Green-Sustainable Chemical
Process project). We also thank RIKEN Advance Science Institute
Advanced Technology Support Division for their assistance in ele-
mental, XPS, and ICP analyses.
(8) For homogeneous catalysis in water, see: (a) Nordstrøm, L.
U.; Madsen, R. Chem. Commun. 2007, 5034.
(b) Gunanathan, C.; Milstein, D. Angew. Chem. Int. Ed.
2008, 47, 8661. (c) Kawahara, R.; Fujita, K.; Yamaguchi, R.
J. Am. Chem. Soc. 2010, 132, 15108. (d) Saidi, O.; Blacker,
A. J.; Farah, M. M.; Marsden, S. P.; Williams, J. M. J. Chem.
Commun. 2010, 46, 1541. (e) Saidi, O.; Blacker, A. J.;
Lamb, G. W.; Marsden, S. P.; Taylor, J. E.; Williams, J. M.
J. Org. Process Res. Dev. 2010, 14, 1046. (f) Kawahara, R.;
Fujita, K.; Yamaguchi, R. Adv. Synth. Catal. 2011, 353,
1161.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
(9) For heterogeneous catalysis in organic solvents, see:
Review: (a) Narayanan, S.; Deshpande, K. Appl. Catal., A
2000, 199, 1. Examples: (b) Valotl, F.; Fachel, F.; Jacquot,
R.; Spagnol, M.; Lemairel, M. Tetrahedron Lett. 1999, 40,
3689. (c) Martínez, R.; Ramón, D. J.; Yus, M. Org. Biomol.
Chem. 2009, 7, 2176. (d) Kim, J. W.; Yamaguchi, K.;
Mizuno, N. J. Catal. 2009, 263, 205. (e) Kwon, M. S.; Kim,
S.; Park, S.; Bosco, W.; Chidrala, R. K.; Park, J. J. Org.
Chem. 2009, 74, 2877.
References
(1) (a) Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.;
Walter, P. Molecular Biology of the Cell, 5th ed.; Garland
Science: New York, 2008. (b) The RNA World; Gesteland,
R. F.; Cech, T.; Atkins, J. F., Eds.; 3rd ed.; Cold Spring
Harbor Laboratory Press: Cold Spring Harbor, 2005.
(2) Tooley, C. E. S.; Petkowski, J. J.; Muratore-Schroeder, T. L.;
Balsbaugh, J. L.; Shabanowitz, J.; Sabat, M.; Minor, W.;
Hunt, D. F.; Macara, I. G. Nature 2010, 466, 1125.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2093–2100

2100
Y. M. A. Yamada et al.
SPECIAL TOPIC
(10) (a) Yamada, Y. M. A.; Sarkar, S. M.; Uozumi, Y. J. Am.
Chem. Soc. 2012, 134, 9285. (b) Yamada, Y. M. A.; Sarkar,
S. M.; Uozumi, Y. J. Am. Chem. Soc. 2012, 134, 3190.
(c) Sarkar, S. M.; Uozumi, Y.; Yamada, Y. M. A. Angew.
Chem. Int. Ed. 2011, 50, 9437. (d) Yamada, Y. M. A.; Jin,
C.-K.; Uozumi, Y. Org. Lett. 2010, 12, 4540. (e) Yamada, Y.
M. A.; Watanabe, T.; Torii, K.; Uozumi, Y. Chem. Commun.
2009, 5594. (f) Yamada, Y. M. A.; Guo, H.; Uozumi, Y.
Org. Lett. 2007, 9, 1501. (g) Yamada, Y. M. A.; Uozumi, Y.
Tetrahedron 2007, 63, 8492. (h) Uozumi, Y.; Yamada, Y.
M. A.; Beppu, T.; Fukuyama, N.; Ueno, M.; Kitamori, T.
J. Am. Chem. Soc. 2006, 128, 15994. (i) Yamada, Y. M. A.;
Maeda, Y.; Uozumi, Y. Org. Lett. 2006, 8, 4259.
(j) Yamada, Y. M. A.; Uozumi, Y. Org. Lett. 2006, 8, 1375.
(11) For reviews on Shibasaki’s homogeneous heterobimetallic
multifunctional catalysts, see: (a) Shibasaki, M.; Kanai, M.;
Matsunaga, S.; Kumagai, N. Acc. Chem. Res. 2009, 42,
1117. (b) Shibasaki, M.; Kanai, M.; Funabashi, K. Chem.
Commun. 2002, 1989. (c) Shibasaki, M.; Yoshikawa, N.
Chem. Rev. 2002, 102, 2187. (d) Shibasaki, M.; Sasai, H.;
Arai, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1236.
(e) Wheatley, N.; Kalck, P. Chem. Rev. 1999, 99, 3379.
(f) van den Beuken, E. K.; Feringa, B. L. Tetrahedron 1998,
54, 12985. For recent examples, see: (g) Handa, S.;
Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. J. Am.
Chem. Soc. 2010, 132, 4925. (h) Iwata, M.; Yazaki, R.;
Suzuki, Y.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc.
2009, 131, 18244. (i) Nitabaru, T.; Nojiri, A.; Kobayashi,
M.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc. 2009,
131, 13860.
examples, see: (c) Takizawa, S.; Somei, H.; Jayaprakash, D.;
Sasai, H. Angew. Chem. Int. Ed. 2003, 42, 5711. (d) Ding,
K.; Wang, Z.; Wang, X.; Liang, Y.; Wang, X. Chem. Eur. J.
2006, 12, 5188. For an example of the catalyst analogue
concept, see: (e) Arai, T.; Sekiguchi, T.; Otsuki, K.;
Takizawa, S.; Sasai, H. Angew. Chem. Int. Ed. 2003, 42,
2144.
(13) Partial results have been reported as a rapid communication,
see: Ohta, H.; Yuyama, Y.; Uozumi, Y.; Yamada Yoichi, M.
A. Org. Lett. 2011, 12, 3892.
(14) (a) Lang, A.; Knizek, J.; Nöth, H.; Schur, S.; Thomann, M.
Z. Anorg. Allg. Chem. 1997, 623, 901. (b) Chikkali, S. H.;
Gudat, D.; Lissner, F.; Nieger, M.; Schleid, T. Dalton Trans.
2007, 3906.
(15) (a) Maki, T.; Ishihara, K.; Yamamoto, H. Tetrahedron 2007,
63, 8645. (b) Ishihara, K.; Kurihara, H.; Matsumoto, M.;
Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920.
(16) Danjo, H.; Hirata, K.; Yoshigai, S.; Azumaya, I.;
Yamaguchi, K. J. Am. Chem. Soc. 2009, 131, 1638.
(17) See the experimental section for the preparation of 2.
(18) See the experimental section for the preparation of 1·NEt3.
(19) In the reaction mixture, iridium species were detected
(0.008%; ICP-AES analysis).
(20) The reaction in H2O at 100–150 °C without the use of
microwaves was sluggish.
(21) Abe, T.; Haga, T.; Negi, S.; Morita, Y.; Takayanagi, K.;
Hamamura, K. Tetrahedron 2001, 57, 2701.
(22) Imm, S.; Bähn, S.; Neubert, L.; Neumann, H.; Beller, M.
Angew. Chem. Int. Ed. 2010, 49, 8126.
(23) Pingen, D.; Müller, C.; Vogt, D. Angew. Chem. Int. Ed.
2010, 49, 8130.
(12) For reviews on heterobimetallic self-supported catalysts,
see: (a) Wang, Z.; Chen, G.; Ding, K. Chem. Rev. 2009, 109,
322. (b) Lu, J.; Toy, P. H. Chem. Rev. 2009, 106, 815. For
(24) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R.
K.; Timmers, F. J. Organometallics 1996, 15, 1518.
Synthesis 2013, 45, 2093–2100
© Georg Thieme Verlag Stuttgart · New York