A flexible approach to Pd-catalyzed carbonylations via aroyl dimethylaminopyridinium salts

Article abstract of DOI:10.1039/c5sc02949j

4-Dimethylaminopyridine (DMAP) is shown to undergo Pd/P^tBu₃ catalyzed coupling with aryl halides and carbon monoxide to form electrophilic aroyl-DMAP salts. The reaction is easily scalable to prepare multigram quantities with low catalyst loadings, while the precipitation of these salts as they form leads to products with low impurities. These reagents rapidly react with a variety of nucleophiles, including those that contain potentially incompatible functional groups under standard carbonylative conditions.

Full text of DOI:10.1039/c5sc02949j

Chemical
Science
View Article Online
View Journal
EDGE ARTICLE
A flexible approach to Pd-catalyzed carbonylations
via aroyl dimethylaminopyridinium salts†
Cite this: DOI: 10.1039/c5sc02949j
*
Jeffrey S. Quesnel, Alexander Fabrikant and Bruce A. Arndtsen
4-Dimethylaminopyridine (DMAP) is shown to undergo Pd/PtBu3 catalyzed coupling with aryl halides and
carbon monoxide to form electrophilic aroyl–DMAP salts. The reaction is easily scalable to prepare
multigram quantities with low catalyst loadings, while the precipitation of these salts as they form leads
to products with low impurities. These reagents rapidly react with a variety of nucleophiles, including
those that contain potentially incompatible functional groups under standard carbonylative conditions.
Received 10th August 2015
Accepted 30th September 2015
DOI: 10.1039/c5sc02949j
www.rsc.org/chemicalscience
products also leads to practical concerns of cost, waste of
precious metal, and product contamination with palladium.
Introduction
The latter can be a signicant challenge in preparing APIs
(active pharmaceutical ingredients).9
Activated carboxylic acid derivatives play a fundamental role in
synthetic chemistry. Their use ranges from simple esterication
and amidation reactions to Friedel–Cras acylation, peptide
coupling, heterocycle synthesis, polymer chemistry, or metal-
catalyzed bond-forming reactions.1–5 Classic approaches to
generate these reagents involve either the use of stoichiometric
activating agents (e.g. DCC, HOBt, etc.), or, for even greater
electrophilicity, the conversion of carboxylic acids into acyl
halides. While effective, these can require large amounts of high
energy, costly, or sometimes toxic activating agents (thionyl
chloride, oxalyl chloride, or PCl3), and generate signicant
waste. These concerns have led to the search for more efficient
methods to construct amides, esters, and related compounds.6
An alternative platform to prepare carbonyl-containing
products is through the palladium-catalyzed carbonylation of
organic halides.7,8 Introduced over 40 years ago, these reactions
provide a synthetic route to ketones, esters, amides, and related
carboxylic acid derivatives using simple CO as the carbonyl unit.
In spite of its atom economy, there remain a number of
inherent drawbacks to carbonylations. For example, the puta-
tive palladium–aroyl intermediates are much less electrophilic
than common acylating reagents such as acid chlorides,
necessitating pressing reaction conditions even for relatively
simple ester or amide syntheses.8 Reactions with weak or
sterically encumbered nucleophiles are oen unknown.
Secondly, competitive and undesired side reactions, or catalyst
poisoning, can occur with substrates containing functionalities
that can be activated by transition metals. The oen high
catalyst loadings and coordinating ability of the carbonylated
Some efforts to alleviate the scope limitations of carbonyla-
tions have been reported through the work of Buchwald,
Skrydstrup, Manabe, Grushin, and others via the in situ
formation of phenoxyesters,10 thioesters,11 N-hydrox-
ysuccinimido esters,12 and related derivatives13 as precursors to
carbonyl-containing derivatives (Fig. 1a). Alternatively, we
recently described the catalytic synthesis of acid chlorides from
aryl halides, CO, and chloride salts (Fig. 1b).14,15 In contrast to
the moderate reactivity of esters and thioesters, the high elec-
trophilicity of acid chlorides allows the application of carbon-
ylations to a range of nucleophiles. Nevertheless, a challenge
encountered in this latter transformation is the reactivity of the
Department of Chemistry, McGill University, 801 Sherbrooke St. W., Montreal, QC,
Canada, H3A 0B8. E-mail: bruce.arndtsen@mcgill.ca; Fax: +1-514-398-3797; Tel:
+1-514-398-6999
† Electronic supplementary information (ESI) available: Experimental procedures,
characterization data, and NMR spectra for compounds. See DOI:
10.1039/c5sc02949j
Fig. 1 Palladium-catalyzed formation of active carboxylic acid deriv-
atives via carbonylation.
This journal is © The Royal Society of Chemistry 2015
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Table 1 Palladium-catalyzed carbonylation of PhI with DMAPa
acid chloride itself. Unlike most palladium-catalyzed coupling
reactions, the acid chloride product is more reactive than the
aryl halide substrate towards the catalyst, and its build-up
strongly inhibits the reaction. Thus, heating, high pressures, or
high catalyst loading are required to achieve good conversion.
Acid chlorides are also sensitive reagents with similar physical
properties (e.g. boiling and melting points) to the aryl halide
starting materials, making isolation a challenge.
Entry
L
Yieldb (%) Entry
L
Yieldb (%)
In considering the above, we became interested in designing
a more efficient catalytic route to synthesize activated acylating
reagents that is: (a) not inhibited by product build-up, and
therefore can allow for rapid and efficient catalysis, (b) leads to
the formation of easily isolated products, yet (c) creates potent
acylating reagents with the reactivity of acid chlorides. We
report herein the design of such a method via the use of 4-
dimethylaminopyridine (DMAP, Fig. 1c). Acyl–DMAP reagents
are potent electrophiles commonly generated in situ to facilitate
nucleophilic attack, although these compounds are rarely
synthesized as isolated products.16,17 The use of carbonylations
to generate cationic products such as aroyl–DMAP salts has to
our knowledge not been previously reported. The latter is likely
due to the challenge of achieving reductive elimination of
a cationic product from 1 relative to those with anionic nucle-
ophiles (e.g. ROꢀ, R2Nꢀ). As described below, the use of highly
sterically encumbered palladium catalysts can provide a facile
method to carbonylate aryl halides into aroylated–DMAP salts.
These cationic products are easily separable, even during
catalysis, which can therefore allow for a rapid reaction, low
catalyst loadings, and generate activated carboxylic acid deriv-
atives for subsequent reactions. This has allowed the applica-
tion of Pd-catalyzed carbonylations to a range of new classes of
nucleophilic substrates.
1
2
3
4
PtBu3/Bu4NClc 33
8
9
10
11
dppf
dcpe
dppp
dppb
3
0
1
1
—
PPh3
P(o-tolyl)3
3
—
2
5
6
3
12
1
8
13
14
6
7
PCy3
10
PtBu3
97d
a
PhI (102 mg, 0.50 mmol), DMAP (73 mg, 0.60 mmol), [Pd] ¼
Pd2dba3$CHCl3 (13 mg, 25 mmol), L (50 mmol), CO (1 atm), THF
b
(0.75 mL). NMR yield of benzamide when quenched with BnNH2
(55 mg, 0.51 mmol), EtNiPr2 (100 mL, 0.57 mol). 1.0 equiv. Isolated
c
d
yield of 2a.
Table 2 Palladium-catalyzed synthesis of aroyl DMAP salts 2a,b
Results and discussion
Initial examination of this carbonylation involved the reaction
of phenyl iodide, DMAP, and CO. Our postulate was the catalytic
formation of acid chloride in the presence of DMAP would lead
to the formation of the ionic 2a, and could drive the reaction
forward under mild conditions. As anticipated from our
previous report, the combination of Pd2dba3$CHCl3/PtBu3 with
Bu4NCl as a chloride source did indeed allow the formation of
2a in modest yield (Table 1, entry 1).14a In attempting to improve
the efficiency of this reaction, we questioned if stoichiometric
chloride is required for this reaction, and if DMAP may instead
itself bind to palladium for reductive elimination. The omission
of chloride leads to minimal product formation with most of the
catalysts examined (entries 2–13), likely due to the difficult
reductive elimination step of a cationic product. This includes
a number of ligands which are active in other palladium-cata-
lyzed coupling (entries 3–6, 12) and carbonylation reactions
(entries 8–11, 13).8,18 However, the use of the largest cone angle
trialkyl phosphine, PtBu3, which would generate a highly steri-
cally encumbered palladium–aroyl complex 1 for reductive
elimination (vide infra), results in a dramatic increase in
activity, and the near quantitative formation of DMAP salt 2a
(entry 14).
a
Aryl iodide (0.50 mmol), DMAP (73 mg, 0.6 mmol), Pd(PtBu3)2
(12.8 mg, 25 mmol, 5 mol%), CO (1 atm), in THF (1 mL) at 45 ꢁC for
24 h. Isolated yields.
b
Chem. Sci.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Edge Article
As shown in Table 2, this reaction can be used to prepare
Chemical Science
Table 4 Palladium-catalyzed synthesis of DMAP bromide salts 3a,b
a diverse array of aroylated products from the corresponding
aryl iodides under mild conditions.19 This includes both elec-
tron-poor substrates (2c, 2e, 2f), those with reactive functional
groups (2c, 2l) and deactivated electron-rich aryl iodides (2b,
2g). Similarly, steric encumbrance does not appear to hinder the
reaction, with 2-methoxy and 2-tolyl reagents forming products
in high yield (2g, 2h).
A feature of this transformation is the insolubility of the
aroylated DMAP product 2 in the reaction solvent. The product
can therefore be isolated at the end of the reaction by simple
ltration. These solid reagents hydrolyse relatively slowly in
their solid state, making them suitable candidates for medium
to long term storage.20 The precipitation of 2 as it forms also
limits the potential for product inhibition. As such, the reaction
is scalable to generate multigram quantities of product, and
with as low as 0.5 mol% palladium catalyst under more pressing
conditions (Table 3). In addition, the precipitation of the DMAP
salt leaves the palladium catalyst in solution, and provides in
some instances a route to generate carbonylated products with
low palladium contamination. Analysis of 2a formed with 5
mol% Pd and a slight excess of PhI by ICP-OES shows 98 ppm
Pd in the product (or the removal of 99.5% Pd), without any
special precautions beyond ltration. Similar results are
observed with the other aryl iodides (100–500 ppm: 2b–2f),21
although higher Pd content is noted with more sterically
encumbered aryl iodides (ca. 2000 ppm in 2g, 2h, 2j).22 Subse-
quent conversion of these products to esters or amides (Table 5)
a
Aryl bromide (0.50 mmol), DMAP (73 mg, 0.6 mmol), Pd(PtBu3)2
(12.8 mg, 25 mmol), CO (4 atm), toluene (2 mL), 100 ꢁC, 24 h.
b
c
d
Isolated yield. PtBu3 (30 mg, 0.15 mmol). Table 2 conditions
using 10 mol% Pd(PtBu3)2.
leads to isolated products with negligible palladium
(<10 ppm).23
Table 3 Low catalyst loading synthesis of aroyl DMAP salts 2a
We next turned our attention to more challenging, yet widely
available, aryl bromide substrates. We have recently reported
the carbonylation of aryl bromides to acid chlorides, although
in this case very pressing conditions are required and the high
reactivity of the acid chloride product towards palladium rela-
tive to the reagent (aryl bromides) oen leads to incomplete
conversion.14b As shown in Table 4, bromide substrates can be
similarly converted to aroyl–DMAP salts with the Pd(PtBu3)2
catalyst in high yield.24 The products are again isolated by
ltration and no formal purication steps are required. In
addition to substituted arenes, the use of bromide reagents
permits the use of various heteroaromatic compounds (e.g.
quinoline-, thiophene-, indole- and pyridine-containing
substrates, 3d, 3e, 3i, 3l), which are generally more accessible
than the corresponding iodides.
Product
Time (h)
Yield (%)
Aroyl–DMAP salts are potent electrophiles commonly
employed as intermediates to activate neutral acylating agents
towards coupling with nucleophiles. This reactivity makes it
convenient to apply carbonylation reactions to a diverse array of
nucleophiles that can be challenging or not viable as substrates
in palladium catalysis. For example, the addition of amines or
alcohols to catalytically generated 2 furnishes the correspond-
ing amides and esters without long reaction times or heating
common in carbonylations (Table 5). Substrates include both
primary amines and alcohols (e.g. 4a, 4b, 4g–l) and more steri-
cally encumbered nucleophiles such as tert-butylamine (4s),
2a
2b
2c
2d
2e
2f
2g
2j
2l
7
24
7
13
30
64
4
99
99
97
99
93
98
99
99
97
24
7
a
Aryl iodide (10 mmol), DMAP (1.46 g, 12 mmol), Pd(PtBu3)2 (25 mg,
50 mmol), CO (20 atm), THF (10 mL), 80 ꢁC, 24 h.
This journal is © The Royal Society of Chemistry 2015
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Table 5 Synthesis of carboxylic acid derivatives with orthogonal
functionalitya
Scheme 1 Proposed mechanism of catalytic aroyl–DMAP formation.
dissolution of the aroylating reagent becomes a visual indicator
of reaction progression. This approach also allows for the use of
nucleophiles containing functional groups that can otherwise
lead to unwanted side reactions under typical carbonylative
conditions. As examples, terminal alkynes (e.g. 5f, 5g), alkenes,
including styrene (e.g. 5a), or sulfur-containing reagents (5m)
can be employed on the nucleophile without competitive side
reactions, as can aryl iodides or heteroaryl bromides containing
substrates (e.g. 5b–e, 5l). Overall, this provides a method to
perform carbonylations under mild conditions with a broad
range of nucleophiles.
We have performed preliminary studies to probe the mech-
anism of this catalytic reaction. Kinetic analysis shows that
catalysis is accelerated by both phosphine and CO concentra-
tion, but inhibited by excess DMAP (see ESI†). A plausible
reaction mechanism that accounts for these factors is shown in
Scheme 1. Oxidative addition of aryl iodide and CO insertion to
palladium are established to be rapid, and generate the three-
coordinate complex 1b with PtBu3.14a However, control experi-
ments with a pre-synthesized 1b (X ¼ I) demonstrate that DMAP
can displace PtBu3 from this complex at high concentrations.
We therefore postulate that the benecial effects of added
PtBu3, and inhibition of catalysis by excess DMAP, arise from
this equilibrium, as excess DMAP can create a Pd(II) complex
unable to undergo reductive elimination. As noted in Table 1,
the PtBu3 ligand is required to allow the catalytic formation of 2
under mild conditions. This is analogous to that we have noted
in the generation of weak C–Cl bonds in acid chlorides14 and
presumably arises from the tertiary steric bulk at phosphorus in
this ligand, which can induce reductive elimination with even
a weak, neutral nucleophile such as DMAP as a mechanism to
relieve strain. The association of CO to 1b, and the precipitation
of the product 2, likely further facilitate this step.26
a
DMAP salt (0.50 mmol), nucleophile (0.75 mmol), EtN(iPr)2 (175 mL,
1 mmol), 1 mL CH2Cl2 at r.t. for 2 h; isolated yield of second step.
b
16 h.
diisopropyl amine (4r) or tertiary alcohols (5n, 5o). The latter are
oen difficult to employ in carbonylation chemistry.25 Weaker
nitrogen nucleophiles such as aniline and phenol are viable
substrates (4m, 4n). These reactions are rapid, with many
Conclusions
nucleophiles (e.g. aliphatic amines and alcohols) proceeding to In summary, a palladium-catalyzed, carbonylative synthesis of
completion within seconds. As these DMAP salts are only aroyl-DMAP salts has been developed. The precipitation of these
slightly soluble in the reaction solvent (dichloromethane), products avoids catalyst inhibition, allows the reaction to be
Chem. Sci.
This journal is © The Royal Society of Chemistry 2015

View Article Online
Edge Article
Chemical Science
performed in high yields with low palladium loadings, and
generates potent aroylating reagents with negligible impurities
upon simple ltration. These products react with a variety of
in Process Chemistry, Springer Berlin Heidelberg, 2004, vol.
6, pp. 263–283; (c) C. E. Garrett and K. Prasad, Adv. Synth.
Catal., 2004, 346, 889.
nucleophiles under mild conditions, including those with 10 (a) D. A. Watson, X. Fan and S. L. Buchwald, J. Org. Chem.,
functional groups that can be incompatible under standard
carbonylative conditions or are poorly nucleophilic. These
2008, 73, 7096; (b) T. Ueda, H. Konishi and K. Manabe,
Org. Lett., 2012, 14, 5370.
features suggest the potential general utility of aroyl–DMAP 11 M. N. Burhardt, R. H. Taaning and T. Skrydstrup, Org. Lett.,
formation in carbonylation chemistry, especially with prob- 2013, 15, 948.
lematic substrates. Experiments directed towards exploiting 12 (a) R. Lou, M. vanAlstine, X. Sun and M. P. Wentland,
this reactivity in new classes of carbonylation reactions are
currently in progress.
Tetrahedron Lett., 2003, 44, 2477; (b) A. M. de Almeida,
T. L. Andersen, A. T. Lindhardt, M. V. de Almeida and
T. Skrydstrup, J. Org. Chem., 2015, 80, 1920.
13 Aroyl azides (a) F. M. Miloserdov and V. V. Grushin, Angew.
Chem., Int. Ed., 2012, 51, 3668, Acyl uorides (b) T. Okano,
N. Harada and J. Kiji, Bull. Chem. Soc. Jpn., 1992, 65, 1741;
(c) T. Sakakura, M. Chaisupakitsin, T. Hayashi and
M. Tanaka, J. Organomet. Chem., 1987, 334, 205; (d)
T. Ueda, H. Konishi and K. Manabe, Org. Lett., 2013, 15,
Acknowledgements
We thank NSERC, the Canadian Foundation for Innovation
(CFI), and the FQRNT supported Centre for Green Chemistry
and Catalysis for funding this research.
5370,
Weinreb
amides
(e)
J.
R.
Martinelli,
Notes and references
D. M. M. Freckmann and S. L. Buchwald, Org. Lett., 2006,
8, 4843, N-acyl pyrroles (f) S. Ho, G. Bondarenko, D. Rosa,
B. Dragisic and A. Orellana, J. Org. Chem., 2012, 77, 2008.
1 (a) G. A. Olah, Friedel–Cras and Related Reactions,
Interscience Publishers, New York, 1963; (b) G. A. Olah,
Friedel–Cras Chemistry, John Wiley-Interscience, New 14 (a) J. S. Quesnel and B. A. Arndtsen, J. Am. Chem. Soc., 2013,
York, 1973.
135, 16841; (b) J. S. Quesnel, L. V. Kayser, A. Fabrikant and
B. A. Arndtsen, Chem.–Eur. J., 2015, 20, 9550.
2 C. A. G. N. Montalbetti and V. Falque, Tetrahedron, 2005, 61,
10827.
15 For acid chloride syntheses from non-aryl halide
electrophiles: (a) J. Tsuji, M. Morikawa and J. Kiji, J. Am.
Chem. Soc., 1964, 86, 4851; (b) W. T. Dent, R. Long and
G. H. J. Whiteld, J. Chem. Soc., 1964, 1588; (c)
M. C. Bonnet, N. Carmona and I. Tkatchenko, J. Mol.
Catal. A: Chem., 1999, 143, 181; (d) T. A. Cernak and
T. H. Lambert, J. Am. Chem. Soc., 2009, 131, 3124.
3 (a) I. J. Turchi and M. J. S. Dewar, Chem. Rev., 1975, 75, 389;
(b) J. B. Wright, Chem. Rev., 1951, 48, 397; (c) N. S. Isaacs,
Chem. Soc. Rev., 1976, 5, 181; (d) G. W. Gribble, in
Mesoionic Ring Systems from the Chemistry of Heterocyclic
Compounds, ed. A. Padwa and W. H. Pearson, Wiley-Vch,
2002, vol 59, pp. 682–753; (e) D. M. D'Souza and
¨
¨
¨
T. J. J. Muller, Chem. Soc. Rev., 2007, 36, 1095.
16 (a) G. Hoe, W. Steglich and H. Vorbruggen, Angew. Chem.,
Int. Ed., 1978, 17, 569; (b) E. F. V. Scriven, Chem. Soc. Rev.,
1983, 12, 129; (c) U. Ragnarsson and L. Grehn, Acc. Chem.
Res., 1998, 31, 494; (d) D. J. Berry, C. V. Digiovanna,
S. S. Metrick and R. Murugan, ARKIVOC, 2001, 2, 944; (e)
A. C. Spivey and S. Arseniyadis, Angew. Chem., Int. Ed.,
2004, 43, 5436; (f) N. de Rycke, F. Couty and O. R. P. David,
Chem.–Eur. J., 2011, 17, 12852.
4 (a) H. H. Yang, Kevlar Aramid Fiber, J. Wiley, Chichester,
1993; (b) H. G. Chae and S. J. Kumar, Appl. Polym. Sci.,
2006, 100, 791.
5 R. K. Dieter, Tetrahedron, 1999, 55, 4177.
6 (a) D. J. C. Constable, P. J. Dunn, J. D. Hayler,
G. R. Humphrey, J. J. L. Leazer, R. J. Linderman, K. Lorenz,
J. Manley, B. A. Pearlman, A. Wells, A. Zaks and
T. Y. Zhang, Green Chem., 2007, 9, 411; (b) E. Valeur and 17 (a) E. Guibe-Jampel, G. Le Corre and M. Wakselman,
M. Bradley, Chem. Soc. Rev., 2009, 38, 606; (c) C. L. Allen
and J. M. J. Williams, Chem. Soc. Rev., 2011, 40, 3405; (d)
V. R. Pattabiraman and J. W. Bode, Nature, 2011, 480, 471.
7 (a) A. Schoenberg, I. Bartoletti and R. F. Heck, J. Org. Chem.,
1974, 39, 3318; (b) A. Schoenberg and R. F. Heck, J. Org.
Chem., 1974, 39, 3327.
Tetrahedron Lett., 1979, 20, 1157; (b) J. A. King and
G. L. Bryant, J. Org. Chem., 1992, 57, 5136; (c) M. S. Wolfe,
Synth. Commun., 1997, 27, 2975; (d) R. Weiss, M. Bess,
S. M. Huber and F. W. Heinemann, J. Am. Chem. Soc.,
2008, 130, 4610.
18 W. Fang, H. Zhu, Q. Deng, S. Liu, X. Liu, Y. Shen and T. Tu,
Synthesis, 2014, 46, 1689.
8 For reviews see: (a) H. Neumann and M. Beller, Angew.
Chem., Int. Ed., 2009, 48, 4114; (b) C. F. J. Barnard, 19 For ease of reaction set-up and manipulation, (PtBu3)2Pd was
Organometallics, 2008, 27, 5402; (c) R. Grigg and
S. P. Mutton, Tetrahedron, 2010, 66, 5515; (d)
employed as a catalyst, although the combination of
Pd2dba3/PtBu3 (Table 1) can also be used. In addition, the
reaction can be performed on the bench using standard
Schlenk techniques with only slightly diminished yields
(using Pd2dba3/tBu3PHCl as the catalyst precursor). See
ESI† for details.
¨
A. Brennfuhrer, X.-F. Wu, H. Neumann and M. Beller,
Chem. Soc. Rev., 2011, 40, 4986.
9 For select examples and reviews see: (a) J. Magano, in
Transition Metal-Catalyzed Couplings in Process Chemistry,
Wiley-VCH Verlag GmbH & Co. KGaA, 2003, pp. 313–355;
(b) J. Bien, G. Lane and M. Oberholzer, in Organometallics
This journal is © The Royal Society of Chemistry 2015
Chem. Sci.

View Article Online
Chemical Science
Edge Article
20 This was judged by exposing 2a to the open atmosphere for 23 The products were obtained using the procedure in Table 5
10 days where aer which 11% hydrolysis was observed (by
1H NMR analysis).
21 ICP-OES palladium content analysis show removal of 98–
and puried by standard silica gel column chromatography.
ICP-OES palladium content analysis: 4a ¼ 7 ppm; 5f < 1 ppm;
5h < 1 ppm.
99% Pd in: 2b ¼ 450 ppm (65 ꢁC, 4 atm); 2c ¼ 270; 2d ¼ 24 The reaction of aryl bromides can also be performed at 1 atm
199; 2e ¼ 522 ppm. General conditions employed: ArI (0.6
CO at slightly diminished yields (e.g. 3a, 84% yield at 1 atm
CO).
25 M. Majek and A. Jacobi von Wangelin, Angew. Chem., Int. Ed.,
2015, 54, 2270 and references therein.
mmol), DMAP (0.5 mmol), Pd(PtBu3) (5 mol%), CO (1 atm),
ꢁ
THF (1 mL), 45 C, 24 h.
22 2g ¼ 2132 ppm; 2h ¼ 2635 ppm; 2j ¼ 1780 ppm. We
postulate that the higher Pd content may arise from the 26 It is also possible that the sterically encumbered palladium
diminished ability of these aryl iodides to sequester
palladium in solution.
intermediate undergoes aroyl-halide reductive elimination,
followed by reaction of this product with DMAP. At
present, we cannot distinguish between these possibilities.
Chem. Sci.
This journal is © The Royal Society of Chemistry 2015