Dienyl homoallyl alcohols via palladium catalyzed ene-type reaction of aldehydes with 1,3-dienes

Article abstract of DOI:10.1021/ja1072417

The combination of Pd catalyst and Xantphos ligand in the presence of Et₃B nicely promotes the allylation of aldehydes with conjugated dienes to provide dienyl homoallyl alcohols in excellent yields. The reaction occurs selectively at the C-C double bond bearing higher electron density.

Full text of DOI:10.1021/ja1072417

Published on Web 10/28/2010
Dienyl Homoallyl Alcohols via Palladium Catalyzed Ene-Type Reaction of
Aldehydes with 1,3-Dienes
Masahiro Fukushima, Daiki Takushima, and Masanari Kimura*
Department of Applied Chemistry, Faculty of Engineering, Nagasaki UniVersity, Bunkyo-machi,
Nagasaki 852-8521, Japan
Received August 16, 2010; E-mail: masanari@nagasaki-u.ac.jp
Scheme 2. Reductive Coupling Reaction of Diene and Aldehydes
by Ni and Rh Catalysts in the Presence of Et3B
Abstract: The combination of Pd catalyst and Xantphos ligand
in the presence of Et3B nicely promotes the allylation of aldehydes
with conjugated dienes to provide dienyl homoallyl alcohols in
excellent yields. The reaction occurs selectively at the C-C
double bond bearing higher electron density.
The carbonyl ene reaction is one of the most powerful tools in
the fundamental C-C bond formation. In general, activated
carbonyls, such as arylglyoxals and glyoxylates, are effectively
utilized for the ene reactions.1 Although dienyl alcohols are among
the most important components in the synthesis of terpenoids, insect
pheromones, physiologically active molecules, and other natural
products,2 it is extremely difficult to use conjugated dienes as the
dienyl alcohol fragment for carbonyl ene reactions due to compli-
cated side reactions, e.g., Diels-Alder reaction and oligomeriza-
tion.3
dppf, DPEphos, and BINAP, had marginal success in the formation
of the coupling product 1a (entries 3-5, Table 1). Xantphos, which
has been effectively used for transition-metal-catalyzed cross-
coupling reactions and aminations,8 was the most appropriate
phosphine ligand in the present reaction quantitatively giving rise
to the desired alcohol 1a (entry 6, Table 1). Other organoboranes,
such as Ph3B and n-Bu3B, yielded an intractable mixture of products
contrary to the result of Et3B (entries 8 and 9, Table 1). Although
Et2Zn also served as a promoter of the reaction, 1a was obtained
in an unsatisfactory yield (entry 10, Table 1).
As attractive strategies for C-C bond formations involving
conjugated dienes, transition-metal-catalyzed reductive coupling
reactions of dienes and carbonyls have been developed.4 For
instance, under hydrogenation and hydrogen autotransfer conditions,
Ru-catalyzed regioselective formation of branched homoallylic
alcohols by allylation of carbonyls with diene was achieved by M. J.
Krische et al. (Scheme 1).5 Furthermore, we have previously
developed the homoallylation of aldehydes with conjugated dienes
in the presence of Et3B to provide bishomoallyl alcohols via a Ni(0)
catalyst (Scheme 2).6 Under similar conditions, Rh(I) catalyzed the
allylation of aldehydes with dienes to afford homoallyl alcohols
with excellent regio- and stereoselectivities.7 Et3B serves not only
as a Lewis acid but also as a reducing agent to accomplish the
reductive coupling reaction of the diene and carbonyls through the
allylmetal species. Thus, the linear regioselectivity observed in
the Ni catalytic system is in sharp contrast to the branched
regioselectivity promoted by Rh and Ru catalytic systems. Herein,
we report that a system of a Pd catalyst with Et3B nicely promotes
the ene-type reaction of carbonyls with conjugated dienes to afford
dienyl homoallyl alcohols as an efficient C-C bond transformation.
The coupling reaction of isoprene with PhCHO was conducted
in the presence of a Pd catalyst and phosphine ligand, as shown in
Table 1. In the absence of both Et3B and a phosphine ligand, no
reaction occurred. Although a monophosphine ligand was not
effective (entry 2, Table 1), bidentate phosphine ligands, such as
Table 1. Pd/Xantphos Promoted Allylation of PhCHO with
Isoprenea
Entry
Ligand
Organometal
Time (h)
Yield of 1a (%)
1
2
3
4
5
6
7
8
9
none
PPh3
dppf
DPEphos
BINAP
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Et3B
Et3B
Et3B
Et3B
Et3B
Et3B
none
Ph3B
n-Bu3B
Et2Zn
21
24
30
48
41
24
72
72
72
48
0
0
16
33
64
99
complex mixture
complex mixture
complex mixture
24
10
a The reaction was undertaken in the presence of isoprene (4 mmol),
benzaldehyde (1 mmol), Pd(OAc)2 (10 mol %), ligand (10 mol %), and
organometal (2 mmol) at room temperature under
atmosphere.
a nitrogen
The coupling reaction of various types of conjugated dienes with
PhCHO was examined under the optimized Pd/Xantphos system.
The results are shown in Table 2.9 2,3-Dimethyl-1,3-butadiene
underwent the coupling reaction to provide dienyl alcohol 1b in
high yield (entry 1, Table 2). 1,3-Dimethyl-1,3-butadiene reacted
with PhCHO at the less substituted CdC double bond terminus to
give dienyl alcohol 1c exclusively (entry 2, Table 2). Myrcene
reacted with the aldehyde at the C1 position to give the trienyl
alcohol 1d in a 3:1 ratio with respect to the internal olefin geometry
(entry 3, Table 2). Methyl sorbate underwent the C-C bond
Scheme 1. Ru-Catalyzed C-C Coupling Reaction Employing
Diene via Transfer Hydrogenation
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10.1021/ja1072417  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Pd/Xantphos Promoted Allylation of Aldehyde with
formation at the R-position to provide (2E,4E)-hexadiene 1e as a
single isomer (entry 4, Table 2). The present reaction is more
efficient and provides an alternative method for formation of
stereodefined ꢀ-branched Baylis-Hillman adducts in comparison
to the DABCO/DMSO protocol.10 It is of profound interest that
the present reaction is distinct from the homoallylation promoted
by the Ni/Et3B system but nevertheless is similarly easy to
perform.6a
Isoprene
A wide structural variety of aldehydes was examined next,
as summarized in Table 3. For aromatic aldehydes with an
electron-donating group or a halogen, the C-C bond formation
reaction proceeded smoothly to afford the dienyl alcohols in good
to quantitative yields (entries 1 and 2, Table 3). Aliphatic
aldehydes participated in the reaction to give the corresponding
dienyl alcohols in reasonable yields (entries 3-5, Table 3).
Encouraged by the compatibility of homoallylation of hemiac-
etals with Et3B or in the presence of water,6d we conducted the
reaction with five- and six-membered lactols, which resulted in
the formation of the desired homoallyl alcohols (entries 6 and
7, Table 3).
Table 2. Pd/Xantphos Promoted Allylation of PhCHO with Dienea
a The reaction was undertaken in the presence of diene (4 mmol),
benzaldehyde (1 mmol), Pd(OAc)2 (10 mol %), Xantphos (10 mol %),
and triethylborane (2 mmol) at room temperature under a nitrogen
atmosphere.
Scheme 3. A Plausible Reaction Mechanism
a The reaction was undertaken in the presence of diene (4 mmol),
benzaldehyde (1 mmol), Pd(OAc)2 (10 mol %), Xantphos (10 mol %),
and triethylborane (2 mmol) at room temperature under a nitrogen
atmosphere.
At this moment, although it is premature to give rationale
behind these reactivities, a preliminary reaction mechanism for
the coupling reaction of isoprene with benzaldehyde might be
proposed, as shown in Scheme 3. The Pd/Xantphos complex
activates isoprene to enhance its nucleophilicity. Reaction with
the aldehyde, promoted by Et3B as a Lewis acid, forms an
oxapalladacyclopentane intermediate.11 Next, an ethyl group is
transferred from Et3B to the allylpalladium species. Bidentate
phosphine ligands with a very large bite angle tend to form trans
complexes, which are reluctant to undergo reductive elimina-
tion.12 Therefore, subsequent ꢀ-hydride elimination of allyleth-
ylpalladium to give the dienyl homoallyl alcohol predominates
over the reductive elimination and is accompanied with the
formation of the more stable Xantphos/Pd complex as the key
catalytic species.13
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 supported by the Asahi
Glass Foundation.
Supporting Information Available: Experiment procedure and
NMR spectra for all products. This material is available free of charge
via the Internet at http://pubs.acs.org.
In summary, we have developed a Pd/Xantphos/Et3B system that
promotes the coupling reaction of aldehydes and conjugated dienes
to afford dienyl homoallyl alcohols. The applicability and scope
of this method for the efficient preparation of physiologically active
molecules such as terpenoids and aymmetric ene-type reactions are
currently under investigation in our laboratory.
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