Decarboxylative C-C bond cleavage reactions via oxapalladacycles

Article abstract of DOI:10.3987/COM-10-S(E)46

In the presence of Pd(0) catalyst and triethylborane, 3-hydroxy-4-pentenoic acids undergo C-C bond cleavage reactions via oxapalladacyclopentanones to provide conjugated dienes with evolution of carbon dioxide. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-S(E)46

HETEROCYCLES, Vol. 82, No. 1, 2010
281
HETEROCYCLES, Vol. 82, No. 1, 2010, pp. 281 - 287. © The Japan Institute of Heterocyclic Chemistry
Received, 5th June, 2010, Accepted, 26th July, 2010, Published online, 27th July, 2010
DOI: 10.3987/COM-10-S(E)46
DECARBOXYLATIVE C-C BOND CLEAVAGE REACTIONS VIA
OXAPALLADACYCLES
Masanari Kimura,* Tomohiko Kohno, Kei Toyoda, and Takamichi Moriꢀ
Graduate School of Science and Technology, Nagasaki University, 1-14
Bunkyo-machi, Nagasaki, 852-8521, Japan. E-mail; masanari@nagasaki-u.ac.jp
Dedicated to Prof. Dr. Albert Eschenmoser's on the occasion of his 85th birthday.
Abstract
–
In the presence of Pd(0) catalyst and triethylborane,
3-hydroxy-4-pentenoic acids undergo C-C bond cleavage reactions via
oxapalladacyclopentanones to provide conjugated dienes with evolution of carbon
dioxide.
Metallacycles are attractive key intermediates for constructing important fundamental constituents of
1
complex molecules and fine chemicals. Oxidative cyclizations of conjugated dienes and carbonyl
compounds with transition metals are efficient strategies for highly regio- and stereocontrolled C-C bond
2
formation via oxametallacycles. Although the C-C bond cleavage reaction involving metallacycles has
received less attention in comparison to C-C bond formation, it is equally capable of significant synthetic
3
utility for efficient chemical transformations.
We have previously developed a smooth transformation of vinyl cyclic carbonates into the corresponding
!-dienyl aldehydes by decarboxylative fragmentation through a key oxapalladacyclopentane intermediate,
4
triggered by oxidative addition of a Pd(0) catalyst to the allylic C-O bond (Scheme 1). Furthermore,
4-pentene-1,3-diols of a wide structural variety, which can be prepared in a straightforward manner from
mono- or bicyclic ketones with ",#-unsaturated aldehydes, also underwent the dehydrative #-carbon
5
elimination of oxapalladacycles promoted by Ph3B and Pd(0) catalyst. This procedure is superior to the
cyclic carbonate method, not simply because we can save one step (carbonation), but because we can
utilize a wide variety of stereoisomers of diols that cannot form carbonates as single isomers due to steric
reasons.

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HETEROCYCLES, Vol. 82, No. 1, 2010
Pd catalyst
O
O
!-carbon
elimination
-CO2
O
Pd
O
O
n
n
Pd catalyst
n
OH OH
!-carbon
elimination
B-Ph-9-BBN
O
Pd
n = 0 ~ 8
O
Scheme 1. Pd-Catalyzed !-Carbon Elimination via Oxapalladacycle
Herein, we report that Et B nicely activates 3-hydroxy-4-pentenoic acids which are prepared from esters
3
or lactones with !,"-unsaturated aldehydes to undergo the decarboxylative "-carbon elimination via an
oxapalladacyclopentane to afford a conjugated diene (Scheme 2). While it has been reported that
3-acetoxy-4-pentenoic acid underwent a similar decarboxylative C-C bond cleavage reaction promoted by
6
Pd catalyst in the presence of triethylamine, the present study is more convenient for the stereodefined
construction of conjugated dienes from readily available starting materials as mixtures of diastereomeric
7
isomers. Furthermore, the Pd-catalyst/Et B system is also superior for the direct generation of
3
#-allylpalladium species from allyl alcohols.
R
R
Pd0 catalyst
1) aldol reaction
2) hydrolysis
O
O
R
O
Et3B
-CO2
OR'
OH OH
1
2
Scheme 2. Efficient Synthesis of Conjugated Diene via Decarboxylative C-C Bond
Cleavage Reaction of 3-Hydroxy-4-pentenoic Acid Prepared from Acrolein and Esters
The reaction was undertaken with great ease just by exposing the 3-hydroxy-4-pentenoic acids to a
mixture of Pd(PPh ) catalyst and Et B in THF under nitrogen atmosphere. Among these investigations
3 4
3
with excess amount of Et B, the reaction required 3.6 equivalents of Et B at 67 ˚C to consume the
3
3
8
substrate completely.
Table 1 summarizes the results obtained for a wide structural variety of
9
3-hydroxy-4-pentenoic acids under optimized conditions.

HETEROCYCLES, Vol. 82, No. 1, 2010
283
R1
cat. Pd(PPh3)4
R2
O
R2
(1)
R1
Et3B
1
OH OH
2
Table 1. Pd-Et3B Promoted Decarboxylative C-C Bond Cleavage Reactiona
product
% isolated yield [E:Z]
substrate
[ratio]
run
time (h)
Ph
1
1
2a: 95% [18:1]
2b: 78% [5:1:1] b
2c: 86% [E]
O
Ph
Ph
Ph
Ph
[3:1]
1a
OH OH
Ph
2
3
4
1
18
72
Me
O
Me
[1:1]
[2:1]
[1:1]
1b
OH OH
Ph
Me
Ph
O
Me
1c
OH OH
Ph
c
Me
2d: 65% [26:7:1]
2e: 64% [3:1]
2f: 48% [3:1]
Ph
Me
O
Me
1d
Me
OH OH
OH
OH
5
6
3
3
[2:1]
O
OH OH
OH
1e
OH
Ph
[2:1]
O
Ph
1f
OH OH
HO
7
8
3
1
2g: 84% [11:1]
2h: 99% [4:1]
OH
CO2H
OH
1g
[single]
CO2H
HO
HO
1h
[2:1]
OH
a Reaction conditions: substrate (0.5 mmol), Pd(PPh3)4 (5 mol %), Et3B (3.6 eq) in THF
(2.5 mL) at 67 ˚C under N2. b Ratio of 1-phenyl-2,4-hexadiene. (2E,4E):(2E,4Z):(2Z,4E) =
5:1:1. c Ratio of 4-methyl-1-phenyl-2,4-hexadiene. (2E,4E):(2E,4Z):(2Z,4E) = 26:7:1.

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HETEROCYCLES, Vol. 82, No. 1, 2010
A mixture of syn-1a and anti-1a in a 3:1 ratio, which was prepared from cinnamaldehyde and methyl
3-phenylpropionate, clearly undergoes "-decarboxylative C-C bond cleavage to provide (E,E)-pentadiene
2a with high stereoselectivity in excellent yield (run 1). A methyl group substituted allylic alcohol 1b
afforded (2E,4E), (2E,4Z), and (2Z,4E)-1-phenyl-2,4-hexadiene 2b in a 5:1:1 ratio (run 2).
"-Methallyl alcohol shows exclusive E-stereoselectivity to give (E)-2c as the sole product owing to the
bulky steric repulsion between the benzyl group and the methyl substituent on the allylic moiety (run 3).
",$-Dimethyl substituted allylic alcohol 1d displays moderate yield with three isomers of (2E,4E),
(2E,4Z), and (2Z,4E)-2d in a 26:7:1 ratio (run 4). 3-Hydroxy-4-pentenoic acids possessing
o-hydroxyphenyl groups participate in similar C-C bond cleavage reactions in 48-64% yields (runs 5 and
6). The lower yields stem from competing partial lactonization, which leads to the original
10
dihydrocoumarin skeletons.
"-Hydroxycarboxylic acids 1g and 1h, which were prepared from
7-membered ring lactones with acrolein, provided the desired dienyl alcohols 2g and 2h in excellent to
quantitative yields (runs 7 and 8).
The stereochemical outcome of the dienyl moiety may be rationalized according to the proposed reaction
mechanism shown in Scheme 3. We postulate that syn-oxapalladacyclopentanone-I is generated by
oxidative addition of the Pd(0) metal to the allylic position of anti-1 activated by Et3B with inversion of
configuration. The intermediate syn-I then isomerizes to the sterically more stable anti-I form by
%&#&% interconversion via the seven-membered ring palladacycle II. Thus, the #-allylpalladium
intermediates syn-I and anti-I could both undergo the C3-C4 bond fission with evolution of carbon
dioxde to provide (Z)-2 and (E)-2, respectively.
R
R
Pd0
- Pd0
R
O
O
Et3B
- Et2B(OH)
- C2H6
- CO2
O
Pd
syn-I
OH OH
(Z)-2
anti-1
$-carbon
elimination
oxidative
addition
R
O
!"#"! isomerization
O
Pd
II
R
R
Pd0
- Pd0
O
O
Et3B
R
- Et2B(OH)
- C2H6
OH OH
O
Pd
- CO2
(E)-2
syn-1
anti-I
$-carbon
elimination
oxidative
addition
Scheme 3. Reaction Mechanism for Pd-Catalyzed Decarboxylative C-C Bond Cleavage

HETEROCYCLES, Vol. 82, No. 1, 2010
285
As a result of the formation of (2E,4E)-2b as a major product along with (2E,4Z) and (2Z,4E)-2b from a
mixture of syn-(E)-1b and anti-(E)-1b (runs 2, Table 1), a plausible mechanism for the C-C bond
cleavage reaction of 2,5-disubstituted-3-hydroxy-4-pentenoic acids 1 might be illustrated in Scheme 4.
R
R'
R
O
R'
Pd0
- Pd0
R
O
Et3B
R'
OH OH
- CO2
- Et2B(OH)
- C2H6
O
Pd
anti-(E)-1
(Z,E)-2
syn-(E)-I
R
O
O
anti-II
Pd
R
R'
H
- Pd0
O
R
- CO2
O
Pd R'
R'
(E,Z)-2
(E,E)-2
anti-(Z)-I
R
R
O
R'
Pd0
- Pd0
O
R'
R'
Et3B
R
OH OH
- CO2
- Et2B(OH)
- C2H6
O
Pd
syn-(E)-1
anti-(E)-I
very fast
R
O
O
Pd
H
syn-II
R'
R'
R
- Pd0
R
O
- CO2
O
Pd
R'
(Z,Z)-2
very slow
syn-(Z)-I
Scheme 4. C-C Bond Cleavage of 2,5-Disubstituted-3-hydroxy-4-pentenoic Acids

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HETEROCYCLES, Vol. 82, No. 1, 2010
It seems that anti-(E)-1b provides a mixture of (Z,E)- and (E,Z)-2b in modest yields being in equilibrium
with syn-(E)-I and anti-(Z)-I via seven-membered palladacycle anti-II. On the contrary, formation of
anti-(E)-I from syn-(E)-1b by oxidative addition of Pd(0) catalyst with Et3B predominates over the
formation of syn-(Z)-I by %&#&% interconversion through syn-II, and causes the C-C bond cleavage
reaction smoothly providing (E,E)-2b in excellent yield. Selective formation of (Z,Z)-2b through the
unstable intermediate syn-(Z)-I is extremely improbable owing to the most unfavorable stereochemistry.
In summary, we have shown that a combination of Pd(0) catalyst and Et3B effectively activates
3-hydroxy-4-pentenoic acid to undergo "-decarboxylative C-C bond cleavage reaction via
"-vinyloxapalladacyclopentanone to form a conjugated diene with high stereoselectivity. The present
methodology would be utilized for the convenient and stereodefined construction of conjugated dienes
from readily available esters and !,"-unsaturated aldehydes with great operational ease.
ACKNOWLEDGEMENTS
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.
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7. 3-Hydroxy-4-pentenoic acids 1 were easily prepared from lactones or esters with !,"-unsaturated
aldehydes by crossed-aldol reaction followed by hydrolysis in aqueous alkaline conditions.
8. Under similar conditions, no reaction proceeds in the presence of Ph3B, instead of Et3B.
9. Typical reaction procedure (run 1, Table 1): Into a N purged flask containing
2
3-hydroxy-4-pentenoic acid 1a (141 mg, 0.5 mmol), Pd(PPh ) (27.8 mg, 0.025 mmol) purged with
3 4
nitrogen were successively THF (2.5 mL) and triethylborane (1.8 mL, 1 M hexane; Aldrich) were
introduced successively via a syringe. The reaction mixture was stirred at 67 ˚C for 1 h, during
which the reaction was monitored by means of TLC. After dilution with EtOAc (30 mL), the
mixture was washed with sat. aq. NaCl (30 mL). The organic layer was dried (MgSO ) and the
4
solvent was removed in vacuo. The residue was subjected to the column chromatography over
silica gel (Wakogel C-300; eluent: hexane) and (1E,3E)-1,5-diphenylpenta-1,3-diene 2a (209 mg,
95%) was obtained in 18:1 ratio. (1E,3E)-1,5-Diphenylpenta-1,3-diene (2a): IR (neat) 3024 (m),
1
1596 (w), 1495 (m), 1452 (m), 988 (s), 741 (m), 694 (m) cm-1; H NMR (400 MHz, CDCl3, major
isomer): ! 3.48 (d, J = 7.0 Hz, 2 H), 5.96 (dt, J = 14.9, 7.0 Hz, 1 H), 6.25 (dd, J = 14.9, 10.5 Hz, 1
13
H), 6.47 (d, J = 15.7 Hz, 1 H), 6.77 (dd, J = 15.7, 10.5 Hz, 1 H), 7.19 - 7.41 (m, 10 H); C NMR
(400 MHz, CDCl3, major isomer): ! 39.2, 126.0, 126.1, 127.1, 128.3, 128.4, 128.5, 128.8, 130.8,
131.6, 133.5, 137.4, 140.0; 1H NMR (400 MHz, CDCl3, minor isomer): ! 3.65 (d, J = 7.6 Hz, 2 H),
5.69 (dt, J = 10.5, 7.6 Hz, 1 H), 6.25 (t, J = 10.5 Hz, 1 H), 6.61 (d, J = 15.6 Hz, 1 H), 6.77 (dd, J =
15.7, 10.5 Hz, 1 H), 7.19 - 7.41 (m, 10 H); 13C NMR (400 MHz, CDCl3, minor isomer): ! 34.2, 126.0,
126.3, 127.4, 128.3, 128.4, 128.5, 129.5, 130.6, 131.6, 133.0, 137.4, 140.3; High-resolution MS,
calcd for C17H16: 220.3089. Found m/z (relative intensity): 221.1271 (18), 220.1252 (M+, 100),
219.1181 (3).
10. The original dihydrocoumarins by competing lactonization of 1e and 1f were produced in 12% and
20% yields, respectively (runs 5 and 6, Table 1).