Decarboxylative allylation of glyoxylic acids with diallyl carbonate

Article abstract of DOI:10.1002/ejoc.201200766

A catalyst system consisting of Pd(PPh₃)₄ and P(pTol)₃ was found to effectively promote the intermolecular decarboxylative coupling of α-oxocarboxylic acids with diallyl carbonate to give α,β-unsaturated ketones. The key advantage of the new reaction protocol is that preformation of the allyl esters is not required. The reaction is believed to proceed via phosphane-mediated decarboxylation of the α-oxocarboxylates, leading to acyl anion equivalents that are allylated within the coordination sphere of the palladium catalyst. Under the reaction conditions, the double bond then migrates into conjugation with the carbonyl group. Copyright

Full text of DOI:10.1002/ejoc.201200766

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SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200766
Decarboxylative Allylation of Glyoxylic Acids with Diallyl Carbonate
Filipe Manjolinho,[a] Matthias F. Grünberg,[a] Nuria Rodríguez,[a][‡] and Lukas J. Gooßen*[a]
Keywords: Allylation / C–C bond formation / Decarboxylation / Palladium / Organocatalysis
A catalyst system consisting of Pd(PPh3)4 and P(pTol)3 was
phosphane-mediated decarboxylation of the α-oxocarboxyl-
found to effectively promote the intermolecular decarbox-
ates, leading to acyl anion equivalents that are allylated
ylative coupling of α-oxocarboxylic acids with diallyl carbon- within the coordination sphere of the palladium catalyst. Un-
ate to give α,β-unsaturated ketones. The key advantage of
the new reaction protocol is that preformation of the allyl es-
ters is not required. The reaction is believed to proceed via
der the reaction conditions, the double bond then migrates
into conjugation with the carbonyl group.
Introduction
Carbon–carbon bond-forming reactions belong to the
most fundamental transformations in organic synthesis,
and new concepts for regiospecific couplings are constantly
sought. In this context, decarboxylative couplings have re-
cently emerged as valuable alternatives to cross-couplings of
organometallic reagents.[1,2] Among them, decarboxylative
allylations of allyl β-ketocarboxylate derivatives to give γ,δ-
unsaturated ketones have received particular attention.[3]
This catalytic version of the Carroll rearrangement[4] was
first described by Tsuji[5] and Saegusa[6] and has further
been developed by Tunge[7] and Stoltz.[8] However, the
scope of such waste-minimized C–C bond-forming reac-
tions extends only to allyl esters of carboxylic acids that –
upon extrusion of carbon dioxide – form highly stable carb-
anions, for example, enolate, benzyl,[9] α-cyano,[6] or ni-
tronate anions.[10] All described methods start from pre-
formed allyl esters (Scheme 1).
Scheme 1. Approaches to generate acyl anions via decarboxylation.
inside the coordination sphere of the palladium. This reac-
tion is of considerable interest because it is a rare example
of a C–C bond-forming reaction involving unstable acyl
anions as carbon nucleophiles.[12] It constitutes an alterna-
tive to traditional syntheses of α,β-unsaturated compounds,
such as aldol condensations, Wittig or Horner–Wadsworth–
Emmons olefinations,[13] or the Meyer–Schuster rearrange-
ment of propargylic alcohols.[14] However, from a practical
standpoint, the prototype protocol was limited by the
rather troublesome synthesis of the allyl esters. High yields
were achieved only when using expensive coupling reagents.
Attempts to generate the esters in situ from α-oxocarboxyl-
ate salts and allyl halides led to the formation of large quan-
tities of halide salts that inhibited the reaction, so that the
temperature had to be increased to 150 °C.[11]
We herein describe how this limitation was overcome by
employing diallyl carbonate as the allyl source in an inter-
molecular decarboxylative coupling with α-oxocarboxylic
acids.
According to the proposed mechanism (Scheme 2), a key
intermediate in decarboxylative allylations is believed to be
allylpalladium(II) α-oxocarboxylate complex C formed by
We have recently shown that decarboxylative allylations
can also be performed with carboxylates for which the ex-
trusion of CO2 leads to non-stabilized carbon nucleo-
philes.[11] In the presence of a bifunctional catalyst con-
sisting of a palladium complex and an excess amount of
P(pTol)3, allyl α-oxocarboxylates were converted into α,β-
unsaturated ketones via
a decarboxylative allylation/
double-bond migration cascade. In this protocol, the de-
carboxylation step is promoted by the phosphane as an or-
ganocatalyst, whereas the C–C bond formation takes place
[a] Department of Chemistry, University of Kaiserslautern
Erwin-Schrödinger-Strasse 54, 67663 Kaiserslautern, Germany
Fax: +49-631-205-3921
E-mail: goossen@chemie.uni-kl.de
Homepage: http://www.chemie.uni-kl.de/goossen
[‡] Present address: Departamento de Química Orgánica, Facultad
de Ciencias, Universidad Autónoma de Madrid, Cantoblanco,
28049 Madrid, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200766.
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F. Manjolinho, M. F. Grünberg, N. Rodríguez, L. J. Gooßen
SHORT COMMUNICATION
oxidative addition of the ester to palladium(0) species A. Table 1. Development of the catalyst system.[a]
We reasoned that such species could also be generated by
reaction of allylpalladium(II) allyl carbonate species B
formed via the analogous oxidative addition of allyl carb-
onate to palladium(0) in the presence of an α-oxocarboxylic
acid.[15] The release of CO2 gas along with allyl alcohol
Entry
Catalyst
Phosphane
Solvent
Yield [%][b]
would render this step irreversible. The decarboxylation of
the α-oxocarboxylate, which was previously shown to be
mediated by an excess amount of phosphane, should give
rise to acylpalladium(II) allyl complex E. The allyl ketone
would then be liberated via reductive elimination and iso-
merize into the α,β-unsaturated compound under the reac-
tion conditions. Even without auxiliary base, competing
protodecarboxylation should be comparatively slow, as the
allyl alcohol should not be sufficiently acidic to promote
protodeacylation of E with formation of the corresponding
aldehyde and an allyl ether. If this mechanistic concept is
viable, it should be possible to convert α-oxocarboxylic ac-
ids into α,β-unsaturated ketones by reaction with diallyl
carbonate in the presence of a palladium/phosphane cata-
lyst.
1
2
3
4
5
6
7
8
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(acac)2
Pd(OAc)2
[(cinnamyl)PdCl]2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd2(dba)3
–
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
P(pTol)3
PPh3
toluene
mesitylene
1,4-dioxane
diglyme
DMPU
DMF
7
4
77
22
39
13
5
DMSO
ethanol
0
9
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
44
33
17
97
63
33
42
29
95
89
36
0
10
11
12
13
14
15
16
17[c]
18[d]
19
20
21
P(p-F-C6H4)3 1,4-dioxane
PCy3
BINAP
P(pTol)3
P(pTol)3
–
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
–
P(pTol)3
0
[a] Reaction conditions: phenylglyoxylic acid (1, 1.00 mmol), diallyl
carbonate (2, 1.00 mmol), catalyst (5 mol-%), phosphane (25 mol-
%), solvent (8.0 mL), 12 h, 100 °C. [b] Yield determined by GC
analysis using n-dodecane as an internal standard. [c] 4 h. [d] 80 °C.
consist in assisting the coordination of carbon residues, as
reported for Pd-enolates.[3,16]
A test of various palladium sources revealed that palla-
dium(0) complexes displayed higher yields than palladi-
um(II) salts. Almost quantitative conversion was reached
with Pd(PPh3)4. This may in part be due to an increase in
phosphane concentration, as the decarboxylation is medi-
ated by the phosphane. The use of PPh3 instead of
P(pTol)3 led to lower yields (Table 1, entry 13). Further ex-
periments with various phosphanes confirmed that
P(pTol)3 is the optimal decarboxylation catalyst (Table 1,
entry 12), whereas triaryl phosphanes with different elec-
tronic properties (Table 1, entry 14), trialkyl phosphanes
(Table 1, entry 15), or bidentate phosphanes (Table 1, en-
Scheme 2. Proposed decarboxylative allylation mechanism.
Results and Discussion
To search for an effective catalyst system, we chose the try 16) gave inferior yields. Further studies revealed that al-
reaction of phenylglyoxylic acid with diallyl carbonate as a most full conversion could be reached within 4 h at 100 °C
test system and began with the optimized conditions for the (Table 1, entry 17), and that the yields are only marginally
intramolecular decarboxylative allylation of allyl-2-oxoacet- lower at 80 °C (Table 1, entry 18). With Pd(PPh3)4, modest
ate. In the presence of a combination of Pd2(dba)3 and yields were achieved (Table 1, entry 19), presumably due to
P(pTol)3 in toluene at 100 °C, the desired product was in- a partial dissociation of phosphanes from the complex. This
deed formed, albeit in modest yields (Table 1, entry 1).
was confirmed by a control experiment in which a phos-
Systematic studies revealed that the solvent had a pro- phane-free palladium catalyst was used and no additional
found influence on the reaction outcome. Whereas non-po- phosphane was added (Table 1, entry 20). Without palla-
lar solvents gave unsatisfactory yields (Table 1, entries 1 & dium, no conversion was observed (Table 1, entry 21).
2), the use of moderately polar, coordinating solvents and
We next investigated the scope of the optimized intermo-
1,4-dioxane in particular, were substantially more effective lecular decarboxylative allylation protocol. The scope and
(Table 1, entries 3–5). Strongly polar aprotic (Table 1, en- limitations (Table 2) are very similar to those observed for
tries 6 & 7) or protic solvents (Table 1, entry 8) also led to reactions starting from preformed allyl esters.[11] Arylglyox-
low conversions. The beneficial effect of 1,4-dioxane may ylic acids with common functionalities such as halides, cy-
2
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Decarboxylative Allylation of Glyoxylic Acids with Diallyl Carbonate
ano and methoxy groups, as well as heterocyclic derivatives of allyl esters, but obviates the laborious synthesis and puri-
were converted in good yields into the corresponding α,β- fication of these substrates. It is broadly applicable to aryl-
unsaturated ketones. Arylglyoxylic acids bearing electron- glyoxylic acid bearing various functional groups. Present
poor nitro substituents were converted in only 10% yield. work is directed towards extending this decarboxylative al-
The reason for this low yield could not yet be elucidated. lylation strategy to other carboxylic acid substrate classes.
As observed also for intramolecular reactions, the intermo-
lecular version does not yet allow the conversion of alkyl-
glyoxylic acids.
Experimental Section
Table 2. Scope of the intermolecular decarboxylative allylation.[a]
Standard Procedure for the Synthesis of α,β-Unsaturated Ketones
from α-Oxocarboxylic Acids: A 20-mL crimp cap vessel was
charged with tetrakis(triphenylphosphane)palladium(0) (57.6 mg,
0.05 mmol) and tri-p-tolylphosphane (77.6 mg, 0.25 mmol). A solu-
tion of the α-oxocarboxylic acid (1.00 mmol) in 1,4-dioxane (8 mL)
and diallyl carbonate (2; 144 μL, 1.00 mmol) were added via sy-
ringe. The reaction mixture was stirred at 100 °C for 12 h and then
cooled to room temperature. The solvent was removed in vacuo
(40 °C, 107 mbar), and the remaining residue was further purified
by flash chromatography (SiO2; ethyl acetate/hexane, 1:10) to yield
products 3a–p (52–99%).
Synthesis of (E)-1-Phenylbut-2-en-1-one (3a): Compound 3a [CAS:
495-41-0] was prepared following the standard procedure, starting
from phenylglyoxylic acid (1a; 150 mg, 1.00 mmol). After purifica-
tion, 3a was isolated as a yellow oil (145 mg, 99%). 1H NMR
(400 MHz, CDCl3): δ = 7.92 (m, 2 H), 7.56 (m, 1 H), 7.45 (m, 2
H), 7.07 (m, 1 H), 6.93 (dq, J = 1.6 Hz, 1 H), 1.99 (dd, J = 6.8,
1.6 Hz, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 190.7, 144.9,
137.8, 132.5, 128.4 (4 C), 127.5, 18.5 ppm. C10H10O (146.19): calcd.
C 82.16, H 6.19; found C 82.19, H 6.22.
Supporting Information (see footnote on the first page of this arti-
cle): Characterization data for all compounds, copies of the 1H
NMR and 13C NMR spectra.
Acknowledgments
We thank Saltigo GmbH for financial support, the Alexander
von Humboldt Foundation (N. R.) and the Stipendienstiftung
Rheinland-Pfalz (M. F. G.) for fellowships.
[1] For selected examples of decarboxylative couplings, see: a)
A. G. Myers, D. Tanaka, M. R. Mannion, J. Am. Chem. Soc.
2002, 124, 11250–11251; b) L. J. Gooßen, G. Deng, L. Levy,
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St-Onge, K. H. Thesen, M. D. Bailey, F. Bilodeau, J. Am.
Chem. Soc. 2006, 128, 11350–11351; d) L. J. Gooßen, F. Rudol-
phi, C. Oppel, N. Rodríguez, Angew. Chem. 2008, 120, 3085–
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Chem. Soc. 2012, 134, 9938–9941.
[a] Reaction conditions: arylglyoxylic acid 1 (1.00 mmol), diallyl
carbonate (2, 1.00 mmol), Pd(PPh3)4 (5 mol-%), P(pTol)3 (25 mol-
%), 1,4-dioxane (8.0 mL), 12 h, 100 °C, isolated yields. [b] 35 mol-
% P(pTol)3. [c] Yield determined by GC analysis using n-dodecane
as an internal standard.
[2] For recent reviews on decarboxylative couplings, see: a) N.
Rodríguez, L. J. Gooßen, Chem. Soc. Rev. 2011, 40, 5030–5048;
b) R. Shang, L. Liu, Sci. China Chem. 2011, 54, 1670–1687; c)
J. Cornella, I. Larrosa, Synthesis 2012, 653–676; d) W. I. Dzik,
P. P. Lange, L. J. Gooßen, Chem. Sci. 2012, DOI: 10.1039/
C2SC20312J.
[3] For a review on decarboxylative allylations, see: J. D. Weaver,
A. Recio, A. J. Grenning, J. A. Tunge, Chem. Rev. 2011, 111,
1846–1913.
Conclusions
An intermolecular decarboxylative allylation of aryl-
glyoxylic acids with diallyl carbonate has been developed as
an expedient synthetic entry to α,β-unsaturated ketones.
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SHORT COMMUNICATION
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Received: June 8, 2012
Published Online: ᭿
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Decarboxylative Allylation of Glyoxylic Acids with Diallyl Carbonate
Decarboxylative Allylation
F. Manjolinho, M. F. Grünberg,
N. Rodríguez, L. J. Gooßen* ............. 1–5
Decarboxylative Allylation of Glyoxylic
Acids with Diallyl Carbonate
An efficient and mild protocol for the inter-
molecular decarboxylative allylation of
arylglyoxylic acids with diallyl carbonate is
described. Using P(pTol)3 as an organocat-
alyst, acyl anion equivalents are generated
in situ from the corresponding arylglyox-
ylic acid, followed by palladium-catalyzed
allylation and isomerization to afford α,β-
unsaturated ketones in good to excellent
yields.
Keywords: Allylation / C–C bond forma-
tion / Decarboxylation / Palladium / Or-
ganocatalysis
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