Rh-catalyzed reductive coupling reaction of aldehydes with conjugated dienes promoted by triethylborane

Article abstract of DOI:10.1021/ol901527b

Rh(I) catalyzes the reductive coupling reaction of a wide variety of aldehydes with conjugated dienes in the presence of a stoichiometric amount of triethylborane to provide homoallyl alcohols in a single operation.

Full text of DOI:10.1021/ol901527b

ORGANIC
LETTERS
2009
Vol. 11, No. 17
3794-3797
Rh-Catalyzed Reductive Coupling
Reaction of Aldehydes with Conjugated
Dienes Promoted by Triethylborane
Masanari Kimura,*,† Daisuke Nojiri,† Masahiro Fukushima,† Shuichi Oi,‡
Yusuke Sonoda,‡ and Yoshio Inoue‡
Department of Applied Chemistry, Faculty of Engineering, Nagasaki UniVersity, 1-14
Bunkyo-machi, Nagasaki 852-8521, Japan, and Department of Biomolecular Engineering,
Graduate School of Engineering, Tohoku UniVersity, Sendai 980-8579, Japan
masanari@nagasaki-u.ac.jp
Received February 16, 2009
ABSTRACT
Rh(I) catalyzes the reductive coupling reaction of a wide variety of aldehydes with conjugated dienes in the presence of a stoichiometric
amount of triethylborane to provide homoallyl alcohols in a single operation.
Reductive coupling reactions are among the most efficient
strategies for C-C bond formation in modern organic and
Scheme 1
.
Transition-Catalyzed Reductive Coupling Reaction of
Aldehyde and Diene
organometallic chemistry.1 Conjugated dienes are significant
building blocks for the manufacturing of polymers and are
utilized as constituents of physiologically active molecules,
such as terpenoids. In 1998, we first developed the Ni-
catalyzed homoallylation of aldehydes with a wide variety
of conjugated dienes via reductive coupling processes
promoted by triethylborane as a reducing agent to provide
bishomoallyl alcohols (Scheme 1).2 In this case, isoprene
reacts with aldehydes at the C1 position to afford 1,3-anti-
3-methyl-4-penten-1-ol in excellent yield with high regio-
and stereoselectivities in an anti-Markovnikov addition
manner.
Recently, it has been found that Rh catalysts allow
hydrogen to serve as a reducing agent for C-C bond
formation with partitioning of homolytic and heterolytic
hydrogen active species.3 Rh-catalyzed reductive condensa-
tions of conjugated dienes with aldehydes under hydrogen
atmosphere were developed by M. J. Krische et al.4 However,
in this case, the scope of the transformation was limited to
the reaction of 1,3-cyclohexadiene with activated aldehydes
such as aralkyl glyoxals.
† Nagasaki University.
‡ Tohoku University.
(1) (a) Metal Catalyzed Reductive C-C Bond Formation. Topics in
Current Chemistry; Krische, M. J., Ed.; Springer-Verlag: Berlin, Heidelberg,
2007; Vol. 279. (b) Modern Organonickel Chemistry; Tamaru, Y., Ed.;
Wiley-VCH: Weinheim, 2005.
Herein, we would like to report that Rh(I) catalyst in
combination with Et3B nicely promotes the reductive cou-
(2) (a) Kimura, M.; Ezoe, A.; Mori, M.; Iwata, K.; Tamaru, Y. J. Am.
Chem. Soc. 2006, 128, 8559–8568. (b) Tamaru, Y.; Kimura, M. Org. Synth.
2006, 83, 88–96. (c) Kimura, M.; Ezoe, A.; Tanaka, S.; Tamaru, Y. Angew.
Chem., Int. Ed. 2001, 40, 3600–3602. (d) Shibata, K.; Kimura, M.; Shimizu,
M.; Tamaru, Y. Org. Lett. 2001, 3, 2181–2183. (e) Kimura, M.; Fujimatsu,
H.; Ezoe, A.; Shibata, K.; Shimizu, S; Matsumoto, S.; Tamaru, Y. Angew.
Chem., Int. Ed. 1999, 38, 397–400. (f) Kimura, M.; Ezoe, A.; Shibata, K.;
Tamaru, Y. J. Am. Chem. Soc. 1998, 120, 4033–4034.
(3) Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.;
Wiley-VCH: Weinheim, 2005.
(4) (a) Jang, H.- Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653–
661. (b) Jang, H.- Y.; Huddleston, R. R.; Krische, M. J. Angew. Chem.,
Int. Ed. 2003, 42, 4074–4077.
10.1021/ol901527b CCC: $40.75
Published on Web 08/07/2009
 2009 American Chemical Society

pling reaction of cyclic and acyclic conjugated dienes with
a wide variety of aldehydes to provide homoallyl alcohols
according to Markovnikov’s fashion (Scheme 1). It is
noteworthy that the regioselectivity of the reductive coupling
reaction of conjugated dienes and aldehydes by the Rh/Et3B
system is apparently in contrast to that of the Ni/Et3B system;
the former is allylation and the latter is homoallylation.
Although many methods for the synthesis of homoallyl
alcohols promoted by transition metal catalysts have been
well developed so far,5 the direct allylation of carbonyls with
1,3-dienes in a single operation without isolation of the
allylmetal species is extremely rare.
The reaction was conducted by exposing benzaldehyde and
a conjugated diene to a mixture of Rh catalyst and Et3B at
50 °C under nitrogen atmosphere (eq 1). Table 1 shows a
summary of a various Rh(I) catalysts used to promote the
reductive coupling reaction of benzaldehyde with 2,3-
dimethyl-1,3-butadiene. The reaction outcome changes dra-
matically depending on the class of Rh(I) complexes. Chloro,
acetylacetonate, and triflate groups are inappropriate coun-
terions, and no reaction takes place at all (entries 1-5, Table
1).
afford homoallyl alcohol 1a in 80%.6 [Rh(OH)(cod)]2 catalyst
promoted the reaction effectively to provide 1a in quantitative
yield (entry 6, Table 1). Under similar catalytic system, the
lower use of RhOH catalyst (0.01 equiv) was tolerated in
the reaction with reasonable yield (entry 7). Furthermore,
[RhH(cod)]4, which was prepared from [RhCl(cod)]2 and
EtLi according to the literature,7 participated in the desired
reaction giving rise to 1a in excellent yield (entry 8, Table
1). It was proved that RhH catalyst works as an active species
as well as RhOH catalyst. These results might imply that
the hydroxy group of RhOH plays a crucial role to form
RhEt by transmetalation with Et3B followed by ꢀ-hydride
elimination to give an important RhH active species at the
initial stage of the catalytic system.
Table 2. Rh(OH)-Catalyzed Reductive Coupling of PhCHO
with Various Conjugated Dienesa
Table 1. Rh-Catalyzed Reductive Coupling Reaction of PhCHO
and 2,3-Dimethyl-1,3-dienea
entry
Rh catalyst
mmol catalyst
yield of 1a (%)
1
2
3
4
5
6
7
8
RhCl(PPh3)3
Rh(CO)2(acac)
[Rh(cod)2][BF4]
Rh(OTf)(cod)2
[RhCl(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[RhH(cod)]4
0.1
0.1
0.1
0.1
0.05
0.05
0.005
0.025
0
0
0
0
0b
99c
78
94
a The reaction was undertaken in the presence of PhCHO (1 mmol),
2,3-dimethyl-1,3-butadiene (4 mmol), Rh catalyst, and Et3B (3 mmol) in
THF (5 mL) at 50 °C for 24 h under nitrogen atmosphere. b Addition of a
catalytic amount of 4 M KOH solution (25 mL, 0.1 mmol) promoted the
reaction to give 1a in 80% yield. c Stoichiometric amount of each reagent,
PhCHO (1 mmol), 2,3-dimethyl-1,3-butadiene (1 mmol), and Et3B (1 mmol)
were used to give 1a in 89% yield.
a The reaction was undertaken in the presence of PhCHO (1 mmol),
diene (1 mmol), [Rh(OH)(cod)]2 (0.05 mmol), and Et3B (1 mmol) in THF
(5 mL) for 24 h at 50 °C under nitrogen atmosphere. b Stereochemistry of
1e is not determined. c At 67 °C for 24 h.
Although RhH was considered to be active species to
promote the reaction, [Rh(OH)(cod)]2 complex was actually
used as an appropriate catalyst owing to the stability and
easy storage. Once a suitable Rh catalyst was identified, the
reductive coupling reaction was extended to a wide variety
of conjugated dienes (Table 2). 1,3-Butadiene underwent the
reductive allylation to provide 1b in high yield with a 7:1
In contrast, the addition of a catalytic amount of KOH
aqueous solution to an [RhCl(cod)]2 catalytic system induced
the reductive coupling reaction with aldehyde and diene to
(5) (a) Tsuji, J.; Hara, M.; Ohno, K. Tetrahedron 1974, 30, 2143–2145.
(b) Ojima, I. J. Organomet. Chem. 1977, 134, C1–C5. (c) Ojima, I.;
Kumagai, M. J. Organomet. Chem. 1978, 157, 2143–2146. (d) Cornish,
A. J.; Lappert, M. F.; MacQuitty, J. J.; Maskell, R. K. J. Organomet. Chem.
1979, 177, 153–161. (e) Satoh, M.; Nomoto, Y.; Miyaura, N.; Suzuki, A.
Tetrahedron Lett. 1989, 30, 3789–3792. (f) Kobayashi, S.; Nishio, K. J.
Org. Chem. 1994, 59, 6620–6628. (g) Hayashi, N.; Honda, H.; Yasuda,
M.; Shibata, I.; Baba, A. Org. Lett. 2006, 8, 4553–4556. (h) Ru-catalyzed
coupling reaction of diene with alcohols: Shibahara, F.; Bower, J. F.;
Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6338–6339.
(6) The allylation using [RhCl(cod)]2 catalyst and 0.1 equiv of KOH
proceeded smoothly. The formation of RhOH active species might be
b
required at the initial stage of the reaction: see footnote in Table 1.
(7) RhH is generated from RhEt species through ꢀ-hydride elimination,
which is derived from [RhCl(cod)]2 and EtLi; see:Kulzick, M.; Price, R. T.;
Muetterties, E. L. Organometallics 1982, 1, 1256–1258.
Org. Lett., Vol. 11, No. 17, 2009
3795

ratio of syn and anti stereoisomers (entry 1, Table 2).
Isoprene reacted with benzaldehyde at the C-3 and C-2
positions to give a regioisomeric mixture of 1c and 1d in a
6:1 ratio (entry 2, Table 2). Myrcene reacted with aldehyde
at the less-substituted alkene to provide 1e as a single isomer
(entry 3, Table 2). 1,3-Cyclohexadiene serves as a pertinent
allylating agent to exert syn-homoallyl alcohol exclusively
(run 4, Table 2). Rh-catalyzed allylation with cyclic diene
is more selective than that of the Ni-catalyzed allylation,
which has shown marginal success of syn stereoselectivity
(syn:anti ) 4:1).2a An electron-deficient diene, methyl
sorbate, reacted with benzaldehyde at the R-carbon position
with excellent stereoselecivity to provide 1g as a single
isomer (entry 5, Table 2). The stereochemistry of 1g was
unequivocally determined as the syn-(Z) form on the basis
of specral data of the converted acetonide 1g′, which was
derived from 1g by the reduction with NaBH4 followed by
acetonization (Scheme 2). 2-Siloxy-1,3-butadiene underwent
reductive coupling at the C-3 position with high regioselec-
tivity to afford homoallyl alcohol 1h possessing a silyl enol
ether framework (entry 6, Table 2). However, in this case,
exclusive syn stereoselectivity was not observed, and a
mixture of syn- and anti-1h was obtained in good yield.
Table 3. Rh-Catalyzed Reductive Coupling Reaction of
Carbonyls with 2,3-Dimethyl-1,3-butadienea
Scheme 2. Structure Determination of Homoallyl Alcohol 1g
a The reaction was undertaken in the presence of carbonyl (1 mmol),
2,3-dimethyl-1,3-butadiene (4 mmol), Et3B (3 mmol), and [Rh(OH)(cod)]2
(0.05 mmol) in THF (5 mL) at 50 °C for 72 h under nitrogen atmosphere.
generate a fine active RhH species along with evolution of
ethylene.7 RhH active species readily adds to conjugated
diene to form π-allylrhodium intermediate, which subse-
quently serves as an allylic carbanion equivalent toward the
aldehyde to provide homoallyl alcohol through the six-
membered ring transition state. The stereochemical outcome
The results using a wide variety of aldehydes with 2,3-
dimethyl-1,3-butadiene are shown in Table 3. Irrespective
of the substituents and electronic nature of the aromatic ring,
both p-anisaldehyde and p-bromobenzaldehyde provided
homoallyl alcohols in good to excellent yields (entries 1 and
2, Table 3). R,ꢀ-Unsaturated aldehyde and alkylaldehyde also
took part in the reaction in a similar way (entries 3-5, Table
3). Encouraged by the compatibility of the Ni/Et3B-promoted
homoallylation of lactols,2c we examined the applicability
of the present reaction system to the allylation of five- and
six-membered lactols to give the corresponding homoallyl
alcohols in reasonable yields (entries 6 and 7, Table 3). These
results also might greatly contribute to the reaction of
carbohydrate and related chemistry from now on.
Scheme 3
.
Rh-Catalyzed Allylation of Aldehyde with 1,3-Diene
Promoted by Et3B
At this momonet, it is premature to give the rationale
behind these regio- and stereoselectivities; however, a
plausible reaction mechanism for Rh-catalyzed allylation of
aldehydes with conjugated diene promoted by Et3B is
illustrated in Scheme 3. RhOH reacts with Et3B to form RhEt
species, which readily undergoes ꢀ-hydride elimination to
3796
Org. Lett., Vol. 11, No. 17, 2009

seems to derive from the stability of the π-allylrhodium.
Finally, ethyl group transfer from Et3B to the alkoxyrhodium
intermediate results in the formation of RhH active species
via ꢀ-hydride elimination of RhEt, hence accomplishing the
Rh(I) catalytic cycle.
In this case, the regio- and stereoselectivities stem from the
structure of the oxanickelacycle intermediates. On the other
hand, RhOH catalyst readily reacts with Et3B to generate
RhH active species. Assuming that the hydrorhodation of
RhH toward the conjugated diene is extremely faster than
the oxidative cyclization of a Rh(I) species across a diene
and aldehyde, the nucleophilic allylation of aldehyde with
π-allylrhodium would predominate over the homoallylation.
Thus, the reaction feature of the reductive coupling reaction
of aldehyde with diene promoted by Rh/Et3B might be in
marked contrast to that of Ni/Et3B.
Scheme 4. Reductive Coupling Reaction of Aldehyde with
Diene Promoted by Ni/Et3B versus Rh/Et3B
In conclusion, we have developed the Rh(I)-catalyzed
reductive coupling reaction of aldehydes with a wide variety
of conjugated dienes in the presence of Et3B to provide
homoallyl alcohols in a single operation. Asymmetric ally-
lation of aldimines and polyhydroxy aldehydes such as
carbohydrates with 1,3-dienes are currently underway in our
laboratories, and these results will be reported in due course.
Acknowledgment. Financial support from the Ministry
of Education, Culture, Sports, Science, and Technology,
Japanese Government (Grant-in-Aid for Scientific Research
(B) 21350055) is gratefully acknowledged. This work was
partially supported by the Asahi Glass Foundation.
A comparison between Ni/Et3B-promoted homoallylation
and Rh/Et3B-promoted allylation of aldehyde with diene
would be worth considering (Scheme 4). Under the Ni/Et3B
system, oxidative cyclization of a Ni(0) species across the
conjugated diene and aldehyde successfully proceeds to form
an oxanickelacycle intermediate, which undergoes σ-bond
metathesis with Et3B giving rise to bis-homoallyl alcohols.2
Supporting Information Available: Experimental pro-
cedures and NMR spectra for all homoallyl alcohols. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL901527B
Org. Lett., Vol. 11, No. 17, 2009
3797