Carbon-carbon bond formation by reactions of allylic alcohol with enoxysilane in the presence of Ir-complex

Article abstract of DOI:10.1016/S0040-4039(01)02297-3

Substitution of allylic alcohols to form a carbon-carbon bond is accomplished by a simple reaction of the allylic alcohol itself with an enoxysilane, catalyzed by [Ir(cod)(PPh₃)₂]X which is activated by H₂ molecule. The anion part X of the complexes plays an important role to enhance the rate and product yields of the reactions. The efficacy of the catalyst increases with switching X in the order of PF₆^-4^--.

Full text of DOI:10.1016/S0040-4039(01)02297-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1043–1046
Carbonꢀcarbon bond formation by reactions of allylic alcohol
with enoxysilane in the presence of Ir-complex
Isamu Matsuda,* Shogo Wakamatsu, Ken-ichi Komori, Tatsuya Makino and Kenji Itoh
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa,
Nagoya 464-8603, Japan
Received 17 September 2001; revised 19 November 2001; accepted 30 November 2001
Abstract—Substitution of allylic alcohols to form a carbonꢀcarbon bond is accomplished by a simple reaction of the allylic
alcohol itself with an enoxysilane, catalyzed by [Ir(cod)(PPh3)2]X which is activated by H2 molecule. The anion part X of the
complexes plays an important role to enhance the rate and product yields of the reactions. The efficacy of the catalyst increases
with switching X in the order of PF6−<ClO4−<TfO−. © 2002 Elsevier Science Ltd. All rights reserved.
Cationic Ir(I) complexes are interesting in their promi-
nent ability as a catalyst precursor for the hydrogena-
tion of highly substituted alkenes1 in which the
direction of the incoming hydrogen is controlled by the
hydroxy group contained in the substrates.2 A second
feature of these complexes is the high performance for
the isomerization of olefinic double bonds in allylic
alcohols,3 silyloxyallyl compounds,4 and alkenes con-
taining a trimethylsilyl group at a remote position.5 On
the other hand, some alkoxy iridium complexes6
formed by oxidative addition of an alcohol have been
scrutinized in relation to transfer hydrogenation of
alkynes7 and asymmetric hydrogenation of ketones8 or
imines.9 However, there are no examples of the hydroxy
function of alcohols behaving as a leaving group in
reactions catalyzed by a cationic Ir(I) complex10 or by
Brønsted acid. We focussed on finding this type of
catalytic reaction. We report here that the hydroxy
group of allylic alcohols is readily substituted by benzyl
alcohol or an enoxysilane in the presence of a catalytic
amount of a cationic Ir(I) complex.
of 1,3-diphenylpropan-1-one by simply stirring a
CH2Cl2 solution of 2a (0.72 mmol), benzyl alcohol (3,
0.79 mmol) and 1a (0.037 mmol) for 3 h at 25°C (Eq.
(1)). On the other hand, 1,1-dibenzyloxy-3-phenyl-
propane (43%) was isolated as the sole product in a
reaction of cinnamyl alcohol with 3 under similar
conditions.
Ph
Ph
OH
2a
Ph
Ph
Ph
1a/H2 (cat.)
+
O
CH2Cl2
25 °C, 3 h
77%
HO Ph
4a
3
(1)
The result of Eq. (1) implies that the hydroxy group of
2a was kicked off to form a cationic site at the allylic
carbon in the presence of 1a. This stimulated us to
design Ir-catalyzed CꢀC bond forming reactions
between an allylic alcohol and an enoxysilane as a facile
homologation method, because we have already found
that enoxysilane behaves as a good nucleophile in Ir(I)-
catalyzed aldol-type and Michael-type couplings.11
Thus, we arranged a series of Ir-catalyzed reactions
between allylic alcohol 2 and enoxysilane 5.
At the first stage of this project, it was observed that
[Ir(cod)(PPh3)2]PF6 (1a) activated by H2 works as a
catalyst for substitution of the hydroxy group at the
allylic position and for isomerization of alkenes. 3-Ben-
zyloxy-1,3-diphenyl-1-popene (4a) was isolated in 77%
yield with the concomitant formation of a trace amount
A coupling product 6aa was isolated in 54% yield with
the concomitant formation of 7a (14%) and 8a (17%),
when a mixture of 2a (1 mmol) and 5a (2 mmol) was
heated for 21 h at 80°C in a sealed tube containing 2
mol% of 1a activated in advance by H2 gas at −78°C.
Keywords: allylic substitution; cationic Ir(I) complex; allylic alcohols;
enoxysilanes.
* Corresponding author. Tel.: +81-52-789-5113; fax: +81-52-789-3205;
e-mail: matsudai@apchem.nagoya-u.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02297-3

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I. Matsuda et al. / Tetrahedron Letters 43 (2002) 1043–1046
1a/H2 (cat.)
Ph
Ph
OH
Ph
about significant acceleration and high selectivity for
+
the formation of 6ab, whereas the diastereoselectivity of
6ab could not be improved by the choice of catalyst.
Similarly, 1c accelerated the coupling rate to give 6aa
and 6ac in the reactions of 2a with 5a and 5c, respec-
tively (entries 3 and 9 in Table 1).
OSiMe3
CH2Cl2
80 °C, 21 h
2a
5a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
OSiMe3
+
+
O
The present type of allylic substitution was extended to
some other alcohols as illustrated in Eq. (3). Two
regioisomers were formed in the reaction of unsymmet-
rically substituted allylic alcohols. The results are sum-
marized in Table 2. 1-Phenyl-2-buten-1-ol 2b reacted
readily with 5a to give a pair of regioisomers, 6ba and
6ba% (entry 1 in Table 2). In sharp contrast to 2b,
4-phenyl-3-buten-2-ol 2c was not amenable to the
allylic substitution, but the trimethylsilyl ether derived
from 2c was the sole product in the reaction with 5a
catalyzed by 1a (entry 3 in Table 2). Only 7% yield of
6ca was isolated in a similar reaction catalyzed by 1c
(entry 4 in Table 2). On the other hand, an additional
methyl group on the carbinol carbon of 2c remarkably
enhanced the lability of the hydroxy group as a leaving
group to give 6eb% and 6ec% (identical with 6db and 6dc,
respectively) with high regioselectivity as exemplified in
the reactions of 2e with 5b and 5c (entries 9 and 10 in
Table 2). The identical products 6db and 6dc were also
obtained with high selectivity in the reactions of 2d with
the corresponding enoxysilane. The rate of the reac-
tions was much enhanced by using TfO− as the anion
part, X of 1, whereas the ratio of diastereomers did not
O
Ph
6aa (54%)
7a (14%)
8a (17%)
(2)
Detailed results are summarized in Table 1. This type
of coupling to form 6aa proceeded even at 25°C,
though slow addition of 2a through a micro-feeder was
required in order to suppress the formation of 8a. It is
noted that the yield of 6aa was lower than in the
reaction of 2a itself in the reactions using 7a and the
acetate of 2a as the starting substrate (entries 4 and 5 in
Table 1).
In contrast to 5a, enoxysilane 5b derived from pentan-
3-one gave poor yield of 6ab under similar conditions
using 1a as a catalyst (entry 6 in Table 1). However,
this defect was surmounted by tuning the anion part of
[Ir(cod)(PPh3)2]X. When complexes 1b (X=ClO4)12 and
1c (X=OTf, trifluoromethanesulfonate) were used as a
catalyst, rate acceleration and improvement in the yield
of 6ab were observed in the reaction of 2a with 5b
(entries 7 and 8 in Table 1). In particular, 1c brought
Table 1. Reactions of 2a with enoxysilanes in the presence of 1a

I. Matsuda et al. / Tetrahedron Letters 43 (2002) 1043–1046
1045
Table 2. Reactions of allylic alcohols with enoxysilanes in the presence of 1a
vary so much regardless of X (entries 5, 6 and 7 in
Table 2). Other alcohols 2f and 2g reacted with 5b to
give the corresponding product 6fb and 6gb, respec-
tively (entries 11 and 12 in Table 2). Regioselectivity
was not observed in the reaction of 2b; however, a less
substituted site was selected preferentially as the con-
necting site in the reaction of models containing differ-
ent numbers of substituents on the two allylic termini.
Unfortunately, diastereo-control in these reactions was
not satisfactory similarly to the results reported in
transition-metal catalyzed substitution of allylic
esters.13
signal in accord with the decrease of an Ir–H species in
the H NMR spectrum of a stoichiometric mixture of 1
1
activated by H2 gas and 5c.11a The rate of the corre-
sponding interaction strongly depended on the anionic
part of 1: the rate increases in the order of 1a (X=
PF6)<1b (X=ClO4)<1c (X=OTf). Although the precise
behavior of the Ir-species is obscure at present, this
appreciable rate deviation on the anionic part of 1
seems to reflect the remarkable rate acceleration in the
present allylic substitution. This rate acceleration can
be elucidated by the intervention of XH which may be
formed by the equilibrium as shown in Eq. (4).14 In
fact, the presence of catalytic amount of CF3SO3H
instead of 1c realized the substitution of 2a with the
efficiency similar to 1c (entries 3, 8 and 9 in Table 1).
However, we observed that free CF3SO3H reacts
rapidly with an equivalent mole of 5c to form
Me3SiOTf and acetone in CDCl3 (Eq. (5)). Formation
R3
R6
1/H2 (cat.)
R1
R4
R5
+
R2 OH
OSiMe3
CH2Cl 2
2
5
R1
R2
R3
R4
1
R1
R3
R4
of Me3SiOTf was not observed in the H NMR spec-
+
trum (CDCl3) of a mixture of [Ir(H)2(cod)(PPh3)2]OTf
and four equivalent moles of 5c. Excess of 5c remained
intact for over 2 h in the sample. Unfortunately, the
participation of CF3SO3H cannot be completely
excluded in the present transformation as shown in
Eqs. (2) and (3), because the starting allylic alcohol may
behave as a proton source. Detailed study on this point
is now in progress.
R2
R6
R6
R5
R5
O
O
6'
6
(3)
We have postulated the presence of an Ir–Si species on
the basis of the appearance of a new trimethylsilyl

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I. Matsuda et al. / Tetrahedron Letters 43 (2002) 1043–1046
[Ir(H)2(cod)(PPh3)2]X
Ir(H)(cod)(PPh3)2 + HX
(4)
2. Crabtree, R. H.; Davis, M. W. J. Org. Chem. 1986, 51,
2655.
3. Baudy, D.; Ephritikhine, M.; Felkin, H. Chem. Commun.
CDCl3
+
CF3SO3H
1978, 694.
OSiMe3
5c
4. Ohmura, T.; Yamamoto, Y.; Miyaura, N. Organometal-
lics 1999, 18, 413.
5. Matsuda, I.; Kato, T.; Sato, S. Tetrahedron Lett. 1986,
27, 5747.
+
CF3SO3SiMe3
(5)
O
6. (a) Milstein, D.; Calabrese, J. C.; Williams, I. D. J. Am.
Chem. Soc. 1986, 108, 6387; (b) Lapido, F. L.; Kooti, M.;
Merola, J. S. Inorg. Chem. 1993, 32, 1681; (c) Newman,
L. J.; Bergman, R. G. J. Am. Chem. Soc. 1985, 107, 5314;
(d) Glueck, D. S.; Winslow, L. J. N.; Bergman, R. G.
Organometallics 1991, 10, 1462; (e) Tani, K.; Iseki, A.;
Yamagata, T. Angew. Chem., Int. Ed. 1998, 37, 3381.
7. Tani, K.; Iseki, A.; Yamagata, T. Chem. Commun. 1999,
1821.
8. Mashima, K.; Abe, T.; Tani, K. Chem. Lett. 1998, 1199
and 1201.
9. Kainz, S.; Brinkmann, A.; Leitner, W.; Pfalz, A. J. Am.
Chem. Soc. 1999, 121, 6421.
10. In the previous report on the Ir(I)-catalyzed substitution
of allylic alcohols, the process of the reaction is eluci-
dated by presuming intervention of a malonate ester
derived from allylic alcohols: Takeuchi, R.; Kashio, M. J.
Am. Chem. Soc. 1998, 120, 8647.
11. (a) Matsuda, I.; Hasegawa, Y.; Makino, T.; Itoh, K.
Tetrahedron Lett. 2000, 41, 1405; (b) Matsuda, I.;
Makino, T.; Hasegawa, Y.; Itoh, K. Tetrahedron Lett.
2000, 41, 1409.
12. It is known that perchlorate compounds are explosive.
Although we have not experienced an explosion in the
reaction using 1b, manipulations with this reagent should
be performed with care.
13. (a) Godleski, S. A. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 4, p. 585; (b) Tsuji, J. In Palladium Reagents
and Catalysts; John Wiley & Sons: New York, 1995; p.
290; (c) Harrington, P. J. In Comprehensive Organometal-
lic Chemistry II; Abel, E. W.; Stone, F. G. A.; Wilkinson,
G., Eds.; Pergamon Press: Oxford, 1995; Vol. 12, p. 797;
(d) Trost, B. M.; Varanken, D. L. V. Chem. Rev. 1996,
96, 395; (e) Recent successful examples of diastereocon-
trol for allylic substitutions: Trost, B. M.; Surivet, J.-P. J.
Am. Chem. Soc. 2000, 122, 6291; (f) Braun, M.; Laicher,
F.; Meier, T. Angew. Chem., Int. Ed. 2000, 39, 3494.
14. The authors thank one of the reviewers who pointed out
the possibility of this equilibrium and gave the opportu-
nity to add the results of control experiments using
CF3SO3H.
Mechanistic consideration aside, the most important
point of this transformation is the fact that allylic
alcohols themselves are suitable for the substitution
using an enoxysilane as a nucleophile. Our finding
provides a new variation in the allylic substitution
regardless of the source of catalyst. Although remark-
able difference in the efficiency of catalyst is not
observed between 1c and CF3SO3H at present, the
following points are advantageous for the use of Ir
complexes as a catalyst: (i) the required quantity of
catalyst is precisely controlled by weight, because they
are solid stable in the atmosphere, (ii) the required
property as a catalyst can be adjusted by tuning ligands
and (iii) the present transformation is extendable to an
asymmetric version by choosing prompt ligands.
In summary, we have found that the hydroxy group of
allylic alcohols behaves as a leaving group in the pres-
ence of a catalytic amount of [Ir(cod)(PPh3)2]X acti-
vated in advance by H2 to form a carbonꢀoxygen bond
or a carbonꢀcarbon bond at the allylic position. It
should be stressed that the present method is performed
by simply stirring a mixed solution of the substrates
under almost neutral conditions, though considerable
effort is required for the control of regio- and stereo-
chemistry at present.
Acknowledgements
We gratefully acknowledge financial support from the
Ministry of Education, Science, Sports and Culture,
Japan.
References
1. (a) Crabtree, R. H. Acc. Chem. Res. 1979, 12, 331; (b)
Suggs, J. W.; Cox, S. D.; Crabtree, R. H.; Quirk, J. M.
Tetrahedron Lett. 1981, 22, 303.