Iridium-catalyzed coupling reaction of primary alcohols with 1-aryl-1-propynes leading to secondary homoallylic alcohols

Article abstract of DOI:10.1021/ol901366q

We report iridium-catalyzed coupling of 2-alkynes such as 1-aryl-1-propynes with primary alcohols leading to secondary homoallylic alcohols as products. This reaction involves an iridium-catalyzed novel catalytic transformation of 2-alkynes and primary al

Full text of DOI:10.1021/ol901366q

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3510-3513
Iridium-Catalyzed Coupling Reaction of
Primary Alcohols with 1-Aryl-1-propynes
Leading to Secondary Homoallylic
Alcohols
Yasushi Obora,* Shintaro Hatanaka, and Yasutaka Ishii*
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials
and Bioengineering, High Technology Research Center, and ORDIST,
Kansai UniVersity, Suita, Osaka 564-8680, Japan
obora@ipcku.kansai-u.ac.jp; ishii@ipcku.kansai-u.ac.jp
Received June 17, 2009
ABSTRACT
We report iridium-catalyzed coupling of 2-alkynes such as 1-aryl-1-propynes with primary alcohols leading to secondary homoallylic alcohols
as products. This reaction involves an iridium-catalyzed novel catalytic transformation of 2-alkynes and primary alcohols through the formation
of hydrido(π-allyl)iridium as a possible key intermediate.
Recently, iridium-catalyzed hydrogen autotransfer processes
involving the use of alcohols as alkylating agents have been
the topic of intensive investigation.1 We succeeded in
developing the iridium-catalyzed direct R-alkylation of
ketones and active methylene compounds like cyanoacetate
with alcohols and diols as well as ꢀ-alkylation of primary
alcohols (Guerbet reaction) using alcohols as alkylated
agents.2 On the other hand, the transition metal-catalyzed
addition of alcohols to alkynes is an important methodology
leading to a wide variety of oxygen-containing compounds
which are mainly referred to as the hydroalkoxylation
reaction.3 In addition, several iridium-catalyzed reactions of
terminal alkynes with alcohols are also reported.4
Quite recently, Krische and co-workers reported an
ruthenium or iridium-catalyzed transformation of alcohols
with diene, allyl acetate, and allene to afford homoallylic
alcohols as products.5 In addition, the same group also
reported the ruthenium-catalyzed direct C-H vinylation
reaction of alcohols and alkynes to afford allylic alcohols
as products.6
In this Letter, we wish to report iridium-catalyzed coupling
of 2-alkynes such as 1-aryl-1-propynes with primary alcohols
leading to secondary homoallylic alcohols as products.7 This
work is a novel iridium-catalyzed transformation of alcohols
(3) For reviews see: Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV,
2004, 104, 3079.
(4) (a) Hirabayashi, T.; Okimoto, Y.; Saito, A.; Morita, M.; Sakaguchi,
S.; Ishii, Y. Tetrahedron 2006, 62, 2231. (b) Konkol, M.; Schmidt, H.;
Steinborn, D. J. Mol. Catal. A: Chem. 2007, 269, 119.
(1) (a) Iridium Complexes in Organic Synthesis; Oro, L. A., Claver, C.,
Eds.; Wiley: Weinheim, Germany, 2009. (b) Guillena, G.; Ra´mon, D. J.;
Yus, M. Angew. Chem., Int. Ed. 2007, 46, 2. (c) Ishii, Y.; Sakaguchi, S.
Bull. Chem. Soc. Jpn. 2004, 77, 909. (d) Takeuchi, R.; Kezuka, S. Synthesis
2006, 3349. (e) Fujita, K.; Yamaguchi, R. Synlett 2005, 560, and references
cited therein.
(5) (a) Bower, J. F.; Kim, I. S.; Patman, R. L.; Krische, M. J. Angew.
Chem., Int. Ed. 2009, 48, 34. (b) Patman, R. L.; Williams, V. M.; Bower,
J. F.; Krische, M. J. Angew. Chem., Int. Ed. 2008, 47, 5220. (c) Kim, I.;
Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6340. (d)
Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130,
14120. (e) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2009,
131, 2514. (f) Kim, I. S.; Ngai, M.-Y.; Kriche, M. J. J. Am. Chem. Soc.
2008, 130, 14891.
(2) (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. (c) Morita, M.; Obora,
Y.; Ishii, Y. Chem. Commun. 2007, 2850. (d) Matsu-ura, T.; Sakaguchi,
S.; Obora, Y.; Ishii, Y. J. Org. Chem. 2006, 71, 8306.
(6) Patman, R. L.; Chaulagain, M. R.; Williams, V. M.; Krische, M. J.
J. Am. Chem. Soc. 2009, 131, 2066.
10.1021/ol901366q CCC: $40.75
Published on Web 07/13/2009
 2009 American Chemical Society

and alkynes to afford homoallylic alcohols as products
through the formation of hydrido(π-allyl)iridium as a possible
key intermediate, which indicated different reaction pathway
from that used in Krische’s work using alkynes.6
The reaction of 1-butanol (1a) with 1-phenyl-1-propyne
(2a) was chosen as a model reaction and was carried out
under various conditions (Table 1). For instance, 1a (1 mmol)
decrease of 3a (65%) (entry 1 vs. entry 11). In this reaction,
the formation of allylbenzene byproduct (3-20% based on
1a used) was unavoidable (vide infra, Scheme 1).
As for the iridium complex, [IrCl(cod)]2 also realized high
catalytic activity and gave 3a in high yield (entry 13).
However, other selected iridium complexes such as
-
[Ir(cod)2]+BF4 , [IrCl(coe)2]2, and [Cp*IrCl2]2 showed low
or no catalytic activities (entries 14-16). Needless to say,
no 3a was formed in the absence of an Ir complex (entry
17).
Table 1. Ir-Catalyzed Reaction of 1-Butanol (1a) with
1-Phenyl-1-propyne (2a) under Various Conditionsa
In the present reaction, various solvents can be employed.
Under the reaction conditions identified in Table 1, entry 1
produces yields of 3a in various solvents as follows: octane
(99%), DMSO (95%), dioxane (90%), THF (81%), DMF
(84%), 1,4-dichlorobutane (69%), and benzonitrile (20%).
Under optimized conditions, reactions of various primary
alcohols (1) with 1-aryl-1-propynes (2) were carried out to
afford the corresponding homoallylic alcohols in good to
excellent yields (Table 2). Ethanol (1b), isobutyl alcohol (1c),
1-hexanol (1d), 1-octanol (1e), crotyl alcohol (1f), and
ꢀ-methallyl alcohol (1g) were allowed to react with 2a
affording the corresponding homoallylic alcohols (3b-g) in
high to excellent yields (entries 1-6). In addition, various
1-aryl-1-propynes (2b-e) can also be employed in this
reaction and gave the corresponding homoallylic alcohols
(3h-k) in high yields (entries 7-10). Unfortunately, 1-alkyl-
1-propynes such as 2-butyne and 2-octyne were sluggish
substrates to give only low yields of the desired homoallylic
alcohols (<10% yield). The methyl substituent on the alkynes
plays a crucial role in achieving the reaction. Thus, no
coupling product was obtained from 4-octyne and phenyl-
ethylacetylene.
entry
Ir-catalyst (mol %)
ligand (mol %)
yield of 3a/%b
1
2
3
4
5
6
7
8
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (2.5)
[Ir(OH)(cod)]2 (5)
[Ir(OH)(cod)]2 (5)
[IrCl(cod)]2 (5)
P(n-Oct)3 (30)
P(n-Oct)3 (10)
P(n-Bu)3 (30)
P(i-Pr)3 (30)
PCy3 (30)
P(OMe)3 (30)
P(OPh)3 (30)
dppe (15)
quant (95)
9
80
trace
trace
4
4
11
9
none
n.d.c
80
10d
11e
12f
13
14
15
16
17
P(n-Oct)3 (15)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
P(n-Oct)3 (30)
65
35
90
55
-
[Ir(cod)2]+BF4 (10)
[IrCl(coe)2]2 (5)
[Cp*IrCl2]2 (5)
none
34
n.d.c
n.d.c
a Conditions: 1a (1 mmol) was allowed to react with 2a (2 mmol) in
the presence of Ir catalyst (2.5-10 mol %) combined with phosphine ligand
in toluene (1 mL) at 100 °C for 15 h. b GC yields based on 1a used. The
number in parentheses shows the isolated yield. In this reaction, allylbenzene
(3-20% based on 2a) was obtained as byproduct. c Not detected by GC.
d [Ir(OH)(cod)]2 (2.5 mol %) and P(n-Oct)3 (15 mol %) were used as catalyst.
e The reaction was performed with 1a (1 mmol) and 2a (1 mmol). f Reaction
was performed at 60 °C.
Scheme 1
.
Ir-Catalyzed Reaction of Secondary Alcohols (4)
with 1-Phenyl-1-propyne (2a)
was allowed to react with 2a (2 mmol) in the presence of
[Ir(OH)(cod)]2 (0.05 mmol) combined with tri(n-octyl)phos-
phine (0.30 mmol) in toluene (1 mL) at 100 °C for 15 h and
gave 3-phenyl-1-hepten-4-ol (3a) in quantitative yield (95%
isolated yield) (entry 1). The reaction is highly stereoselective
to afford an anti isomer exclusively. In this reaction, the
highest catalytic activity was attained by adding tri(n-
octyl)phosphine as a ligand (entry 1). The addition of a lesser
amount of tri(n-octyl)phosphine (10 mol %, Ir/P ) 1:1)
resulted in a considerably decreasing yield of 3a (entry 2).
Other added aryl and alkyl phosphine ligands indicated low
catalytic activity, and no 3a was obtained in the absence of
the phosphine ligand (entries 3-9).
To obtain further insight into the reaction pathway, we
carried out the reaction of secondary alcohols such as
1-phenyl-1-ethanol (4a) and 2-butanol (4b) with 2a under
these reaction conditions (Scheme 1). As a result, allylben-
zene (5a) derived from 2a was formed in quantitative yield
with concomitant formation of acetophenone (6a from 4a)
or 2-butanone (6b from 4b) in quantitative yields based on
alcohols used. Similarly, the reaction of isopropyl alcohol
(4c) with 2a under these reaction conditions gave 5a in
quantitative yield (based on 4c used). These results suggest
The yield of 3a was still high (80%) even though the
catalyst amount was reduced to half (2.5 mol %) (entry 10).
Furthermore, the highest yield of 3a was obtained with the
ratio of 1a:2a ) 1:2, and the use of an equimolar amount of
1a and 2a under these reaction conditions resulted in a
(7) Communicated in part in the following: (a) Hatanaka, S.; Obora,
Y.; Ishii, Y., Abstract of Papers of the 88th Annual Meeting of Chemical
Society of Japan, Tokyo, Japan, 2008; Chemical Society of Japan: Tokyo,
Japan, 2008, 4H3-40. (b) Hatanaka, S.; Obora, Y.; Ishii, Y. 55th Symposium
on Organometallic Chemistry, Osaka, Japan, 2008; The Kinki Chemical
Society: Osaka, Japan, 2008, P2B-27.
Org. Lett., Vol. 11, No. 15, 2009
3511

Table 2. Ir-Catalyzed Reaction of Alcohols (1) with Alkynes (2) Leading to Homoallylic Alcohols (3)a
a Conditions: 1 (1 mmol) was allowed to react with 2 (2 mmol) in the presence of [Ir(OH)(cod)]2 (0.05 mmol) and P(n-Oct)3 (0.3 mmol) in toluene (1
mL) at 100 °C for 15 h. b GC yields. The numbers in parentheses show isolated yields.
that these alcohols behave as a hydrogen source and
transferred to the Ir complex to form Ir-hydride species,8
which was followed by the formation of π-allyl iridium
species9 as a key intermediate.
Quite recently, a stoichiometric transformation of 2-pro-
pynes with an osmium-dihydride complex was reported and
led to a hydrido(π-allyl)osmium complex.10 This study
demonstrated the first example of the catalytic transformation
of 1-aryl-1-propynes with primary alcohols as products
through the formation of hydrido (π-allyl)iridium as a
possible intermediate.
A stoichiometric reaction of 1a, 2a, and [Ir(OH)(cod)]2/
P(n-Oct)3 was carried out in an NMR tube in toluene-d8. 1H
NMR spectra of the reaction mixture showed several peaks
at around -23 ppm which can be assigned as proton signals
of Ir-hydride.8 However, due to instability of the complex,
we could not determine the full structure of the expected
π-allyl iridium intermediate at this point.
Accordingly, a detailed reaction mechanism of this reaction
is not confirmed at this stage, but the reaction mechanism
would be explained by the following sequential pathway
(Scheme 2). First, the iridium catalyst serves as the hydrogen
acceptor from 1 giving aldehydes (A) and an iridium-
dihydride species (B).2,8 Then alkynes (2) was inserted by
Ir-H bond of B to form the hydrido(alkenyl)iridium species
(C). The C was subjected to hydrogenation by Ir-H, followed
(8) Papers for iridium hydride: (a) Burk, M. J.; Crabtree, R. H.; McGrath,
D. V. Chem. Commun. 1985, 1829. (b) Gupta, M.; Hagen, C.; Kaska, W. C.;
Cramer, R. E.; Jensen, C. M. J. Am. Chem. Soc. 1997, 119, 840. (c) Liu,
F.; Goldman, A. S. Chem. Commun. 1999, 655.
(9) Papers for π-allyl iridium: (a) Green, M.; Taylor, S. H. Dalton Trans.
1975, 1143. (b) Schwartz, J.; Hart, D. W.; McGiffert, B. J. Am. Chem.
Soc. 1974, 96, 5613. (c) Green, M.; Taylor, S. H. Chem. Commun. 1974,
361.
(10) Esteruelas, M. A.; Hernandez, Y. A.; Lo´pez, A. M.; Oliva´n, M.;
On˜ate, E. Organometallics 2007, 26, 2193.
3512
Org. Lett., Vol. 11, No. 15, 2009

In conclusion, we reported the Ir-catalyzed coupling
reaction of 1-aryl-1-propynes with primary alcohols to afford
secondary homoallylic alcohols through the formation of
hydrido(π-allyl)iridium as a possible intermediate. Further
study of the characterization of the active intermediate
species is currently under investigation.
Scheme 2. A Plausible Reaction Mechanism
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan, “High-Tech Research Center” Project for Private
Universities: matching fund subsidy from the Ministry of
Education, Culture, Sports, Science and Technology, 2005-
2009.
Supporting Information Available: Experimental pro-
cedure and compound characterization data (1H NMR, 13C
NMR, IR, and MS) of all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
by abstraction of hydrogen from the methyl group of 2
resulting in the formation of hydrido(π-allyl)iridium species
(D) as an intermediate,10 which further reacts with aldehydes
(A) to afford homoallylic alcohols (3) as products through
the formation of a six-membered transition state (E).
OL901366Q
Org. Lett., Vol. 11, No. 15, 2009
3513