Pd(0)-catalyzed amphiphilic activation of bis-allyl alcohol and ether

Article abstract of DOI:10.1021/ja0479787

Pd(0)·Et₃B catalyzes amphiphilic activation of symmetric allylic diol 1 to promote electrophilic allylation at the α-position of aldehydes and nucleophilic allylation at the aldehyde CO, furnishing 3-methylenecyclopentalols 2 and thus generatio

Full text of DOI:10.1021/ja0479787

Published on Web 08/21/2004
Pd(0)-Catalyzed Amphiphilic Activation of Bis-allyl Alcohol and Ether
Ryutaro Mukai, Yoshikazu Horino, Shuji Tanaka, Yoshinao Tamaru,* and Masanari Kimura‡
Department of Applied Chemistry, Faculty of Engineering, Nagasaki UniVersity, 1-14 Bunkyo-machi,
Nagasaki 852-8521, Japan, and Graduate School of Science and Technology, Nagasaki UniVersity,
1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Received April 8, 2004; E-mail: tamaru@net.nagasaki-u.ac.jp
Scheme 1. Pd(0)-Catalyzed Amphiphilic Activation of Bis-allyl
Alkylation of carbonyl compounds at the R-position and at the
Alcohol 2a toward Electrophilic and Nucleophilic Allylation of
Aldehydes
carbonyl carbon is among the most important methods to elaborate
molecules. Especially, the most useful and studied is the Pd(0)-
catalyzed R-allylation of active methylene compounds that proceeds
via a π-allylpalladium(II) species (the Tsuji-Trost reaction).1
Among many nucleophilic alkylation methods, allylation with allyl
alcohols and ethers via a π-allylpalladium(II) species is unique,
since the reaction is electronically opposite to the Tsuji-Trost
reaction (umpolung).2
Here we would like to demonstrate a salient reactivity of
symmetric bis-allyl alcohol, 2-hydroxymethyl-2-propen-1-ol (2a);
Table 1. Pd(0)‚Et3B Promoted Electrophilic (1 f 3) and
Nucleophilic (3 f 6) Allylation of Aldehydes with Bis-allyl
Alcohol 2aa
one of the allyl alcohol moieties of 2a undergoes electrophilic
allylation at the R-position of aldehydes3 to give 3′, and the other
remaining allyl alcohol moiety, on the other hand, selectively reacts
as an allylic nucleophile toward the aldehyde CO4 to furnish
3-methylenecyclopentanols 6 in good yields (Scheme 1). These two
processes can be catalytically promoted by Pd(OAc)2 in combination
with triethylborane. That is, by the catalysis of Pd(OAc)2‚Et3B,
commercially available 2a can be utilized as a synthetic equivalent
of a zwitterionic trimethylenemethane species (Scheme 1).
When a mixture of R-phenylpropionaldehyde 1a (1 mmol), 2a
(1.1 mmol), Pd(OAc)2 (10 mol %), PPh3 (20 mol %), and Et3B
(2.4 mmol) in dry THF (5 mL) containing Et3N (1.2 mmol) and
LiCl (1.0 mmol) was stirred at room temperature for 12 h, an
R-allylation product 3a′ was isolated as its hemiacetal form 3a in
93% isolated yield (eq 1 and run 1, Table 1). In the absence of
a Reaction conditions (1 f 3): 1 (1 mmol) and 2a (1.1 mmol), Pd(OAc)2
(10 mol %), PPh3 (20 mol %), Et3B (2.4 mmol), Et3N (1.2 mmol), and
LiCl (1.0 mmol) in dry THF (5 mL) at room temperature under N2; (3 f
6): the same as above except the absence of Et3N and LiCl. b Reaction
time (h) at room temperature, unless otherwise noted. c Reaction time (h)
at 50 °C. d Diastereomeric mixture in a ratio of trans:cis ) 2.2:1.
Et3N and LiCl, under otherwise identical conditions (room tem-
perature for 39 h), 3a then undergoes intramolecular nucleophilic
allylation and provides 6a in 82% isolated yield (eq 2; run 1, Table
1). Thus, the additives Et3N and LiCl nicely tune the electrophilic
and nucleophilic allylation with allyl alcohols, i.e. these reagents
promote electrophilic allylation while prohibiting nucleophilic
allylation catalyzed by Pd(OAc)2‚Et3B.3c
The reaction is applicable to sec-aliphatic aldehydes 1b and 1c
with less acidic R-protons (runs 2 and 3, Table 1). The cyclization
of 3 to 6 shows remarkable stereoselectivity and 6a and 6b are
obtained either as a single diastereomer or as a mixture of trans:
cis ) 2.2:1, respectively. In both cases, the hydroxy group is cis
with respect to the smallest methyl group. The structure was
determined on the basis of NOE experiments.
Bis-benzyl ether 2b showed similar reactivity to 2a for the
reaction with 1c and provided 4a, a benzyl ether derivative of 3c,
in somewhat lower yield under the conditions shown in eq 1 (65%,
16 h at room temperature). Use of DPPF, in place of PPh3, greatly
improved the combined isolated yield of 4a and 5b (eq 3 and Table
2). Cyclohex-1-enecarbaldehyde (1d) selectively undergoes the
‡ Graduate School of Science and Technology.
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10.1021/ja0479787 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Pd(0)‚Et3B-Promoted Electrophilic (1 f 4 + 5)a and
Nucleophilic (4 or 5 f 6) Allylationb of Aldehydes with Bis-allyl
Ether 2b
Scheme 2. Pd(0)-Catalyzed Nucleophilic “1” and Electrophilic “2”
Allylationa
a
(a) Trimethylenemethane-palladium chemistry. (b) Bis-π-allylpalla-
dium chemistry.
The ease of the experimental procedure and the amphiphilic
activation as an allyl cation and as an allyl anion of a commercially
available symmetrical diol 2a may be the remarkable and useful
features of the present reaction. That there is no need to take care
of moisture is a further useful feature to be noted. Indeed, two moles
of water are liberated as the side product (eqs 4-6).
a Reaction conditions: (1c,d f 4 + 5): 1 (1 mmol) and 2b (1.1 mmol),
Pd(OAc)2 (10 mol %), DPPF (10 mol %), Et3B (2.4 mmol), Et3N (1.2
mmol), and LiCl (1.0 mmol); (1e f 4c): 1e (2.2 mmol), 2b (2 mmol),
Pd(OAc)2 (10 mol %), DPPF (10 mol %), Et3B (0.6 mmol) in dry THF (5
mL) at room temperature under N2. b Reaction conditions (4 or 5 f 6): 4
or 5 (1 mmol), Pd(OAc)2 (10 mol %), PPh3 (20 mol %), and Et3B (4.8
mmol) in dry THF (5 mL) at 50 °C under N2. c Reaction time (h) at room
temperature. d Reaction time (h) at 50 °C. e Contamination with an olefinic
isomer, 3-methyl-spiro[4.5]deca-3-en-1-ol (ca 10%). f Diastereomeric mix-
ture of syn:anti ) 2:1. g Diastereomeric mixture of 2.5:1.
Acknowledgment. We thank the Ministry of Education, Sci-
ence, Sports, and Culture, Japanese Government, for financial
support.
Supporting Information Available: Typical experimental proce-
dures and spectral data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org,
allylation at the R-position via deprotonation of a γ-proton3c and
furnishes a mixture of 4b and 5b (Table 2). The acetals 5 may be
derived from 4 via an intermediate, π-allylpalladium(II) benzylox-
ide: nucleophilic addition of benzyloxy anion upon the aldehyde
CdO followed by cyclization of the thus-formed aldehyde oxyanion
toward a π-allylpalladium(II) intermediate.5 The conversion of 4
and 5 to 6 was carried out separately at 50 °C under conditions
similar to those applied to the conversion of 3 to 6. The results are
summarized in Table 2. â-Keto-aldehyde 1e is so acidic that
alkylation proceeds even in the absence of Et3N.3a
As are shown in eqs 4-6, for aldehydes that possess the R-proton
with relatively high acidity and hence undergo facilely R-allylation,3a
the electrophilic and nucleophilic allylations can be successfully
performed with a single operation under the conditions applied to
the nucleophilic allylation, i.e. in the absence of Et3N and LiCl.
Both 6a and 6g are obtained as a single diastereomer.
The present Pd(0)‚Et3B-based reaction is reminiscent of the Trost
trimethylenemethane-palladium chemistry,6 Scheme 2a, and the
Yamamoto bis-π-allylpalladium chemistry,7 Scheme 2b, especially
the Trost one, because of the structural similarity of the products.
However, the difference between the present reaction and the two
precedents is apparent by taking the reaction sequence into
consideration. While the reactions shown in Scheme 2 proceed in
a sequence of nucleophilic-electrophilic alkylation, the present
reactions proceed in the opposite order: electrophilic-nucleophilic.
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