Ruthenium complex-catalysed Heck reactions of areneboronic acids; mechanism, synthesis and halide tolerance

Article abstract of DOI:10.1002/adsc.200404231

Ruthenium-arene complexes can act as efficient catalysts for the coupling of areneboronic acids with electrophilic alkenes. The chemoselectivity is completely different from palladium coupling, with full tolerance for halogen in the arene. NMR and ES-MS studies have been carried out to elucidate the reaction pathway.

Full text of DOI:10.1002/adsc.200404231

FULL PAPERS
Ruthenium Complex-Catalysed Heck Reactions of Areneboronic
Acids; Mechanism, Synthesis and Halide Tolerance
Edward J. Farrington,a Christopher F. J. Barnard,b Elizabeth Rowsell,b
John M. Browna,*
a
Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK
Fax: (þ44)-1865-285002, e-mail: john.brown@chem.ox.ac.uk
b
Johnson Matthey Technical Centre, Blountꢀs Court, Sonning Common, Reading RG4 9NH, UK
Received: July 21, 2004; Accepted: September 8, 2004; Published online: January 11, 2005
Abstract: Ruthenium-arene complexes can act as effi- ES-MS studies have been carried out to elucidate
cient catalysts for the coupling of areneboronic acids the reaction pathway
with electrophilic alkenes. The chemoselectivity is
completely different from palladium coupling, with Keywords: areneboronic acids; catalysis; ES-MS;
full tolerance for halogen in the arene. NMR and Heck reaction; NMR; ruthenium
Introduction
whether ruthenium complexes, intrinsically less expen-
sive but less widely explored in organic synthesis, could
In the late 1960s, R. F. Heck[1] published the coupling re- fulfil a similar role. Several catalytic reactions seem to
action between arylmercuric compounds and alkenes depend on the C C bond-forming transfer of an organic
catalysed by transition metals, introducing the reaction entity from ruthenium to an alkene, encouraging the
that would ultimately bear his name. Typically, phenyl- possibility. The most conspicuous example arises from
mercuric chloride reacted with methyl acrylate in the Muraiꢀs demonstration that directed C H activation
presence of an equivalent of Li2PdCl4 to give methyl cin- by simple Ru phosphine complexes leads to an organo-
namate in good yield. It was indicated that Hg-Pd trans- ruthenium intermediate which can then be transferred
metallation was a likely route. Most of the original ex- to an alkene.[5] The overall process is reductive, leading
ꢀ
ꢀ
ꢀ
amples were stoichiometric, since the reaction between to the formal catalytic addition of Ar H (or its vinylic
a nucleophile and an alkene leading to a new substituted equivalent) to an alkene. An oxidative variant that
alkene must lead to formal reduction of the palladium does not require a directing group and leads to alkene
catalyst. Notably for the present work, this early publi- substitution, but which occurs only under forcing condi-
cation also indicated that RuCl3 could also promote tions, has been described.[6] Ruthenium complexes can
the reaction, albeit in low yield. The constraint on catal- catalyse an analogue of the Baylis–Hillman reaction,[7]
ysis was recognized in the first papers, and examples the addition of alkynes to alkenes,[8] or Michael addition
[9]
ꢀ
where the palladium is reoxidised by CuCl2 or air al- of dimethyl malonate, by procedures that involve C H
lowed up to 50 catalytic turnovers based on palladium activation. In particular, the alkyne activation chemistry
salt. An initial example of the complementary protocol, has been applied to good effect through the work of
namely the palladium-promoted electrophilic arylation Trost and co-workers.[10] These diverse procedures are
of an alkene, was described by Mizoroki.[2] It is intrinsi- summarised in Scheme 1.
cally catalytic because the oxidation state of the palladi-
Before our preliminary communication on rutheni-
um is maintained. The procedure is frequently describ- um-catalysed oxidative Heck reactions,[11] there had
ed, especially but unsurprisingly by Japanese workers, been one report of a conventional Heck-type procedure
as the “Mizoroki–Heck” reaction. In its modern form, in which the coupling reaction between vinyl halides and
the Mizoroki–Heck reaction is the coupling reaction be- electron-poor olefins was carried out in good yield in the
tween an alkene and an aryl or vinyl halide or triflate un- presence of (COD)(COT)Ru.[12] Since that publication,
der palladium complex catalysis to give a substituted al- catalysis of Heck reactions by ruthenium black under
kene. Largelythrough Heckꢀs earlyefforts,[3] this reaction very simple conditions has been demonstrated.[13] Fur-
has become a standard part of the armoury of synthetic ther examples of oxidative Heck reactions involving pal-
organic chemistry and has been substantially reviewed.[4] ladium or rhodium have appeared.[14]
Given the ubiquitous application of palladium com-
plexes in coupling catalysis, we were interested to learn
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Scheme 2. Easy aryl migration/H elimination described in
Ref.[15]
metric arylation of a,b-unsaturated carbonyl com-
pounds, first demonstrated by Hayashi and Miyaura.[17]
Since this results in ArH addition to the alkene, there
is no change in oxidation state of rhodium through the
catalytic cycle. In a related case, Lautens has shown
that either Ar-H addition or formal displacement of vi-
nyl-H by Ar can occur depending on the structure of the
reactant.[18] In palladium catalysis, the best precedent is
due to Uemura, who showed that arylboronic acids react
with alkenes to give the product expected from a Heck
reaction.[19] No re-oxidant was reported in this case (ad-
ventitious air?) but the utility of added oxidant has been
confirmed in closely related reactions carried out more
recently.[14]
The first aim of the present project was to determine
whether mild carbon nucleophiles were capable of aryl
transfer to ruthenium. Combining SnBu3Ph with (p-
cymene)(PPh3)RuCl2 in dry toluene gave a dark yellow
solution which on work-up yielded (p-cymene)-
(PPh3)RuClPh as a crystalline yellow solid in 50%
yield.[13,20] Likewise, benzeneboronic acid and (p-cy-
mene)(PPh3)RuCl2 were combined in THF in the pres-
ence of CsF to give the same product as a yellow solid
ꢀ
Scheme 1. Prior examples of Ru-catalysed C C couplings.
Discussion
Development of a Ruthenium-Catalysed Reaction
Having decided that ruthenium-catalysed coupling was in 69% yield. Arylboronic acids are more readily avail-
both feasible and desirable, two specific sets of prece- able, easier to handle and less toxic than aryltin reagents,
dent guided our approach. The first was due to Faller making this reaction the preferred approach. In a pre-
and Chase, as shown in Scheme 2.[15] The C C bond- liminary experiment, the feasibility of catalysis was
ꢀ
forming step in their sequence is a clear model for ruthe- demonstrated by reacting PhB(OH)2 with methyl acryl-
nium Heck chemistry. Thus, (p-cymene)(PPh3)RuCl2 re- ate and Et3N, in the presence of 0.5 equivalents of (p-
acted with PhMgBr by single displacement. The halide cymene)(PPh3)RuCl2. Methyl cinnamate was formed
was removed as its silver salt in the presence of ethene in 28% yield after 24 h at 808C. This encouraged further
to give the alkene hydride complex, which exists as a efforts and especially inclusion of CuCl2 as a reoxidant.
pair of diastereomers. An aryl-ethene complex was not This led to slow but definable catalysis for the reaction
detected, although it is a likely intermediate (Scheme 2). between PhB(OH)2 and butyl acrylate in THF
Further direct precedent arises from Pfefferꢀs group, (Scheme 3). Although rather primitive, this represented
who demonstrate the reactivity of cycloruthenated com- the first example of a Ru-catalysed oxidative Heck reac-
plexes towards alkene insertion.[16]
tion with catalytic turnover. In an assay of reaction con-
These observations demonstrate that a C Ru bond ditions involving high-throughput screening (HTPS),[21]
can indeed be formed by nucleophilic displacement, it was noted that the phosphine-free complex [(p-cym-
and that the alkene insertion step is straightforward. In ene)RuCl2]2 induced catalytic turnover at ambient tem-
tandem with this, there have been sporadic observations perature, but that Cu(II) remained the preferred oxidiz-
of catalytic alkene coupling with nucleophiles. The most ing agent. It was also established through 1H NMR stud-
conspicuous example is the rhodium-catalysed asym- ies that both the dimeric halide and (p-cymene)
ꢀ
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Ruthenium Complex-Catalysed Heck Reactions of Areneboronic Acids
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Scheme 3. The preferred conditions for Ru Heck reactions.
(PPh3)RuCl2 were responsive to coordinating solvents,
with reversible bridge-breaking or phosphine dissocia-
tion observed in DMSO and methanol. The aryl com-
plex ClRuPh(PPh3)(p-cymene) was not altered in these
solvents, however. This suggested using the phosphine-
free complex as catalyst and a considerable improve-
ment in reactivity was observed, indicating that PPh3 is
in fact an inhibitor of catalytic turnover. The HPTS stud-
ies additionally appeared to suggest a unique role for the
ruthenium-arene complexes. There are precedents in
Scheme 4. Conditions:
2.5 mol %
[Ru(p-cymene)Cl2]2,
Cu(OAc)2, quinuclidinone, THF, 24 h, room temperature.
Butyl acrylate was present in excess over benzeneboronic
acid, allowing the possibility of isotopic fractionation in the
starting material and enhancing the deuterium content of
the product.
the literature for the liberating of a coordination site for the missing 21%. A perfectly stereospecific cis-addi-
by ring slippage of Ru arenes (h6 –h4) and this would tion/cis-elimination process (or, in principle, a trans-ad-
be expected to facilitate the areneboronic acid addition dition, trans-elimination process) would lead to 10% re-
step.[22]
tention of deuterium, and the larger amount indicates
Finally a systematic assay of bases was carried out, imperfect stereoselectivity, e.g., by competing 1,2-mi-
providing the conclusion that quinuclidine, or better gration in the alkylruthenium intermediate. An unselec-
its 3-hydroxy or 3-keto derivative, is superior to triethyl- tive reaction would lead to a bias towards retention of
amine. Under these conditions a satisfactory rate of deuterium, assuming a normal primary kinetic isotope
turnover can be achieved under ambient conditions effect. In the absence of phenylboronic acid, there is
(Scheme 3), and no further optimisation experiments no scrambling or loss of deuterium observed under the
were attempted.
reaction conditions. This indicates that the predominant
pathway in ruthenium catalysis parallels that already es-
tablished for palladium catalysis.
Mechanistic Studies
Stereoselectivity
NMR Analysis of Reactive Intermediates
One of the main planks used to establish the mechanism The implication of observations to date is that transme-
of the Heck reaction is the demonstrated stereoselectiv- tallation from boron to ruthenium occurs and that the
ꢀ
ity involving cis-addition of Pd Ar and cis-elimination species formed reacts with alkene to form the desired
of Pd H. This was first demonstrated by Heck,[23] and re- product. AdditionofPhB(OH)2 toa solution of[(p-cym-
ꢀ
inforced by manylater observations although occasional ene)RuCl2]2 and Et3N in CDCl3 led to changes in the
trans-elimination of Pd H has been observed.[24] In or- 1H NMR spectrum (especially in Ar-H of cymene) con-
ꢀ
der to explore the specificity of the ruthenium-catalysed sistent with the formation of a phenylruthenium species.
Heck reaction, the method outlined by Hill and New- On addition of PPh3 and work-up, the described phos-
kome[25] was modified to give stereoselectively 2H-label- phine complex, (p-cymene)(PPh3)RuClPh, was charac-
led butyl acetate. By accurate NMR simulation, the terised. Likewise, if methyl acrylate was added to the
product from the sequence of Scheme 4 was an 8:1:1 solution containing a phenylruthenium species, methyl
mixture of isotopomers, as indicated. The product was cinnamate was observed in the spectrum within 30 sec-
subjected to the standard conditions of Ru catalysis onds. In a separate experiment, the phenylruthenium in-
and the product butyl cinnamate isolated. It can be termediate was generated and both methyl acrylate and
seen from the ensuing NMR spectrum that the vinyl sig- p-methoxyphenylboronic acid were added simultane-
nal at 7.72 ppm is reduced in intensity to 0.79 H relative ously. The only product formed was methyl cinnamate;
to the undeuterated compound and there is some resid- the uncomplexed arylboronic acid did not participate.
ual deuterium, revealed by a 2H-coupled signal at
6.46 ppm under the second vinylic proton, accounting by the reaction sequence shown in Figure 1, derived
Further evidence for transmetallation was obtained
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Edward J. Farrington et al.
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when 2,6-difluorophenylboronic acid was reacted with tion of standard formulae at the coalescence tempera-
the standard Ru complex in CD3CN. In this case the s- ture, the rotation barrier is 49 kJ·molꢀ1
aryl complex gave rise to a broad signal at ꢀ85 ppm as
.
the main component in the 19F NMR spectrum, that sep-
arated into two distinct 19F signals at ꢀ358C, coales- ES-MS Analysis of Reactive Intermediates
cence being observed at around ꢀ58C. This indicates
the formation of a metal-aryl with restricted rotation In order to study the transmetallation step, the reacting
ꢀ
about the Ru C bond, providing two distinct magnetic components including p-bromophenylboronic acid
environments for the two 19F nuclei. From the applica- were combined in acetonitrile. After 30 minutes, the
Figure 1. Temperature dependence of the 19F NMR spectrum of the 2,6-diflurophenylruthenium complex in CD3CN.
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Table 1. Relative intensity (vs. 475 amu) of the alkene-bound
Ru complex under standard conditions.
Entry
1
Alkene
%
39
Entry
5
Alkene
%
1.6
2
2.6
6
51
3
4
0
0
7
8
0
0
was added to the yellow-orange solution and the reac-
tion mixture stored at ꢀ208C for 15 h. As well as the
Scheme 5. Cations observed by ES-MS, CV¼5 V; amu values species described above, additional ions were observed
are based on 102Ru, 81Br, 35Cl. The boxed ions are observed in
in the ESI spectrum centred at 408, 520, and 561 amu.
the presence of methyl acrylate, and standing; structures are
Although only present at low concentration, these cor-
drawn to indicate likely bonding.
respond to fragments containing one or more alkene
molecules bound to ruthenium and are clearly visible
and in all cases, p-cymene was also bound to Ru. To de-
mass spectrum showed monocationic species centred at termine the properties of the alkene which are required
393, 434, and 699 amu that correspond to the species for binding to Ru, a variety of alkenes ranging from elec-
shown in Scheme 5. Ruthenium and bromine both give tron-poor to electron-rich were tested for Ru coordina-
very distinctive isotopic distribution patterns, allowing tion. A sample of dimer was combined with p-bromo-
fragments to be easily identified. The spectra clearly benzeneboronic acid in acetonitrile to give a solution
show the presence of various s-bound aryl-ruthenium for which aryl-ruthenium complexes were observed by
complexes; in all cases the p-cymene ring is still bound ESI-MS as before. This was then split into eight, and
to the metal atom. Both monomeric and dimeric Ar- an excess of a different alkene was added to each vial.
Ru species are observed, but the dimer is present in The vials were left at ꢀ208C for 15 h and the ESI
very low concentration. No insertion was seen into the mass spectra were run. The ion corresponding to
ꢀ
C Br bond and there was no evidence of species con- (MeCN)2(p-cymene)RuAr at 475 amu provides a con-
taining a metal B(OH)2 bond. The additional species venient calibration for the spectra, and the values given
ꢀ
observed at 353 and 408 amu correspond to (MeCN)2 in Table 1 are the relative intensities of the (MeCN)(al-
(C10H14)RuCl and (C10H14)(NEt3)RuCl2, respectively. kene)(p-cymene)RuAr ions expressed as a percentage
The ratio of (MeCN)(p-cymene)RuAr to (MeCN)2(p- of this.
cymene)RuAr remains approximately constant at
To determine more precisely whether coordination
¼
¼
1:1.12 as the cone voltage (CV) increases from þ5 V takes place via a C O bond or a C C bond, a direct com-
to þ30 V. At a CV of þ5 V, the signal at 393 amu has parison was carried out between di-tert-butyl methyl-
an intensity which is 6% of the intensity of (MeCN)(p- enemalonate and di-tert-butyl malonate. The [(p-cym-
cymene)RuAr, but its intensity increases dramatically ene)RuCl2]2 dimer and p-bromobenzeneboronic acid
at þ20 V. At þ30 V, the majority of the Ru is present were combined in acetonitrile:triethylamine (100:1)
as (p-cymene)RuAr. The variation of the concentration and the solution split into two portions. A 10-fold excess
with cone voltage suggests that the complexes observed of di-tert-butylmethylene malonate was added to one
are the result of fragmentation of (MeCN)2(p-cym- sample and a 10-fold excess of di-tert-butyl malonate
ene)RuBrAr in the inlet cone.
Further ESI-MS experiments were carried out in the and the ESI spectra taken (Figure 2).
to the other. The samples were left at ꢀ208C for 15 h
presence of methyl acrylate to determine whether al-
The sample containing di-tert-butyl methylenemalo-
kene coordination to ruthenium could be observed. nate showed a strong signal at 621 amu in the ESI-MS
[(p-cymene)RuCl2]2 and p-bromobenzeneboronic acid corresponding tocoordinated alkene complex. The sam-
were dissolved in acetonitrile:triethylamine solution ple containing di-tert-butyl malonate gave a vanishingly
(100:1) and s-bound aryl-ruthenium complexes were weak signal at 609 amu [corresponding to (MeCN)(p-
observed as before. A 10-fold excess of methyl acrylate cymene)(di-tert-butyl malonate)RuAr]. It is clear that
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Figure 2. Positive ion electrospray MS (CH3CN) of bromo-
phenylruthenium complexes taken in the presence of (a) di-
tert-butyl malonate and (b) di-tert-butyl methylenemalonate
at a cone voltage of 5 V. Sample preparation conditions as
in text. m/z values are quoted for the 102Ru, 81Br, 35Cl iso-
topomer.
di-tert-butyl methylenemalonate binds to the ruthenium
arene complex far more effectively than does di-tert-bu-
¼
tyl malonate. This underpins the suggestion that a C C
double bond is important in order for complexation to
occur, and this is also likely to be the case for simple al-
kenes such as butyl acrylate.
Synthetic Scope
By itself, the ability to react an acrylate and an arenebor-
onic acid under ruthenium catalysis does not constitute a
useful synthetic method, since it duplicates what is al-
ready readily available in palladium chemistry. Since
the ruthenium-based procedure as described here uses
Scheme 6. (a) Ruthenium-catalysed Heck reactions of haloar-
ylboronic acids under standard conditions. (b) Atempted Pd-
catalysed haloboronic acid coupling. (c) Tandem Ru/Pd catal-
ysis using the product from (a) in a conventional Heck reac-
an inexpensive and readily available catalyst, and func- tion.
tions at ambient temperature, it would be an attractive
alternative if unique regio- or chemoselectivity were ob- ple work-up procedure the products were obtained in
served. The general response to ring-substituents was a good state of purity (Figure 3). Variation of the alkene
checked in three cases, shown in Scheme 3 earlier. Inter- component was attempted, but with less success, since
estingly, the most electron-rich boronic acid is least ef- the efficiency of turnover was substantially lower with
fective. An important aspect of ruthenium chemistry unsaturated amides. Interestingly, the use of methyl vi-
in the formal oxidation state (II) is a reluctance to react nyl ketone led to a formal addition rather than addi-
with organohalides by oxidative addition. This in turn tion-elimination. This implies that an intermediate pal-
ꢀ
led us to examine the reaction of butyl acrylate with ladium enolate formed by the Ru Ar addition step
ring-substituted haloarylboronic acids by ruthenium can then be protonated, releasing the ruthenium in a for-
catalysis under the conditions described above. The re- mal þII oxidation state and obviating the need for reox-
sults exceeded expectations, in that the halogen was in- idation. The successful reaction sequences are collected
variably unaffected by the coupling process, and good in Scheme 6a. The control experiment with a palladium
yields of haloaryl acrylates were obtained. After a sim- catalyst demonstrated that this outcome was unique to
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Figure 3. 1H and 13C NMR spectra of the product from the ruthenium Heck reaction of bromobenzeneboronic acid and butyl
acrylate after work-up and silica gel filtration.
ruthenium, since an analogous experiment did not af- cate a distinct chemoselectivity associated with rutheni-
ford a useful outcome (Scheme 6b). The distinct chemo- um catalysis. The oxidative addition of ArHal is not
selectivity of Ru and Pd catalysts encouraged a tandem competitive with the addition of ArB(OH)2. This per-
reaction, employing the product from Ru-coupling of p- mits the development of reaction sequences in which a
iodobenzeneboronic acid and butyl acrylate in a second, haloaromatic compound is the nucleophilic partner in
ꢀ
Pd-catalysed reaction with methyl acrylate which gave the sequence, leaving the C X bond intact for subse-
the unsymmetrical bis-cinnamate (Scheme 6c). Phenyl- quent transformations.
ene-bis-acrylate esters belong to a well-studied class of
compoundsthatshowcharacteristic photochemicalprop-
erties in film and solid states and behave as photocross-
linkable monomers in simple polymer mixtures.[26] Poly-
mers containing derivatives of 1,4-phenylene-bis(acrylic
acid) show liquid crystalline properties and have been
Experimental Section
used in applications such as photooptical recorders and
photoresists.[27] Thistechniqueoffersasimpleroutetoun-
symmetrical 1,4-phenylene-bis(acrylic acid) derivatives,
with scope for variation of the carbonyl functionality.
Techniques, Materials and Instrumentation
For standard procedures and purifications see recent publica-
tions from this laboratory, and standard sources.[28] The follow-
ing compounds were prepared as previously described: [(p-
cymene)RuCl2]2, [(benzene)RuCl2]2, (p-cymene)(PPh3)RuCl2,
(benzene)(PPh3)RuCl2;[29] (p-cymene)2Ru(OTf)2;[30] di-tert-
butyl methylenemalonate;[31] b-[2H]-methyl propiolate, and
Summary and Conclusions
As well as extending the boundaries of the conventional
Mizoroki–Heck reaction, the results reported here indi- its anthracene Diels–Alder adduct.[32]
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Edward J. Farrington et al.
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which was purified by recrystallisation from DCM/pentane to
give butyl cis-9,10-ethano-9,10-dihydroanthracene-12-[2H]-
11-carboxylate; yield: 0.31 g (91%); mp 1188C; MS (CIþ):
m/z¼325.1 [MNH4þ], 308.1 [MHþ]; 1H NMR (400 MHz,
CDCl3): d¼0.87 (3H, t, J¼3.4 Hz, CH3), 1.32 (2H, m, CH2),
1.55 (2H, m, CH2), 1.99 (1H, dd, J¼2.6 and 8.1 Hz, H3), 2.89
(1H, dd, J¼2.6 and 7.8 Hz, H2), 3.97 (2H, t, J¼1.7 Hz,
OCH2), 4.69 (1H, d, J¼2.7 Hz, H4), 4.35 (1H, d, J¼2.7 Hz,
H4), 7.12 (4H, m, H6, H7), 7.29 (4H, m, H6, H7); 13C NMR
(100.6 MHz, CDCl3): d¼13.3 (CH3), 21.5 (CH2), 30.4 (CH2),
44.0 (C3), 43.7 (C2), 44.0 (C4), 46.8 (C4), 64.5 (OCH2), 123.3,
123.5, 125.2, 125.5, 126.0, 142.4 (Ar-C), 173.5 (C5); IR (nujol):
Synthesis of (p-Cymene)(PPh3)RuClPh
(p-Cymene)(triphenylphosphine)ruthenium
dichloride
(50 mg, 8.8ꢁ10ꢀ5 mol) was dissolved in dry THF (5 mL) and
degassed twice. Benzeneboronic acid (53.6 mg, 4.4ꢁ10ꢀ4
mol) and triethylamine (5 mL) were added against a flow of ar-
gon and the mixture stirred at 508C for 2 h. The reaction was
accompanied by a colour change from red to dark yellow.
The solvent was removed under vacuum to yield a dark yellow
oil. This was purified by filtration through a short plug of silica
gel, eluting with dichloromethane and collecting the yellow
band. The solvent was removed under vacuum. Trituration
with pentane and removal of the solvent under vacuum afford-
ed (p-cymene)(PPh3)RuClPh as a fine yellow powder (yield:
37 mg, 69%) which was dried under vacuum. X-ray quality
crystals were grown by slow precipitation from a dichlorome-
thane solution with heptane at ambient temperature; mp
1308C (dec.); MS (APCIþ): m/z¼353.9 [RuC10H14PhMeCN];
1H NMR (500 MHz; CDCl3): d¼0.96 [3H, d, J¼6.7 Hz,
C(CH3)2], 1.09 [3H, d, J¼6.7 Hz, C(CH3)2], 1.56 (3H, s, CH3),
1.94 [1H, m, CH(Me)2], 5.01 (1H, d, J¼6.3 Hz, Cy-H), 5.03
(1H, d, J¼5.7 Hz, Cy-H), 5.11 (1H, d, J¼5.7 Hz, Cy-H), 5.38
(1H, d, J¼6.3 Hz, Cy-H), 6.77 (2H, m, Ar-H), 6.84 (1H, m,
Ar-H), 6.99 (2H, m, Ar-H), 7.21 (3H, m, PPh3-H), 7.48 (8H,
m, PPh3-H), 7.55 (2H, m, PPh3-H), 7.87 (2H, m, PPh3-H);
13C NMR (125.8 MHz, CDCl3): d¼18.7 (CH3), 22.8
[C(CH3)2], 23.5 [C(CH3)2], 30.2 [C(CH3)2], 86.7, 87.3 (Cy-C),
88.0, 88.2 (Cy-C), 109.3, 117.0, 121.8 (Ar-C), 127.5, 128.6,
128.7, 128.9, 129.0, 129.8, 130.6, 131.8, 133.8, 134.9 , 135.0,
136.0, 136.2, 143.1 (br), 160.7, 160.9 (aromatic C); IR (KBr):
ꢀ
¼
nmax ¼3026, 2990 (C H), 1721.1 (C O), 1501, 1422 (C-C), 1248,
1220 cmꢀ1; HRMS: 308.176 (calcd. for C21H22O2D: 308.176).
This product (0.25 g, 0.8 mmol) was placed in one arm of an
A-frame distillation apparatus and flushed with argon. The ap-
paratus was sealed and the first arm was heated to 3008C in a
Woodꢀs metal bath while the second was cooled to ꢀ1968C
in liquid nitrogen. After one hour, a colourless liquid had col-
lected in the second arm and white crystals of anthracene
had sublimed around the neck of the apparatus. The colourless
liquid was slowly warmed to ambient temperature to furnish
butyl cis-3[2H]-acrylate; yield: 42 mg (39%); bp 1458C; MS
(APCIþ): m/z¼130 [MHþ]; 1H NMR (400 MHz, CDCl3):
d¼0.94 (3H, t, J¼3.2 Hz, CH3), 1.40 (2H, m, CH2), 1.62 (2H,
m, CH2), 4.19 (2H, t, J¼6.7 Hz, OCH2), 5.83 (1H, d, J¼
10.3 Hz, H3), 6.13 (1H, dt, J¼10.3 Hz and 2.5 Hz, H2);
13C NMR (100.6 MHz, CDCl3): d¼13.7 (CH3), 18.7 (CH2),
30.5 (CH2), 64.3 (OCH2), 128.4 (C2), 130 (t, C3), 166.2 (C1).
nmax ¼3060 (C H), 1567, 1436 (C-C), 695, 525, 343 cmꢀ1; ele-
ꢀ
mental analysis: C34H34PClRu requires C 66.8, H 5.57; found:
C 66.9, H 5.4.
Coupling of Butyl cis-3-[2H]Acrylate with
Phenylboronic Acid
Use of Ph4Sn (toluene, 808C, 2 h) gave the same product in
51% yield.
Benzeneboronic acid (10 mg, 8.2ꢁ10ꢀ5 mol), [ (p-cymene)R-
uCl2]2 (1.25 mg, 4.1ꢁ10ꢀ7 mol) and copper acetate (40.9 mg,
0.21 mmol) were combined in an MS vial and THF (0.9 mL)
and triethylamine (0.1 mL) added. The vial was sealed and
the reaction mixture stirred at ambient temperature for 17 h.
The solvent was removed under vacuum and the product puri-
fied by filtration through a short plug of silica gel, eluting with
diethyl ether to afford butyl trans-cinnamate; yield: 40 mg
(49%); bp 1578C/15 mmHg); 1H NMR (500 MHz, CDCl3):
Reduction of Diels–Alder Adduct with p-
Toluenesulphonyl Hydrazide
Methyl 9,10-etheno-9,10-dihydroanthracene-12-[2H]-11-car-
boxylate (the Diels–Alder adduct of methyl 3-[2H]-propiolate
and anthracene) (1 g, 3.79 mmol) was dissolved/suspended in
dry toluene (10 mL) and p-toluenesulphonyl hydrazide
(1.42 g, 7.5 mmol) added. Triethylamine (2 mL) was added
and the reaction mixture was refluxed at 1108C while monitor-
ing by TLC. After 5 h, the mixture was cooled and a white pre-
cipitate formed which was filtered and washed with cold tol-
uene (2 mL). Recrystallisation from methanol afforded white
crystals; yield: 0.358 g (36%); mp 1268C; MS (CIþ): m/z¼
¼
d¼0.99 (3H, t, J 7.3 Hz, CH3), 1.44 (2H, m, CH2), 1.72 (2H,
m, CH2), 4.23 (2H, t, J¼6.7 Hz, OCH2), 6.48 (1H, d, J¼
16 Hz, H2), 7.40 (3H, m, H2’, H4’’), 7.53 (2H, m, H3’), 7.77
(1H, d, J¼16 Hz, H3); 13C NMR (125.8 MHz, CDCl3): d¼
13.6 (CH3), 19.1 (CH2), 30.6 (CH2), 64.3 (OCH2), 118.2 (C1),
127.9, 128.7, 130.1, 134.3, (C1’, C2’, C3’, C4’), 144.4 (C3),
167.0 (C1); UV/VIS (MeOH): l¼276 nm (e¼22000).
283.2 [MNH4þ]; H NMR (400 MHz, CDCl3): d¼2.02 (1H,
1
dd, J¼2.6 Hz and 10.4 Hz, H2), 2.91 (1H, dd, J¼2.6 Hz and
10.4 Hz, H2), 3.61 (3H, s, CH3), 4.36 (1H, d, J¼2.68 Hz, H6),
4.7 (1H, d, J¼2.68 Hz, H6), 7.13 (4H, m, Ar-H), 7.28 (4H, m,
Ar-H); 13C NMR (100.6 MHz, CDCl3): d¼43.6 (t, C4), 46.7
(C3), 46.8 (C5) 51.8 (C1), 123.4, 124.5, 125.6, 126.0, 127.5,
129.3, 130.1, 136.4, 139.9, 140.3, 141.9 (C6, C7, C8)), 173.9
Electrospray Mass-Spectrometric Measurements
(a): (p-Cymene)ruthenium dichloride dimer (10 mg, 3.26ꢁ
10ꢀ5 mol) and p-bromobenzeneboronic acid (6.5 mg, 3.26ꢁ
10ꢀ5 mol) were combined in acetonitrile (20 mL) and triethyl-
amine (3.3 mg, 3.26ꢁ10ꢀ5 mol) was added. The reaction mix-
ture was subjected to ultrasound for 5 minutes to ensure com-
plete dissolution and left to stand for 30 minutes before the
ESI-MS was run.
ꢀ
¼
(C2); IR (nujol): nmax ¼3018, 2960 (C H), 1731 (C O), 1481,
ꢀ1
ꢀ
1432 (C C), 1253, 1220, 1080, 757 cm
.
This product (0.3 g, 1.1 mmol) was dissolved in n-butanol
and p-toluenesulphonic acid (0.19 g, 1.1 mmol) was added.
The mixture was refluxed for 24 h in air. The solvent was re-
moved under vacuum to the give butyl ester as a white solid
192
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 185–195

Ruthenium Complex-Catalysed Heck Reactions of Areneboronic Acids
FULL PAPERS
(b): (p-Cymene)ruthenium dichloride dimer (10 mg, 3.26ꢁ
10ꢀ5 mol) and p-bromobenzeneboronic acid (6.5 mg, 3.26ꢁ
10ꢀ5 mol) were combined in acetonitrile (20 mL) and triethyl-
amine (3.3 mg, 3.26ꢁ10ꢀ5 mol) was added. The reaction mix-
ture was subjected to ultrasound for 5 minutes to ensure com-
plete dissolution and left to stand for 30 minutes. ESI-MS
showed aryl-ruthenium species as before. Methyl acrylate
(28 mg, 0.3 mmol) was added and the solution left at ꢀ208C
for 15 h before the ESI-MS was run.
OCH2), 6.45 (1H, d, J¼16 Hz, H2), 7.12 (1H, dd, J¼6.9 Hz
and 7.6 Hz, H5’), 7.49 (1H, dd, J¼1.5 Hz and 7.6 Hz, H4’)
7.58 (1H, d, J¼16 Hz, H3), 7.7 (1H, d, J¼1.5 Hz and 6.9 Hz,
H6’), 7.88 (1H, dd, J¼1.5 Hz, H2’); 13C NMR (125.8 MHz,
CDCl3): d¼13.6 (CH3), 19.1 (CH2), 30.8 (CH2), 64.5 (OCH2),
119.5 (C2), 127.3, 130.3, 136.5, 138.8 (C2’, C4’, C5’, C6’),
128.7, 137.4 (C1’, C3’) 142.6 (C3) 166.5 (C1); IꢀR1 (nujol):
¼
¼
ꢀ
nmax ¼2859, 1713 (C O), 1679 (C C), 1177 cm
(C O);
HRMS found: 331.0190 (calcd. for C13H16O2I: 331.0195).
Butyl-E-4-bromocinnamate:[33] As for butyl trans-cinna-
mate, butyl E-4-bromocinnamate; yield: 71.7 mg (63%); MS
1
(APCIþ): m/z¼226 [M – Bu]; H NMR (500 MHz, CDCl3):
Synthesis of Coupling Products
d¼0.97 (3H, t, J¼7.3 Hz, CH3), 1.45 (2H, m, CH2), 1.71 (2H,
m, CH2), 4.22 (2H, t, J¼6.7 Hz, OCH3), 6.45 (1H, d, J¼
16 Hz, H2), 7.40 (2H, AA’ of AA’XX’, J¼8.5 Hz, H2’), 7.52
(2H, XX’ of AA’XX’, J¼8.5 Hz, H3’), 7.63 (1H, d, J¼16 Hz,
H3); 13C NMR (125.8 MHz, CDCl3): d¼13.6 (CH3), 19.1
(CH2), 30.6 (CH2), 64.4 (OCH2), 118.9 (C2), 124.3, 133.3 (C1’,
C4’), 129.3, 132.0 (C2’, C3’), 143.0 (C3), 166.7 (C1); IꢀR1 (nujol):
Butyl trans-cinnamate: Benzeneboronic acid (49.2 mg,
0.4 mmol), [(p-cymene)RuCl2]2 (6.2 mg, 0.02 mmol), copper
acetate monohydrate (199 mg, 1 mmol) and 3-quinuclidinone
(126 mg, 1 mmol) were combined in a dry Schlenk tube, which
was sealed and placed under vacuum for 30 minutes. The
Schlenk tube was flushed with argon then butyl acrylate
(155 mg, 1.2 mmol) and freshly distilled toluene (10 mL)
were added via syringe. The reaction mixture was stirred for
48 h at ambient temperature. The solvent was removed under
vacuum and the product purified by silica gel chromatography,
eluting with diethyl ether to give butyl trans-cinnamate as a col-
ourless liquid; yield: 54 mg (66%); bp 1578C/15 mmHg); MS
¼
¼
ꢀ
nmax ¼2960, 1699 (C O/C C overlapping) 1173 cm (C O);
HRMS found: 283.0335 (calcd. for C13H16O2Br: 283.0335).
Butyl E-3-bromocinnamate: As for butyl trans-cinnamate,
butyl E-3-bromocinnamate; yield: 122 mg (96%); MS
(APCIþ): m/z¼284 [MHþ], 226 [M
–
Bu]; 1H NMR
(500 MHz, CDCl3): d¼0.96 (3H, t, J¼7.3 Hz, CH3), 1.44
(2H, m, CH2), 1.70 (2H, m, CH2), 4.22 (2H, t, J¼6.7 Hz,
OCH2), 6.46 (1H, d, J¼16 Hz, H1), 7.26 (1H, dd, J¼8 Hz
and 7.9 Hz, H5’), 7.46 (1H, d, J¼1.5 Hz and 8 Hz, H4’), 7.52
(1H, d, J¼1.5 Hz and 7.9 Hz, H6’), 7.61 (1H, d, J¼16 Hz,
H3), 7.68 (1H, dd, J¼1.5 Hz, H2’); 13C NMR (125.8 MHz,
CDCl3): d¼13.6 (CH3), 19.1 (CH2), 30.6 (CH2), 64.5 (OCH2),
119.7 (C2), 126.5, 130.3, 130.6, 132.9 (C2’, C4’, C5’, C6’),
1
(CIþ): m/z¼205 [MHþ]; H NMR (500 MHz, CDCl3): d¼
0.99 (3H, t, J¼7.3 Hz, CH3), 1.44 (2H, m, CH2), 1.72 (2H, m,
CH2), 4.23 (2H, t, J¼6.7 Hz, OCH2), 6.48 (1H, d, J¼1 6 Hz,
H2), 7.40 (3H, m, H2’, H4’’), 7.53 (2H, m, H3’), 7.77 (1H, d,
J¼16 Hz, H3); 13C NMR (125.8 MHz, CDCl3): d¼13.6
(CH3), 19.1 (CH2), 30.6 (CH2), 64.3 (OCH2), 118.2 (C2),
127.9, 128.7 (C1’, C4’), 130.1, 134.3 (C2’, C3’), 144.4 (C3),
167.0 (C1); UV-VIS: (MeOH): lmax ¼276 nm (e¼22000).
Butyl E-4-iodocinnamate: p-Iodobenzeneboronic acid
(100 mg, 0.4 mmol), [(p-cymene)RuCl2]2 (6.2 mg, 0.02 mmol),
copper acetate (199 mg, 1 mmol) and quinuclidinone
(126 mg, 1 mmol) were combined in a dry Schlenk tube, which
was sealed and placed under vacuum for 30 minutes. The
Schlenk tube was flushed with argon, then butyl acrylate
(155 mg, 1.2 mmol) and freshly distilled toluene (10 mL)
were added via syringe. The reaction mixture was stirred for
24 h at ambient temperature. The solvent was removed under
vacuum and the product purified by silica gel chromatography,
eluting with diethyl ether to give butyl-E-3-iodocinnamate;
yield: 108 mg (77%); MS (APCIþ): m/z¼349 [MNH4þ], 332
[MHþ], 274 [MHþ – Bu], 222, 205 [MHþ – I]; 1H NMR
(500 MHz, CDCl3): d¼0.97 (3H, t, J¼7.3 Hz, CH3), 1.45
(2H, m, CH2), 1.71 (2H, m, CH2), 4.22 (2H, t, J¼6.7 Hz,
OCH2), 6.47 (1H, d, J¼16 Hz, H2), 7.25 (2H, AA’ of
AA’XX’, J¼8.3 Hz, H2’), 7.61 (1H, d, J¼16 Hz, H3), 7.73
(2H, XX’ of AA’XX’, J¼8.3 Hz, H3’); 13C NMR (125.8 MHz,
CDCl3): 13.6 (CH3), 19.1 (CH2), 30.6 (CH2), 64.5 (OCH2),
122.9, 136.4 (C1’, C3’), 142.7 (C3) 166.5 (C1); IR (nujol):
ꢀ1
¼
¼
ꢀ
nmax ¼2921, 1727 (C O), 1642 (C C) 1172 cm
(C O);
HRMS found: 283.0335 (calcd. for C13H16O2Br: 283.0335).
Butyl E-3-chlorocinnamate:[34] As for butyl trans-cinna-
mate, butyl E-3-chlorocinnamate; yield: 74 mg (77%); MS
(APCIþ): m/z¼257 [MNH4þ], 240 [MHþ]; 1H NMR
(400 MHz, CDCl3): d¼0.97 (3H, t, J¼7.3 Hz, CH3), 1.43
(2H, m, CH2), 1.69 (2H, m, CH2), 4.22 (2H, t, J¼6.7 Hz,
OCH2), 6.46 (1H, d, J¼16 Hz, H2), 7.34 (1H, dd, J¼8 Hz
and 7.9 Hz, H5’), 7.35 (1H, dd, J¼1.5 Hz and 8 Hz, H6’), 7.41
(1H, dd, J¼1.5 Hz and 7.9 Hz, H4’), 7.52 (1H, dd, J¼1.5 Hz,
H2’), 7.63 (1H, d, J¼16 Hz, H3); 13C NMR (62.9 MHz,
CDCl3): d¼14.1 (CH3), 19.2 (CH2), 30.6 (CH2), 64.5 (OCH2),
119.7 (C2), 126.2, 127.7, 130, 130.1, (C2’, C4’, C5’, C6’), 134.9,
136.2 (C1’, C3’), 142.9 (C3), 166.7 (C1); ꢀI1R (nujol): nmax
¼
¼
¼
ꢀ
2924, 1742 (C O), 1641 (C C), 1177 cm (C O); HRMS
found: 239.0844 (calcd. for C13H16O2Cl: 239.0844).
Butyl E-4-chlorocinnamate:[34] As for butyl trans-cinna-
mate, butyl E-4-chlorocinnamate; yield: 89 mg (93%: contains
ca. 5% of biphenyl product); MS (APCIþ): m/z¼256 [MNH4þ],
1
240 [MHþ]; H NMR (400 MHz, CDCl3): d¼0.94 (3H, t, J¼
118.9 (C2), 127.3, 133.8 (C1’, C4’), 137.4, 138.0 (C2’, C3’),
2
ꢀ
7.3 Hz, CH3), 1.45 (2H, m, CH2), 1.7 (2H, m, CH2), 4.22 (2H,
t, J¼6.7 Hz, OCH2), 6.43 (1H, d, J¼16 Hz, H1), 7.36 (2H,
AA’ of AA’XX’, J¼8 Hz, H2’), 7.49 (2H, XX’ of AA’XX’,
J¼8 Hz, H3’), 7.68 (1H, d, J¼16 Hz, H3); 13C NMR
(100.6 MHz, CDCl3): d¼13.6 (CH3), 19.1 (CH2), 30.6 (CH2),
64.5 (OCH2), 118.8 (C2), 128.2, 129.0 (C2’, C3’), 132.8, 134.9
143.2 (C3) 166.7 (C1); IR (nujol): nmax ¼3054 (sp C H; weak
ꢀ
¼
in all such compounds), 2920 (C H), 1721 (C O), 1681
(C C), 1176 cm (C O); HRMS found: 331.0191 (calcd. for
C13H16O2I: 331.0195).
ꢀ1
¼
ꢀ
Butyl E-3-iodocinnamate: As for butyl trans-cinnamate, bu-
tyl-E-3-iodocinnamate; yield: 102 mg (76%); MS (APCIþ):
1
m/z¼349 [MNH4þ], 332 [MHþ], 275 [MHþ – Bu]; H NMR
(C1’, C4’), 143.0 (C3), 166.7 (C1); IR (nujol): nmax ¼2924,
ꢀ1
¼
¼
ꢀ
(500 MHz, CDCl3): d¼0.96 (3H, t, J¼7.3 Hz, CH3), 1.44
(2H, m, CH2), 1.68 (2H, m, CH2), 4.18 (2H, t, J¼6.7 Hz,
1725 (C O), 1643 (C C), 1173 cm (C O); HRMS found:
239.0844 (calcd. for C13H16O2Cl: 239.0844).
Adv. Synth. Catal. 2005, 347, 185–195
asc.wiley-vch.de
ꢁ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
193

Edward J. Farrington et al.
FULL PAPERS
Butyl E-4-trifluoromethoxycinnamate: p-Trifluorometh-
oxybenzeneboronic acid (16.9 mg, 0.082 mmol), [(p-cymene)-
RuCl2]2 (1.25 mg, 4.1ꢁ10ꢀ6 mmol), copper acetate (40.9 mg,
0.205 mmol) and quinuclidinone (51.5 mg, 0.41 mmol) were
combined in a dry Schlenk tube, which was sealed and placed
under vacuum for 30 minutes. The Schlenk tube was flushed
with argon, then butyl acrylate (10.9 mg, 0.082 mmol) and
freshly distilled toluene (1 mL) were added via syringe. The re-
action mixture was stirred for 24 h at ambient temperature.
The solvent was removed under vacuum and the product puri-
fied by silica gel chromatography, eluting with diethyl ether to
give butyl E-4-trifluoromethoxycinnamate; yield: 17 mg
(70%); MS (APCIþ): m/z¼306 [MNH4þ], 289 [MHþ], 232
d, CH3), 1.31 (2H, m, CH2), 1.7 (2H, m, CH2), 3.82 (3H, s,
OCH3), 4.23 (2H, t, OCH2), 6.47 (1H, d, J¼16 Hz, H2), 7.12
(1H, d, J¼18 Hz, H2’’), 7.42 (2H, m, H2’), 7.63 (2H, m, H3’),
7.71 (1H, d, J¼18 Hz, H3’’), 7.77 (1H, d, J¼16 Hz, H3’);
13C NMR (125.8 MHz, CDCl3): d¼14.2 (CH3), 19.6 (CH2),
30.8 (CH2), 52.3 (OCH3), 65.0 (OCH2) 119.3, 119.9 (C2, C2’’),
126.0, 129.4, 129.2, 132.5 (C1’, C2’, C3’, C4’), 143.8, 144.2 (C3,
C3’’), 167.3, 167.7 (C1, C1’’); HRMS found: 288.155 (calcd.
for C17H20O4: 288.155).
N-Morpholino E-4-Iodocinnamate[35]
1
[MHþ – Bu]; H NMR (500 MHz, CDCl3): d¼0.98 (3H, t,
p-Iodobenzeneboronic acid (100 mg, 0.4 mmol), (6.2 mg,
0.02 mmol), copper acetate (201 mg, 1 mmol) and quinuclidi-
none (126 mg, 1 mmol) were combined in a dry Schlenk tube
which was sealed and placed under vacuum for 30 minutes.
The Schlenk tube was flushed with argon then N-acryloylmor-
pholine (176 mg, 1.2 mmol) and freshly distilled toluene
(10 mL) were added via syringe. The reaction mixture was stir-
red for 48 h at ambient temperature under argon. The solvent
was removed under vacuum and the product purified by silica
gel chromatography, eluting with diethyl ether to give N-mor-
pholino p-iodo-trans-cinnamate as a white solid; yield: 39.9 mg
J¼7.4 Hz, CH3), 1.44 (2H, m, CH2), 1.71 (2H, m, CH2), 4.22
(2H, t, J¼6.7 Hz, OCH2), 6.44 (1H, d, J¼16 Hz, H1), 7.24
(2H, AA’ of AA’XX’, J¼8.3 Hz, H2’), 7.56 (2H, XX’ of
AA’XX’, J¼8.3 Hz, H3’), 7.67 (1H, d, J¼16 Hz, H3);
13C NMR (125.8 MHz, CDCl3): d¼13.6 (CH3), 19.1 (CH2),
30.6 (CH2), 64.5 (OCH2), 119.1 (C2), 121.0 (CF3), 129.3, 142.6
(C1’, C4’), 133.0, 134.4 (C2’, C3’), 150.2 (C3) 166.6 (C1).
Butyl E-4-methoxycinnamate: As for butyl trans-cinna-
mate, butyl E-4-methoxycinnamate; yield: 8 mg (25%); MS
1
(APCIþ): m/z¼235 [MHþ], 178 [MHþ – Bu], 161; H NMR
(30%); mp 898C; MS (APCIþ): m/z¼344 [MHþ], 257 [MHþ
–
(500 MHz, CDCl3): d¼0.97 (3H, t, J¼7.4 Hz, CH3), 1.43
(2H, m, CH2), 1.71 (2H, m, CH2), 3.84 (3H, s, CH2), 4.22 (2H,
t, J¼6.7 Hz, OCH2), 6.33 (1H, d, J¼15.9 Hz, H1), 6.92 (2H,
AA’ of AA’XX’, J¼8.7 Hz, H3’), 7.49 (2H, XX’ of AA’XX’,
J¼8.7 Hz, H2’), 7.65 (1H, d, J¼15.9 Hz, H3); 13C NMR
(125.8 MHz, CDCl3): d¼13.6 (CH3), 19.1 (CH2), 30.8 (CH2),
55.3 (OCH2), 64.2 (OCH3), 114.2 (C2), 129.6, 133.0, (C1’,
C4’), 127.1, 128.7 (C2’, C3’), 144.1 (C3), 167.4 (C1).
morpholine]; 1H NMR (400 MHz, CDCl3): d¼3.73 (4H, m,
CH2), 6.87 (1H, d, J¼15.41 Hz, H2), 7.26 (2H, AA’ of
AA’XX’, J¼8.4 Hz, H2’), 7.64 (1H, d, J¼15.41 Hz, H3’),
7.73 (2H, XX’ of AA’XX’, J¼8.4 Hz, H3); 13C NMR
(100.6 MHz, CDCl3): d¼42.5, 46.2 (CH2), 117.2 (C2), 137.9,
129.3 (C2’, C3’), 128.3, 134.6 (C1’, C4’), 142.0 (C3), 165.2 (C1).
Butyl-E-4-formylcinnamate: As for butyl trans-cinnamate,
butyl E-4-formylcinnamate; yield: 17 mg (86%); MS (APCIþ):
m/z¼250 [MNH4þ], 233 [MHþ], 176 [MHþ – Bu], 159;
1H NMR (400 MHz, CDCl3): d¼0.97 (3H, t, J¼7.4 Hz,
CH3), 1.45 (2H, m, CH2), 1.72 (2H, m, CH2), 4.24 (2H, t, J¼
6.7 Hz, OCH2), 6.58 (1H, d, J¼16.1 Hz, H1), 7.67 (2H, AA’
of AA’XX’, J¼8.2 Hz, H2’), 7.68 (1H, XX’ of AA’XX’, J¼
16.1 Hz, H3’), 7.92 (2H, d, J¼8.2 Hz, H3), 10.0 (1H, s, CHO);
13C NMR (100.6 MHz, CDCl3): d¼13.7 (CH3), 19.2 (CH2),
30.7 (CH2), 64.7 (OCH2), 121.4 (C2), 128.5, 140.1 (C1’, C4’),
130.2, 137.1 (C2’, C3’), 142.8 (C3) 166.5 (C1), 191.5 (CHO).
N,N-Dimethyl E-3-Chlorocinnamide[36]
3-Chlorobenzeneboronic acid (130 mg, 0.82 mmol), [(p-cyme-
ne)RuCl2]2 (12.5 mg, 0.04 mmol), Cu(OAc)2 (410 mg, 2 mmol)
and quinuclidinone (513 mg, 4.1 mmol) were combined in adry
Schlenk tube which was sealed and placed under vacuum for 30
minutes. The Schlenk tube was flushed with argon then N,N-di-
methylacrylamide (81 mg, 0.82 mmol) and freshly distilled tol-
uene (10 mL) were added via syringe. The reaction mixture
was stirred for 48 h at ambient temperature under argon. The
solvent was removed under vacuum and the product purified
by silica gel chromatography, eluting with 50:50 ethyl ace-
tate/pentane to give N,N-dimethyl E-3-chlorocinnamide as a
white solid; yield: 52 mg (30%); MS (APCIꢀ): m/z¼210
[MHþ]; 1H NMR (400 MHz, CDCl3): d¼3.11 (3H, s, NCH3),
3.21 (3H, s, NCH3), 6.75 (1H, d, J¼15 Hz, H2), 7.32 (1H, dd,
J¼7.8 Hz and 8.1 Hz, H3’), 7.4 (1H, d, J¼1.5 Hz and 8.1 Hz,
H2’), 7.41 (1H, d, J¼1.5 Hz and 7.8 Hz, H4’), 7.52 (1H, dd,
J¼1.5 Hz, H6’), 7.53 (1H, d, J¼15 Hz, H3); 13C NMR
(100.6 MHz, CDCl3): d¼36.4 (NCH3), 37.7 (NCH3), 113.9
(C2), 126.9, 129.6, 130.9, 134.6 (C2’, C3’, C4’, C6’), 135.2,
136.7 (C1’, C5’), 141.8 (C3), 167.0 (C1).
Palladium-Catalysed Heck Reaction of Butyl E-4-
Iodocinnamate with Methyl Acrylate
Butyl E-4-iodocinnamate (50 mg, 0.15 mmol), tris(o-tolyl)-
phosphine (4.56 mg, 0.015 mmol) and tris(dibenzylidineace-
tone)dipalladium(0) (7.8 mg, 0.0076 mmol) were combined
in a dry Schlenk tube under an argon atmosphere. Methyl
acrylate (65 mg, 0.76 mmol), triethylamine (76 mg,
0.76 mmol) and dry DMF (5 mL) were added via syringe and
the reaction mixture was stirred at ambient temperature for
24 h to give a dark yellow solution with a small amount of black
precipitate. The solvent was removed under vacuum and the
solid residue was filtered through a plug of silica, eluting with
diethyl ether to give 3-[4-(2-methoxycarbonylvinyl)-phenyl]a-
crylic acid butyl ester as an amorphous white solid; yield: 39 mg
(90%); mp 69–718C; MS (APCIþ): m/z¼305.2 [MNH4þ],
Acknowledgements
We thank EPSRC and Johnson Matthey plc for a CASE award
in support of EJF. Johnson Matthey kindly provided a loan of
Ru complexes and other precious metal salts.
1
235.1 [MHþ – BuO]; H NMR (500 MHz, CDCl3): 0.91 (3H,
194
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Adv. Synth. Catal. 2005, 347, 185–195

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