Straightforward synthesis of allylated keto esters: The palladium-catalysed haloketone alkoxycarbonylation/allylation domino reaction

Article abstract of DOI:10.1002/adsc.201100848

The palladium-catalysed α-chloro ketone methoxycarbonylation and allylic alkylation reactions can be efficiently combined to provide a new catalytic domino reaction. The first, carbonylative, step generates the β-keto ester, which acts as the nucleophile in a subsequent allylation step. The use of allyl phenates in combination with Xantphos ligand are the key features allowing one to obtain the allylated β-keto esters in good yields Copyright

Full text of DOI:10.1002/adsc.201100848

FULL PAPERS
DOI: 10.1002/adsc.201100848
Straightforward Synthesis of Allylated Keto Esters: The
Palladium-Catalysed Haloketone Alkoxycarbonylation/
Allylation Domino Reaction
Benoit Wahl,a Steven Giboulot,b Andrꢀ Mortreux,a Yves Castanet,a
Mathieu Sauthier,a,* Frꢀdꢀric Liron,b and Giovanni Polib
a
Unitꢀ de Catalyse et Chimie du Solide, UMR CNRS 8181, Universitꢀ Lille Nord de France, ENSCL BP 90108, 59652
Villeneuve d’Ascq, France
Fax : (+33)-3-2033-6301; e-mail: mathieu.sauthier@univ-lille1.fr
UPMC Univ Paris 06, Institut Parisien de Chimie Molꢀculaire, UMR CNRS 7201, FR2769, case 183, F-75252, Paris cedex
b
05, France
Received: October 28, 2011; Revised: December 22, 2011; Published online: March 27, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100848.
Abstract: The palladium-catalysed a-chloro ketone allyl phenates in combination with Xantphos ligand
methoxycarbonylation and allylic alkylation reac- are the key features allowing one to obtain the ally-
tions can be efficiently combined to provide a new lated b-keto esters in good yields
catalytic domino reaction. The first, carbonylative,
step generates the b-keto ester, which acts as the nu- Keywords: allylic alkylation; carbon monoxide; cat-
cleophile in a subsequent allylation step. The use of alysis; domino reaction; selectivity
Introduction
a non-exhaustive list: hydroformylation (with syngas)/
acetal formation and related sequences,[6] radical reac-
The multi-step synthesis of complex organic mole- tions involving CO,[7] multicomponent carbonylative
cules often results in the generation of large amounts coupling reactions[8] such as 1,3-dipolar cycloadditions
of wastes due to the numerous solvent-consuming pu- involving mꢁnchnones,[9] carbopalladation/carbonyla-
rification procedures at each stage of the synthesis.[1] tion sequences,[10] and allylic alkylation/Pauson–
Domino-type transformations that involve metal-cata- Khand sequences.[11] In most cases the carbonylation
lysed reactions have consequently emerged as green step occurs at the end of the sequence, which closes
and efficient synthetic tools as they allow the one- through an intra- or intermolecular trapping of a palla-
step construction of elaborated molecules with a re- dium-carbonyl intermediate.
duced environmental impact.[2] However, the elabora-
Our project focussed on the development of a palla-
tion of a domino reaction may often meet with drastic dium-catalysed pseudo-domino type I[12] sequence in-
difficulties and limitations. Indeed, a number of in- volving the alkoxycarbonylation of an a-chloro
compatibilities between the reactants and the catalytic ketone, followed by allylation of the transiently
system, present from the outset of the reaction, may formed b-keto ester (Scheme 1).
arise and lead to side products and/or catalyst poison-
ing. Hence, the consecutive elementary steps building
up a domino process have to be carefully and ration- Results and Discussion
ally chosen when planning a new such sequence.
We targeted to develop new catalytic domino[3] se- Our primary objective was to find out the common
quences involving carbon monoxide as a cheap and key parameters allowing the achievement of the two
readily available carbonyl source,[4] for the straightfor- consecutive reactions using the same catalytic system
ward one-pot construction of specific building blocks. and enolising system.
The literature witnesses several precedents of domino
We then settled to study first the second step of our
and/or multicomponent sequences entailing carbony- sequence, taking as a model the reaction between
lative steps.[5] The following examples represent
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Scheme 1. The palladium-catalysed methoxycarbonylation/allylation domino sequence.
Scheme 2. The palladium-catalysed reaction between methyl acetoacetate and cinnamyl acetate.
methyl acetoacetate and cinnamyl acetate (Scheme 2 sired domino reaction, the allylic alkylation was also
and Table 1). performed under a CO atmosphere. Under such con-
The palladium-catalysed methoxycarbonylation of ditions, the allylic alkylation still proceeded, although
a-chloro ketones[13] (that would represent the first it was accompanied by the formation of methyl ester
step of our sequence) is best effected using PPh3 as 4, arising from the methoxycarbonylation of cinnamyl
ancillary ligand, MeOH as the solvent, and tributyla- acetate.[17] Interestingly, the selectivity of the reaction
mine as the base.[14] Accordingly, we started our study was strongly dependent on the nature of the ligand
using the catalytic system [PdACTHNURGTENUNG(acac)2/PPh3 (1/4 ratio)], used. In particular, large amounts of 4 were obtained
MeOH as the solvent, and NBu3 as the base.[15] We when using PPh3 (entry 3), to the detriment of the tar-
also decided to use an excess of the allyl acetate geted products 1aa and 2aa, whereas the allylation re-
(2.5 equiv.), as this reaction partner may be involved action remained efficient with Xantphos (entry 4).
(and thus consumed) in side reactions (see below). This observation is coherent with the fact that mono-
This experiment gave a mixture of mono- and bis-al- phosphines are more commonly used than diphos-
lylated linear b-keto esters 1aa and 2aa in 18:82 ratio phines for the carbonylation of allylic acetates, halides
(entry 1). The reaction also yielded cinnamyl methyl or carbonates.
ether[16] 3 as side product, resulting from attack of
Although the side products 3 and 4 were formed in
methanol on the h3-allylpalladium intermediate non-negligible amounts, the compatibility of the reac-
formed in excess. The starting materials were entirely tion conditions used for a-chloro ketone methoxycar-
converted and the overall yield in 1aa and 2aa was es- bonylation in b-keto ester allylation was at this point
sentially limited by the competitive formation of the clearly established.
methyl ether 3. A similar result was obtained on
The feasibility of the complete pseudo-domino re-
switching from PPh3 to Xantphos (entry 2). In view of action was studied using chloroacetone as a cheap,
the need of carbonylative conditions during the de- commercially available a-chloro ketone and cinnamyl
derivatives bearing various leaving groups (Scheme 3
and Table 2).
Table 1. The allylic alkylation reaction in methanol.[a]
The reactions were performed under 20 bar of
carbon monoxide with 1% of palladium catalyst asso-
ciated with a phosphorus-based ligand (4/1 P/Pd
ratio) at 708C for 16 h. In line with what was previ-
ously observed in the allylation performed under CO
pressure (Table 1, entry 3), the reaction with PPh3
Entry
Ligandc
PCO
mmol (Yield [%])[a]
1aa
2aa
3
4
1
2
3
4
PPh3
Xantphos
PPh3
0
0
20
20
0.5 (16)
0.3 (10)
0.7 (23)
0.6 (20)
2.3 (77)
2.4 (80)
0.6 (20)
1.8 (60)
0.5
0.7
0.1
0.8
–
–
1.2
0.2
yielded exclusively the carbonylated product
4
(entry 1). Apparently, with the above reaction condi-
Xantphos
[a]
The reaction was carried out at 708C using methyl ace-
toacetate (3.0 mmol), NBu3 (7.5 mmol; 2.5 equiv.),
PdACHTUNGTRENNUNG(acac)2 (0.03 mmol), PPh3 (0.12 mmol) or Xantphos
(0.06 mmol) in MeOH (10 mL) for 16 h.
Amounts determined by GC with undecane as internal
standard. Yields calculated with respect to methyl ace-
toacetate.
[b]
Scheme 3. The palladium-catalysed methoxycarbonylation/
cinnamylation as a pseudo-domino sequence.
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Straightforward Synthesis of Allylated Keto Esters
Table 2. The palladium-catalysed alkoxycarbonylation/allylation domino reaction.[a]
Entry
Ligandc
X (equiv.)[c]
mmol (Yield [%])[b]
1aa
2aa
3
4
1
2
3
4d
5
6
7
PPh3
OAc (2.2)
OAc (2.2)
OAc (3.5)
OAc (2.2)
Cl (2.2)
traces
traces
traces
2.2
4.3
2.5
2.1
4.4
0.9
1.6
0.3
1.0
0.5
0.6
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
0.3 (10)
0.1 (3)
0.3 (10)
0.5 (17)
0.2 (7)
0.4 (13)
1.3 (43)
1.3 (43)
1.1 (35)
1.5 (50)
1.8 (60)
2.5 (83)
MeOCOO (2.2)
OPh (2.2)
1.6
0.6
[a]
The reaction was carried out at 708C using chloroacetone (3.0 mmol), allylic substrate (7.5 mmol, 2.5 equiv.), tributyl-
amine (13.5 mmol; 4.5 equiv.), CO (20 bar), Pd(acac)2 (0.03 mmol), PPh3 (0.12 mmol) or Xantphos (0.06 mmol) in 10 mL
of MeOH for 16 h.
Amounts determined by GC with undecane as internal standard, yields calculated from the amount of chloroacetone
used.
G
ACHTUNGTRENNUNG
[b]
[c]
[d]
Number of equivalents of allylic derivative versus chloroacetone.
The reaction was performed in the presence of AcONa (2.0 equiv. with respect to chloroacetone).
tions, methoxycarbonylation of chloroacetone did not
occur, thereby leaving free access to methoxycarbony-
lation of cinnamyl acetate. However, when PPh3 was
changed for Xantphos, encouraging amounts of the al-
lylated b-keto esters 1aa and 2aa were obtained, al-
though the methyl ether 3 was still the major product
(entry 2). This result suggests that in this case methox-
ycarbonylation of the cinnamyl residue occurs concur-
rently to alkylation. The use of larger amounts of cin-
namyl acetate (entry 3) did not produce better yields,
leading essentially to an increase of the side products
3 and 4. Use of chloride, or methyl carbonate as the
allylic leaving group, classically exploited in palladi-
um-catalysed allylic substitutions, allowed only slight
improvements in the yield of 1 and 2, the formation
of methyl ether 3 remaining in both cases strongly
limiting (entries 5 and 6). Finally, use of the less reac-
tive phenoxy leaving group[18] at the allylic position
Scheme 4. Catalytic cycles involved in the pseudo-domino
sequence. The dashed arrows emphasise the competing oxi-
dative addition paths.
gave the best yields of 1aa and 2aa, which almost at- products. If not, the allylic derivative would be irre-
tained those observed when starting directly from the mediably transformed into the ether 3 or the methyl
b-keto ester, to the detriment of the side products 3 ester 4, and the tardily generated b-keto ester would
and 4 (compare entry 7 of Table 2 with entry 2 of not find any more h3-allyl complex intermediate to in-
Table 1).
This result indicates that under these conditions
tercept.
We believe that the rates of oxidative addition of
methoxycarbonylation of chloroacetone proceeds cinamyl acetate, chloride or methyl carbonate to the
very efficiently and faster than methoxycarbonylation palladium (0) centre are higher than or of the same
of the cinnamyl derivative.
order of magnitude as that of a-chloroacetone. Conse-
The global transformation involves two sequential quently, when using these leaving groups, products 3
catalytic cycles, both initiated by an oxidative addition and 4 are obtained in proportions similar to the ally-
step at the Pd(0) centre (Scheme 4). The former one lated derivatives 1aa and 2aa. On the other hand, use
is started by the a-chloro ketone, whereas the latter of the less reactive phenoxy leaving group allows the
one by the allylic derivative. As the product of the chloro ketone oxidative addition to take place first,
former catalytic cycle becomes the substrate for the thereby permitting the pseudo-domino chain to work
latter one, the success of this pseudo-domino se- efficiently. This picture is clearly confirmed by the
quence depends on the relative rates of the two comparison of the reaction profiles of catalytic runs
cycles. More specifically, the carbonylation rate of the performed with cinnamyl acetate and phenyl cinnam-
ketone derivative has to be higher than leakage of the yl ether (Figure 1). The reaction with cinnamyl ace-
allyl derivative from the second cycle to give the side tate is fast and almost complete within 3 h. Both start-
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~
&
^
Figure 1. Evolution of the allylic starting material ( ), chloroacetone ( ), methyl acetoacetate( ), reactions products 1 (ꢃ)
and 2 ( ), during the domino reaction under 20 bar CO. The dotted lines are drawn to guide the eye. The reaction was per-
J
formed at 708C with 6 mmol of chloroacetone, 13.2 mmol of the noted allylic starting material, 27 mmol of tributylamine,
1 mol% of PdACHTUNGTRENNUNG(acac)2, 2 mol% of Xantphos, and 20 mL of distilled MeOH.
ing materials are rapidly converted, and products 1aa
While chloroacetone always led to mixtures of
and 2aa are formed from the early minutes of the re- mono- and bis-allylated b-keto esters 1aa and 2aa, the
action. Methyl acetoacetate is only obtained in very analogous reaction with chloropinacolone resulted in
small amounts and is likely almost instantaneously the exclusive formation of the mono-allylated product
converted into the allylated products. On the other (entry 4). This fact is very likely due to the steric hin-
hand, the reaction with phenyl cinnamyl ether is drance of the enolate of 1b, which bears a tetrasubsti-
much slower and appears to be more sequential. tuted alkene with a vicinal quaternary carbon atom.
Chloroacetone is still relatively rapidly converted into a-Chloroacetophenone yielded 23% of 1 and 55% of
methyl acetoacetate, whose formation reaches a maxi- 2 (entry 5). On the other hand, variable and more bal-
mum after 2 h. Due to its lower propensity to oxida- anced proportions of allylation products 1 and 2 were
tively add to the Pd(0) centre, a delayed consumption obtained on moving to different aryl-substituted
of phenyl cinnamyl ether is observed. While most of chloroketones (entries 6 and 7). With 2-chloro-
the cinnamyl acetate has reacted within two hours, 1-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-1-ethanone
more than 8 h of reaction were needed to reach (entry 8) the bis-allylated derivative 2 is obtained as
a complete conversion of phenyl cinnamyl ether.
minor product. No correlation could be drawn be-
Using these optimised conditions, the scope of the tween the electronic effect of the ketone substituent
domino reaction was studied with various a-chloro and the 1/2 ratio.
ketones and alcohols (Scheme 5, Table 3).
Secondary chloro ketones led to the formation of
As MeOH is the main alcohol used in alkoxycarbo- quaternary carbons through the allylic alkylation step.
nylation reactions, we settled to extend our study to In this case half the amount of allylic starting material
other less common alcohols, featuring different elec- was used. The derivatives efficiently yielded the ex-
tronic and/or steric properties. In the event, n-BuOH pected products, albeit with lower yields (entries 9–
and i-PrOH showed reactivities similar to that ob- 11).
served with MeOH, affording the mono- and bis-ally-
lated b-keto esters with comparable ratios and yields
(entries 2 and 3). However, with the latter solvent, Conclusions
generation of the ether 3 was favored, to the detri-
ment of the alkoxycarbonylated ester 4. This fact sug- In conclusion, we have shown that the alkoxycarbony-
gests that i-PrOH intercepts more readily the h3-allyl lation of a-chloro ketones and their allylic alkylation
palladium complex than its corresponding acylpalladi- reactions can be efficiently combined to build a new
um complex.
Pd-catalyzed pseudo-domino type I sequence wherein
the same catalytic system drives the two concatenated
cycles. The b-keto ester is intermediately generated
through a carbonylation reaction before being in situ
engaged as nucleophile in the final allylic alkylation
cycle. Tuning the allylic leaving group in the starting
material, as well as the ancillary ligand proved to be
keys to attain the successful combination of the two
Scheme 5. Scope of the reaction.
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Straightforward Synthesis of Allylated Keto Esters
Table 3. Scope of the reaction.[a]
Experimental Section
Entry a-Chloro ketone R’OH
(Yield [%][b])
ACHTUNGTRENNUNG
General Procedure for the Carbonylation/Allylation
Domino Reaction (Table 3)
1
2
1
MeOH
1aa (13) 2aa (83)
Reactions were performed in a stainless steel autoclave
equipped with a magnetic stirrer. 9,9-Dimethyl-4,5-bis(di-
phenylphosphino)xanthene (34.7 mg, 0.06 mmol), and (E)-
cinnamyl phenyl ether (1.577 g, 7.5 mmol) were placed in
the reactor, and the contents were placed under N2. In
2
n-BuOH 1ab (14) 2ab (77)
3[c]
i-PrOH
1ac (12)
1b (62)
2ac (85)
2b (0)
a Schlenk tube, and under N2, a solution of PdACHTUNGTRENNUNG(acac)2
4
5
MeOH
(9.1 mg, 0.03 mmol), tributylamine (3.2 mL, 13.5 mmol) and
chloro ketone (3 mmol) in 10 mL of alcohol was stirred until
a homogeneous solution was obtained. Then, this solution
was transferred to the reactor with a syringe and the reactor
was charged with 15 bar of carbon monoxide. The mixture
was stirred at 908C for 16 h. Then, the reactor was cooled
until room temperature and carefully degassed. The mixture
was diluted with diethyl ether, washed with an HCl solution
(1N), followed by an NaOH solution (1N) until neutralisa-
tion, dried over MgSO4 and concentrated under vacuum.
After flash column chromatography on silica gel (petroleum
ether/ethyl acetate 100:0 to 90:10), the mono-allylated, bis-
allylated, ether and ester were isolated.
MeOH
MeOH
1c (23)
1d (37)
2c (55)
2d (39)
6
7
MeOH
1e (30)
2e (54)
(E)-Methyl
2-acetyl-2-cinnamyl-5-phenylpent-4-enoate
1
8
MeOH
MeOH
1f (65)
1g (53)
2f (5)
(2aa): H NMR (CDCl3, 300 MHz): d=7.27–7.14 (m, 10H,
Ph), 6.40 (d, 2H, J=15.0 Hz, Ph-CH), 5.94 (dt, 2H, 3J=
15.0, 7.5 Hz, CH-CH2), 3.68 (s, 3H, O-CH3), 2.79 (br dd, J=
7.5, 14.5 Hz, 2H, CH2), 2.72 (br dd, J=7.5, 14.5 Hz, 2H,
9[d]
–
CH2), 2.18 (s, 3H, O=C CH3); 13C NMR (CDCl3, 75 MHz):
À
À
À
d=204.2 (CH3 C=O), 172.1 (O C=O), 137.0 (CAr), 134.3
À
(CH=CH< CH2), 128.6 (CHAr), 127.6 (CHAr), 126.3
À
À À
(CHAr), 123.7 (CH=CH CH2), 64.0 (O=C C C=O), 52.6
10[d]
MeOH
MeOH
1h (20)
1i (23)
–
–
À
À
À
(O CH3), 35.9 (CH2 CH=CH), 27.3 (O=C CH3); HR-MS
(ESI): m/z=349.18034, calcd. for C23H25O3 [M+H+]:
349.17982.
(E)-Butyl
2-acetyl-2-cinnamyl-5-phenylpent-4-enoate
11[d]
1
(2ab): H NMR (CDCl3, 300 MHz): d=7.33–7.23 (m, 10H,
À
À
À
HAr), 6.47 [d, 2H, J=15.0 Hz, ( CH=CH CH2 )2], 6.03 [dt,
2H, J=15.0, 7.5 Hz, (CH=CH CH2 )2], 4.18 (t, J=7.2 Hz,
2H, CH2), 2.88 (br dd, J=7.5, 14.5 Hz, 2H, CH2), 2.80 (br
dd, J=7.5, 14.5 Hz, 2H, CH2), 2.22 (s, 3H, O=C CH3), 1.63
(quint, J=7.2 Hz, 2H, O CH2 CH2), 1.37 (sext, J=7.2 Hz,
À
À
[a]
The reaction were carried out at 908C using chloro
ketone (3.0 mmol), phenylcinamyl phenyl ether
À
(7.5 mmol,
2.5 equiv.),
tributylamine
(13.5 mmol,
À
À
4.5 equiv.), PdACHTUNGTRENNUNG(acac)2 (0.03 mmol), Xantphos (0.06 mmol)
in 10 mL of alcohol for 16 h.
À
À
À
2H, O CH2 CH2), 0.92 (t, J=7.2 Hz, 3H, CH2 CH3);
C NMR (CDCl3, 75 MHz): d=204.3 (CH3 C=O), 171.7
13
À
[b]
[c]
[d]
Isolated yields calculated from the amount of chloroace-
tone.
With MeOH, 3 (0.6 mmol) and 4 (0.6 mmol); with i-
PrOH 3 (1 mmol) and 4 (0.1 mmol).
Reaction performed with 3.75 mmol of phenyl cinnamyl
ether.
À
À
(O C=O), 137.0 (CAr), 134.2 (CH=CH CH2), 128.6 (CHAr),
À
127.6 (CHAr), 126.3 (CHAr), 123.8 (CH=CH CH2), 65.5
À
À
À À
À
(CH2 CH2 CH2), 64.0 (O=C C C=O), 35.9 (CH2 CH=
CH), 30.6 (CH2 CH2 CH2), 27.3 (O=C CH3), 19.3 (CH2
À
À
À
À
À
CH3), 13.7 (CH2 CH3); HR-MS (ESI): m/z=391.22738,
calcd. for C26H31O3 [M+H+]: 391.22677.
(E)-Isopropyl
2-acetyl-5-phenylpent-4-enoate
(1ac):
1H NMR (CDCl3, 300 MHz): d=7.23–7.13 (m, 5H, HAr),
metal-catalysed reactions in the correct succession. In
particular, the use of less reactive phenates allowed
great improvements compared to acetates, as revealed
by kinetic experiments. Noteworthy, the reaction in-
volves only a single palladium catalyst to promote the
two steps at relatively moderate catalyst loadings.
Further studies are aimed at applying this procedure
to intramolecular domino sequences for the synthesis
of highly functionalised cyclic structures.
À
À
À
6.38 (d, J=16.0 Hz, 1H, CH=CH CH2 ), 6.04 (dt, J=16.0,
À
À
À
6.0 Hz, 1H, CH=CH CH2 ), 5.00 (sept, J=6.3 Hz, 1H,
À
À
O CH), 3.48 (t, J=7.4 Hz, 1H, O=C CH), 3.48 (t, J=
7.4 Hz, 2H, CH2), 2.18 (s, 3H, O=C CH3), 1.17 (d, J=
6.0 Hz, 3H, CH CH3), 1.16 (d, J=6.0 Hz, 3H, CH CH3);
C NMR (CDCl3, 75 MHz): d=202.7 (CH3 C=O), 168.9
(O C=O), 137.1 (CAr), 132.8 (CH=CH CH2), 128.6 (CHAr),
127.5 (CHAr), 126.3 (CHAr), 125.9 (CH=CH CH2), 69.3
À
À
À
13
À
À
À
À
À
À
À
À
[(CH3)2 CH], 59.9 (CH2 CH C=O), 31.6 (CH2 CH=CH),
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Benoit Wahl et al.
FULL PAPERS
À
À
À
29.3 (O=C CH3), 21.9 (CH CH3), 21.8 (CH CH3); HR-MS
(ESI): m/z=261.14857, calcd. for C16H21O3 [M+H+]:
261.14852.
14.5 Hz, 1H, CH2); 13C NMR (CDCl3, 75 MHz): d=193.3
À
À
(Ar C=O), 169.7 (O C=O), 140.4 (CAr), 137.0 (CAr), 134.5
À
(CAr), 133.0 (CH=CH CH2), 130.2 (CHAr), 129.3 (CHAr),
À
(E)-Isopropyl 2-acetyl-2-cinnamyl-5-phenylpent-4-enoate
(2ac): H NMR (CDCl3, 300 MHz): d=7.24–7.15 (m, 10H,
HAr), 6.39 [d, 2H, J=15.0 Hz, ( CH=CH CH2 )2], 5.95 [dt,
2H, J=15.0, 7.5 Hz, (CH=CH CH2 )2], 5.02 (sept, J=
128.6 (CHAr), 127.6 (CHAr), 126.3 (CHAr), 125.8 (CH=CH
1
À
À
À
À
CH2), 54.2 (CH2 CH C=O), 52.8 (O CH3), 32.5 (CH2
CH=CH); HR-MS (ESI): m/z=329.09433, calcd. for
C19H18ClO3 [M+H+]: 329.09390.
À
À
À
À
À
À
6.3 Hz, 1H, O CH), 2.77 (br dd, J=7.5, 14.5 Hz, 2H, CH2),
(E)-Methyl 2-(4-chlorobenzoyl)-2-cinnamyl-5-phenylpent-
1
À
2.70 (br dd, J=7.5, 14.5 Hz, 2H, CH2), 2.13 (s, 3H, O=C
4-enoate (2d): H NMR (CDCl3, 300 MHz): d=7.74 (d, J=
CH3), 1.17 [d, J=6.0 Hz, 6H, (CH3)2]; 13C NMR (CDCl3,
8.0 Hz, 2H, Hortho), 7.35 (d, J=8.0 Hz, 2H, Hmeta), 7.22–7.13
À
À
À
À
À
75 MHz): d=204.3 (CH3 C=O), 171.0 (O C=O), 137.0
(m, 10H, HAr), 6.29 [d, J=16.0 Hz, 2H, ( CH=CH CH2
À
À
À
À
(CAr), 134.0 (CH=CH CH2), 128.5 (CHAr), 127.5 (CHAr),
)2], 5.89 [dt, J=16.0, 7.5 Hz, 2H, ( CH=CH CH2 )2], 3.60
À
À
À
126.2 (CHAr), 123.7 (CH=CH CH2), 69.2 [(CH3)2 CH], 63.8
(s, 3H, O CH3), 2.95 (br dd, J=7.5, 14.5 Hz, 2H, CH2), 2.87
(br dd, J=7.5, 14.5 Hz, 2H, CH2); 13C NMR (CDCl3,
À À
À
À
(O=C C C=O), 35.7 (CH2 CH=CH), 27.1 (O=C CH3),
21.7 [(CH3)2]; HR-MS (ESI): m/z=377.21170, calcd. for
C25H29O3 [M+H+]: 377.21112.
À
À
75 MHz): d=195.0 (Ar C=O), 173.2 (O C=O), 139.6 (CAr),
137.1 (CAr), 134.6 (CAr), 134.3 (CH=CH CH2), 130.0
(CHAr), 129.2 (CHAr), 128.7 (CHAr), 127.7 (CHAr), 126.4
À
(E)-Methyl
5-phenyl-2-pivaloylpent-4-enoate
(1b):
1H NMR (CDCl3, 300 MHz): d=7.28 (m, 5H, HAr), 6.46 (d,
(CHAr), 123.3 (CH=CH CH2), 61.4 (O=C C C=O), 52.7
À
À À
À
À
À
À
À
J=16.0 Hz, 1H, CH=CH CH2 ), 6.12 (dt, J=16.0, 7.0 Hz,
(O CH3), 37.1 (CH2 CH=CH); HR-MS (ESI): m/z=
445.15802, calcd. for C28H26ClO3 [M+H+]: 445.15650.
À
À
À
1H, CH=CH CH2 ), 4.07 (dd, J=7.2, 7.2 Hz, 1H, CH),
À
3.72 (s, 3H, O CH3), 2.77 (ddd, J=7.0, 7.2, 14.5 Hz, 1H,
CH2), 2.73 (ddd, J=7.0, 7.2, 14.5 Hz, 1H, CH2), 1.19 [s, 9H,
(CH3)3]; C NMR (CDCl3, 75 MHz): d=209.5 [(CH3)3CH
C=O), 169.8 (O C=O), 137.1 (CAr), 132.8 (CH=CH CH2),
128.6 (CHAr), 127.5 (CHAr), 126.2 (CH=CH CH2 and
CHAr), 52.5 (O CH3 and CH C=O), 45.5 [C
(E)-Methyl
2-(4-fluorobenzoyl)-5-phenylpent-4-enoate
(1e): 1H NMR (CDCl3, 300 MHz): d=8.07 (m, 2H, HAr),
13
À
À
7.38–7.14 (m, 7H, HAr), 6.50 [d, J=16.0 Hz, 2H, ( CH=
CH CH2 )2], 6.19 [dt, J=16.0, 7.0 Hz, 2H, ( CH=CH
CH2 )2], 4.47 (dd, J=7.2, 7.2 Hz, 1H, CH), 3.72 (s, 3H, O
À
À
À
À
À
À
À
À
À
À
À
(CH3)3], 33.5
CH3), 2.94 (ddd, J=7.0, 7.2, 14.5 Hz, 1H, CH2), 2.92 (ddd,
J=7.0, 7.2, 14.5 Hz, 1H, CH2); 13C NMR (CDCl3, 75 MHz):
À
(CH2 CH=CH), 26.2 [(CH3)3]; HR-MS (ESI): m/z=
275.16441, calcd. for C17H23O3 [M+H+]: 275.16417.
d=192.8 (Ar C=O), 169.7 (O C=O), 137.0 (CAr), 132.9
(CAr), 131.5 (CAr), 131.4 (CH=CH CH2), 128.5 (CHAr),
127.4 (CHAr), 126.2 (CHAr), 125.8 (CHAr), 116.2 (CHAr),
115.9 (CH=CH CH2), 54.1 (CH2 CH C=O), 52.7 (O
À
À
À
(E)-Methyl
2-benzoyl-5-phenylpent-4-enoate
(1c):
1H NMR (CDCl3, 300 MHz): d=7.94 (d, J=8.0 Hz, 2H,
Hortho), 7.52 (t, J=7.5 Hz, 1H, Hpara), 7.42 (t, J=7.6 Hz, 2H,
À
À
À
À
À
À
Hmeta), 7.22–7.13 (m, 5H, HAr), 6.40 (d, J=16.0 Hz, 1H,
CH=CH CH2 ), 6.14 (dt, J=16.0, 7.0 Hz, 1H, -CH=CH
CH2 ), 4.42 (dd, J=7.2, 7.2 Hz, 1H, CH), 3.62 (s, 3H, O
CH3), 32.4 (CH2 CH=CH); HR-MS (ESI): m/z=313.12385,
calcd. for C19H18FO3 [M+H+]: 313.12345.
À
À
À
À
À
(E)-Methyl 2-cinnamyl-2-(4-fluorobenzoyl)-5-phenylpent-
4-enoate (2e): H NMR (CDCl3, 300 MHz): d=7.93 (m, 2H,
HAr), 7.38–7.21 (m, 10H, HAr), 7.15 (m, 2H, HAr), 6.39 [d,
1
CH3), 2.85 (ddd, J=7.0, 7.2, 14.5 Hz, 1H, CH2), 2.83 (ddd,
J=7.0, 7.2, 14.5 Hz, 1H, CH2); 13C NMR (CDCl3, 75 MHz):
À
À
À
À
À
d=194.5 (Ph C=O), 170.0 (O C=O), 137.2 (CAr), 136.2
À
(CAr), 133.8 (CH=CH CH2), 132.9 (CHAr), 129.0 (CHAr),
128.8 (CHAr), 128.6 (CHAr), 127.5 (CHAr), 126.3 (CHAr),
126.1 (CH=CH CH2), 54.2 (CH2 CH C=O), 52.7 (O
À
À
À
À
À
À
CH3), 32.6 (CH2 CH=CH); HR-MS (ESI): m/z=295.13306,
(Ar C=O), 173.3 (O C=O), 137.1 (CAr), 134.6 (CAr), 131.4
calcd. for C19H19O3 [M+H+]: 295.13287.
(CAr), 131.2 (CH=CH CH2), 128.7 (CHAr), 127.6 (CHAr),
(E)-Methyl 2-benzoyl-2-cinnamyl-5-phenylpent-4-enoate
(2c): 1H NMR (CDCl3, 300 MHz): d=7.88 (d, J=8.0 Hz,
2H, Hortho), 7.57 (t, J=7.5 Hz, 1H, Hpara), 7.47 (t, J=7.6 Hz,
2H, Hmeta), 7.34–7.22 (m, 10H, HAr), 6.38 [d, J=16.0 Hz,
126.4 (CHAr), 123.4 (CHAr), 116.1 (CHAr), 115.8 (CH=CH
À À
À
CH2), 61.3 (O=C C C=O), 52.7 (O CH3), 37.1 (CH2 CH=
CH); HR-MS (ESI): m/z=429.18749, calcd. for C28H26FO3
[M+H+]: 429.18605.
À
À
À
À
2H, ( CH=CH CH2 )2], 6.02 [dt, J=16.0, 7.5 Hz, 2H, (
(E)-Methyl
2-(2,5-dimethyl-1-phenyl-1H-pyrrole-3-car-
CH=CH CH2 )2], 3.69 (s, 3H, O CH3), 3.06 (br dd, J=7.5,
bonyl)-5-phenylpent-4-enoate (1f): 1H NMR (CDCl3,
300 MHz): d=7.52–7.46 (m, 3H, HAr), 7.34–7.16 (m, 7H,
À
À
À
14.5 Hz, 2H, CH2), 2.99 (br dd, J=7.5, 14.5 Hz, 2H, CH2);
C NMR (CDCl3, 75 MHz): d=196.2 (Ph C=O), 176.3 (O
C=O), 137.2 (CAr), 136.0 (CAr), 134.4 (CH=CH CH2), 133.0
(CHAr), 128.8 (CHAr), 128.6 (CHAr), 128.5 (CHAr), 127.6
13
À
À
À
À
À
HAr), 6.49 (d, J=16.0 Hz, 1H, CH=CH CH2 ), 6.40 (s,
1H, CHpyrrole), 6.23 (dt, J=16.0, 6.0 Hz, 1H, CH=CH
À
À
À
À
À
CH2 ), 4.20 (t, J=7.2 Hz, 1H, CH), 3.74 (s, 3H, O CH3),
2.90 (ddd, J=7.0, 7.2, 14.5 Hz, 1H, CH2), 2.88 (ddd, J=7.0,
À
À À
(CHAr), 126.4 (CHAr), 123.6 (CH=CH CH2), 61.4 (O=C C
À
À
C=O), 52.6 (O CH3), 37.1 (CH2 CH=CH); HR-MS (ESI):
7.2, 14.5 Hz, 1H, CH2), 2.32 (s, 3H, CH3pyrrole), 1.98 (s, 3H,
m/z=411.19575, calcd. for C28H27O3 [M+H+]: 411.19547.
CH3pyrrole); C NMR (CDCl3, 75 MHz): d=190.3 (pyrr C=
13
À
À
(E)-Methyl
2-(4-chlorobenzoyl)-5-phenylpent-4-enoate
O), 170.8 (O C=O), 138.0 (CAr), 137.4 (CAr), 137.1 (CAr)
(entry 1d): 1H NMR (CDCl3, 300 MHz): d=7.88 (d, J=
8.0 Hz, 2H, Hortho), 7.38 (d, J=8.0 Hz, 2H, Hmeta), 7.22–7.14
132.1 (CAr), 129.5 (CAr), 129.2 (CH=CH CH2), 128.8
À
(CHAr), 128.5 (CHAr), 128.0 (CHAr), 127.2 (CHAr), 127.1
À
À
À
(m, 5H, HAr), 6.40 (d, J=16.0 Hz, 1H, CH=CH CH2 ),
(CHAr), 126.2 (CHAr), 119.3 (CH=CH-CH2), 107.6
À
À
À
À
À
À
6.09 (dt, J=16.0, 7.0 Hz, 1H, CH=CH CH2 ), 4.36 (dd,
(CHpyrrole), 56.0 (O=C CH ), 52.3 (O CH3), 32.7 (CH2),
13.2 (CH3pyrrole), 12.8 (CH3pyrrole); HR-MS (ESI): m/z=
388.19156, calcd. for C25H26NO3 [M+]: 388.19072.
À
J=7.2, 7.2 Hz, 1H, CH), 3.62 (s, 3H, O CH3), 2.83 (ddd,
J=7.0, 7.2, 14.5 Hz, 1H, CH2), 2.81 (ddd, J=7.0, 7.2,
1082
asc.wiley-vch.de
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1077 – 1083

Straightforward Synthesis of Allylated Keto Esters
(E)-Methyl 2-acetyl-2-methyl-5-phenylpent-4-enoate (1g):
1H NMR (CDCl3, 300 MHz): d=7.33–7.23 (m, 5H, HAr),
6.45 (d, J=16.0 Hz, 1H, CH=CH CH2 ), 6.06 (dt, J=16.0,
[4] a) G. P. Chiusoli, M. Costa, in: Handbook of Organo-
palladium Chemistry for Organic Synthesis, (Ed.: E.
Negishi), John Wiley & Sons, Hoboken, N.J., 2002, Vol.
2, pp 2595–2621; b) X.-F. Wu, H. Neumann, M. Beller,
Chem. Soc. Rev., 2011, 40, 4986, and references quoted
therein.
À
À
À
À
À
À
À
6.0 Hz, 1H, CH=CH CH2 ), 3.76 (s, 3H, O CH3), 2.81
(br dd, J=7.5, 14.5 Hz, 2H, CH2), 2.67 (br dd, J=7.5,
À
14.5 Hz, 2H, CH2), 2.20 (s, 3H, O=C CH3), 1.41 (s, 3H,
13
À
CH3); C NMR (CDCl3, 75 MHz): d=205.1 (CH3 C=O),
[5] A. Heumann, M. Rꢀglier, Tetrahedron 1996, 52, 9289.
[6] Topics in Organometallic Chemistry, (Ed.: M. Beller),
Vol 18, Springer-Verlag, Berlin, Heidelberg, 2006.
[7] a) I. M. Brinza, A. G. Fallis, J. Org. Chem. 1996, 61,
3580–3581; b) S. Tsunoi, I. Ryu, S. Yamasaki, M.
Tanaka, N. Sonoda, M. Komatsu, Chem. Commun.
1997, 1889–1890; c) I. Ryu, H. Kuriyama, S. Minakata,
M. Komatsu, J.-Y. Yoon, S. Kim, J. Am. Chem. Soc.
1999, 121, 12190–12191; d) K. Miura, M. Tojino, N. Fu-
jisawa, A. Hosomi, I. Ryu, Angew. Chem. 2004, 116,
2477–2479; Angew. Chem. Int. Ed. 2004, 43, 2423–2425.
[8] M. D. Mihovilovic, P. Stanetty Angew. Chem. 2007, 119,
3684–3688; Angew. Chem. Int. Ed. 2007, 46, 3612–3615.
[9] A. R. Siamaki, B. A. Arndtsen, J. Am. Chem. Soc.
2006, 128, 6050–6051. R. Dhawan, R. D. Dghaym, D. J.
St. Cyr, B. A. Arndtsen, Org. Lett. 2006, 8, 3927–3930.
[10] a) T. Sugihara, C. Copꢀret, Z. Owczarczyk, L. S. Har-
ring, E.-I. Negishi J. Am. Chem. Soc. 1994, 116, 7923–
7924; b) E.-i. Negishi, G. Wang, G. Zhu, Top. Organo-
met. Chem, 2006, 19, 1–48.
[11] N. Jeong, S. D. Seo, J. Y. Shin, J. Am. Chem. Soc. 2000,
122, 10220–10221; S. U. Son, K. H. Park, Y. K. Chung,
J. Am. Chem. Soc. 2002, 124, 6838–6839.
[12] a) G. Poli, G. Giambastiani, Tetrahedron 2000, 56,
5959–5989; b) G. Poli, G. Giambastiani, J. Org. Chem.
2002, 67, 9456–9459; c) G. Prestat, G. Poli, Chemtracts:
Org. Chem. 2004, 17, 97–103.
[13] a) J. K. Stille, P. K. Wong, J. Org. Chem. 1975, 40, 532–
534; b) S. R. Adapa, C. S. N. Prasad, J. Chem. Soc.
Perkin Trans. 1 1989. 1, 1706–1707.
À
À
173.0 (O C=O), 137.0 (CAr), 134.0 (CH=CH CH2), 128.5
(CHAr), 127.4 (CHAr), 126.2 (CHAr), 124.2 (CH=CH CH2),
59.9 (O=C C C=O), 52.5 (O CH3), 38.7 (CH2 CH=CH),
À
À À
À
À
À
26.4 (O=C CH3), 19.2 (CH3); HR-MS (ESI): m/z=
247.13340, calcd. for C15H19O3 [M+H+]: 247.13287.
(E)-methyl 2-benzoyl-2,5-diphenylpent-4-enoate (1h):
1H NMR (CDCl3, 300 MHz): d=7.65 (d, J=8.0 Hz, 2H,
HAr), 7.53 (d, J=8.0 Hz, 2H, HAr), 7.33–7.11 (m, 11H, HAr),
À
À
À
6.18 (d, J=16.0 Hz, 1H, CH=CH CH2 ), 6.06 (dt, J=16.0,
À
À
À
À
6.0 Hz, 1H, CH=CH CH2 ), 3.51 (s, 3H, O CH3), 3.25
(br dd, J=7.5, 14.5 Hz, 2H, CH2), 2.96 (br dd, J=7.5,
14.5 Hz, 2H, CH2); 13C NMR (CDCl3, 75 MHz): d=195.1
À
À
(Ph C=O), 171.5 (O C=O), 138.2 (CAr), 137.4 (CAr), 135.8
(CAr), 133.8 (CH CH CH2), 132.7 (CHAr), 129.7 (CHAr),
128.7 (CHAr), 128.6 (CHAr), 128.3 (CHAr), 128.0 (CHAr),
À
À
À
127.6 (CHAr), 127.4 (CHAr), 126.3 (CHAr), 124.9 (CH=CH
À À
À
À
CH2), 66.3 (O=C C C=O), 52.5 (O CH3), 43.6 (CH2 CH=
CH); HR-MS (ESI): m/z=371.16519, calcd. for C25H23O3
[M+H+]: 371.16417.
(E)-Methyl
2-benzoyl-2-methyl-5-phenylpent-4-enoate
1
(1i): H NMR (CDCl3, 300 MHz): d=7.86 (d, J=8.0 Hz, 2H,
H
ortho), 7.56 (t, J=7.5 Hz, 1H, Hpara), 7.46 (t, J=7.6 Hz, 2H,
À
Hmeta), 7.31–7.22 (m, 5H, HAr), 6.39 (d, J=16.0 Hz, 1H,
CH=CH CH2 ), 6.07 (dt, J=16.0, 6.0 Hz, 1H, CH=CH
CH2 ), 3.67 (s, 3H, O CH3), 2.98 (br dd, J=7.5, 14.5 Hz,
2H, CH2), 2.89 (br dd, J=7.5, 14.5 Hz, 2H, CH2), 1.59 (s,
3H, CH3); C NMR (CDCl3, 75 MHz): d=197.0 (Ph C=
O), 174.3 (O C=O), 137.1 (CAr), 135.4 (CAr), 134.0 (CH=
CH CH2), 132.8 (CHAr), 128.7 (CHAr), 128.6 (CHAr), 128.5
(CHAr), 127.4 (CHAr), 126.3 (CHAr), 124.1 (CH=CH CH2),
À
À
À
À
À
À
13
À
À
À
À
[14] a) J. R. Zoeller, European Patent Application, EP 1 676
830A1, 2005; b) A. L. Lapidus, O. L. Eliseev, T. N.
Bondarenko, O. E. Sizan, E. G. Ostapenko, I. P. Belet-
skaya, Kinet. Catal. 2004, 45, 234–238; c) G. Cavinato,
L. Toniolo, J. Mol. Catal. A: Chem. 1999, 143, 325–330.
[15] b-Keto esters can undergo Pd-catalysed allylation
under base-free conditions: G. Giambastiani, G. Poli, J.
Org. Chem. 1998, 63, 9608–9609.
À À
À
À
57.3 (O=C C C=O), 52.5 (O CH3), 40.4 (CH2 CH=CH),
21.3 (CH3); HR-MS (ESI): m/z=309.14909, calcd. for
C20H21O3: 309.14852 [M+H+].
Acknowledgements
[16] a) T. Mandai, in: Handbook of Organopalladium
Chemistry for Organic Synthesis, (Ed.: E.-I. Negishi),
Vol 2, Chapt. V.2.2, pp 1845–1858, Wiley, New York,
2002; b) Z. Liu, H. Du, Org. Lett. 2010, 12, 3054–3057;
c) C. Goux, M. Massacret, P. Lhoste, D. Sinou, Organo-
metallics 2008, 27, 585 À4593; d) H. Kim, C. Lee, Org.
Lett. 2002, 4, 4, 4369–4371.
[17] a) S.-I. Murahashi, Y. Imada, Y. Taniguchi, S. Higa-
shiura, J. Org. Chem. 1993, 58, 1538–1545; b) R. J. van
Haaren, H. Oevering, P. C. J. Kamer, K. Goubitz, J.
Fraanje, P. W. N. M. van Leeuwen, G. P. F. van Strij-
donck, J. Organomet. Chem. 2004, 689, 3800–3805.
[18] a) J. Tsuji, Y. Kobayashi, H. Kataoka, T. Takahashi,
Tetrahedron Lett. 1980, 21, 1475–1478; b) R. Moser, T.
Nishikata, B. H. Lipshutz, Org. Lett. 2010, 12, 28–31.
Support from ANR CP2D 2008 (DOMINO CO) and COST
Action D40 “Innovative Catalysis: New Processes and Selec-
tivities” is gratefully acknowledged
References
[1] a) R. A. Sheldon, Chemtech 1994, 24, 38–47; b) K. H.
Shaughnessy, R. B. DeVasher, Curr. Org. Chem. 2005,
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Tietze, G. Brasche, K Gericke, Domino Reactions in
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[3] Otherwise named cascade or tandem reactions.
Adv. Synth. Catal. 2012, 354, 1077 – 1083
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1083