Synthesis of ω-hydroxy carboxylic acids and α,ωdimethyl ketones using α,ω-diols as alkylating agents

Article abstract of DOI:10.1021/jo9027165

"Chemical equation presented" Synthesis of ω-hydroxy carboxylic acids and α,ω-dimethyl diketones was successfully achieved by using α,ω-diols as alkylating agents under the influence of an iridium catalyst. For example, the alkylation of butyl cyanoacetate with 1,13-tridecanediol in the presence of [IrCl(cod)]₂ or [rrCl(coe) ₂]₂ gave rise to butyl 2-cyano-15-hydroxypentadecanoate in good yield which is easily converted to cyclopentadecanolide (CPDL). In addition, the alkylation of acetone with 1,10-decanediol in the presence of [IrCl(cod)]₂ and KOH resulted in an important muscone precursor, 2,15-hexadecanedione (HDDO), in good yield.

Full text of DOI:10.1021/jo9027165

pubs.acs.org/joc
reported recently.4-6 Shiina et al. reported that CPDL was
Synthesis of ω-Hydroxy Carboxylic Acids and r,ω-
Dimethyl Ketones Using r,ω-Diols As Alkylating
Agents
prepared by the lactonization by the treatment of CPDA
with 2-methyl-6-nitrobenzoic anhydride (MNBA) in
4-(dimethylamino)pyridine (DMAP).4 Mukaiyama et al re-
ported that the CPDL was obtained by the cyclization of
CPDA with an equimolar amount of di-2-thienyl carbonate
(2-DTC) combined with a catalytic amount of DMAP
followed by treatment with 1-4 equiv of iodine.5 Further-
more, Otera et al reported the synthesis of CPDL from
CPDA by distannoxane-catalyzed macrolactonization.6
Although CPDA is an important compound for the
synthesis of CPDL, it is conventionally prepared via a
multistep synthesis. Typically, CPDA was prepared by con-
densation of 1,12-dodecanedioate with γ-butyrolactone in
the presence of Na, followed by treatment with NaOH and
reduction by hydrazine.7 Therefore, the development of a
novel synthetic route to ω-hydroxy carboxylic acids is highly
desired.
Yosuke Iuchi, Megumi Hyotanishi, Brittany E. Miller,
Kensaku Maeda, Yasushi Obora, and Yasutaka Ishii*
Department of Chemistry and Materials Engineering, Faculty
of Chemistry, Materials and Bioengineering and High
Technology Research Center, Kansai University, Suita,
Osaka 564-8680, Japan
r091001@ipcku.kansai-u.ac.jp
Received December 25, 2009
On the other hand, R,ω-dimethyl diketones like 2,15-
hexadecanedione (HDDO) are also attractive precursors
for macrocyclic musks.2 Tsuji et al. reported the preparation
of HDDO through six steps from the butadiene telomer.8 In
addition, HDDO is derived from alkyl methyl ketone di-
methylhydrazones9 or from imidazolium salt and Grignard
reagent.10 A well-known method to obtain HDDO is the
reaction of 1,10-dibromodecane with 2 equiv of ethyl aceto-
acetate followed by decarboxylation.11 By the use of this
method, HDDO is prepared in 46% overall yield.12 How-
ever, these methods also need multistage reactions, and some
of these are difficult to carry out on a large scale. Therefore, it
is important to explore a more convenient synthetic route to
HDDO.
During the course of our investigation to develop an
efficient and facile synthetic method for preparation CPDA
and HDDO, we have demonstrated a novel Ir-catalyzed
selective alkylation of cyanoacetates13 and methyl ketones14
using alcohols as alkylating agents, leading to the corre-
sponding R-alkylated compounds in good yields. If the
alkylation of cyanoacetate and acetone with R,ω-diols is
achieved, this strategy would provide a very attractive
selective route to ω-hydroxy carboxylic acids like CPDA
and R,ω-dimethyl diketones like HDDO, respectively,
among the methods reported so far.7-12 In this paper, we
Synthesis of ω-hydroxy carboxylic acids and R,ω-dimeth-
yl diketones was successfully achieved by using R,ω-diols
as alkylating agents under the influence of an iridium
catalyst. For example, the alkylation of butyl cyanoace-
tate with 1,13-tridecanediol in the presence of [IrCl(cod)]2
or [IrCl(coe)2]2 gave rise to butyl 2-cyano-15-hydroxy-
pentadecanoate in good yield which is easily converted to
cyclopentadecanolide (CPDL). In addition, the alkyla-
tion of acetone with 1,10-decanediol in the presence of
[IrCl(cod)]2 and KOH resulted in an important muscone
precursor, 2,15-hexadecanedione (HDDO), in good
yield.
ω-Hydroxy carboxylic acids and R,ω-dimethyl diketones
are very important class of compounds in organic syn-
thesis, particularly in the perfumery industry.1-3 For instance,
ω-hydroxy carboxylic acids like 15-hydroxypentadecanoic
acid (CPDA) and R,ω-dimethyl diketones like 2,15-hexade-
canedione (HDDO) are useful starting materials to musk
and its related compounds. In particular, CPDA is an
important precursor of most widely produced macrocyclic
synthetic musk lactone, cyclopentadecanolide (CPDL),2 and
several synthetic methods for the synthesis of CPDL
from CPDA through intramolecular cyclization have been
(5) Oohashi, Y; Fukumoto, K.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
2005, 78, 1508.
(6) Otera, J.; Yano, T.; Himeno, Y.; Nozaki, H. Tetrahedron Lett. 1986,
27, 4501.
(7) (a) Horinaka, A. JP 05271126 (Earth Chemical Co, Japan); Chem. Abstr.
1994, 120, 76676. (b) Kato, T.; Hata, T.; Eto, T.; Ito, N. (Toray Industries, Inc.),
Japan; Soda Aromatic Co., Ltd.; Chem. Abstr. 2002, 137, 247596.
(8) Tsuji, J.; Kaito, M.; Takahashi, T. Bull. Chem. Soc. Jpn. 1978, 51, 547.
(9) Yamashita, M.; Matsumiya, K.; Morimoto, H.; Suemitsu, R. Bull.
Chem. Soc. Jpn. 1989, 62, 1668.
(10) Bay, Y.; Lu, J.; Yang, B. Synlett 2001, 544.
(1) Perfumery Practice and Principles; Calkin, R. R., Jellinek, J. S., Eds.;
Wiley: New York, 1994.
(2) Williams, A. S. Synthesis 1999, 1707.
(3) Kraft, P.; Bajgrowicz, J. A.; Denis, C.; Frater, G. Angew. Chem., Int.
Ed. 2000, 39, 2980.
(11) Stoll, M.; Rouve, A. Helv. Chim. Acta 1947, 30, 2019.
(12) Tanabe, Y.; Matsumoto, N.; Higahi, T.; Misaki, T.; Itoh, T.;
Yamamoto, M.; Mitarai, K.; Nishi, Y. Tetrahedron 2002, 58, 8269.
(13) Morita, M.; Obora, Y.; Ishii, Y. Chem. Commun. 2007, 2850.
(14) (a) Taguchi, K.; Nakagawa, H.; Hirabayashi, T; Sakaguchi, S.; Ishii,
Y. J. Am. Chem. Soc. 2004, 126, 72. (b) Maeda, K.; Obora, Y.; Sakaguchi, S.;
Ishii, Y. Bull. Chem. Soc. Jpn. 2008, 81, 689.
(4) Shiina, I.; Kubota, M.; Oshiumi, H.; Hashizume, M. J. Org. Chem.
2004, 69, 1822.
DOI: 10.1021/jo9027165
r
Published on Web 02/01/2010
J. Org. Chem. 2010, 75, 1803–1806 1803
2010 American Chemical Society

Iuchi et al.
JOCNote
SCHEME 1. Synthesis of CPDA and CPDL
TABLE 2. Reaction of Butyl Cyanoacetate (1) with R,ω-Diols (2) by
[IrCl(cod)]2 Catalysta
SCHEME 2. Synthesis of HDDO
TABLE 1. Reaction of Butyl Cyanoacetate (1) with 1,12-Dodecanediol
(2a) by Ir Catalyst under Various Conditionsa
entry
catalyst
ligand
yield of 3ab (%)
1
2
3
4
5
6
7
8
9
[IrCl(cod)]2
[IrCl(coe)2]2
[Ir(OH)(cod)]2
[Ir(OMe)(cod)]2
[Ir(OAc)(cod)]2
[Cp*IrCl2]2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PCy3
P(OPh)3
dppe
none
PPh3
PPh3
PPh3
82
85 (70)
35
31
7
3
trace
trace
4
aButyl cyanoacetate (1) (1.0 mmol) was allowed to react with R,
ω-diols (2) (3.0 mmol) in the presence of [IrCl(cod)]2 (0.05 mmol) and
PPh3 (0.2 mmol) in dioxane (1 mL) at 120 °C for 20 h. bGC yield based on
1 unless otherwise noted. The numbers in the parentheses show isolated
yields. cNMR yields based on 1 using triphenylmethane as internal
standard.
IrCl3 3H2O
3
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
10c
11
12e
13f
14g
66
n.d.d
53
catalyst in this reaction (entries 3-5). [Cp*IrCl2]2, which
shows high catalytic performance in the Guerbet reaction of
primary alcohols,15 was almost inert the present reaction
(entry 6). In this reaction, the highest catalytic activity was
attained by combination of [IrCl(coe)2]2 with triphenylpho-
sphine (PPh3) as a ligand. Other selected phosphine ligands
such as tricyclohexylphosphine (Cy3P) and triphenyl phos-
phate(P(OPh)3) were found to be almost inert (entries 8 and 9),
but bidentate phosphine ligands like diphenylphosphi-
noethane (dppe) showed moderate catalytic activity (entry 10).
No reaction took place in the absence of phosphine ligand
(entry 11). The optimized reaction temperature was 120 °C,
the reaction at 100 °C resulted in a considerable decrease of
the yield of 3a (53%) (entry 12), and no alkylation product
was observed at 80 °C (entry 13). At 150 °C, the yield of 3a
was low (entry 14).
Under the conditions identified in Table 1, entry 1, 3a was
obtained in substantial yields in various solvents as follows:
diglyme (76%), triglyme (75%), THF (75%), toluene (71%),
and decane (73%). In addition, the reaction took place
without solvent to give 3a in considerable yield (73%).
Table 2 shows the results for the reaction of 1 with several
R,ω-diols under the same conditions as Table 1, entry 1.
n.d.d
23
aButyl cyanoacetate (1) (1.0 mmol) was allowed to react with 1,12-
dodecanediol (2a) (3.0 mmol) in the presence of Ir catalyst (0.05 mmol)
and PPh3 (0.2 mmol) in 1,4-dioxane (1 mL) at 120 °C for 20 h. bGC yield
based on 1a. The number in the parentheses shows isolated yield. cdppe
(1,2-bis(diphenylphosphino)ethane) (10 mol %) was used. dNot detected
by GC. eReaction was performed at 100 °C. fReaction was performed at
80 °C. gReaction was performed at 150 °C.
report the Ir-catalyzed selective synthesis of ω-hydroxy
carboxylic acids and R,ω-dimethyl diketones by the reaction
of cyanoacetate and acetone with R,ω-diols (Schemes 1
and 2).
We first chose the reaction of butyl cyanoacetate (1) with
1,12-dodecanediol (2a) as a model reaction and the catalytic
performance of various iridium complexes was examined
(Table 1).
The reaction of 1 (1.0 mmol) with 2a (3.0 mmol) using
[IrCl(cod)]2 complex (5 mol %) in the presence of PPh3
ligand (20 mol %) in 1,4-dioxane at 120 °C for 20 h resulted
in butyl 2-cyano-14-hydroxytetradecanoate (3a) (82%) in
good yield (entry 1). When [IrCl(coe)2]2 was employed as a
catalyst, 3a was obtained in 85% yield (entry 2). However,
the catalytic activity of [Ir(OH)(cod)]2, and [Ir(OMe)(cod)]2
was moderate, and [Ir(OAc)(cod)]2 complex was poor
(15) Matsu-ura, T.; Sakaguchi, S.; Obora, Y.; Ishii, Y. J. Org. Chem.
2006, 71, 8306.
1804 J. Org. Chem. Vol. 75, No. 5, 2010

Iuchi et al.
JOCNote
The alkylation of 1 with 1,5-pentanediol (2b) afforded
butyl 2-cyano-7-hydroxyheptanoate (entry 1). In the same
manner, long-chain diols such as 1,6-hexanediol (2c), 1,8-
octanediol (2d), 1,9-nonanediol (2e), 1,10-decanediol (2f),
and 1,13-tridecanediol (2g) gave rise to the corresponding
alkylated products, butyl 2-cyano-8-hydroxyoctanoate (3c),
butyl 2-cyano-10-hydroxydecanoate (3d), butyl 2-cyano-11-
hydroxyundecanoate (3e), butyl 2-cyano-12-hydroxydode-
canoate (3f), and 2-cyano-15-hydroxypentadecanoate (3g),
respectively, in good yields (entries 2-6).
The synthesis of macrolactones from 3g was examined
(eq 1). Thus, refluxing of 3f with KOH (4 equiv) in ethylene
glycol for 6 h gave 15-hydroxypentadecanoic acid (4) in 75%
yield.16 Subsequently, treatment of 4 with the fluoroalkyl-
distannoxane catalyst (Otera’s catalyst)17 [{Cl(C6F13CH2-
CH2)SnOSn(CH2CH2C6F13)2Cl}2]2 in a mixed solvent of
FC-72 and decane, by employing Otera’s method for the
synthesis of lactones,6 led to cyclopentadecanolide (5).
TABLE 3. Reaction of Acetone (6) with 1,10-Decanediol (2f) by Ir
Catalyst under Various Conditionsa
yieldc (%)
7a 8a
entry
catalyst
6 (mmol)
baseb (mol %)
1
2
3
4
5
6
7
8
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[Ir(OH)(cod)]2
IrCl(PPh3)3
Ir(acac)(cod)
[Cp*IrCl2]2
2
5
KOH (40)
KOH (40)
KOH (40)
KOH (30)
KOH (20)
KOH (10)
28
75
4
13
10
10
10
10
10
10
10
10
10
10
90 (77) n.d.
82
26
3
23
1
13
n.d.
tert-BuOK (20) 43
KOH (20)
KOH (40)
KOH (40)
KOH (40)
KOH (40)
76
83
74
n.d.
n.d.
3
9d
10d
11
12d
n.d.
n.d.
n.d.
n.d.
IrCl3 3H2O
3
aAcetone (6) was allowed to react with 1,10-decanediol (2e) (1.0
mmol) in the presence of Ir catalyst (0.05 mmol), PPh3 (0.15 mmol),
and KOH in toluene (0.5 mL) at 100 °C for 2 h. bBased on 2f used. cGC
yield based on 2e. The number in the parentheses shows isolated yield.
dIr catalyst (10 mol %) was used.
affected to the yield of 7a (entries 3-6). The yield of 7a was
decreased to 82% in the reaction of 30 mol % of KOH
(entry 4). When KOH was reduced to 20 mol %, diketone 7a
(26%) was formed along with ω-hydroxy ketone 8a (23%)
(entry 5). Almost no alkylation was induced when KOH was
reduced to 10 mol % (entry 6). In order to reduce the quantity
of base, a strong base like t-BuOK was employed instead of
KOH, but the result was almost the same as that of KOH
(entry 7). The use of [IrOH(cod)]2 in place of [IrCl(cod)]2 led to
7a in 76% yield even by the use of 20 mol % of KOH (entry 8).
As expected, the reaction using IrCl(PPh3)3 proceeded without
phosphine ligand to give 7a in satisfactory yield (83%)
(entry 9). The catalytic activity of [Ir(acac)(cod)] was similar
to that of [IrOH(cod)]2 (entry 10). Trivalent iridium complexes
In a previous paper, we reported the Ir-catalyzed alkyla-
tion of methyl ketones with R,ω-diols.14b Thus, this strategy
was extended to the general method for synthesizing of R,ω-
dimethyl diketones like 2,15-hexadecanedione (HDDO)
which is an important precursor of muscone by the use of
acetone (6) to 1,10-decanediol (2f) (eq 2). This method
provides the direct route to HDDO (7a) by one-step reaction
from readily available starting material like acetone and diol.
like [Cp*IrCl2]2 and IrCl3 3H2O were found to be inactive for
3
the present reaction (entries 11 and 12). Although the forma-
tion of an aldol condensation product of 6 under the present
conditions is apprehensive, aldol products of 6 were slight
(<5% based on 6) in all runs in Table 3.
Table 4 shows the preparation of several R,ω-dimethyl
diketones from 6 and R,ω-diols (2). The reaction of 6 with
various R,ω-diols (2) was carried out under the same condi-
tions as Table 3, entry 3. The reactions except for 1,4-butane-
diol (2h) and 1,5-pentanediol (2g) proceeded satisfactorily to
give the corresponding R,ω-dimethyl diketones in good
yields (entries 1-5). In the case of the reaction with 2g and
2h, monohydroxyketones were formed in low yields, but
diketones were not formed at all (entries 6 and 7). For
instance, the reaction of 6 with 2g produced 7-hydroxy-2-
heptanone (8g) (23%) and polymeric products, but diketone
7g was not detected by GC analysis. Since the conversion of
2h was 98%, it is thought that most of the 2h polymerized to
form a complex mixture of polymers by the Guerbet-type
reaction.15
Table 3 shows the representative results for the reaction of
acetone (6) with 1,10-decanediol (2f) by several iridium
complexes under various conditions.
A stoichiometric reaction for double alkylation of 6 (2.0
mmol) with 2f (1.0 mmol) using [IrCl(cod)]2 complex (5 mol
%) in the presence of PPh3 ligand (15 mol %) and KOH (40
mol %) in toluene at 100 °C for 2 h resulted in 2,15-
hexadecanedione (7a) (HDDO) (28%) and 13-hydroxytri-
decan-2-one (8a) (4%) in low yields because of the formation
of polymeric products of 2f (entry 1). When 5 equiv
(5.0 mmol) of 6 toward 2f was used under these conditions,
7a was obtained in 75% yield along with monoalkylated
product, 13-hydroxytridecan-2-one (8a) (13%) (entry 2).
However, when excess 6 (10 equiv) to 2f was used, the
reaction gave rise to 7a in 90% yield (77% isolated yield)
without formation of 8a (entry 3). In the present double
alkylation of 6 with 2f, the amount of KOH was considerably
Compound 7a has been utilized as a precursor for mus-
cone synthesis. Tanabe et al. reported that cyclization of 3a
with TiCl4/Bu3N gave 3-hydroxy-3-methylcyclopentadeca-
none in 52% yield.12 (()-Muscone was prepared by dehy-
dration of 3-hydroxy-3-methylcyclopentadecanone followed
by hydrogenation.12
(16) Zimmerman, H. E.; Suryanarayan, V. Eur. J. Org. Chem. 2007, 4091.
(17) Xiang, J.; Toyoshima, S.; Orita, A.; Otera, J. Angew. Chem., Int. Ed.
2001, 40, 3670.
ω-Hydroxy methylketones (8) are also attractive com-
pounds, but these compounds are difficult to be synthesized
J. Org. Chem. Vol. 75, No. 5, 2010 1805

Iuchi et al.
JOCNote
TABLE 4. Reaction of Acetone (6) with R,ω-Diols (2) by Ir Catalysta
cyanoacetate and acetone with R,ω-diols, respectively, under
the influence of Ir complex and base. This method provides a
novel methodology using R,ω-diols as alkylating agents, which
is difficult to carry out so far, and a short route to ω-hydroxy
carboxylic acids and R,ω-dimethyldiketones, which are im-
portant precursors in organic synthesis.
Experimental Section
Typical Reaction Procedure for the Preparation of 3a (Table 1,
Entry 2). To a mixture of [IrCl(coe)2]2 (45 mg, 0.05 mmol) and
PPh3 (53 mg, 0.20 mmol) were added 1a (141 mg, 1.0 mmol), 2a
(607 mg, 3.0 mmol), and 1,4-dioxane (1.0 mL) under Ar in a
15 mL pressure tube. The reaction mixture was stirred at 120 °C
for 20 h. The conversions and yields of products were estimated
from the peak areas based on the internal standard techniques
using GC which showed that 3a was obtained in 85% yield.
The product (3a) was isolated by column chromatography
(230-400 mesh silica gel, n-hexane/ethyl acetate = 2/1) in
1
70% yield (238 mg): white solid (mp 48-50 °C); H NMR δ
4.17 (t, J = 6.6 Hz, 2H), 3.61 (t, J = 6.6 Hz, 2H), 3.46 (t, J = 6.9
Hz, 1H), 1.91 (q, J = 7.6 Hz, 2H), 1.67-1.60 (m, 2H), 1.57-1.24
(m, 22 H), 0.92 (t, J = 7.0 Hz, 3H); 13C NMR δ 166.3 (C), 116.6
(C), 66.5 (CH2), 63.0 (CH2), 37.6 (CH), 32.7 (CH2), 30.3 (CH2),
29.8 (CH2), 29.52 (CH2), 29.45 (CH2, 2C), 29.36 (CH2, 2C), 29.1
(CH2), 28.7 (CH2), 26.7 (CH2), 25.7 (CH2), 18.9 (CH2), 13.6
(CH3); IR (neat, cm-1) 3416, 2921, 2851, 2247, 1731, 1470, 1291,
1277, 1057, 1025, 721; GC-MS (EI) m/z (relative intensity) 325
(0.1) [M]þ, 308 (0.6), 252 (7), 224 (10), 196 (19), 140 (12), 57 (85),
41 (100). Anal. Calcd for C19H35NO3: C, 70.11; H, 10.84; N,
4.30. Found: C, 70.24; H, 10.75; N, 4.13.
Typical Reaction Procedure for the Preparation of 7a (Table 3,
Entry 3)12. To a mixture of [IrCl(cod)]2 (34 mg, 0.05 mmol),
PPh3 (39 mg, 0.15 mmol), and KOH (23 mg, 0.4 mmol) were
added 6 (581 mg, 10 mmol), 2f (174 mg, 1.0 mmol), and toluene
(0.5 mL) under Ar in a 15 mL pressure tube. The reaction
mixture was stirred at 100 °C for 2 h. The conversions and yields
of products were estimated by GC, and the product 7a was
obtained in 90% yield. The product (7a) was isolated by column
chromatography (230-400 mesh silica gel, n-hexane/ethyl acet-
ate = 10/1) in 77% yield (196 mg).
aAcetone (6) (10 mmol) was allowed to react with R,ω-diols (2)
(1.0 mmol) in the presence of Ir catalyst (0.05 mmol), PPh3 (0.15 mmol),
and KOH (0.40 mmol) in toluene (0.5 mL) at 100 °C for 2 h. bGC yield
based on 2. The numbers in the parentheses show isolated yields.
c7-Hydroxy-2-heptanone (8g) was obtained in 23%. d8-Hydroxy-2-
octanone (8h) was obtained in 22%.
by a simple reaction. Our method is expected to apply the
synthesis of ω-hydroxy methylketones by allowing 6 to react
with R,ω-diols (2). Thus, we next try the synthesis of
ω-hydroxy ketones from 6 and 2.
For instance, the reaction of 6 (3.0 mmol) and 2f (12 mmol)
in the presence of [IrCl(cod)]2 (5 mol %), KOH (40 mol %),
and PPh3 (15 mol %) at 80 °C for 0.5 h gave 8a in 48%
isolated yield and a trace amount of 7a (eq 3), although
conventional synthetic methods of the compound 8a call for
multistep reactions.18
Procedure for the Preparation of 8a (eq 3)19. To a mixture of
[IrCl(cod)]2 (101 mg, 0.15 mmol), PPh3 (118 mg, 0.45 mmol), and
KOH (68 mg, 1.2 mmol) were added 6 (174 mg, 3.0 mmol), 2f
(2.09 g, 12.0 mmol), and toluene (1.5 mL) under Ar in a 15 mL
pressure tube. The reaction mixture was stirred at 80 °C for 0.5 h. The
product (8a) was isolated by column chromatography (230-400
mesh silica gel, n-hexane/ethyl acetate = 3/1) in 48% yield (309 mg).
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research on Priority Areas “Advanced
Molecular Transformations of Carbon Resources” from the
Ministry of Education, Culture, Sports, Science and Tech-
nology, Japan, and “High-Tech Research Center” Project
for Private Universities: matching fund subsidy from the
Ministry of Education, Culture, Sports, Science and Tech-
nology, 2005-2009. We are grateful to Professor Junzo
Otera of Okayama University of Science for useful discus-
sions and the generous gift of the distannoxane catalysts.
It is thought that the reaction proceeds through a similar
reaction pathway as described in previously reported rele-
vant works.13,14 Thus, the iridium-catalyzed dehydrogena-
tion of diols 2 take place to form aldehyde and Ir hydride,
followed by cross-aldol condensation with 1 or 6 and hydro-
genation with the Ir hydride, giving the desired products
(3, 7, and 8) (Figures S1 and S2, Supporting Information).
In conclusion, ω-hydroxycarboxylic acids and R,ω-dimethyl
diketones were successfully prepared by one-step reaction of
Supporting Information Available: Figures S1 and S2,
experimental procedure, spectra data, and copies of 1H and
13C NMR of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
(18) Ishmuratov, G. Yu.; Yakovleva, M. P.; Kharisov, R. Ya.; Botsman,
O. V.; Izibairov, O. I.; Mannapov, A. G.; Tolstikov, G. A. Chem. Nat.
Compd. 2001, 37, 190.
(19) Stoll, M. Helv. Chim. Acta 1951, 34, 1817.
1806 J. Org. Chem. Vol. 75, No. 5, 2010