Double-Chelation-Assisted Rh-Catalyzed Intermolecular Hydroacylation between Salicylaldehydes and 1,4-Penta- or 1,5-Hexadienes

Article abstract of DOI:10.1021/jo035395u

Intermolecular hydroacylation between salicylaldehydes 1, 26-40 and 1,4-penta- or 1,5-hexadienes 4-13 by Rh-catalyst proceeded under mild reaction conditions to give a mixture of iso- and normal-hydroacylated products 14-25, 41-55, and 57-60. In the hydroacylation reaction, chelation of both salicylaldehyde and diene to the Rh-complex plays a crucial role. The ratio of iso- and normal-hydroacylated products could be regulated by the addition of salicylic acid or amines. The effects of various Rh-complexes, solvents, and additives were examined, and the plausible mechanisms of the catalytic cycle were proposed on the basis of the deuterium-labeling salicylaldehyde experiments.

Full text of DOI:10.1021/jo035395u

Dou ble-Ch ela tion -Assisted Rh -Ca ta lyzed In ter m olecu la r
Hyd r oa cyla tion betw een Sa licyla ld eh yd es a n d 1,4-P en ta - or
1,5-Hexa d ien es
Masanori Imai,‡ Masakazu Tanaka,*,† Keitaro Tanaka,† Yoichiro Yamamoto,†
Naoko Imai-Ogata,† Masato Shimowatari,† Shinji Nagumo,‡ Norio Kawahara,‡ and
Hiroshi Suemune*,†
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, J apan,
and Hokkaido College of Pharmacy, Hokkaido 047-0264, J apan
mtanaka@phar.kyushu-u.ac.jp; suemune@phar.kyushu-u.ac.jp
Received September 24, 2003
Intermolecular hydroacylation between salicylaldehydes 1, 26-40 and 1,4-penta- or 1,5-hexadienes
4-13 by Rh-catalyst proceeded under mild reaction conditions to give a mixture of iso- and normal-
hydroacylated products 14-25, 41-55, and 57-60. In the hydroacylation reaction, chelation of
both salicylaldehyde and diene to the Rh-complex plays a crucial role. The ratio of iso- and normal-
hydroacylated products could be regulated by the addition of salicylic acid or amines. The effects
of various Rh-complexes, solvents, and additives were examined, and the plausible mechanisms of
the catalytic cycle were proposed on the basis of the deuterium-labeling salicylaldehyde experiments.
SCHEME 1
In tr od u ction
Carbon-carbon bond-forming reactions via C-H bond
activation have extensively been the focus of study in the
fields of organic and organometallic chemistry.1 Rhodium
complexes have widely been used as catalysts, as in
hydrogenation, decarbonylation, and isomerization, and
also for C-C bond formation.2 Among them, Rh-catalyzed
intramolecular hydroacylation of 4-pentenals, i.e., cy-
clization of 4-pentenals into cyclopentanones via C-H
activation, was discovered by Sakai in 1972, albeit at that
time the reaction required a stoichiometric amount of
RhCl(PPh3)3 (Wilkinson complex) (Scheme 1, eq 1).3 After
the discovery, the Rh-promoted intramolecular hydro-
acylation was developed into catalytic reactions and also
asymmetric reactions.3,4 However, the competitive de-
carbonylation reaction prevented us and the other groups
from developing the hydroacylation into an intermolecu-
lar version (eq 2). Exclusively Rh-catalyzed hydroformyla-
tion2d and the exceptional intermolecular hydroacylation
of ethylene were reported by several groups.5 Recently,
the J un group reported that novel Rh-catalyzed inter-
molecular hydroacylation reactions occurred in the case
where 2-amino-3-picoline was added as a cocatalyst.6,7
Also, the Miura group reported that Rh-catalyzed inter-
molecular hydroacylation of alkynes or allenes occurred
in the case where salicylaldehyde was used as an alde-
hyde and an Rh-complex having a phosphinoferrocene
ligand was used as the Rh-complex, albeit the reaction
between salicylaldehyde and olefins could not proceed.8
In both Rh-catalyzed hydroacylations, the chelation of
* To whom correspondence should be addressed. Tel: + 81-92-642-
6604. Fax: + 81-92-642-6545.
† Kyushu University.
‡ Hokkaido College of Pharmacy.
(1) (a) Labinger, J . A.; Bercaw, J . E. Nature 2002, 417, 507. (b)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (c)
Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826. (d) Dyker, G.
Angew. Chem., Int. Ed. 1999, 38, 1699.
(2) (a) Rossen, K. Angew. Chem., Int. Ed. 2001, 40, 4611. (b)
O’Connor, J . M.; Ma, J . J . Org. Chem. 1992, 57, 5075. (c) Morrill, T.
C.; D’Souza, C. A. Organometallics 2003, 22, 1626. (d) Breit, B.; Seiche,
W. Synthesis 2001, 1. (e) Kitagaki, S.; Hashimoto, S. J . Synth. Org.
Chem. J pn. 2001, 59, 1157. (f) Ojima, I.; Moralee, A. C.; Vassar, V. C.
Top. Catal. 2002, 19, 89.
(3) (a) Sakai, K.; Ide, J .; Oda, O.; Nakamura, N. Tetrahedron Lett.
1972, 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. (e) Tanaka, M.; Sakai, K.; Suemune, H. Cur. Org. Chem.
2003, 7, 353 and references therein.
(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. (e) Tanaka, K.; Fu, G. C. J . Am. Chem. Soc. 2003, 125,
8078 and references therein.
(5) (a) Lochow, C. F.; Miller, R. G. J . Am. Chem. Soc. 1976, 98, 1281.
(b) Vora, K. P. Synth. Commun. 1983, 13, 99.
(6) (a) J un, C.-H.; Hong, J .-B.; Lee, D.-Y. Synlett 1999, 1. (b) J un,
C.-H.; Chung, J .-H.; Lee, D.-Y.; Loupy, A.; Chatti, S. Tetrahedron Lett.
2001, 42, 4803. (c) J un, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J .
2002, 8, 2423 and references therein.
(7) Willis, M. C.; Sapmaz, S. Chem. Commun. 2001, 2558.
10.1021/jo035395u CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/16/2004
1144
J . Org. Chem. 2004, 69, 1144-1150

Hydroacylation of Salicylaldehydes and Dienes
salicylaldehyde or an imine bearing 2-amino-3-picoline
to the Rh-complex suppresses the decarbonylation side
reaction. However, both reactions require rigorous condi-
tions, and the hydroacylation does not occur at room
temperature. Here we describe for the first time that
“double-chelation” of both aldehyde and olefin to the Rh-
complex promotes intermolecular hydroacylation, and the
reactions between salicylaldehyde derivatives and 1,4-
penta- or 1,5-hexadienes proceed under remarkably mild
reaction conditions to give a mixture of iso- and normal-
hydroacylated products in good yields.9
was acylated in a ratio of 5:3 and that of 1,4-pentadien-
3-ol 6 exclusively gave the normal-product 18b in 93%
yield (entry 8). The hydroacylation of 1,4-pentadienes
proceeded faster than that of 1,5-hexadiene, but 1,4-
pentadiene, having a terminal substituent at the olefin
(1,4-hexadiene), was less reactive (9% yield). The hy-
droacylation of 1,6-heptadiene gave only a low yield of
product (4%), suggesting that the distance between the
two olefins is too long for the chelation to the Rh-complex.
The reaction of 2-substituted 1,5-hexadienes 7-10 af-
forded iso-products 19a -22a , which were reacted at the
less-substituted olefin, in preference to normal-19b-22b
(entries 9-12). The internal exo-olefin in the triene 10
did not react at all, but the terminal olefin site reacted
to give 22a ,b in 74% yield. The hydroacylation of 2,5-
dimethylhexa-1,5-diene did not proceed. In the case of
1,5-heptadiene 11, which is a 1,5-hexadiene bearing a
methyl group at the terminus, the reaction gave hydroa-
cylated products 23a -c in 60% total yields but no
acylated product at the C6-position of 11 (entry 13). In
the case of triene 12, the internal disubstituted olefin was
more reactive than the terminal monosubstituted olefin,
and the hydroacylation afforded 24a -c in 35% total
yields (entry 14). Addition of a base, such as NaOAc and
K2CO3, may deprotonate the phenolic hydroxyl group and
accelerate the reaction, and thus the yield of products
24 was increased to 69% (entry 15). In the case of
4-vinylcyclohexene 13, which is a 1,5-hexadiene with one
olefin existing in the ring, the hydroacylation gave a
mixture of 25a -c in 17% yield (entry 16). The low yield
may be attributed to the hindrance of the vinyl function
and the lesser flexibility of the diene structure. 1,5-
Cyclooctadiene, 1,3-hexadiene, and 1,3-cyclohexadiene
were not suitable for the Rh-catalyzed hydroacylation.
Thus, these results suggest that the 1,4-penta- or 1,5-
hexadiene structure, which chelates to the Rh-complex,
is crucial for the intermolecular hydroacylation.11
Effect of Su bstitu en t in Sa licyla ld eh yd e on th e
Rh -Ca ta lyzed Hyd r oa cyla tion . Next, we examined the
effect of aldehydes by treatment with RhCl(PPh3)3 (0.2
equiv) and 4 (6.0 equiv) at room temperature. The results
are summarized in Table 2. The hydroacylation of ben-
zaldehydes bearing no 2-hydroxyl function, such as
benzaldehyde, o-phthalaldehyde, 2-vinylbenzaldehyde,
o-anisaldehyde, 3-hydroxybenzaldehyde, or 4-hydroxy-
benzaldehyde, did not proceed or proceeded in very low
yields, but that of various 2-hydroxybenzaldehydes pro-
ceeded to give the products 41-55 as a mixture of iso
(a ) and normal (b), with preferentially iso-compound (a )
as a major product. The Rh-catalyzed hydroacylation was
tolerant of various functional groups such as hydroxy,
methoxy, halogeno, and the nitro function in the aromatic
ring. However, another hydroxyl group at the C3-, C4-,
or C5-position of 2-hydroxybenzaldehyde was practically
ineffective; this may be attributed to the fact that the
hydroxyl group may coordinate to the Rh-complex or the
poor solubility of some dihydroxybenzaldehydes in CH2-
Cl2 (entries 1, 8, and 11). Alkyl substituents and naph-
thalene skeletons were also somewhat disadvantageous,
but the steric and electronic effects of the substituents
are not clear. In the case of 1,3-dicarbaldehyde 40,
Resu lts a n d Discu ssion
Rh -Ca ta lyzed Hyd r oa cyla tion betw een Sa licyla -
ld eh yd e a n d Olefin s. Miura’s Rh-catalyzed intermo-
lecular hydroacylation between salicylaldehyde 1 and
some alkynes stimulated us to scrutinize the hydroacy-
lation reaction between 1 and olefins by using RhCl-
(PPh3)3. Fortunately, the hydroacylation between salicy-
laldehyde 1 and 1-hexene 2 in the presence of RhCl(PPh3)3
(0.2 equiv) yielded a hydroacylated product 14b, even
though the reaction required long reaction time (72 h)
and the yield of 14b was very poor (4%, entry 1). The
hydroacylation reaction did not proceed at all when
benzaldehyde was used instead of 1. Therefore, the
chelation of the phenolic hydroxyl function plays a vital
role in the Rh-catalyzed intermolecular hydroacylation.
The isolation of 14b prompted us to study the further
hydroacylation of salicylaldehyde with various olefins.
Unfortunately, the hydroacylation between salicylalde-
hyde and olefins such as 2-octene, styrene, and cyclohex-
ene did not proceed at all, but that between 1 and allyl
alcohol 3 proceeded to produce a mixture of 15a and 15b
in the ratio 1:9 in 14% yield (entry 2). Refluxing in
dichloroethane was detrimental to the hydroacylation
because isomerization of olefin in allyl alcohol occurred.
Next, we examined 1,4-penta- and 1,5-hexadienes as
olefins because in the case of Rh-catalyzed hydroformy-
lation some dienes were rapidly reacted.10 The results
are summarized in Table 1.
The hydroacylation of 1 with 1,5-hexadiene 4 (6.0
equiv) by RhCl(PPh3)3 (0.2 equiv) proceeded at room
temperature to afford the hydroacylated product 16.
Even the use of 10 mol% Rh-complex or 1.5 equiv of 4
promoted the reaction to proceed in excellent yields
1
(entries 3-6). The H NMR spectrum of 16 showed the
methine signal at δ 3.54 (sextet, J ) 6.9 Hz) and
methylene signal 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-16a and normal-16b in
a 4:1 ratio. Increasing the equivalent of the Rh-complex
promotes the hydroacylation and seems to improve the
ratio of iso- and normal-products. The hydroacylation of
3-methyl-1,4-pentadiene 5 afforded the products 17a ,b
in 91% yield (entry 7); preferentially the terminal site
(8) (a) Miura, M.; Nomura, M. J . Synth. Org. Chem. J pn. 2000, 58,
578. (b) Kokubo, K.; Matsumasa, K.; Nishinaka, Y.; Miura, M.; Nomura,
M. Bull. Chem. Soc. J pn. 1999, 72, 303.
(9) A part of the work has been reported as a preliminary com-
munication. Tanaka, M.; Imai, M.; Yamamoto, Y.; Tanaka, K.; Shi-
mowatari, M.; Nagumo, S.; Kawahara, N.; Suemune, H. Org. Lett.
2003, 5, 1365.
(11) Carbonylation of 1,5-hexadiene using Pd-catalyst. Shaughnessy,
K. H.; Waymouth, R. M. Organometallics 1997, 16, 1001 and references
therein.
(10) (a) Brown, C. K.; Wilkinson, G. J . Chem. Soc. A 1970, 17, 2753.
(b) Brown, C. K.; Wilkinson, G. Tetrahedron Lett. 1969, 1725.
J . Org. Chem, Vol. 69, No. 4, 2004 1145

Imai et al.
TABLE 1.
a
Cyclohexene, 2-octene, styrene, 1,5-cyclooctadiene, 5-hexen-2-one, 1,3-hexadiene, 1,3-cyclohexadiene, and 2,5-dimethylhexa-1,5-diene
b
were also examined, but the reaction did not proceed at all. The hydroacylation proceeded even using 3.0 equiv of 1,5-hexadiene (quant),
and 1.5 equiv of 1,5-hexadiene (95%). c NaOAc (0.2 equiv) was used as an additive.
monohydroacylated products 55a and 55b were obtained
in 64% yield, accompanied by bishydroacylated products
in 21% yield (entry 15).
In this process, at first the Rh-complex and 1,5-hexadiene
were worked as an oxidizer, and the 2-hydroxybenzyl
alcohol 56 was converted into the salicylaldehyde 1, and
then the produced 1 and 1,5-hexadiene 4 reacted to give
16a ,b.
Instead of salicylaldehyde, 2-hydroxybenzyl alcohol 56
could be used for the hydroacylation.12 That is to say, the
reaction of 2-hydroxybenzyl alcohol 56 and 1,5-hexadiene
4 (6.0 equiv) by RhCl(PPh3)3 at room temperature af-
forded the hydroacylated products 16a ,b in 45% yields.
The hydroacylation of 1,4-pentadienes with 5-halogeno-
2-hydroxybenzaldehydes was also examined because the
hydroacylation of 1,5-hexadiene 4 with 5-halogeno-2-
hydroxybenzaldehydes reacted faster than with salicy-
laldehyde. However, the hydroacylation of 1,4-pentadiene
5 or 6 with 5-halogeno-2-hydroxybenzaldehyde 29 or 30
(12) J un, C-. H.; Huh, C-. W.; Na, S-. J . Angew. Chem., Int. Ed. 1998,
37, 145 and references therein.
1146 J . Org. Chem., Vol. 69, No. 4, 2004

Hydroacylation of Salicylaldehydes and Dienes
TABLE 2.
a
Benzaldehyde, o-phthaladehyde, 2-vinylbenzaldehyde, and o-anisaldehyde were also examined, but the reaction did not proceed.
b
Reaction of 3-hydroxybenzaldehyde afforded a hydroacylated product in merely 3% yield. Bishydroacylated products were formed in
21% yield as a regioisomeric mixture. c The use of 0.1 equiv of Rh-complex afforded almost the same yield of products.
SCHEME 2
complexes on the hydroacylation. The results are sum-
marized in Tables 4 and 5. In CH2Cl2, CHCl3, EtOH, and
ClCH2CH2Cl as solvent or even without a solvent (neat),
the reaction proceeded smoothly, but the use of CH3CN,
DMF, toluene, THF, or CH3NO2 was not effective.
Especially, the solvent of 5% EtOH in CH2Cl2 was
superior to that of CH2Cl2 only. Concentration of the
reaction affects the ratio of iso- and normal-products 16
and accelerates the rate of hydroacylation.
reacted slower than with salicylaldehyde, and the yield
of product decreased, as shown in Table 3. The hydro-
acylation of 5 preferentially gave the normal-products (b)
(entries 1 and 2), and that of 1,4-pentadien-3-ol 6
exclusively afforded the normal-products (b) but no iso-
products (a ) (entries 3 and 4). The hydroxyl group in 6
may affect the reaction to give the normal-product (b)
exclusively, but the reason is not clear.13
Addition of a base such as Na2CO3, NaOAc, and CsF
accelerates the rate of hydroacylation, presumably as a
result of the deprotonation of phenolic hydrogen (entries
1-3), whereas the addition of AgOTf or AgClO4 also
accelerates the reaction rate because the Rh-complex
probably become a cationic species (entries 4 and 5).
Above all, the hydroacylation between 1 and 4 by 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 at room temperature and in 30 min
Effect of Solven ts, Ad d itives, a n d Rh -Com p lexes.
We examined the effect of solvents, additives, and Rh-
(13) J un, C-. H.; Han, J -. S.; Kang, J -. B.; Kim, S-. I. J . Organomet.
Chem. 1994, 474, 183.
J . Org. Chem, Vol. 69, No. 4, 2004 1147

Imai et al.
TABLE 3.
TABLE 4. Effect of Solven t on Rh -ca ta lyzed In ter m olecu la r Hyd r oa cyla tion .
entry
RhCl(PPh3)3 (equiv)
1,5-hexadiene (equiv)
solvent
reaction time (h)
products 16 yield % (ratio a :b)
1
2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
6
6
6
6
6
6
6
6
6
6
2
CH2Cl2
24
24
72
72
72
72
72
72
72
72
18
quant (4:1)
90 (5:1)
39 (3:1)
16 (7:1)
12 (7:1)
8 (7:1)
neat
3
CH3CN
DMF
toluene
THF
CH3NO2
CHCl3
EtOH
4
5
6
7
6 (6:1)
8
77 (5:1)
77 (1:1)
50 (4:1)
quant (2:1)
9
10
ClCH2CH2Cl
CH2Cl2
b
11a
a
b
Na2CO3 (0.10 equiv) was used as an additive. 5% EtOH in CH2Cl2 was used as a solvent.
TABLE 5. Effect of Rh -Com p lex a n d Ad d itive on In ter m olecu la r Hyd r oa cyla tion
entry
Rh-complexa (0.2 equiv)
additive
reaction time (h)
products 16 yield % (ratio a :b)
1
2
RhCl(PPh3)3
Na2CO3 (0.50 equiv)
NaOAc (0.20 equiv)b
CsF (0.20 equiv)
AgOTf (0.20 equiv)
AgClO4 (0.05 equiv)
AgClO4 + NaOAcb,c
salicylic acid (0.20 equiv)
salicylic acid (1.0 equiv)
13
4
quant (3:1)
quant (5:1)
quant (6:1)
quant (4:1)
90 (2:3)
RhCl(PPh3)3
3
RhCl(PPh3)3
5
4
RhCl(PPh3)3
4
2
5
RhCl(PPh3)3
6
RhCl(PPh3)3
15 min
72
72
72
72
72
72
72
72
72
8
72
72
72
72
72
72
93 (1:1)
7
RhCl(PPh3)3
quant (10:1)
74 (20:1)
25 (3:1)
8
RhCl(PPh3)3
9
[RhCl(C8H14)]2
10d
11
12
13
14
15
16
17
18
19
20
21e
22
[RhCl(C8H14)]2 + PPh3 × 2
[RhCl(C8H14)]2 + dppef
[RhCl(C8H14)]2 + dppe
[RhCl(C8H14)]2 + dppb
[RhCl(C8H14)]2 + dppf
[RhCl(C8H14)]2 + (o-MePh)3P × 2
[RhCl(C8H14)]2 + (o-MePh)3P × 2
[RhCl(C8H14)]2 + (i-PrO)3P × 2
[RhCl(C8H14)]2 + (PhO)3P × 2
[RhCl(C8H14)]2 + Et3N × 2
[RhCl(C8H14)]2 + (i-Pr)2NH × 2
[Rh(PPh3)2]ClO4
60 (4:1)
9 (1:4)
AgClO4 + NaOAcb,c
AgClO4 + NaOAcb,c
48 (2:1)
20 (3:2)
44 (7:1)
quant (12:1)
quant (12:1)
22 (1:1)
20 (5:3)
46 (1:7)
63 (1:8)
57 (4:1)
[Rh(dppe)]ClO4
30 (4:3)
a
The reaction was carried out using salicylaldehyde (1.0 equiv) and 1,5-hexadiene (6.0 equiv) at room temperature in CH2Cl2 under
an Ar atmosphere. 5% EtOH in CH2Cl2 was used as a solvent. c AgClO4 (0.20 equiv) and NaOAc (0.20 equiv) were added. In entries
10-18, Rh(phosphine)2Cl was prepared in situ from [RhCl(cyclooctene)]2 and ligands. e In entries 21 and 22, Rh-complex was prepared
in situ from [Rh(norbornadiene)(ligands)n]ClO4 by hydrogenation. f dppe ) 1,2-bis(diphenylphosphino)ethane; dppb ) 1,2-bis(diphe-
nylphosphino)butane; dppf ) 1,1′-bis(diphenylphosphino)ferrocene; C8H14 ) cyclooctene.
b
d
at 0 °C, and the products 16a ,b were obtained in a 1:1
ratio in 93% yield (entry 6). Interestingly, the addition
of salicylic acid changed the ratio of iso- and normal-
products 16 (entries 7 and 8). When 1.0 equiv of salicylic
acid was added, the iso-product 16a was preferentially
obtained in a 20:1 ratio. As the Rh-complex, neutral Rh-
1148 J . Org. Chem., Vol. 69, No. 4, 2004

Hydroacylation of Salicylaldehydes and Dienes
SCHEME 3
SCHEME 4. P la u sible Ca ta lytic Cycle of Hyd r oa cyla tion a
a
M ) H, Na, or K; n ) 0 or 1.
complexes such as Rh(PPh3)2Cl, Rh(dppb)Cl, and Rh-
(dppf)Cl, prepared in situ from [RhCl(cyclooctene)]2 and
phosphine ligands, and cationic Rh-complexes such as
[Rh(PPh3)2]ClO4 and [Rh(dppe)]ClO4, prepared in situ
from [Rh(norbornadiene)(ligands)n]ClO4 by hydrogena-
tion,3c catalyzed the hydroacylation to give a mixture of
products 16a ,b (entries 9-14, 21, and 22). The use of
neutral Rh[(o-MePh)3P]2Cl dominantly afforded the iso-
hydroacylated product 16a in a 12:1 ratio (entries 15 and
16). Replacement of phosphine ligands with phosphite
ligands could also work, but the catalytic activity seemed
to be low (entries 17 and 18). It is noteworthy that the
use of [RhCl(cyclooctene)]2 and amines as a catalyst
changed the ratio of hydroacylated products and afforded
the normal-hydroacylated 16b preferentially as a major
product (entries 19 and 20).
spectrum also supported the existence of deuterium in
16a ,b-d (Scheme 3).
These results may be attributed to the fact that rapid
interconversion processes exist, and the 1,5-hexadiene 4
and salicylaldehyde 1-d rapidly coordinate to the Rh-
complex and dissociate from the Rh-complex. As a result,
nondeuterated salicylaldehyde 1 is yielded in the cycle,
and it reacts with 4 faster than the deuterated 1-d reacts.
The deuterium might be transferred into the 1,5-hexa-
diene, and also may partly be exchanged for the phenolic
hydrogen atom.14 On the basis of these experiments, we
present a plausible catalytic cycle, which can explain the
accelerated hydroacylation, as outlined in Scheme 4.
Intermediates i-iii, in which both the diene and salicy-
laldehyde bind to the Rh-complex by “double-chelation”,
play vital roles in the intermolecular hydroacylation. The
addition of a base, such as NaOAc, Na2CO3, and CsF, may
deprotonate the phenolic hydroxyl function and change
the chelation effects, and that of an Ag salt such as AgOTf
and AgClO4 may affect the property of the Rh-complex.
The proposed catalytic cycle is a plausible explanation,
but all chelations of salicylaldehyde, 1,5-hexadiene, and
bisphosphine ligand may afford a hepta-coordinated Rh-
complex.15 Thus, the real intermediates may be µ2-ligand-
Rh-complexes or η6-Ph-bi-Rh-complexes,16 and the “double-
P la u sib le Mech a n ism s of R h -Ca t a lyzed H yd r o-
a cyla tion . We examined the hydroacylation using deu-
terated salicylaldehyde 1-d. At first, the reaction between
1-d (1.0 equiv) and 1,5-hexadiene 4 (6.0 equiv) by RhCl-
(PPh3)3 (0.2 equiv) was performed, but no deuterium was
1
detected in the isolated products 16a ,b by the H NMR
and MS spectra. Thus, the reaction was performed using
0.9 equiv of 1,5-hexadiene 4; in this case, the deuterium
was introduced into the products, i.e., the methyl signal
at δ 1.22 (m, 2.4H; ca. 60% deuterium content) in 16a -d
and methylene signals at δ 1.74-1.79 (m, 1.3H; ca. 70%
deuterium content) in 16b-d by the 1H NMR spectra, and
the molecular ion peak m/z 205 (M + H)+ in the MS
(14) A solution of 1-d (100% deuterium content) and RhCl(PPh3)3
in CDCl3 was stirred at room temperature for 4 h, and the 1H NMR
spectrum of the solution showed an aldehyde (-CHO) proton peak at
δ 9.90 (ca. 0.3H), meaning ca. 70% deuterium content.
(15) Nagashima, H.; Tatebe, K.; Ishibashi, T.; Nakaoka, A.; Sakak-
ibara, J .; Itoh, K. Organometallics 1995, 14, 2868.
J . Org. Chem, Vol. 69, No. 4, 2004 1149

Imai et al.
column chromatography on silica gel. The fraction eluted with
chelation” in those dimeric intermediates may affect the
Rh-catalyzed hydroacylation.17
15% EtOAc in hexane afforded 18b (192 mg, 93%) as a
colorless oil. IR (neat) 3396 (br), 2929, 1639 cm-1 1H NMR
;
(CDCl3) δ 12.28 (s, 1H), 7.80 (br d, J ) 9 Hz, 1H), 7.46 (br t,
J ) 9 Hz, 1H), 6.97 (br d, J ) 9 Hz, 1H), 6.89 (br t, J ) 9 Hz,
1H), 5.95 (m, 1H), 5.28 (d, J ) 17.2 Hz, 1H), 5.15 (d, J ) 10.5
Hz, 1H), 4.24 (m, 1H), 3.14 (t, J ) 7.3 Hz, 2H), 1.90-2.11 (m,
3H); FAB(+)HRMS calcd for C12H15O3 (M+ + H) 207.1021,
found 207.0978.
Con clu sion
We have achieved the Rh-catalyzed intermolecular
hydroacylation between salicylaldehydes and 1,4-penta-
or 1,5-hexadienes. The reaction proceeded under very
mild conditions to give a mixture of iso- and normal-
hydroacylated products. By the selection of additives and
Rh-complexes, we could regioselectively prepare iso- or
normal-hydroacylated products. The Rh-catalyzed inter-
molecular hydroacylation might proceed via double-
chelated intermediates, and the “double chelation” of
aldehyde and diene to the Rh-complex might accelerate
the reaction. The application of the “double chelation”
concept to other reactions is currently underway.
R h -Ca t a lyzed In t er m olecu la r H yd r oa cyla t ion b e-
tween 5-Br om o-2-h ydr oxyben zaldeh yde (29) an d 3-Meth -
yl-1,4-p en t a d ien e (5). The RhCl(PPh3)3-catalyzed hydro-
acylation between 5-bromo-2-hydroxybenzaldehyde 29 and
3-methyl-1,4-pentadiene 5 at room temperature afforded 57a ,b
(75%) as a mixture of isomers in the ratio of 1 (iso) to 2
(normal). A colorless oil: IR (neat) 3069, 2967, 1644, 1609
cm-1; 1H NMR (CDCl3) δ 12.5 (s, 0.33H), 12.3 (s, 0.67H), 7.84
(m, 1H), 7.51 (br d, J ) 9 Hz, 1H), 6.88 (br d, J ) 9 Hz, 1H),
5.70 (m, 1H), 4.94-5.05 (m, 2H), 3.39 (quintet, J ) 7.0 Hz,
0.33H), 2.94 (br t, J ) 7.0 Hz, 1.34H), 2.65 (sestet, J ) 7.0 Hz,
0.33H), 2.22 (septet, J ) 7.0 Hz, 0.67H), 1.60-1.86 (m, 1.34H),
1.18 (d, J ) 7.0 Hz, 0.99H), 1.07 (d, J ) 7.0 Hz, 2.01H), 1.04
(d, J ) 7.0 Hz, 0.99H); FAB(+)HRMS calcd for C13H16Br1O2
(M+ + H) 283.0334, found 283.0316.
Gen er a l P r oced u r e for th e Hyd r oa cyla tion betw een
Sa licyla ld eh yd e a n d 1,5-Hexa d ien e by Rh -Com p lexes. A
mixture of [RhCl(cyclooctene)]2 (49 mg, 0.10 mmol) and bis-
phosphine (0.20 mmol) in CH2Cl2 (3 mL) was stirred at room
temperature for 1 h. Then, a solution of salicylaldehyde 1 (122
mg, 1.0 mmol) and 1,5-hexadiene 4 (493 mg, 6.0 mmol) in CH2-
Cl2 (1 mL) was added dropwise to the stirred solution. After
being stirred at room temperature for 1-72 h, the solution
was concentrated in vacuo to leave the residue, which was
dissolved in ether, and the precipitated Rh-complex was
filtered off. Removal of the solvent afforded the residue, which
was purified by column chromatography on silica gel to give
the hydroacylated products.
Exp er im en ta l Section
Gen er a l P r oced u r e for Rh Cl(P P h 3)3-Ca ta lyzed Hy-
d r oa cyla tion betw een Sa licyla ld eh yd es a n d Dien es. A
solution of 2-hydroxybenzaldehyde (1.00 mmol), diene (6.00
mmol), and RhCl(PPh3)3 (184 mg, 0.20 mmol) in CH2Cl2 (2.5
mL) was stirred at room temperature under an Ar atmosphere.
After being stirred for 1-72 h, the solution was evaporated
and diluted with ether, and the precipitated Rh-complex was
filtered off. The filtrate was concentrated in vacuo, and the
residue was purified by column chromatography on silica gel
(EtOAc in hexane) to give the hydroacylated products.
4-Hyd r oxy-1-(2-h yd r oxyp h en yl)h ex-5-en -1-on e (18b). A
solution of salicylaldehyde 1 (122 mg, 1.00 mmol), 1,4-
pentadien-3-ol 6 (504 mg, 6.00 mmol), and RhCl(PPh3)3 (184
mg, 0.20 mmol) in CH2Cl2 (2.5 mL) was stirred at room
temperature under an Ar atmosphere. After being stirred for
1 h, the solution was evaporated, and the residue was diluted
with Et2O. The precipitate was filtered off, and the filtrate was
evaporated to give an oily residue, which was purified by
Ack n ow led gm en t. This work was partly supported
by a Grant-in-Aid for Scientific Research (C) from J apan
Society for the Promotion of Science.
(16) (a) Colebrooke, S. A.; Duckett, S. B.; Lohman, J . A. B. Chem.
Commun. 2000, 685. (b) Gridnev, I. D.; Higashi, N.; Asakura, K.;
Imamoto, T. J . Am. Chem. Soc. 2000, 122, 7183. (c) Aubry, D. A.;
Bridges, N. N.; Ezell, K.; Stanley, G. G. J . Am. Chem. Soc. 2003, 125,
11180.
(17) Double chelation of aldehyde and diene derived from Rh-
complex [Rh(diene)Cl]2 was observed by J un; see: J un, C. H. J .
Organomet. Chem. 1990, 390, 361. Also, see refs 6a and 13.
Su ppor tin g In for m ation Available: Preparation of dienes
8-10 and 1-d, experimental procedure for 15, 25 and 58-60,
1
and copies of the H NMR spectra of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O035395U
1150 J . Org. Chem., Vol. 69, No. 4, 2004