Iridium Complex-Catalyzed C2-Extension of Primary Alcohols with Ethanol via a Hydrogen Autotransfer Reaction

Article abstract of DOI:10.1021/acs.joc.0c01540

The development of a C2-extension of primary alcohols with ethanol as the C2 source and catalysis by [Cp*IrCl2]2 (where Cp? = pentamethylcyclopentadiene) is described. This new extension system was used for a range of benzylic alcohol substrates and for aliphatic alcohols with ethanol as an alkyl reagent to generate the corresponding C2-extended linear alcohols. Mechanistic studies of the reaction by means of intermediates and deuterium labeling experiments suggest the reaction is based on hydrogen autotransfer.

Full text of DOI:10.1021/acs.joc.0c01540

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Note
Iridium Complex Catalyzed C2-Extension of Primary
Alcohols with Ethanol via Hydrogen Autotransfer Reaction
Masaki Kobayashi, Satoshi Itoh, Keisuke Yoshimura, Yuya Tsukamoto, and Yasushi Obora
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01540 • Publication Date (Web): 11 Aug 2020
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The Journal of Organic Chemistry
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Iridium Complex Catalyzed C2-Extension of Primary Alcohols
with Ethanol via Hydrogen Autotransfer Reaction
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Masaki Kobayashi, Satoshi Itoh, Keisuke Yoshimura, Yuya Tsukamoto, and Yasushi Obora*
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai
University, Suita, Osaka 564-8680, Japan
cat. [Cp*IrCl2]2
+
R
OH
OH
R
OH
KOtBu
100 °C, 24 h
ABSTRACT: The development of a C2-extension of primary alcohols with ethanol as the C2 source and catalysis by [Cp*IrCl2]2
(where Cp* = pentamethylcyclopentadiene) is described. This new extension system was used for a range of benzylic alcohol substrates
and for aliphatic alcohols with ethanol as alkyl reagent to generate the corresponding C2-extended linear alcohols. Mechanistic studies
suggest by means of intermediates and deuterium labeling experiments.
Alcohols are one of the most important classes of organic
compounds. Ethanol is of particular interest because it is a
biological product1 and is useful as a chemical starting material.2 It
can be produced in large quantity by fermentation of sugar-
containing crops and lignocellulosic materials.3 Recently, reactions
that use ethanol as a carbon source have been increasingly
reported.4 However, these reactions have poor selectivity and need
high temperature because of the low reactivity of ethanol.5 The
development of good selectivity in reactions using ethanol would
be beneficial for the chemical industry.
ruthenium complex in basic solution. Our group reported the homo
β-alkylation of primary alcohols to Guerbet alcohol.19,2a However,
cross β-alkylation of different primary alcohols has been scarcely
reported in the synthesis of linear primary alcohols.
In this article, we report the first example of [Cp*IrCl2]2 catalyzed
C2-extension of various alcohols using ethanol as the carbon source.
Conventionally, alkylation reactions use a halogen reagent as the
alkyl source. However, alkyl halides are toxic reagents and
generate halogen-salt waste.20 The reaction developed in this work
is easy to perform and provides good selectivity.
Hydrogen autotransfer (borrowing hydrogen) reactions have been
reported as effective strategies for extension of carbon numbers.6
This type of reaction can be carried out as one step, but involves
the following three reactions: 1) hydrogen is temporarily removed
from the alcohol by a catalyst7 to generate aldehyde; 2) aldol-type
condensation between the aldehyde and a nucleophile such as a
ketone,8 ester,9 amine,10 or nitrile4d,11 is facilitated by base; 3)
removed hydrogen is returned to unsaturated or aldehyde
functionalities.12 This feature provides easy access to the product,
is harmless to the environment, and produces water as the sole by-
product. Recently, C-alkylation reactions catalyzed by transition
metal complexes through hydrogen autotransfer have been
extensively investigated for different alcohols.13 Notably, iridium
complexes are well known as active catalysts for this reaction.14
Fujita and co-workers15 and Pérez-Torrente and co-workers16 have
reported the β-alkylation of secondary alcohols with primary
alcohols. Ramón and colleagues17 investigated the cross-
dehydrogenative coupling between primary alcohols to Guerbet
alcohol derivatives, and Mansell and colleagues18 describes
coupling of MeOH and EtOH to give n-PrOH with a further
coupling to produce i-BuOH as a sequel, all catalyzed by a
We investigated the β-alkylation of benzyl alcohol (1a) with
ethanol (2) as model substrate under various conditions (Table 1).
The reaction of benzyl alcohol (1a) (5 mmol) with ethanol (2) (1
mmol) was performed in the presence of [Cp*IrCl2]2 (5 mol %) and
potassium tert-butoxide (KOtBu) (1 mmol) as base in
tetrahydrofuran (THF) (1 mL) at 100 °C for 24 h to give the main
C2-extension product in yield of 65% (entry 1). Moreover, we
found that [Iridium / Phosphine] demonstrated high participation in
hydrogen transfer processes. This catalyst system gave the desired
products in moderate yields (entries 2–5). Other metal catalysts
including ruthenium and rhodium with phosphine (entries 6 and 7,
respectively) were tested, but these complexes did not show high
catalytic activity in this reaction. The reaction did not proceed
without iridium catalyst (entry 8) or base (entry 9), which
confirmed that a catalyst and base are essential for alkylation.
Strong bases such as KOtBu and NaOH gave the product in
moderate yield, but weak bases such as K3PO4 and Cs2CO3 gave
lower yields (entries 10–12). Lowering the reaction temperature to
80 °C (entry 13) showed significantly lower yield than reaction at
100 °C.
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Table 1. C2-Extension of benzyl alcohol with ethanol
Table 2. Iridium complex catalyzed C2-extension of
various benzyl alcohol derivatives with ethanola
1
2
under various conditionsa
3
4
5
6
7
8
9
cat. [Cp*IrCl2]2
Ir-catalyst
OH
OH
OH
OH
+
R
R
+
OH
OH
KOtBu
THF
Base
THF
100 °C, 24 h
2
3
1
2
3a
1a
Catalyst
100 °C, 24 h
Entry Alcohol
1
Product
Yield (%)b
58
Yield (%)b,c
Entry
Base
OH
OH
OH
1
[Cp*IrCl2]2
[Cp*IrCl2]2
[IrCl(cod)]2
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
None
65 [58]
12
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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36
37
38
39
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59
60
1a
3a
2d
3d
4d
5d
6d
7d
8
59
OH
2
72
[Ir(OMe)(cod)]2
[Ir(OH)(cod)]2
[RuCl2(p-cymene)]2
[RhCl(cod)]2
None
40
36
1b
1c
1d
1e
1f
3b
3c
3d
OH
OH
3
83
19
15
OH
OH
OH
OH
n.d.
n.d.
45
4
70
9
[Cp*IrCl2]2
10
11
[Cp*IrCl2]2
NaOH
K3PO4
Cs2CO3
KOtBu
KOtBu
KOtBu
5
79 [56]c
61
O
O
[Cp*IrCl2]2
19
3e
OH
OH
OH
OH
12
13e
14f
15g
[Cp*IrCl2]2
21
tBu
tBu
6
[Cp*IrCl2]2
30
3f
[Cp*IrCl2]2
31
7
30
Cl
Cl
[Cp*IrCl2]2
47
1g
1h
3g
aReaction conditions: 1a (5 mmol) reacted with 2 (1 mmol) in
OH
OH
presence of Ir catalyst (0.05 mmol) and base (1 mmol) in THF (1 mL)
at 100 °C for 24 h. bGC yield based on 2 used. cNumbers in square
brackets show isolated yield. dPPh3 (10 mol %) was used. eAt 80 °C.
f1a (1 mmol) was used. g1,7-Octadiene (10 mol %) was used.
F3C
8
37
C3F
3h
OH
OH
OH
OH
OH
OH
9d
39
Moreover, when benzyl alcohol (1a) was used at lower
concentration (1 equiv.), the observed yield was lower (entry 14).
In a further test, the addition of 1,7-octadiene as hydrogen accepter
did not show a positive effect (entry 15).
1i
1j
3i
10d
75
36
36
3j
O
O
Based on the results, we next examined the reaction of various
benzyl alcohol derivatives with ethanol under the optimized
conditions (Table 2). The isolation of product using benzyl
alcohols bearing methyl groups at the ortho-, meta-, or para-
positions was successful (3b-d). Moreover, benzyl alcohols bearing
electron-donating groups at the para-position gave the
corresponding C2-extension products in high yield (3d-f), while
substrates bearing an electron-withdrawing group gave the desired
alcohol products in low yields (3g, h). The optimized reaction
conditions for solid substrates (1i-k) used slightly lower substrate
concentrations (3 mmol) to give products 3i-k. Using 2-
thiophenemethanol (1l) as the reaction substrate to give to 2-
thiophenepropanol (3l) in 36% yield also showed that heterocyclic
compounds can be used as the primary alcohol substrate.
11d
O
O
1k
3k
OH
OH
12
S
S
1l
3l
aReaction conditions: 1 (5.00 mmol), 2 (1.00 mmol), [Cp*IrCl2]2
(0.05 mmol), and KOtBu (1.00 mmol) stirred at 100 °C for 24 h
under Ar. bYield of isolated product after purification. c1e (50
mmol) reacted with 2 (10 mmol) in presence of [Cp*IrCl2]2
catalyst (0.5 mmol) and base (10 mmol) in THF (10 mL) at 100 °C
for 24 h. d1 (3.00 mmol) was used.
reaction was more complicated than the previous model. Products
were generated by straight C2-extension of 4a with 2 (5a, 1-
octanol), branch C2-extension of 4a with 2 (6a, 2-ethyl-hexanol),
straight C2-extration of 5a with 2 (7a, 1-decanol), β-alkylation of
5a with 2 (8a, 2-ethyl-octanol), and homo β-alkylation by 4a (9a,
2-buthyl-1-octanol). Product yields were 37% for 5a, 7a and 8a
combined (59:22:19), 14% for 6a, and 5% for 9a (entry 1). In the
reaction using only ethanol under these conditions, the amount of
4a produced was negligible.2a Moreover, this reaction system was
sensitive to substrate ratio, because the Guerbet reaction of homo
β-alkylation was observed.19a This problem was addressed by add-
In analyzing the substrate scope of the reaction, we optimized the
reaction using 1-hexanol instead of benzyl alcohol (Scheme 1,
Table S1, and Figure S1). The stock reaction used 1 mol % of
[Cp*IrCl2]2 catalyst, 1-hexanol (4a) (1 mmol), and ethanol (2) (5
mmol) in the presence of 1,7-octadiene (15 mol %) as hydrogen
acceptor2a,19a, with KOtBu (1 mmol) as base in THF (1 mL) at 100
°C for 24 h. Considering the range of generated products, this
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cat.[Cp*IrCl2]2 (1 mol %)
(a)
1
2
3
1,7-Octadiene (15 mol %)
O
+
+
OH
OH
OH
OH
3
5
3
KOtBu (1 mmol)
THF (1 mL)
cat. [Cp*IrCl2]2 (5 mol %)
H
OH
+
OH
1 mmol
5 mmol
22%
14%
6a
KOtBu (1 mmol)
THF (1 mL)
100 °C, 24 h
4a
2
5a
4
5
5 mmol
10
1 mmol
42% (GC)
3a
100 °C, 24 h
2
+
+
OH
OH
OH
7
5
4
6
7
(b)
8%
7a
7%
8a
5%
9a
cat. [Cp*IrCl2]2 (5 mol %)
O
H
OH
OH
+
8
9
KOtBu (1 mmol)
THF (1 mL)
Scheme 1. C2-extension of 1-hexanol with ethanol
5 mmol
1a
1 mmol
11
12% (GC)
3a
100 °C, 24 h
10
11
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ing an excess of ethanol. The utility of the catalytic β-alkylation
reaction was also explored for the C2 extension of different primary
alcohols using ethanol (Table3). The reactions of 1-hexanol and 1-
octanol successfully generated the corresponding C2 products in
modest yields (entries 1 and 2). Use of a branched alcohol did not
generate the desired product (entry 3). Similarly, increasing the side
chain carbon number of benzyl alcohol by one (2-phenylethanol,
4d) generated only the branched alcohol by-product (6d, entry 4).
(c)
cat. [Cp*IrCl2]2 (5 mol %)
OH
CD CD OD
+
3
2
KOtBu (1 mmol)
THF (1 mL)
5 mmol
1 mmol
12
100 °C, 24 h
1a
[21% d]
[26% d]
[36% d]
D
D
D
D D
D
OH
OH
D[12% d]
+
D
Table 3. Iridium complex catalyzed C2-extension of
various primary alcohols with ethanola
14%
13a
39%
14a
cat. [Cp*IrCl2]2
1,7-octadiene
R
Scheme 2. Intermediates considered in iridium
catalyzed C2-extension of primary alcohol with
ethanol
R
R
+
+
OH
OH
OH
OH
KOtBu
THF
4
2
5
6
100 °C, 24 h
Total yield (%)b
Selectivity (5:6)
cohols) with no catalyst to produce the C2-extension alcohol 3a22.
Our stock reaction with benzyl alcohol was also performed using
ethanol-d6. The reaction gave the deuterated benzyl alcohol 13a in
14% yield and deuterated product 14a in 39% yield (Scheme 2c).
When the 1:1 substrate ratio of 1a and 12 was improved deuterium
conversion rate (Scheme S4). These results indicated that the
respective aldehydes were produced as reaction intermediates,
alcohols acted as a hydrogen source through oxidation and
reduction reactions, and hydrogen source depended on the alcohol
concentration. Based on the results of our experiments, we
proposed a plausible reaction mechanism (Scheme S5). First, the
iridium catalyst temporally abstracts hydrogens from the primary
alcohol and ethanol, which generates iridium hydrides and the
respective aldehydes as intermediates. Next, the presence of base
allows aldol-type condensation to proceed, and the unsaturated
aldehyde is produced. Finally, the double bond and aldehyde group
are hydrogenated by iridium hydrides. We confirmed that iridium
hydrides were generated in the reaction by conducting a control
experiment (Figures S2-S4). Adding benzyl alcohol to the iridium
catalyst rapidly resulted in the emergence of upfield resonances
(−10 to −15 ppm) in the 1H NMR spectrum, indicating the presence
of iridium hydride.23 Additional characterization by 13C {1H} NMR
spectroscopy showed resonances at 88.3 and 90.4 ppm that were
assigned to an α-alkoxy bond to the iridium metal center.24 These
peaks were further corroborated by a two-dimensional 1H-13C
HMBC experiment.25 These experiments resulted in the formation
of hydride(α-alkoxy)iridium species. However, we have been
unable to determine the full structure of the expected alkoxy
iridium intermediate.
Entry Desired product
By-product
OH
3
OH
OH
5
1
19 (62:38)
21 (60:40)
5a
5b
6a
6b
OH
5
7
2
3
OH
3
OH
OH
3
Trace
5c
6c
OH
4
2
63 (-:>99)
5d
6d
aReaction conditions: 4 (1.00 mmol), 2 (5.00 mmol), [Cp*IrCl2]2
(0.01 mmol), 1,7-octadiene (0.15 mmol), and KOtBu (1.00 mmol)
were stirred at 100 °C for 24 h under Ar. bIsolated yield.
Our study also investigated the nature of the reaction intermediates
(Scheme 2, Schemes S1-S3). Aldehydes are often generated in
hydrogen autotransfer reactions with alcohols.21 In the current
reaction system, a small amount of benzaldehyde was observed by
gas chromatography (GC), which suggested that aldehydes were
intermediate species. The reaction of benzaldehyde (instead of
benzyl alcohol) with ethanol under optimized conditions gave 3a
in 42% GC yield (Scheme 2a). Acetaldehyde (10) was considered
a possible intermediate, and
was reacted with benzyl alcohol under the same reaction conditions
to give desired product 3a in 12% GC yield (Scheme 2b).
Furthermore, we confirmed that the aldol condensation path was
used in the reaction by heating the respective aldehydes (instead of
the al-
In summary, we report a new method for the C2-extension of
benzylic alcohols with ethanol in the presence of iridium complex.
This reaction system is also applicable to aliphatic alcohols. A brief
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Page 4 of 7
study of the mechanism of reaction suggests the reaction is based
on hydrogen autotransfer.
(CH2), 34.3 (CH2), 62.3 (CH2), 128.3 (2CH), 129.1 (2CH), 135.3
1
2
(C), 138.7 (C); GC-MS (EI) m/z (relative intensity) 150 (1) [M]+,
117 (100), 105 (91), 150 (55), 91 (41).
3-(4-Methoxyphenyl)propan-1-ol (3e). yield 79% (131 mg),
Deep-brown oil. 1H NMR (400 MHz; CDCl3) δ 1.38(s, 1H), 1.83-
1.90 (m, 2H), 2.65 (t, J = 7.7 Hz, 2H), 3.67 (t, J = 6.4 Hz, 2H), 3.79
(s, 3H), 6.83 (d, J = 8.6Hz, 2H), 7.11 (d, J = 8.6Hz, 2H); 13C {1H}
NMR (100 MHz; CDCl3) δ 31.1 (CH2), 34.4 (CH2), 55.3 (CH3),
62.2(CH2), 113.8 (CH), 129.3 (CH), 133.9 (C), 157.8 (C); GC-MS
(EI) m/z (relative intensity) 168 (1) [M]+, 121 (100), 166 (33), 122
(14), 77 (14).
3
4
5
6
7
8
9
EXPERIMENTAL SECTION
General Information GLC analysis was performed with a
flame ionization using a 0.22 mm × 25 m capillary column (BP-5).
All NMR spectra were measured at 400 and 100 MHz, respectively,
in CDCl3 with TMS as an internal standard. All products were
characterized by 1H NMR, 13C {1H} NMR and CC-MS. The
product yields were estimated from the peak areas based on the
internal standard technique using GC. All starting materials were
commercially available and used without any purification.
Compounds 3a26, 3b27, 3c28, 3d27, 3e26, 3f29, 3g27, 3h27, 3i30, 3j31,
3k32, 3l33, 5a34, 6a35, 7a36, 8a26, 9a19a, 5b36, 6b26, 6d37, 13a38were
reported previously. High-resolution mass spectra were performed
at Global Facility Center, Hokkaido University.
3-(4-(tert-Butyl)phenyl)propan-1-ol (3f). yield 61% (117 mg),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Colorless oil. H NMR (400 MHz; CDCl3) δ 1.31-1.46 (m, 9H),
1.46 (s, 1H) 1.88-1.93 (m, 2H), 2.68 (t, J = 7.8 Hz, 2H), 3.69 (t, J
= 6.5 Hz, 2H), 7.13-7.33 (m, 4H); 13C {1H} NMR (100 MHz;
CDCl3) δ 31.4 (3CH3), 31.5 (CH2), 34.2 (CH2),34.3 (C), 62.4
(CH2), 125.3 (2CH), 128.0 (2CH), 138.7 (C), 148.7 (C); GC-MS
(EI) m/z (relative intensity) 177 (1) [M]+, 177 (100), 131 (48), 192
(31), 91 (25).
General Experiment Procedure (Table 1, entry 1). A mixture of
benzyl alcohol 1a (540 mg, 5.0 mmol), ethanol 2 (46 mg, 1.0 mmol),
potassium tert-butoxide (112 mg, 1.0 mmol) and [Cp*IrCl2]2 (40
mg, 0.05 mmol) as a catalyst in THF (1 mL) was stirred at 100 ℃
(oil bath) for 24 h under Ar atmosphere in a pressure tube (ACE
pressure tube, 15 mL). The yield of product was determined from
peak areas base on an internal standard (pentadecane) using GC and
the product 3a was obtained in 65% yield. The reaction mixture
was extracted with diethylether (20 mL×2), dried over sodium
sulfate, vacuum distillation by Kugelrohr and, preparative gel
permeation chromatography. The product (3a) was isolated in 58%
yield (79 mg) as a light-yellow oil.
A gram-scale reaction procedure for Ir complex catalyzed C2-
extension of 1e with ethanol. A mixture of 4-methoxybenzyl
alcohol 1e (5403 mg, 50 mmol), ethanol 2 (460 mg, 10 mmol),
potassium tert-butoxide (1120 mg, 10 mmol) and [Cp*IrCl2]2 (397
mg, 0.5 mmol) as a catalyst in THF (10 mL) was stirred at 100 ℃
for 24 h under Ar atmosphere in a pressure tube (ACE pressure tube,
35 mL). The reaction mixture was extracted with diethylether (20
mL×2), dried over sodium sulfate, and vacuum distillation by
Kugelrohr and preparative gel permeation chromatography. The
product (3e) was isolated in 56% yield (930 mg) as a deep-brown
oil.
3-Phenylpropanol-1-ol (3a). yield 58% (79 mg), Light-yellow oil.
1H NMR (400 MHz; CDCl3) δ 1.57(s, 1H), 1.85-1.92 (m, 2H), 2.70
(t, J = 7.7 Hz, 2H), 3.66 (t, 6.5 Hz, 2H), 7.16-7.31 (m, 5H); 13C
{1H} NMR (100 MHz; CDCl3) δ 32.1 (CH2), 34.2 (CH2),
62.2(CH2), 125.9 (CH), 128.4 (CH), 128.4 (CH), 141.8 (C); GC-
MS (EI) m/z (relative intensity) 136 (27) [M]+, 117 (100), 91 (75),
77 (11).
3-(o-Tolyl)propan-1-ol (3b). yield 72% (108 mg), Light-yellow
oil. 1H NMR (400 MHz; CDCl3) δ1.50 (br, 1H), 1.83-1.89 (m, 2H),
2.32 (s, 3H), 2.66 (t, J = 7.7 Hz, 2H), 3.66 (t, J = 6.5 Hz, 2H), 7.09-
7.15 (m, 4H); 13C {1H} NMR (100 MHz; CDCl3) δ 21.0 (CH3), 31.6
(CH2), 34.3 (CH2), 62.3 (CH2), 128.3 (2CH), 129.1 (2CH), 135.3
(C), 138.7 (C); GC-MS (EI) m/z (relative intensity)164 (1) [M]+,
117 (100), 105 (91), 150 (55), 91 (50).
3-(4-Chlorophenyl)propan-1-ol (3g). yield 30% (51 mg),
1
Colorless oil. H NMR (400 MHz; CDCl3) δ 1.52 (d, J = 7.2 Hz,
3H), 3.67 (s, 3H), 3.79 (q, J = 7.2 Hz, 1H), 7.42 (d, J = 7.6 Hz,
2H), 7.58 (d, J = 7.6 Hz, 2H); 13C {1H} NMR (100 MHz; CDCl3)
δ 31.4 (CH2), 34.0 (CH2), 62.0 (CH2), 128.5 (CH), 129.8 (CH),
131.6 (C), 140.2 (C).
3-(4-(Trifluoromethyl)phenyl)propan-1-ol (3h). yield 37% (76
mg), Light-yellow oil. 1H NMR (400 MHz; CDCl3) δ 1.53 (br, 1H),
1.87-1.94 (m, 2H), 2.77 (t, J = 7.7 Hz, 2H), 3.68 (s, 2H), 7.31 (d, J
= 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H); 13C {1H} NMR (100 MHz;
CDCl3) δ 31.9 (CH2), 33.9 (CH2), 61.9 (CH2), 125.3 (q, 2JC-F = 32.5
1
Hz), 124.3(q, JC-F = 271.4 Hz), 128.7 (4CH), 145.9 (C); GC-MS
(EI) m/z (relative intensity) 204 (1)[M]+, 117 (100), 159 (12), 91
(22), 77 (3).
3-(Naphthalen-1-yl)propan-1-ol (3i). yield 39% (73 mg), Brown
oil. 1H NMR (400 MHz; CDCl3) δ 1.53 (s, 1H), 1.98-2.05 (q, J =
6.8 Hz 2H), 3.16 (t, J = 7.6 Hz, 2H), 3.73 (t, J = 6.4 Hz, 2H), 7.32-
7.52 (m, 4H), 7.70-7.72 (m, 1H), 7.84-8.06 (m, 2H); 13C {1H} NMR
(100 MHz; CDCl3) δ 39.2 (CH2), 43.6 (CH2), 72.6 (CH2), 133.8
(CH) , 135.5 (CH), 135.6 (CH), 135.9 (CH), 136.1 (CH), 136.8
(CH), 138.9 (CH); GC-MS (EI) m/z (relative intensity) 186 (46)
[M]+, 141 (100), 115 (34), 153 (33),128 (12).
3-(Naphthalen-2-yl)propan-1-ol (3j). yield 75% (140 mg), White
solid, m.p. 35-36 °C (lit.15 70-72 °C); 1H NMR (400 MHz; CDCl3)
δ 1.43 (s, 1H), 1.94-2.01 (m, 2H), 2.87 (t, J = 7.7 Hz, 2H), 3.69 (t,
J = 6.4 Hz, 2H), 7.33-7.35 (m, 1H), 7.41-7.45 (m, 2H), 7.63 (s,
1H), 7.77-7.79 (m, 3H); 13C {1H} NMR (100 MHz; CDCl3) δ 29.1
(CH2), 33.5 (CH2), 62.5 (CH2), 123.7 (CH) , 125.5 (CH), 125.5
(CH), 125.8 (CH), 126.0 (CH), 126.7 (CH), 128.8 (CH) 131.8
(CH), 133.9 (CH), 137.9 (CH); GC-MS (EI) m/z (relative intensity)
232 (34) [M]+, 173 (100), 133 (44), 153 (32), 59 (17).
3-(Benzo[1,3]dioxo-5-yl)propan-1-ol (3k). yield 36% (65 mg),
Colorless oil. 1H NMR (400 MHz; CDCl3) δ 1.43 (s, 1H), 1.81-1.88
(m, 2H), 2.63 (t, J = 7.6 Hz, 2H), 3.66 (t, J = 6.4 Hz, 2H), 5.92 (s,
2H), 6.63-6.74 (m, 3H); 13C {1H} NMR (100 MHz; CDCl3) δ
31.7(CH2), 34.4(CH2), 62.1(CH2), 100.7(CH2), 108.1(CH),
108.8(CH), 121.1(CH), 135.6(C), 145.5(C), 147.6(C); GC-MS (EI)
m/z (relative intensity) 180 (43) [M]+, 135(100), 119(5).
3-(Thiophen-2-yl)propan-1-ol (3l). yield 36% (51 mg), Brown oil.
1H NMR (400 MHz; CDCl3) δ 1.42 (m, 1H), 1.92-1.99 (m, 2H),
2.94 (t, J = 7.6 Hz, 2H), 3.71 (t, J = 6.3 Hz, 2H) 6.81-6.82 (m, 1H)
7.13 (dd, 5.2 Hz, 1.2 Hz, 1H), 7.12-7.13 (m, 1H); 13C {1H} NMR
(100 MHz; CDCl3) δ 26.1 (CH2), 34.4 (CH2), 61.9 (CH2), 123.1
(CH), 124.3 (CH), 126.8 (CH), 144.6 (C); GC-MS (EI) m/z
(relative intensity) 142 (32) [M]+, 97 (100), 98 (34), 123 (29), 124
(22).
3-(m-Tolyl)propan-1-ol (3c). yield 83% (125 mg), Light-yellow
oil. 1H NMR (400 MHz; CDCl3) δ 1.38(br, 1H), 1.85-1.92 (m, 2H),
2.33 (s, 3H), 2.67 (t, J = 7.7Hz, 2H), 3.67 (t, J = 6.4Hz, 2H), 6.99-
7.01 (m, 3H), 7.18 (t, J = 7.4Hz, 1H); 13C {1H} NMR (100 MHz;
CDCl3) δ 21.4 (CH3), 32.0 (CH2), 34.3 (CH2), 62.4 (CH2), 125.4
(CH), 126.6 (CH), 128.3 (CH), 129.3 (CH), 138.0 (C), 141.8 (C);
GC-MS (EI) m/z (relative intensity) 164 (1) [M]+, 106 (100), 117
(87), 91 (74), 150 (60).
3-(p-Tolyl)propan-1-ol (3d). yield 70% (105 mg), Light-yellow
oil. 1H NMR (400 MHz; CDCl3) δ 1.50(br, 1H), 1.83-1.89 (m, 2H),
2.32 (s, 3H), 2.66 (t, J = 7.7Hz, 2H), 3.66 (t, J = 6.5 Hz, 2H), 7.09
(s, 4H); 13C {1H} NMR (100 MHz; CDCl3) δ 21.0 (CH3), 31.6
A typical reaction procedure for Ir complex catalyzed C2-
extension of 4a, 4b, and 4d with ethanol. A mixture of 1-hexanol
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The Journal of Organic Chemistry
4a (102 mg, 1.0 mmol), ethanol 2 (230 mg, 5.0 mmol), 1,7-
3-Phenylpropanol-1-ol-d6 (14a). yield 39% (55 mg), Light-
yellow oil. H NMR (400 MHz; CDCl3) δ 1.60(s, 1H), 1.86-1.93
1
1
2
3
4
5
6
7
8
octadiene (17 mg, 0.15 mmol), potassium tert-butoxide (112 mg,
1.0 mmol) and [Cp*IrCl2]2 (8 mg, 0.01 mmol) as a catalyst in THF
(1 mL) was stirred at 100 ℃ for 24 h under Ar atmosphere in a
pressure tube (ACE pressure tube, 15 mL). The reaction mixture
was vacuum distillation by Kugelrohr and preparative gel
permeation of chromatography.
(m, 2H), 2.71 (t, J = 7.7 Hz, 2H), 3.63-3.68 (m, 2H), 7.16-7.30 (m,
5H); 13C {1H} NMR (100 MHz; CDCl3) δ 32.0-32.1 (CH2), 34.0-
34.2 (CH2), 61.7-62.3 (CH2), 125.9 (CH), 128.4 (CH), 128.4 (CH),
141.8 (C); GC-MS (EI) m/z (relative intensity) 137 (22) [M]+,
118(100), 91(96), 77(23). IR (neat, cm-1) 3301, 2928, 1456, 1031,
698 ; HRMS (EI) m/z calcd for C9H9D4O1: 140.1139, found
140.1125.
Octan-1-ol (5a). total yield 19% (25 mg), Colorless oil. 1H NMR
(400 MHz; CDCl3) δ 0.83-0.92 (m, 7H), 1.28-1.60 (m, 20H), 3.55
(d, J = 5.1Hz, 2H), 3.64 (t, J = 6.6 Hz, 1.2H); 13C {1H} NMR (100
MHz; CDCl3) δ 14.1 (CH3), 22.7 (CH2), 25.8 (CH2), 29.3 (CH2),
29.4 (CH2), 31.8 (CH2), 32.8 (CH2), 63.1 (CH2); GC-MS (EI) m/z
(relative intensity) 54 (1) [M]+, 56 (100), 55 (83), 41 (69), 70 (61).
2-Ethylhexan-1-ol (6a). 13C {1H} NMR (100 MHz; CDCl3) δ 11.1
(CH3), 14.1 (CH3), 23.1 (CH2), 23.4 (CH2), 29.1 (CH2), 30.1 (CH2),
42.0 (CH2), 65.3 (CH); GC-MS (EI) m/z (relative intensity) 59 (1)
[M]+, 55 (100), 56 (92), 70 (89), 69 (73).
ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the ACS
Publications website. Experimental procedures and compound
characterization data (PDF).
Decan-1-ol (7a). Brown oil. 1H NMR (400 MHz; CDCl3) δ 0.83-
0.92 (m, 15H), 1.22-2.01 (m, 50H), 3.53-3.66 (m, 5H); 13C {1H}
NMR (100 MHz; CDCl3) δ 14.1 (CH3), 22.7 (CH2), 25.7 (CH2),
29.3 (CH2), 29.4 (CH2), 29.6 (CH2), 31.9 (CH2), 32.8 (CH2), 63.1
(CH2); GC-MS (EI) m/z (relative intensity) 140 (1) [M]+, 70 (100),
55 (98), 56 (93), 43 (91).
AUTHOR INFORMATION
Corresponding Author
Yasushi Obora - Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and
Bioengineering, Kansai University, Suita, Osaka 564-8680,
2-Ethyloctan-1-ol (8a). 13C {1H} NMR (100 MHz; CDCl3) δ 11.1
(CH3), 14.1 (CH3), 23.3 (CH2), 26.9 (CH2), 29.7 (CH2), 30.4 (CH2),
31.9 (CH2), 42.0 (CH2), 65.3 (CH); GC-MS (EI) m/z (relative
intensity) 140 (3) [M]+, 43 (100), 57 (67), 71 (65), 41 (57).
2-Butyloctan-1-ol (9a). 13C {1H} NMR (100 MHz; CDCl3) δ 14.1
(CH3), 22.7 (CH2), 23.1 (CH2), 26.9 (CH2), 29.3 (CH2), 29.7 (CH2),
30.1 (CH2), 30.4 (CH2), 30.6 (CH2), 31.9 (CH2), 40.5 (CH), 65.7
(CH2); GC-MS (EI) m/z (relative intensity) 168 (3) [M]+, 57 (100),
43 (72), 71 (48), 41 (35).
Japan;
orcid.org/0000-0003-3702-9969;
E-mail:
obora@kansai-u.ac.jp
Author Contributions
Masaki Kobayashi - Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and
Bioengineering, Kansai University, Suita, Osaka 564-8680,
Japan
Decan-1-ol (5b). total yield 21% (33 mg), Colorless oil. 1H NMR
(400 MHz; CDCl3) δ 0.86-0.92 (m, 7H), 1.27-1.60 (m, 27H), 3.55
(d, J = 5.1Hz, 1H), 3.64 (t, J = 6.6 Hz, 1H); 13C {1H} NMR (100
MHz; CDCl3) δ 14.1 (CH3), 22.7 (CH2), 25.7 (CH2), 29.3 (CH2),
29.4 (CH2), 29.6 (CH2), 31.9 (CH2), 32.8 (CH2), 63.1 (CH2); GC-
MS (EI) m/z (relative intensity) 54 (1) [M]+, 56 (100), 55 (83), 41
(69), 70 (61).
Keisuke Yoshimura - Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and
Bioengineering, Kansai University, Suita, Osaka 564-8680,
Japan
Satoshi Itoh - Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and
Bioengineering, Kansai University, Suita, Osaka 564-8680,
Japan
2-Ethyloctan-1-ol (6b). 13C {1H} NMR (100 MHz; CDCl3) δ 11.1
(CH3), 14.1 (CH3), 23.3 (CH2), 26.9 (CH2), 29.7 (CH2), 30.4 (CH2),
31.9 (CH2), 42.0 (CH2), 65.3 (CH); GC-MS (EI) m/z (relative
intensity) 74 (1) [M]+, 43 (100), 71 (75), 57 (73), 55 (50).
Yuya Tsukamoto - Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and
Bioengineering, Kansai University, Suita, Osaka 564-8680,
Japan
1
2-Phenylbutan-1-ol (6d). yield 63% (92 mg), Colorless oil. H
NMR (400 MHz; CDCl3) δ 0.80-0.92 (m, 3H), 1.39-1.47 (m, 1H),
1.62-1.78 (m, 2H), 2.66-2.75 (m, 1H), 3.72-3.82 (m, 2H), 7.20-7.39
(m 5H); 13C {1H} NMR (100 MHz; CDCl3) δ 11.9 (CH3), 25.0
(CH2), 50.5 (CH), 67.3 (CH2), 126.7 (CH), 128.0 (CH), 128.6 (CH),
142.2 (C); GC-MS (EI) m/z (relative intensity) 180 (1) [M]+,
91(100), 119(35), 120(23).
Notes
The authors declare no competing financial interest.
A typical reaction procedure for Ir complex catalyzed C2-
extension of 1a with ethanol-d6. A mixture of benzyl alcohol 1a
(540 mg, 5.0 mmol), ethanol-d6 12 (46 mg, 1.0 mmol), potassium
tert-butoxide (112 mg, 1.0 mmol) and [Cp*IrCl2]2 (40 mg, 0.05
mmol) as a catalyst in THF (1 mL) was stirred at 100 ℃ for 24 h
under Ar atmosphere in a pressure tube (ACE pressure tube, 15 mL).
The reaction mixture was extracted with diethylether (20 mL×2),
dried over sodium sulfate, and carried out vacuum distillation by
Kugelrohr and preparative gel permeation of chromatography. The
product (14a) was isolated in 39% yield (55 mg) as a pale oil.
Benzyl alcohol-d2 (13a). yield 14% (15 mg), Light-yellow oil. 1H
NMR (400 MHz; CDCl3) δ 1.99-2.00(m, 1H), 4.64-4.67 (m, 2H),
7.24-7.38 (m, 5H); 13C {1H} NMR (100 MHz; CDCl3) δ 64.8-65.3
(CH2), 127.0 (CH), 127.7 (CH), 128.6 (CH), 140.8 (C); GC-MS
(EI) m/z (relative intensity) 110 (70) [M]+, 109(100), 80(97), 110
(72), 108 (66).
ACKNOWLEDGMENT
High-resolution mass spectra were performed at Global Facility
Center, Hokkaido University.
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