Double-chelation-assisted Rh-catalyzed intermolecular hydroacylation

Article abstract of DOI:10.1021/ol034343o

(Matrix presented) Rh-Catalyzed intermolecular hydroacylation between salicylaldehydes and 1,5-hexadienes proceeded under remarkably mild reaction conditions to afford a mixture of iso- and normal-hydroacylated products in good yields. The experiments using deuterated salicylaldehyde-d revealed that "double chelation" of salicylaldehyde and 1,5-hexadiene to Rh-complex played vital roles in the catalytic cycle of intermolecular hydroacylation.

Full text of DOI:10.1021/ol034343o

ORGANIC
LETTERS
2003
Vol. 5, No. 8
1365-1367
Double-Chelation-Assisted Rh-Catalyzed
Intermolecular Hydroacylation
Masakazu Tanaka,* Masanori Imai,‡ Yoichiro Yamamoto,† Keitaro Tanaka,†
,†
,†
Masato Shimowatari,† Shinji Nagumo,‡ Norio Kawahara,‡ and Hiroshi Suemune*
Graduate School of Pharmaceutical Sciences, Kyushu UniVersity,
Fukuoka 812-8582, Japan, and Hokkaido College of Pharmacy,
Hokkaido 047-0264, Japan
mtanaka@phar.kyushu-u.ac.jp; suemune@phar.kyushu-u.ac.jp
Received February 26, 2003
ABSTRACT
Rh-Catalyzed intermolecular hydroacylation between salicylaldehydes and 1,5-hexadienes proceeded under remarkably mild reaction conditions
to afford a mixture of iso- and normal-hydroacylated products in good yields. The experiments using deuterated salicylaldehyde-d revealed
that “double chelation” of salicylaldehyde and 1,5-hexadiene to Rh-complex played vital roles in the catalytic cycle of intermolecular
hydroacylation.
Rhodium complexes have widely been used as catalysts such
as in hydrogenation, isomerization, and hydroformylation.1
Among them, Rh-catalyzed C-C bond formation via C-H
activation intrigues many organic and organometallic chem-
ists.2 We have reported that an Rh-complex catalyzed an
intramolecular hydroacylation of 4-pentenals, i.e., cyclization
of 4-pentenals into cyclopentanones, albeit an intermolecular
hydroacylation could not proceed due to the competitive
decarbonylation.3,4 Recently, the Jun5 and Miura groups6
independently reported novel Rh-catalyzed intermolecular
hydroacylation based on the chelation of salicylaldehyde or
imine bearing 2-amino-3-picoline, albeit these reactions
require rigorous conditions.7 Here we describe for the first
time that double chelation of both aldehyde and olefin to an
Rh-complex promotes intermolecular hydroacylation under
remarkably mild reaction conditions.
The hydroacylation between salicylaldehyde 1 (X ) H)
and some alkynes stimulated us to scrutinize hydroacylation
between 1 and olefins using RhCl(PPh3)3 (Scheme 1).
Scheme 1
† Kyushu University.
‡ Hokkaido College of Pharmacy.
(1) (a) Hegedus, L. S. Coord. Chem. ReV. 2000, 204, 199. (b) Gridnev,
I. D.; Higashi, N.; Asakura, K.; Imamoto, T. J. Am. Chem. Soc. 2000, 122,
7183. (c) Breit, B.; Seiche, W. Synthesis 2001, 1.
(2) (a) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698. (b) Ritleng,
V.; Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731. (c) Labinger, J. A.;
Bercaw, J. E. Nature 2002, 417, 507 and references therein.
(3) (a) Sakai, K.; Ide, J.; Oda, O.; Nakamura, N. Tetrahedron Lett. 1972,
13, 1287. (b) Taura, Y.; Tanaka, M.; Wu, W.-M.; Funakoshi, K.; Sakai, K.
Tetrahedron 1991, 47, 4879. (c) Tanaka, M.; Imai, M.; Fujio, M.; Sakamoto,
E.; Takahashi, M.; Eto-Kato, Y.; Wu, X.-M.; Funakoshi, K.; Sakai, K.;
Suemune, H. J. Org. Chem. 2000, 65, 5806. (d) Tanaka, M.; Takahashi,
M.; Sakamoto, E.; Imai, M.; Matsui, A.; Fujio, M.; Funakoshi, K.; Sakai,
K.; Suemune, H. Tetrahedron 2001, 57, 1197 and 1205.
Fortunately, the hydroacylation of 1 with 1-hexene pro-
ceeded to afford a hydroacylated product, even though the
isolated yield was merely 4% after 3 days.8 Next, we adopted
1,5- and 1,4-dienes as an olefin because in the case of Rh-
10.1021/ol034343o CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/27/2003

catalyzed hydroformylation, some dienes were rapidly
reacted.1c,9 The results are summarized in Table 1. The
14, which were reacted at the less substituted olefin site,
and iso-products 12a-14a were obtained in preference to
normal-12b-14b. The internal exo-olefin in triene 7 did not
react, but the terminal olefin reacted to give 15a,b in 74%.
The hydroacylation of 2,5-dimethylhexa-1,5-diene did not
proceed at all. In the case of 1,5-heptadiene 8, which was a
1,5-hexadiene bearing a methyl group at the terminus, the
reaction proceeded to give hydroacylated products 16a-c
in 60% total yields but did not afford the product acylated
at the C6-position of 8. In the case of triene 9, the internal
disubstituted olefin was more reactive than the terminal olefin
to give hydroacylated 17a-c in 69% total yields. These
results suggest that the 1,4- or 1,5-diene structure, which
chelates to the Rh metal, is necessary for the hydroacylation.
Next, we examined the effect of aldehydes by treatment
with RhCl(PPh3)3 (0.2 equiv) and 2 (6.0 equiv) at room
temperature. The hydroacylation of benzaldehydes bearing
no 2-hydroxy function such as 3-hydroxy- and 4-hydroxy-
benzaldehydes did not proceed or proceeded in very low
yields, but that of various 2-hydroxybenzaldehydes proceeded
to give the products as a mixture of iso (a) and normal (b).
The results are summarized in Table 2. The hydroacylation
was tolerant of various functional groups in the aromatic ring.
However, another hydroxy group at the C3-, C4-, or C5-
position of 2-hydroxybenzaldehyde was practically ineffec-
tive; this may be attributed to the fact that the hydroxy group
may coordinate to the Rh metal. Alkyl substituents and
naphthalene skeletons were also somewhat disadvantageous,
but the steric and electronic effects of the substituents are
not clear.
Table 1. Rh-Catalyzed Intermolecular Hydroacylation between
Salicylaldehyde 1 and Dienes 2-9
a Cyclohexene, 1,5-cyclooctadiene, 5-hexen-2-one, 1,3-hexadiene, 1,3-
cyclohexadiene, or 2,5-dimethylhexa-1,5-diene was also examined, but the
reaction did not proceed at all. b Reaction was usually completed in 24 h.
In the cases that the hydroacylation did not proceed completely, the reaction
was terminated after 72 h. c NaOAc (0.2 equiv) was added as an additive.
To obtain mechanistic information, we examined the
reaction using deuterated salicylaldehyde 1-d. The reaction
of 1-d (1.0 equiv) and 2 (6.0 equiv) by RhCl(PPh3)3 (0.2
equiv) afforded products 10a,b in which no deuterium was
detected. Therefore, the reaction was performed using 0.9
equiv of diene 2; in this case, the isolated 10a-d showed the
methyl signal at δ 1.22 (m, 2.4H; ca. 60% deuterium content)
and 10b-d showed methylene signals at δ 1.74-1.79 (m,
hydroacylation of 1 with 1,5-hexadiene 2 (6.0 equiv) in the
presence of RhCl(PPh3)3 (0.2 equiv) proceeded at room
temperature to give the hydroacylated product 10; even the
use of 10 mol % Rh-complex or 1.5 equiv of 2 caused the
1
reaction to proceed in quantitative yield. The H NMR
spectrum of 10 showed the methine signal at δ 3.54 (sestet,
J ) 6.9 Hz) and methylene signals at δ 3.07 (t, J ) 7.3 Hz),
as well as the methyl signal at δ 1.22 (d, J ) 6.9 Hz),
suggesting that the product was a mixture of iso-10a and
normal-10b in a ratio of 4 to 1. The hydroacylation of
3-methyl-1,4-pentadiene 3 afforded the products 11a,b in
80% yield; preferentially the terminal site was acylated in a
ratio of 5 to 3. The hydroacylation of 1,6-heptadiene gave
only a low yield of product (4%).10 The reaction of
2-substituted 1,5-hexadienes 4-6 afforded the products 12-
(4) (a) Larock, R. C.; Oertle, K.; Potter, G. F. J. Am. Chem. Soc. 1980,
102, 190. (b) Bosnich, B. Acc. Chem. Res. 1998, 31, 667. (c) Sato, Y.;
Oonishi, Y.; Mori, M. Angew. Chem., Int. Ed. 2002, 41, 1218. (d) Aloise,
A. D.; Layton, M. E.; Shair, M. D. J. Am. Chem. Soc. 2000, 122, 12610
and references therein.
(5) (a) Jun, C.-H.; Hong, J.-B.; Lee, D.-Y. Synlett 1999, 1. (b) Jun, C.-
H.; Chung, J.-H.; Lee, D.-Y.; Loupy, A.; Chatti, S. Tetrahedron Lett. 2001,
42, 4803. (c) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J. 2002, 8,
2422, and references therein.
(6) (a) Miura, M.; Nomura, M. J. Synth. Org. Chem. Jpn. 2000, 58, 578.
(b) Kokubo, K.; Matsumasa, K.; Nishinaka, Y.; Miura, M.; Nomura, M.
Bull. Chem. Soc. Jpn. 1999, 72, 303.
(7) Willis, M. C.; Sapmaz, S. Chem. Commun. 2001, 2558.
(8) See Supporting Information.
(9) (a) Brown, C. K.; Wilkinson, G. J. Chem. Soc. A 1970, 17, 2753. (b)
Brown, C. K.; Wilkinson, G. Tetrahedron Lett. 1969, 22, 1725.
(10) Distance between the two olefins is too long for the chelation.
Figure 1. Plausible mechanisms for hydroacylation of 1-d.
Org. Lett., Vol. 5, No. 8, 2003
1366

Table 2. Hydroacylation between 2-Hydroxybenzaldehydes 18-32 and 1,5-Hexadiene 2
entry
aldehydea
products: % yield (ratio of a :b)
1
2
3
4
5
6
7
8
2,5-dihydroxybenzaldehyde 18
33: 90 (3:1)
34: quantitative (3:1)
35: 42 (3:1)
36: quantitative (5:1)
37: quantitative (4:1)
38: 73 (2:1)
2-hydroxy-5-methoxybenzaldehyde 19
2-hydroxy-5-methylbenzaldehyde 20
5-bromo-2-hydroxybenzaldehyde 21
5-chloro-2-hydroxybenzaldehyde 22
2-hydroxy-5-nitrobenzaldehyde 23
2-hydroxy-5-trifluoromethoxybenzaldehyde 24
2,3-dihydroxybenzaldehyde 25
39: 73 (3:1)
40: 58 (3:1)
9
2-hydroxy-3-methoxybenzaldehyde 26
2-hydroxy-3-methylbenzaldehyde 27
2,4-dihydroxybenzaldehyde 28
2-hydroxy-4-methoxybenzaldehyde 29
2-hydroxy-1-naphthaldehyde 30
41: quantitative (3.5:1)
42: 71 (4.5:1)
43: 75 (4:1)
44: quantitative (2:1)
45: 56 (2:1)
10
11
12
13
14
15
1-hydroxy-2-naphthaldehyde 31
2-hydroxy-5-methylbenzene-1,3-dicarbaldehyde 32
46: 82 (2:1)
47: 64 (3:1)b
a Benzaldehyde, o-phthalaldehyde, 2-vinylaldehyde, or o-anisaldehyde was also tested, but the hydroacylation did not proceed. The reaction of
3-hydroxybenzaldehyde afforded a hydroacylated product in merely 3% yield. b Bishydroacylated products were also formed in 21% as a regiomeric mixture.
1
1.3H; ca. 70% deuterium content) in the H NMR spectra,
and also MS spectra supported the existence of deuterium
in 10a,b-d.8 These results mean that rapid interconversion
processes exist, and the diene 2 rapidly coordinates to the
Rh metal and dissociates from the Rh metal. On the basis of
these experiments, we present a tentative catalytic cycle as
outlined in Figure 1. Intermediates i-iii, in which both the
diene and salicylaldehyde bind to the Rh-complex by
chelation, play vital roles in the intermolecular hydroacyla-
tion.11
We have achieved Rh-catalyzed intermolecular hydroa-
cylation under very mild reaction conditions based on the
“double-chelation” concept.15 The application of the double
chelation to other metals and reactions is currently under-
way.16
Acknowledgment. Dedicated to Prof. K. Sakai in memory
of the discovery of Rh-catalyzed hydroacylation 30 years
ago. This work was partly supported by a Grant-in-Aid for
Scientific Research (C) from Japan Society for the Promotion
of Science.
Concentration of the reaction and addition of AgClO4,
AgOTf, CsF, Na2CO3, or NaOAc affect the ratio of iso- and
normal-products 10 and also accelerate the rate of hydro-
acylation. In CHCl3, ClCH2CH2Cl, or EtOH as a solvent,
the reaction proceeded smoothly, but the use of MeCN or
MeNO2 was not effective.12,13 Neutral Rh complexes such
as {Rh[P(PhMe)3] }Cl and [Rh(dppf)]Cl and cationic Rh
complexes such as [Rh(PPh3)2]ClO4 and [Rh(dppe)]ClO4
prepared in situ could be also used as a catalyst.8,14
Supporting Information Available: Synthetic scheme
of 1,5-dienes and 1-d, reaction conditions, experimental
procedures, and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
2
OL034343O
(11) As an intermediate, µ2-ligand- or η6-Ph-bi-Rh-complex or hepta-
coordinated Rh may exist in chelations of both salicylaldehyde and diene.
See: Nagashima, H.; Tatebe, K.; Ishibashi, T.; Nakaoka, A.; Sakakibara,
J.; Itoh, K. Organometallics 1995, 14, 2868. See also ref 1b.
(12) Hydroacylation between 1 and 2 using RhCl(PPh3)3 (0.2 equiv),
NaOAc (0.2 equiv), and AgClO4 (0.2 equiv) in the solvent of 5% EtOH in
CH2Cl2 was completed in 15 min, and 10a,b were obtained in 90%.
(13) Additives of bases and alcohols may affect the phenolic hydroxy
group and change the chelation effects, and those of Ag salts may affect
the property of the Rh complex.
(14) Ratio of regioisomers was very sensitive to the reaction conditions.
(15) Double chelation of aldehyde and diene derived from Rh-complex
[Rh(diene)Cl]2 was observed by Jun. See ref 5a and: Jun, C.-H. J.
Organomet. Chem. 1990, 390, 361. Also, for chelations of imine bearing
picoline and allyl alcohol, see: Jun, C.-H.; Han, J.-S.; Kang, J.-B.; Kim, S.
J. Organomet. Chem. 1994, 474, 183.
(16) (a) Chelation-assisted hydroesterificatin by ruthenium: Ko, S.; Na,
Y.; Chang, S. J. Am. Chem. Soc. 2002, 124, 750. (b) For chelation-assisted
hydrosilylation by RhCl(PPh3)3, see ref 11.
Org. Lett., Vol. 5, No. 8, 2003
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