Synthesis of diketones and ω-hydroxy ketones from methyl ketones and α,ω-diols by an [IrCl(eod)]2/PPh3/KOH system

Article abstract of DOI:10.1246/bcsj.81.689

ω-Hydroxy ketones and diketones, which are important starting materials for the synthesis of cycloalkanones and heterocyclic compounds, were prepared by the one-step reaction of methyl ketones with α,ω-diols under the influence of an iridium complex and a base. The selectivity of ω-hydroxy ketones and diketones could be controlled by varying the starting ratio of methyl ketones to α,ωdiols. For example, reaction using acetophenone (5 equiv) with respect to 1,6-hexanediol (1 equiv) in the presence of [IrCl(cod)]₂, PPh₃, and KOH without solvent gave 1,10-diphenyl-1,10-decane-dione in almost quantitative yield, while reaction using acetophenone (1 equiv) to 1,6-hexanediol (4 equiv) led to 8-hy-droxy-l-phenyl-l-octanone in 92% yield. This methodology was successfully extended to the reaction of arylacetonitriles with α.ω-odiols leading to diaryldinitriles.

Full text of DOI:10.1246/bcsj.81.689

Ó 2008 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 81, No. 6, 689–696 (2008)
689
BCSJ Award Article
Synthesis of Diketones and !-Hydroxy Ketones
from Methyl Ketones and ꢀ,!-Diols
by an [IrCl(cod)]2/PPh3/KOH System
ꢀ
Kensaku Maeda, Yasushi Obora, Satoshi Sakaguchi, and Yasutaka Ishii
Department of Chemistry and Materials Engineering, Faculty of Chemistry,
Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680
High Technology Research Center, Kansai University, Suita, Osaka 564-8680
Received January 7, 2008; E-mail: ishii@ipcku.kansai-u.ac.jp
!-Hydroxy ketones and diketones, which are important starting materials for the synthesis of cycloalkanones and
heterocyclic compounds, were prepared by the one-step reaction of methyl ketones with ꢀ,!-diols under the influence of
an iridium complex and a base. The selectivity of !-hydroxy ketones and diketones could be controlled by varying the
starting ratio of methyl ketones to ꢀ,!-diols. For example, reaction using acetophenone (5 equiv) with respect to 1,6-
hexanediol (1 equiv) in the presence of [IrCl(cod)]2, PPh3, and KOH without solvent gave 1,10-diphenyl-1,10-decane-
dione in almost quantitative yield, while reaction using acetophenone (1 equiv) to 1,6-hexanediol (4 equiv) led to 8-hy-
droxy-1-phenyl-1-octanone in 92% yield. This methodology was successfully extended to the reaction of arylaceto-
nitriles with ꢀ,!-diols leading to diaryldinitriles.
Hydroxy ketones and diketones are a very important class
O
cat.
Ir / PPh3 / KOH
of compounds which are ubiquitous in nature and represent
a basic key structure in organic synthesis. Acyloin condensa-
tion1 and aldol reaction2 are well-known synthetic methods
to obtain ꢀ-hydroxy and ꢁ-hydroxy ketones, respectively.
On the other hand, a variety of synthetic methods for the prep-
aration of diketones have been disclosed,3 since diketones
are important starting materials for the synthesis of cyclo-
alkanones and heterocyclic compounds. To the best of our
knowledge, however, there have been few methods reported
so far for the preparation of hydroxy ketones and diketones
via the same methodology. Therefore, it seems very attractive
to explore a facile synthetic route to diketones from readily
available starting materials. In the course of our study to ex-
tend iridium-catalyzed synthetic reactions,4 we have found
that ꢀ-alkylation of ketones with alcohols leading to higher
alkylated ketones is efficiently promoted by iridium com-
plexes like [IrCl(cod)]2.5 Many groups have also reported re-
lated work on iridium- or ruthenium-catalyzed ꢀ-alkylations
using alcohols as alkylating agents.6,7 If our strategy could
be extended to the reaction between ketones and ꢀ,!-diols,
the reaction would provide a very convenient synthetic tool
for preparing !-hydroxy ketones and diketones. In this paper,
we would like to report a novel synthetic method for preparing
!-hydroxy ketones and diketones from methyl ketones and
ꢀ,!-diols by the action of iridium complexes (eq 1).
+
HO nOH
R
100 °C, 15 h
no solvent
1
2
OH
O
O
+
+
R
R
R
R
R
nOH
3
4
5
O
O
O
O
+
ð1Þ
R
R
n
n-1
6
7
In order to confirm optimum reaction conditions, the reac-
tion of acetophenone (1a) with 1,6-hexanediol (2a) was chosen
and examined in the presence of several Ir complexes and
KOH under various reaction conditions (Table 1).
The reaction of 1a (10.0 mmol) with 2a (2.0mmol) in the
presence of [IrCl(cod)]2 (0.1 mmol), PPh3 (0.4 mmol), and KOH
(0.4 mmol) without any solvent at 100 ꢁC for 15 h (standard condi-
tions) gave a homogeneous solution and was found to produce dou-
ble-alkylated product, 1,10-diphenyl-1,10-decanedione (7aa), in
almost quantitative yield (>99%) (86% isolated yield) along with
a small amount of aldol condensate of 1a, 1,3-diphenyl-2-buten-1-
one (4a) (10%) (Entry 1). When the amount of 1a was reduced to 2
equiv (4.0 mmol) needed for the double-alkylation with 2a, 7aa
Published on the web June 11, 2008; doi:10.1246/bcsj.81.689

690 Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008) BCSJ AWARD ARTICLE
Table 1. Reaction of Acetophenone (1a) with 1,6-Hexane-
diol (2a) Catalyzed by Ir Complexes under Various Con-
ditionsa)
On the basis of these results, several methyl ketones were
reacted with ꢀ,!-diols under the standard conditions as shown
in Entry 1 in Table 1 (Table 2).
The reaction of 1a with various ꢀ,!-diols 2b, 2c, 2d, and 2e
afforded the corresponding diketones 7ab, 7ac, 7ad, and 7ae in
high yields (Entries 1–4). However, the reaction of 1a with
lower carbon-numbered ꢀ,!-diols like 1,4-butanediol and
1,5-pentanediol did not produce diketones at all. This is be-
lieved to be due to the occurrence of homo-aldol reaction be-
tween aldehydes derived from the diols in preference to the
cross-aldol reaction with 1a. In fact, the reaction of 1,4-bu-
tanediol alone under these conditions resulted in a complex
mixture of poly-aldol products. Several aliphatic methyl ke-
tones 1b–1e were allowed to react with 2a under similar con-
ditions to form the corresponding diketones 7ba, 7ca, 7da, and
7ea in 75–80% yields (Entries 5–8). The reaction of acetone
with 2a led to oligoketones rather than diketone as major prod-
ucts, since both methyl groups in acetone are capable of under-
going alkylation with 2a.
Reaction of excess ꢀ,!-diols with methyl ketones would be
expected to provide !-hydroxy ketones by the present method.
Thus, reaction of 1 with 2 to obtain !-hydroxy ketones was
performed under several reaction conditions (eq 2) (Table 3).
In the preceding reaction where methyl ketones 1 are used in
excess with respect to ꢀ,!-diols 2 (vide supra), it was possible
to carry out the reaction without any solvent since viscous
ꢀ,!-diols are readily dissolved in methyl ketones existing in
excess to form a clean non-viscous solution. However, reac-
tions using excess viscous ꢀ,!-diols to prepare !-hydroxy ke-
tones gave highly viscous liquids which are difficult to stir
magnetically. Thus, the reaction to prepare !-hydroxy ketones
was carried out by adding a small amount of solvent like
1,4-dioxane.
Product/%b)
Entry
Ir Complex
3ac)
4ac)
5aa
6aa
7aa
1
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(coe)2]2
Ir(acac)(cod)
0
0
58
0
70
0
0
10
11
14
0
8
29
9
0
0
9
0
11
0
2
20
0
0
0
2
0
2
0
2
4
0
>99(86)
2d)
3e)
4f)
5
60
27
0
22
>99
74
20
0
6g)
7e),g),h) IrCl(PPh3)3
8h)
[Cp IrCl2]2
0
0
7
0
ꢀ
9g),i) IrCl3 3H2O
ꢂ
a) 1a (10.0 mmol) was allowed to react with 2a (2.0 mmol) in
the presence of Ir complex (0.1 mmol), PPh3 (0.4 mmol), and
KOH (0.4 mmol) without solvent at 100 ꢁC for 15 h. b) GLC
yields based on 2a unless otherwise noted. The number in
parentheses shows isolated yield. c) Based on 1a used. d) 1a
(4.0 mmol) was used. e) Reaction was performed without
addition of PPh3. f) Reaction was performed in the absence
of KOH. g) Ir complex (0.2 mmol) was used. h) Reaction
was performed with KOH (0.8 mmol) in 1,4-dioxane (1.0 mL).
i) Reaction was performed at 120 ꢁC.
was formed in 60% yield (Entry 2), but hydroxy ketone, 8-hy-
droxy-1-phenyl-1-octanone (5aa), which is a precursor of 7aa,
was found to be scarcely formed. This indicates that 5aa was more
reactive than diol 2a. In a previous paper, we showed that the se-
lectivity of the alkylation of ketones with alcohols is considerably
affected by phosphine ligands.5 In the present reaction, the
[IrCl(cod)]2 complex, without a phosphine ligand, catalyzed pref-
erentially hydrogen transfer from 2a to 1a rather than alkylation of
1a with 2a to lead to 1-phenylethanol (3a) (58%) in preference to
5aa (9%) and 7aa (27%) (Entry 3). Recently, we reported that the
alkylation of active methylene compounds like cyanoacetates with
alcohols is promoted by [IrCl(cod)]2 in the absence of any base to
O
cat.
Ir / PPh3 / KOH
+
HO nOH
R
100 °C, 15 h
1,4-Dioxane
1
2
give ꢀ
-alkylated derivatives.8 Unfortunately, however, the present
reaction was not induced at all in the absence of base (Entry 4). We
next examined the catalytic performance of several iridium
complexes in the double-alkylation of 1a with
ð2Þ
O
OH
O
O
+
+
R
nOH
ꢀ,!-diol 2a.
R
R
R
n
[IrCl(coe)2]2 complex, which displayed high catalytic activity in
the alkylation of cyanoacetates with alcohols8 and the oxidative di-
merization of primary alcohols to esters,9 was less active than
[IrCl(cod)]2 to form 7aa (22%) in low yield (Entry 5). It is difficult
to explain the lower activity of the [IrCl(coe)2]2 complex com-
pared to the [IrCl(cod)]2 complex, but the [IrCl(coe)2]2 complex
seems to easily liberate the weakly coordinated cyclooctene
(coe) ligand from the iridium metal. On the other hand, Ir(acac)-
(cod) complex was very active leading to 7aa in almost quantita-
tive yield (Entry 6). It is interesting to note that the catalytic activ-
ity of IrCl(PPh3)3 complex was high without further addition of
phosphine ligand to form 7aa in 74% yield (Entry 7). These results
indicate that Ir complexes bearing strongly coordinated ligands are
appropriate for the present alkylation reaction. On the other hand,
3
5
7
The reaction of methyl ketones 1 (2.0 mmol) with ꢀ,!-diols
2 (8.0 mmol) was examined in 1,4-dioxane (1.0 mL) under
several reaction conditions (Table 3).
By the use of 4 equiv of diol 2a with respect to 1a under the
influence of [IrCl(cod)]2, PPh3, and KOH at 100 ꢁC for 15 h,
!-hydroxy ketone 5aa was obtained in 92% yield (Entry 1).
In spite of the use of excess 2a which serves as a hydrogen do-
nor to 1a, hydrogen-transfer from 2a to 1a leading to 3a was
suppressed up to 3%. The reaction of 1a with various aliphatic
ꢀ,!-diols 2b–2e produced the corresponding !-hydroxy ke-
tones 5ab–5ae in good yields (84–91%) (Entries 2–5), while
the reaction of aliphatic methyl ketones 1b–1e with 2a resulted
in !-hydroxy ketones 5ba–5ea in substantial yields (ca. 70%)
(Entries 6–9).
ꢀ
trivalent iridium complex [Cp IrCl2]2, which exhibited high activ-
ity for the Guerbet reaction of primary alcohols,10 showed low cat-
alytic activity (Entry 8). IrCl3 3H2O was inactive even at 120 ꢁC
Although Grigg et al. and our group have shown the mono-
alkylation of arylacetonitriles with primary alcohols by an iri-
ꢂ
(Entry 9).

K. Maeda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008)
691
a)
Table 2. Synthesis of Diketones 7 from Methyl Ketones 1 and ꢀ,!-Diols 2 Catalyzed by [IrCl(cod)]2
Entry
Ketone
Diol
Product
Yield/%b)
96 (84)
O
O
O
O
O
HO 7OH
1
Ph
Ph
Ph
Ph
Ph
7
2b
1a
7ab
HO 8OH
2
1a
>99 (88)
>99 (91)
87 (85)
76 (69)
80 (71)
75 (72)
79 (75)
2c
8
7ac
O
O
O
O
HO 9OH
3
1a
Ph
Ph
Ph
Ph
9
2d
7ad
O
HO 10OH
4
Ph
10
2e
1a
7ae
O
O
O
O
O
5c)
6c)
7c)
8c)
2a
2a
2a
2a
n-C3H7
n-C4H9
n-C3H7
n-C4H9
n-C3H7
n-C4H9
6
1b
7ba
O
6
7ca
1c
O
O
O
O
O
n-C5H11
n-C6H13
n-C5H11
n-C6H13
n-C5H11
n-C6H13
6
1d
7da
O
6
1e
7ea
a) 1 (10.0 mmol) was allowed to react with 2 (2.0 mmol) in the presence of [IrCl(cod)]2 (0.1 mmol),
PPh3 (0.4 mmol), and KOH (0.4 mmol) without solvent at 100 ꢁC for 15 h. b) GLC yields. The numbers
in parentheses show isolated yields. c) KOH (0.6 mmol) and 1,7-octadiene (0.6 mmol) were used.
dium complex in the presence of a base like KOH,11 the pres-
ent methodology was successfully extended to the double-
alkylation of arylacetonitriles with ꢀ,!-diols, although the
reaction must be conducted at higher temperatures.
Table 3. Synthesis of !-Hydroxy Ketones 5 from Methyl
Ketones 1 and ꢀ,!-Diols 2 Catalyzed by [IrCl(cod)]2
a)
Product/%b)
Entry
Ketone
Diol
Phenylacetonitrile (8a) (10.0 mmol) was allowed to react
with 1,5-pentanediol (2f) (2.0 mmol) in the presence of an
iridium complex and a base at 160 ꢁC for 15 h to afford 2,8-
diphenylnonanedinitrile (9af) in fair to good yield (Table 4).
In contrast to the reaction of methyl ketones with ꢀ,!-
3
5
7
1
2
3
4
1a
1a
1a
1a
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2a
2a
2a
2a
3a (3)
3a (1)
3a (1)
3a (2)
3a (2)
3b (8)
3c (6)
3d (7)
3e (7)
5aa (92[87])
5ab (84[77])
5ac (87[84])
5ad (89[81])
5ae (91[82])
5ba (69[66])
5ca (70[64])
5da (70[65])
5ea (70[67])
7aa (5)
7ab (7)
7ac (6)
7ad (8)
7ae (7)
7ba (3)
7ca (3)
7da (4)
7ea (5)
ꢀ
diols where [Cp IrCl2]2 was a poor catalyst, this complex
was found to be the best among the catalysts examined. For
5
6c)
7c)
8c)
9c)
instance, the reaction of 8a with 2a in the presence of
[Cp IrCl2]2 under these conditions produced 9af in 93%
ꢀ
yield (Entry 2), but [IrCl(cod)]2 afforded only 41% yield of
9af in addition to 7-hydroxy-2-phenylheptanenitrile (10af)
(10%) (Entry 1). Another feature of this reaction is that the
double-alkylation of 8a with 2f proceeded smoothly without
any phosphine ligand. In addition, the reaction was promoted
by the addition of Cs2CO3 rather than KOH (Entries 2 and
4), but no reaction was induced in the absence of a base
a) 1 (2.0 mmol) was allowed to react with 2 (8.0 mmol) in the
presence of [IrCl(cod)]2 (0.05 mmol), PPh3 (0.2 mmol), and
KOH (0.2 mmol) in 1,4-dioxane (1.0 mL) at 100 ꢁC for 15 h.
b) GLC yields based on 1 used. Numbers in brackets show iso-
lated yields. c) KOH (0.3 mmol) and 1,7-octadiene (0.3 mmol)
were used.

692 Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008) BCSJ AWARD ARTICLE
Table 4. Reaction of Phenylacetonitrile (8a) with 1,5-Pen-
tanediol (2f) Catalyzed by Ir Complexesa)
[IrCl(cod)]2 (2 mol%)
PPh3 (8 mol%)
O
cat. [Cp*IrCl2]2 / Cs2CO3
KOH (10 mol%)
+
C4D9OH
+
Ph
CN
HO 5OH
100 °C, 4 h
no solvent
63%
Ph
160 °C, 15 h
no solvent
8a
CN CN
2f
1a
1 mmol
11
4 mmol
ð3Þ
CN
+
OH
O
D D
O
D H
D D
CD3
D D
CD3
Ph
Ph
Ph
5
5
+
9af
10af
Ph
Ph
H H H H
12a
D H H H
12b
Yield/%b)
Entry
Ir Complex
[IrCl(cod)]2
9af
10af
63
:
37
1
2
41
10
0
27
0
1H NMR spectrum showed that a 63:37 mixture of 1-phen-
yl-1-hexanone-d7, 12a and 12b, including rearranged deuteri-
um and hydrogen atoms is formed. The formation of 12a
and 12b is rationally explained by considering the following
reaction pathway through the generation of iridium dihydride
as a key species (Scheme 1).
The oxidative addition of C4D9O–H to an Ir complex is
followed by ꢁ-hydride elimination to give butanal-d8 and
LnIrHD. Under the present strongly basic conditions, the deu-
terium atoms at the ꢀ-position of butanal-d8 may undergo rap-
id H–D exchange with C4D9O–H, which exists in excess in the
reaction system, through enolate formation to give eventually
butanal-d6. Aldol condensation with 1a would produce 1-
phenyl-2-hexen-1-one-d6 (13) followed by hydrogenation by
LnIrHD to lead to 12a and 12b. The deuterium exchange at
the ꢀ-position of the resulting 12b with formed water and/or
butanol seems to contribute to the preferential formation of
12a rather than 12b.
Although a detailed reaction mechanism of the double al-
kylation is not confirmed at this stage, the reaction of methyl
ketones 1 with ꢀ,!-diols 2 is thought to proceed in a similar
way to the iridium-catalyzed ꢀ-alkylation of 1 using buta-
nol-d9 shown above (Scheme 2). First, the iridium catalyst
serves as hydrogen acceptor from 2 giving mono-aldehyde A
and an iridium dihydride species. Then, the formed A reacts
with 1 via base-catalyzed aldol condensation giving ꢀ,ꢁ-unsat-
urated !-hydroxy ketone B and water. Subsequently, B was
hydrogenated with the iridium dihydride species to give the
saturated !-hydroxy ketone 5. When the reaction was per-
formed with excess 1, the resulting 5 reacted further with 1
in a similar way through the formation of C and D to give
diketones 7.
ꢀ
[Cp IrCl2]2
[Cp IrCl2]2
ꢀ
[Cp IrCl2]2
93(89)
19
79
3c)
4d)
5e)
6f)
7g)
8h)
9
ꢀ
[Cp IrCl2]2
ꢀ
[Cp IrCl2]2
0
62
49
10
68
52
0
ꢀ
[Cp IrCl2]2
26
43
45
0
ꢀ
[Cp IrCl2]2
ꢀ
[IrCl(coe)2]2
IrCl3 3H2O
10i)
13
ꢂ
a) 8a (10.0 mmol) was allowed to react with 2f (2.0 mmol) in
the presence of Ir complex (0.05 mmol) and Cs2CO3
(0.4 mmol) without solvent at 160 ꢁC for 15 h. b) GLC yields
based on 2f used. The number in parentheses shows isolated
yield. c) Reaction was performed in the presence of PPh3
(0.2 mmol). d) KOH (0.4 mmol) was used as a base. e) Reac-
tion was carried in the absence of base. f) Reaction was carried
out at 140 ꢁC. g) Reaction was carried out at 120 ꢁC. h) Reac-
tion was carried out at 100 ꢁC. i) IrCl3 3H2O (0.1 mmol)
ꢂ
was used.
(Entry 5). The reaction between methyl ketones and diols
occurred at relatively lower temperature (100 ꢁC), but the
reaction of nitrile 8a with 2f at 100–140 ꢁC resulted in 9af
in unsatisfactory yields (Entries 6–8). Other selected iridium
catalysts such as [IrCl(coe)2]2 and IrCl3 3H2O, which were
poor for the reaction with methyl ketones, showed moderate
catalytic activities (Entries 9 and 10).
Under the same reaction conditions as Entry 1 in Table 4,
ꢀ,!-diols 2a, 2b, 2g, and 2h were reacted with various aryl-
acetonitriles 8a–8d affording the corresponding diaryldinitriles
9 in moderate to good yields (Table 5).
ꢂ
Arylacetonitriles bearing electron-donating substituents
were found to be more reactive than those bearing electron-
withdrawing ones (Entries 5–7). To our surprise, the reaction
of phenylacetonitrile 8a with lower carbon-numbered 1,3-,
Conclusion
In conclusion, we have developed an iridium-catalyzed
reaction of methyl ketones with ꢀ,!-diols which provides a
useful approach to diketones and !-hydroxy ketones. This
reaction was extended to the reaction of arylacetonitriles with
ꢀ,!-diols to afford diaryldinitriles in good yields.
ꢀ
1,4-, and 1,5-diols, 2f–2h, was promoted by [Cp IrCl2]2 to
give the corresponding dinitriles, 9af, 9ag, and 9ah, respec-
tively, because the reaction of methyl ketones with 2f and
2h was not promoted at all (Table 4, Entry 2 and Table 5,
Entries 1 and 2).
Experimental
In order to obtain information on the reaction pathway
of the present reaction, the alkylation of 1a with butanol-d9
(1-C4D9OH) (11) was examined as a model reaction under
the conditions shown in eq 3.
All starting materials were commercially available and used
without any purification. GLC analysis was performed with a
flame ionization detector using a 0:22 mm ꢃ 25 m capillary col-
umn (BP-5). 1H and 13C NMR were measured in CDCl3 with

K. Maeda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008)
693
ꢀ
a)
Table 5. Synthesis of Diaryldinitriles from Arylacetonitriles and ꢀ,!-Diols Catalyzed by [Cp IrCl2]2
Entry
1c)
Diol
Product
Yield/%b)
56 (48)
Ar
CN
CN CN
Ar ¼ Ph
8a
Ph
Ph
HO 3OH
3
9ag
CN CN
Ph
2g
2
8a
8a
8a
94 (84)
79 (70)
80 (67)
Ph
Ph
Ph
HO 4OH
4
2h
9ah
CN CN
3d)
Ph
HO 6OH
6
2a
9aa
CN CN
4d)
Ph
HO 7OH
7
9ab
2b
CN CN
5e)
6e)
7e)
Ar = p-MeC6H4
94 (85)
99 (89)
84 (80)
5
HO 5OH
8b
2f
9bf
CN CN
Ar = p-MeOC6H4
HO 5OH
5
9cf
2f
8c
MeO
OMe
CN CN
Ar = p-ClC6H4
HO 5OH
5
9df
8d
2f
Cl
Cl
ꢀ
a) 8 (10.0 mmol) was allowed to react with 2 (2.0 mmol) in the presence of [Cp IrCl2]2 (0.05 mmol) and
CsCO3 (0.4 mmol) at 160 ꢁC for 15 h without solvent. b) GLC yields based on 2 used. The numbers in
parentheses show isolated yield. c) At 140 ꢁC. d) Cs2CO3 (0.6 mmol) was used. e) 8 (4.0 mmol), Cs2CO3
(0.8 mmol), and mesitylene (1.0 mL) were used.
K
LnIrHD
KOH
LnIr
O
Ln
C2D5
CD3(CD2)3OH
CD3(CD2)3O Ir H
D
D D
11
HO
C4D9OH
1a
LnIrHD
O
D
O
C2D5
H H
13
Scheme 1. A possible reaction pathway for the alkylation of 1a with butanol-d9 (11).
C2D5
12a + 12b
Ph
D
base
H
H H
or (D)

694 Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008) BCSJ AWARD ARTICLE
1
O
Base
R
2
HO
HO
n-1
A
n-1
O
B
LnIr
LnIrH2
H2O
1
O
R
O
Base
O
R
R
5
n-1
n-1
O
C
LnIr
LnIrH2
H2O
D
7
Scheme 2. A possible reaction path for the formation of 5 and 7.
Me4Si as an internal standard. The products were characterized by
1H NMR, 13C NMR, and GC-MS. The yields of products were es-
timated from peak areas based on an internal standard using GLC.
Compounds 5aa,12 5ac,13 5ae,14 5ea,15 6aa,16 7aa,17 7ab,18
7ac,19 7ad,20 7ae,21 7ba,22 7ca,23 7da,24 7ea,25 9aa,26 and 9ag27
were reported previously.
A Typical Reaction Procedure for the Formation of Dike-
tone (7aa) by the Reaction of 1a and 2a is as Follows (Table 1,
Entry 1). To a mixture of [IrCl(cod)]2 (67 mg, 0.1 mmol), PPh3
(105 mg, 0.4 mmol), and KOH (22 mg, 0.4 mmol) was added 1a
(1.20 g, 10.0 mmol) and 2a (236 mg, 2.0 mmol) under Ar. The re-
action mixture was stirred at 100 ꢁC for 15 h. The conversions and
yields of products were estimated from peak areas based on an
internal standard using GC and the product 7aa was obtained in
quantitative yield along with the formation of 4a (10%). The prod-
uct 7aa was isolated by column chromatography (230–400 mesh
silica gel, Hexane/ethyl acetate = 10/1) in 86% yield (555 mg).
A Typical Reaction Procedure for the Formation of !-Hy-
droxy Ketone (5aa) by the Reaction of 1a and 2a is as Follows
Reaction of 1a with 11 (eq 3). To a mixture of [IrCl(cod)]2
(13 mg, 0.02 mmol), PPh3 (21 mg, 0.08 mmol), and KOH (6 mg,
0.1 mmol) was added 1a (120 mg, 1.0 mmol) and 11 (332 mg,
4.0 mmol) under Ar. The reaction mixture was stirred at 100 ꢁC
for 4 h. A 63:37 mixture of 1-phenyl-1-hexanone-d7 12a and
12b was isolated by column chromatography (230–400 mesh
silica gel, Hexane/ethyl acetate = 10/1) in 63% yield (116 mg).
5ab: 1H NMR (270 MHz, CDCl3) ꢂ 1.34–1.74 (m, 13H), 2.96
(t, J ¼ 7:4 Hz, 2H), 3.64 (t, J ¼ 6:3 Hz, 2H), 7.43–7.98 (m, 5H);
13C NMR (67.5 MHz, CDCl3) ꢂ 24.3 (CH2), 25.6 (CH2), 29.20
(CH2), 29.24 (CH2), 29.4 (CH2), 32.7 (CH2), 38.6 (CH2), 63.0
(CH2), 128.0 (C), 128.5 (C), 132.9 (C), 137.1 (C), 200.6 (C); IR
(neat, cmꢄ1) 689, 744, 1072, 1448, 1470, 1683, 2852, 2920,
3242; GC-MS (EI), m=z (relative intensity) 234 (3) [M]þ, 133
(13), 120 (100), 105 (90), 77 (42); HRMS (EI) m=z calcd for
C15H22O2 [M]þ 234.1621, found 234.1618; Anal. Found: C,
76.97; H, 9.64%. Calcd for C15H22O2: C, 76.88; H, 9.46%.
5ad: 1H NMR (270 MHz, CDCl3) ꢂ 1.30–1.78 (m, 17H), 2.96
(t, J ¼ 7:3 Hz, 2H), 3.63 (t, J ¼ 6:4 Hz, 2H), 7.43–7.97 (m, 5H);
13C NMR (67.5 MHz, CDCl3) ꢂ 24.3 (CH2), 25.7 (CH2), 29.29
(CH2), 29.34 (CH2), 29.4 (CH2), 29.5 (CH2), 32.7 (CH2), 38.6
(CH2), 63.0 (CH2), 128.0 (C), 128.5 (C), 132.8 (C), 137.0 (C),
200.6 (C); IR (neat, cmꢄ1) 688, 734, 1072, 1447, 1471, 1684,
2850, 2919, 3244; GC-MS (EI), m=z (relative intensity) 262 (5)
[M]þ, 133 (15), 120 (100), 105 (80), 77 (34); HRMS (EI) m=z
calcd for C17H26O2 [M]þ 262.1934, found 262.1925.
(Table 3, Entry 1).
To a mixture of [IrCl(cod)]2 (34 mg,
0.05 mmol), PPh3 (53 mg, 0.2 mmol), KOH (11 mg, 0.2 mmol) in
1,4-dioxane (1.0 mL) was added 1a (240 mg, 2.0 mmol) and 2a
(0.95 g, 8.0 mmol) under Ar. The reaction mixture was stirred at
100 ꢁC for 15 h. The conversions and yields of products were es-
timated from peak areas based on an internal standard using GC
and the product 5aa was obtained in 92% yield along with the for-
mation of 3a (3%) and 7aa (5%). The product 5aa was isolated by
column chromatography (230–400 mesh silica gel, Hexane/ethyl
acetate = 4/1) in 87% yield (380 mg).
5ba:
1H NMR (270 MHz, CDCl3) ꢂ 0.87–1.63 (m, 16H),
2.35–2.42 (m, 4H), 3.61 (t, J ¼ 6:6 Hz, 2H); 13C NMR (67.5
MHz, CDCl3) ꢂ 13.6 (CH3), 17.1 (CH2), 23.6 (CH2), 25.4
(CH2), 29.0 (CH2), 32.5 (CH2), 42.6 (CH2), 44.5 (CH2), 62.6
(CH2), 211.6 (C); IR (neat, cmꢄ1) 724, 1068, 1383, 1414, 1465,
1697, 2852, 2931, 3221; GC-MS (EI), m=z (relative intensity)
186 (0.6) [M]þ, 143 (10), 125 (20), 99 (16), 86 (75), 71 (100),
58 (75), 43 (95); HRMS (EI, 70 eV) m=z calcd for C11H22O2
[M]þ 186.1621, found 186.1624.
A Typical Reaction Procedure for the Formation of Diaryl-
dinitrile (9af) by the Reaction of 2f and 8a is as Follows
ꢀ
(Table 4, Entry 2).
To a mixture of [Cp IrCl2]2 (40 mg,
0.05 mmol) and Cs2CO3 (130 mg, 0.40 mmol) was added 2f
(208 mg, 2.0 mmol) and 8a (1.17 g, 10.0 mmol) under Ar. The re-
action mixture was stirred at 160 ꢁC for 15 h. The conversions and
yields of products were estimated from peak areas based on an in-
ternal standard using GC and the product 9af was obtained in 93%
yield. The product 9af was isolated by column chromatography
(230–400 mesh silica gel, Hexane/ethyl acetate = 10/1) in 89%
yield (539 mg).
5ca:
1H NMR (270 MHz, CDCl3) ꢂ 0.88–1.62 (m, 18H),
2.39 (t, J ¼ 7:4 Hz, 4H), 3.62 (t, J ¼ 6:2 Hz, 2H); 13C NMR
(67.5 MHz, CDCl3) ꢂ 13.8 (CH3), 22.3 (CH2), 23.7 (CH2), 25.5
(CH2), 25.9 (CH2), 29.1 (CH2), 32.6 (CH2), 42.5 (CH2), 42.7
(CH2), 62.9 (CH2), 211.7 (C); IR (neat, cmꢄ1) 724, 1067, 1384,

K. Maeda et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 6 (2008)
695
1418, 1466, 1698, 2852, 2930, 3227; GC-MS (EI), m=z (relative
intensity) 200 (0.3) [M]þ, 158 (8), 143 (9), 125 (19), 100 (25),
85 (82), 71 (30), 58 (100), 43 (28); HRMS (EI, 70 eV) m=z calcd
for C12H24O2 [M]þ 200.1777, found 200.1773.
(CH2), 36.67 (CH2), 120.3 (C), 128.6 (C), 129.3 (C), 134.0 (C),
134.3 (C); IR (neat, cmꢄ1) 827, 1094, 1465, 1493, 2241, 2862,
2933; GC-MS (EI), m=z (relative intensity) 370 (67) [M]þ, 343
(27), 207 (19), 190 (60), 151 (100), 125 (88); HRMS (EI) m=z
calcd for C21H20N2Cl2 [M]þ 370.1004, found 370.1005.
10af: 1H NMR (270 MHz, CDCl3) ꢂ 1.35–2.03 (m, 9H), 3.59
(t, J ¼ 6:3 Hz, 1H), 3.78 (t, J ¼ 7:4 Hz, 2H), 7.27–7.40 (m, 5H);
13C NMR (67.5 MHz, CDCl3) ꢂ 25.1 (CH2), 26.8 (CH2), 32.3
(CH2), 35.8 (CH2), 37.3 (CH2), 62.4 (CH2), 120.9 (C), 127.2
(C), 128.0 (C), 129.1 (C), 135.9 (C); IR (neat, cmꢄ1) 700, 756,
1054, 1456, 1496, 2241, 2862, 2936, 3367; GC-MS (EI), m=z (rel-
ative intensity) 203 (3) [M]þ, 185 (32), 129 (100), 117 (60);
HRMS (EI, 70 eV) m=z calcd for C13H17NO [M]þ 203.1311,
found 203.1310.
5da:
1H NMR (270 MHz, CDCl3) ꢂ 0.86–1.62 (m, 20H),
2.38 (t, J ¼ 7:4 Hz, 4H), 3.63 (t, J ¼ 6:3 Hz, 2H); 13C NMR
(67.5 MHz, CDCl3) ꢂ 13.9 (CH3), 22.4 (CH2), 23.5 (CH2), 23.7
(CH2), 25.5 (CH2), 29.1 (CH2), 31.3 (CH2), 32.6 (CH2), 42.7
(CH2), 42.8 (CH2), 62.9 (CH2), 211.7 (C); IR (neat, cmꢄ1) 721,
1071, 1419, 1472, 1705, 2851, 2931, 3220; GC-MS (EI), m=z (rel-
ative intensity) 214 (0.3) [M]þ, 158 (8), 143 (10), 125 (21), 114
(25), 99 (49), 85 (22), 71 (100), 58 (68), 43 (96); HRMS (EI,
70 eV) m=z calcd for C13H26O2 [M]þ 214.1934, found 214.1927.
9ab:
1H NMR (400 MHz, CDCl3) ꢂ 1.29–1.59 (m, 10H),
1.79–1.95 (m, 4H), 3.76 (t, J ¼ 7:3 Hz, 2H), 7.29–7.39 (m,
10H); 13C NMR (100 MHz, CDCl3) ꢂ 26.9 (CH2), 28.7 (CH2),
28.9 (CH2), 35.8 (CH2), 37.3 (CH2), 120.8 (C), 127.2 (C), 128.0
(C), 129.0 (C), 135.9 (C); IR (neat, cmꢄ1) 700, 757, 1455,
1495, 2240, 2859, 2930; GC-MS (EI), m=z (relative intensity)
330 (70) [M]þ, 214 (17), 173 (29), 131 (63), 117 (100), 91
(75); HRMS (EI, 70 eV) m=z calcd for C23H26N2 [M]þ
330.2097, found 330.2090.
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Transforma-
tions of Carbon Resources’’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, and ‘‘High-
Tech Research Center’’ Project for Private Universities:
matching fund subsidy from the Ministry of Education, Cul-
ture, Sports, Science and Technology, 2005–2009.
9af: 1H NMR (270 MHz, CDCl3) ꢂ 1.33–1.48 (m, 6H), 1.79–
1.90 (m, 4H), 3.74 (t, J ¼ 7:3 Hz, 2H), 7.26–7.39 (m, 10H);
13C NMR (67.5 MHz, CDCl3) ꢂ 26.57 (CH2), 26.59 (CH2), 28.22
(CH2), 28.24 (CH2), 35.5 (CH2), 37.2 (CH2), 120.8 (C), 127.2
(C), 128.0 (C), 129.1 (C), 135.8 (C); IR (neat, cmꢄ1) 697,
757, 1455, 1493, 2240, 2861, 2949; GC-MS (EI), m=z (relative
intensity) 302 (75) [M]þ, 275 (15), 156 (36), 117 (100), 91 (55);
HRMS (EI) m=z calcd for C21H22N2 [M]þ 302.1784, found
302.1792.
Supporting Information
1H and 13C NMR spectra of compounds 5, 6, 7, and 9. This
material is available free of charge on the web at http://www.csj.
jp/journals/bcsj/.
References
1
For example: a) K. T. Finley, Chem. Rev. 1964, 64, 573. b)
9ah: 1H NMR (400 MHz, CDCl3) ꢂ 1.44–1.56 (m, 4H), 1.86–
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8H); 13C NMR (67.5 MHz, CDCl3) ꢂ 26.6 (CH2), 28.3 (CH2), 35.6
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