base effect in the auto-tandem palladium-catalyzed synthesis of amino-substituted 1-methyl-1H-α-carbolines

Article abstract of DOI:10.1021/ol400064r

An auto-tandem Pd-catalyzed process consisting of an intramolecular direct arylation and an intermolecular Buchwald-Hartwig reaction for C-ring amino-substituted 1-methyl-1H-α-carboline synthesis has been developed. A mechanistic study of the direct arylation reaction revealed a rate effect of the inorganic base on the C-H activation step ( base effect ). The amines, reagents in the tandem protocol, appear to have a similar effect on the direct arylation.

Full text of DOI:10.1021/ol400064r

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
“Base Effect” in the Auto-Tandem
Palladium-Catalyzed Synthesis of Amino-
Substituted 1‑Methyl‑1H‑r-carbolines
Ashok K. Yadav, Stefan Verbeeck, Steven Hostyn, Philippe Franck, Sergey Sergeyev,
and Bert U. W. Maes*
Organic Synthesis, Department of Chemistry, University of Antwerp,
Groenenborgerlaan 171, B-2020 Antwerp, Belgium
bert.maes@ua.ac.be
Received January 9, 2013
ABSTRACT
An auto-tandem Pd-catalyzed process consisting of an intramolecular direct arylation and an intermolecular BuchwaldÀHartwig reaction for C-ring amino-
substituted 1-methyl-1H-r-carboline synthesis has been developed. A mechanistic study of the direct arylation reaction revealed a rate effect of the inorganic
base on the CÀH activation step (“base effect”). The amines, reagents in the tandem protocol, appear to have a similar effect on the direct arylation.
Pyrido[2,3-b]indole (R-carboline) derivatives have at-
tracted much attention because of their interesting biologi-
cal activities.1 In 2009, we reported the synthesis and
antiplasmodial activity of amino-substituted derivatives
of the natural product neocryptolepine (1) (Figure 1).2
N1,N1-Diethyl-N4-(5-methyl-5H-indolo[2,3-b]quinolin-8-yl)-
pentane-1,4-diamine (2) is 2700 times more active than 1 and
1.6 times less cytotoxic. Interestingly, A-ring debenzoneo-
cryptolepine (3), although 5 times less active, is 70 times less
cytotoxic than 1. Therefore, we concluded that the introduc-
Figure 1. Neocryptolepine and analogues.
tion of amino substituents on the C-ring of 1-methyl-1H-R-
carboline (3) has the potential to deliver very potent anti-
plasmodial compounds with low cytotoxicity. To synthesize a
broad set of C-ring-substituted amino-1-methyl-1H-R-carbo-
lines, an efficient synthetic methodology is required, allowing
regiospecific introduction and maximum variation in the
amino substituent from a common intermediate. Auto-
tandem palladium catalysis3 on N-[3-chloro-1-methyl-pyr-
idin-2(1H)-ylidene]-3, -4, and -2-chloroanilines (7aÀc)
consisting of an intramolecular direct arylation and an
intermolecular BuchwaldÀHartwig reaction with amines
looks very attractive to achieve this goal.4 However, auto-
tandem protocols are not easy to develop as one needs to
identify one catalyst suitable for all catalytic processes
(1) For examples, see: (a) Helbecque, N.; Moquin, C.; Bernier, J. L.;
Evelyne, M.; Henichart, J. P. Cancer Biochem. Biophys. 1987, 9, 271–
279. (b) Sennhenn, P.; Mantoulidis, A.; Treu, M.; Tontsch-Grunt, U.;
Spevak, W.; McConnell, D.; Schoop, A.; Brueckner, R.; Jacobi, A.;
Guertler, U. Int. Appl. WO 2006131552, 2006; Chem. Abstr. 2006, 146,
62695. (c) Kim, J.-S.; Shin-ya, K.; Furihata, K.; Hayakawa, Y.; Seto, H.
Tetrahedron Lett. 1997, 38, 3431–3434.
(2) (a) El Sayed, I.; Van der Veken, P.; Steert, K.; Dhooghe, L.;
ꢀ
Hostyn, S.; Van Baelen, G.; Lemiere, G.; Maes, B. U. W.; Cos, P.; Maes,
L.; Joossens, J.; Haemers, A.; Pieters, L.; Augustyns, K. J. Med. Chem.
2009, 52, 2979–2988. (b) Van Baelen, G.; Hostyn, S.; Dhooghe, L.;
(3) For reviews dealing (partly) with auto-tandem catalysis, see: (a) Vlaar,
T.; Ruijter, E.; Orru, R. V. A. Adv. Synth. Catal. 2011, 353, 809–841.
(b) Shindoh, N.; Takemoto, Y.; Takasu, K. Chem.;Eur. J. 2009, 15,
12168–12179. (c) Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004,
248, 2365–2379. (d) Lautens, M.; Alberico, D.; Bressy, C.; Fang, Y.-Q.;
Mariampillai, B.; Wilhelm, T. Pure Appl. Chem. 2006, 78, 351–361.
ꢁ
ꢁ
ꢀ
Tapolcsanyi, P.; Matyus, P.; Lemiere, G.; Dommisse, R.; Kaiser, M.;
Brun, R.;Cos, P.;Maes, L.;Hajos, G.;Riedl, Z.;Nagy, I.; Maes, B. U. W.;
ꢁ
Pieters, L. Bioorg. Med. Chem. 2009, 17, 7209–7217.
r
10.1021/ol400064r
XXXX American Chemical Society

yielding 2,3-dichloro-1-methylpyridinium trifluorometha-
nesulfonate (5), followed by condensation with the correct
chloroaniline.6 In a similar way, N-[3-chloro-1-methylpyr-
idin-2(1H)-ylidene]aniline (6) was synthesized. As a model
substrate, we chose 7aand asamine morpholine (Table 1).7
A complete conversion to 9a was obtained with (t-Bu)3P as
ligand using Pd2(dba)3 or Pd(OAc)2 as Pd source and
K3PO4 as the base (Table 1, entries 1 and 4). For the
analogous tandem reactions involving Cy JohnPhos (L1)
as a ligand, similar results were obtained, but with Pd2-
(dba)3, a significant amount of 1-methyl-1H-R-carboline
(3) (dehalogenated8a) wasisolated(Table 1, entry2). Inall
cases, no 4-(1-methyl-1H-pyrido[2,3-b]indol-5-yl)morpholine
was observed, pointing to a complete regioselective C(6)
direct arylation on 7a. The tandem process is completely
chemoselective as direct arylation was not in competition
with an amination reaction at C(3) of the pyridine ring.
Remarkably, use of JohnPhos (L2) exclusively led to the
ring-closed 8a in moderate yield (Table 1, entries 3 and 6).
Under the optimal reaction conditions for 7a (Table 1,
entries 1 and 5), regioisomeric 7b yielded 9b in 83 and 73%
yield, respectively (Table 1, entries 7 and 8). When 7c was
used as the substrate, the Pd2(dba)3/(t-Bu)3P catalytic
system gave a mixture of 4-(1-methyl-1H-pyrido[2,3-
b]indol-8-yl)morpholine (9c) and 8-chloro-1-methyl-1H-
pyrido[2,3-b]indole (8c) (Table 1, entry 9). This points to a
slow amination reaction which is not surprising taking into
account that the C(8) chloro atom of 8c is located in a peri
position of the carboline scaffold. The presence of 20%
dehalogenation product 3 further supports the hampering
of the amination reaction of 8c due to sterical hindrance.8
For the tandem reaction of 7c with morpholine, a double
Pd2(dba)3/(t-Bu)3P loading was therefore used (Table 1,
entry 10). A similar loading of Pd(OAc)2/L1 proved not to
be sufficient (Table 1, entry 11). Next, we investigated if the
protocol developed for morpholine could also be used for
acyclic secondary amines.7 Dibutylamine (Table 2) and
N-methylaniline (Table 3) were selected. Similarly as for
reactions involving morpholine, the Pd2(dba)3/(t-Bu)3P
catalytic system allowed synthesis of the N,N-dibutylami-
no-substituted carbolines 10aÀc (Table 2, entries 1, 3, and
4) and N,1-dimethyl-N-phenyl-1H-pyrido[2,3-b]indolamines
(11aÀc) (Table 3, entries 1, 3, and 4).
Table 1. Pd-Catalyzed Auto-Tandem Synthesis of 4-(1-Methyl-
1H-pyrido[2,3-b]indol-7,6 and 8-yl)morpholines (9aÀc)
yield
yield
yield
entry
7
Pd source/ligand (%) 3a (%) 8aÀca (%) 9aÀca
1
2
7ab,c Pd2(dba)3/(t-Bu)3P trace
91
53
7ab Pd2(dba)3/L1
7ab Pd2(dba)3/L2
29
3
40
68
4
7ab Pd(OAc)2/(t-Bu)3P trace
7ab Pd(OAc)2/L1
85
82
5
6
7ab Pd(OAc)2/L2
7
7bb Pd2(dba)3/(t-Bu)3P trace
83
73
47
62
20
8
7bb Pd(OAc)2/L1
6
9
7cb
7cd
7cd
Pd2(dba)3/(t-Bu)3P 15
Pd2(dba)3/(t-Bu)3P 20
28
40
10
11
Pd(OAc)2/L1
23
a Isolated yield. b Pd/L: 5 mol %/10 mol %. c K3PO4 (5 equiv) gave 9a
(31%, NMR yield) in 24 h; a similar result was obtained with Cs2CO3
(5 equiv). d Pd/L: 10 mol %/20 mol %.
occurring in one pot. A variety of Pd-catalyzed auto-
tandem reactions have been developed in recent years.3
These are usually focused on functionalized scaffold synthe-
sis in one step, and the final substitution diversity of the
core is limited by the availability of the reagents used.
Halogenated scaffold synthesis and subsequent in situ func-
tionalization offers more possibility to create diversity.
However, examples are still rare.5 We herein report a new
and efficient protocol for the synthesis of 6-, 7-, and 8-amino-
1-methyl-1H-R-carbolines via auto-tandem Pd catalysis on
7aÀc using primary and secondary amines as the reagents.
The substrates 7aÀc were easily synthesized via methy-
lation of commercially available 2,3-dichloropyridine (4),
As observed for morpholine, the Pd(OAc)2/L2 system
on 7a exclusively gave chlorocarboline 8a (Tables 2 and 3,
entries 2). The successful strategy was extended to primary
amines, with hexylamine as a model (Table 4). In this case,
a distinct reactivity was observed. The protocol proved to
be successful provided that Pd(OAc)2 was used as the Pd
source. When using Pd2(dba)3 as catalyst precursor, for 7a,
only chlorocarboline 8awasisolated(Table 4, entry 1), and
(4) For examples of an auto-tandem Pd-catalyzed amination/direct
arylation reaction (reverse sequence), see: (a) Ackermann, L.; Althammer,
A.; Mayer, P. Synthesis 2009, 3494–3503. (b) Bryan, C. S.; Lautens, M. Org.
Lett. 2008, 10, 4633–4636. (c) Bedford, R. B.; Betham, M. J. Org. Chem.
2006, 71, 9403–9410. (d) Bedford, R. B.; Cazin, C. S. J. Chem. Commun.
2002, 2310–2311.
(5) gem-Dihalovinyl systems: (a) Chelucci, G. Chem. Soc. Rev. 2011,
112, 1344–1462. For selected examples, see: (b) Fang, Y.-Q.; Karisch, R.;
Lautens, M. J. Org. Chem. 2007, 72, 1341–1346. (c) Fang, Y.-Q.; Yuen,
J.; Lautens, M. J. Org. Chem. 2007, 72, 5152–5160. (d) Nagamochi, M.;
Fang, Y.-Q.; Lautens, M. Org. Lett. 2007, 9, 2955–2958. (e) Fang, Y.-Q.;
Lautens, M. J. Org. Chem. 2008, 73, 538–549. (f) Chai, D. I.; Lautens, M.
J. Org. Chem. 2009, 74, 3054–3061. (g) Bryan, C. S.; Braunger, J. A.;
Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 7064–7068. (h) Bryan,
C. S.; Lautens, M. Org. Lett. 2010, 12, 2754–2757. (i) Nicolaus, N.;
Franke, P. T.; Lautens, M. Org. Lett. 2011, 13, 4236–4239. (j) Ye, S.; Liu,
J.; Wu, J. Chem. Commun. 2012, 48, 5028–5030. (k) Liu, J.; Chen, W.; Ji,
Y.; Wang, L. Adv. Synth. Catal. 2012, 354, 1585–1592. For examples
ꢀ
(6) Hostyn, S.; Tehrani, A. K.; Lemiere, F.; Smout, V.; Maes,
B. U. W. Tetrahedron 2011, 67, 655–659.
(7) For recent reviews on the BuchwaldÀHartwig reaction, see:
(a) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27–50. (b) Maiti,
D.; Fors, B. P.; Henderson, J. L.; Nakamura, Y.; Buchwald, S. L. Chem.
Sci. 2011, 2, 57–68. (c) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2008, 47, 6338–6361.
ꢁ
dealing with other systems, see: (l) Leclerc, J. P.; Andre, M.; Fagnou, K.
J. Org. Chem. 2006, 71, 1711–1714. (m) Turner, P. A.; Griffin, E. M.;
Whatmore, J. L.; Shipman, M. Org. Lett. 2011, 13, 1056–1057.
(8) Beletskaya, I. P.; Bessertnykh, A. G.; Guilard, R. Tetrahedron
Lett. 1999, 40, 6393–6397.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Pd-Catalyzed Auto-Tandem Synthesis of N,N-Dibutyl-
1-methyl-1H-pyrido[2,3-b]indol-7, 6, and 8-amines (10aÀc)
Table 4. Pd-Catalyzed Auto-Tandem Synthesis of N-Hexyl-1-
methyl-1H-pyrido[2,3-b]indol-7, 6 and 8-amines (12aÀc)
Pd source/
ligand
yield
yield (%) yield (%)
yield
yield
yield
(%) 3a
8aÀca
10aÀca
entry
7
Pd source/ligand (%) 3a (%) 8aÀca (%) 12aÀca
entry
7
7ab Pd2(dba)3/(t-Bu)3P
7ab Pd(OAc)2/(t-Bu)3P
7ab Pd(OAc)2/L2
71
79
36
1
2
3
4
7ab Pd2(dba)3/(t-Bu)3P
7ab Pd(OAc)2/L2
7bb Pd2(dba)3/(t-Bu)3P
6
6
77
1
2
72
12
4
59
8
19
54
70
37
3
7cc
Pd2(dba)3/(t-Bu)3P
4
7ab Pd(OAc)2/L1
87
42
73
59
24
60
43
5
7bb Pd2(dba)3/(t-Bu)3P
7bb Pd(OAc)2/L2
a Isolated yield. b Pd/L: 5 mol %/10 mol %. c Pd/L: 10 mol %/20 mol % .
6
6
32
5
7
7bb Pd(OAc)2/L1
8
7cc Pd2(dba)3/(t-Bu)3P
7cc Pd(OAc)2/L1
58
5
9
26
25
10
7cc Pd(OAc)2/L2
Table 3. Pd-Catalyzed Auto-Tandem Synthesis ofN,1-Dimethyl-
N-phenyl-1H-pyrido[2,3-b]indol-7, 6, and 8-amines (11aÀc)
a Isolated yield. b Pd/L:5mol%/10mol%.c Pd/L:10mol%/20mol%.
To get more insight into the tandem reactions on 7, we
decided to follow the reaction of 7a with morpholine in
function of time using the Pd2(dba)3/(t-Bu)3P catalytic
system. This experiment confirmed that the direct aryla-
tion on 7a is occurring first, followed by a BuchwaldÀ
Hartwig reaction on chlorocarboline 8a (Supporting In-
formation (SI) Figure 3). Interestingly, when lowering the
excess of K3PO4 from 10 to 2.5 equiv, the disappearance rate
of substrate 7a was significantly retarded (SI Figures 3 and 4).
This is remarkable as 2.5 equiv of K3PO4 already does not
completely dissolve in dioxane. A “base effect” with inorganic
bases in BuchwaldÀHartwig reactions has been previously
observed and rationalized by our group via a rate-determin-
ing interphase deprotonation of the Pd-amine complex.9
A similar effect of insoluble excess of inorganic base on the
rate of direct arylations is only reported once.10 However, it is
unclear at which stage of the catalytic cycle the base influences
the direct C(sp2)ÀH functionalization process.11,12 To
date, five main reaction mechanisms (oxidative addition,
Heck-type, σ-bond metathesis, electrophilic substitution,
base-assisted metalation) have been proposed for the
C(sp2)ÀH activation of (hetero)arenes.13 We decided to
yield
yield (%) yield (%)
entry
7
Pd source/ligand
(%) 3a
8aÀca
11aÀca
1
2
3
4
7ab Pd2(dba)3/(t-Bu)3P
7ab Pd(OAc)2/L2
6
66
87
10
7bb Pd2(dba)3/(t-Bu)3P
70
52
7cc
Pd2(dba)3/(t-Bu)3P
19
a Isolated yield. b Pd/L: 5 mol %/10 mol %. c Pd/L:10mol%/20mol%.
forsubstrates7band 7c, a mixtureofchlorocarboline8 and
end compound 12 was obtained (Table 4, entries 5 and 8).
Substrate 7c again required a higher catalyst loading for a
complete conversion (Table 4, entry 9). Interestingly, the
Pd(OAc)2/L2 system almost exclusively gave chlorocarbo-
line 8a starting from 7a (Table 4, entry 3) as seen with the
other amine classes.
Inspired by the potent antiplasmodial activity of 2 and
the presence of this amino side chain in the antimalarial
drug chloroquine, we decided to test the more challenging
N1,N1-diethylpentane-1,4-diamine. For each of the sub-
strates 7aÀc, the catalyst systems identified to give the
highest yield in the corresponding reactions with n-hexyla-
mine were selected. Gratifyingly, the N1,N1-diethyl-N4-(1-
methyl-1H-pyrido[2,3-b]indol-7, 6, and 8-yl)pentane-1,4-
diamines (13aÀc) were obtained in moderate to good yields
(Table 5, entries 1À3). Only in the auto-tandem reaction
with 7c was a substantial amount of dehalogenation product
3 observed, but even in this case, 47% of the target
compound was obtained without further optimization.
(9) For an example of a mechanistic study of the “base effect” in Pd-
catalyzed amination reactions with aryl iodides, see: Meyers, C.; Maes,
ꢀ
B. U. W.; Loones, K. T. J.; Bal, G.; Lemiere, G. L. F.; Dommisse, R. A. J.
Org. Chem. 2004, 69, 6010–6017. For a review discussing this effect, see ref 7b.
(10) Meyers, C.; Rombouts, G.; Loones, K. T. J.; Coelho, A.; Maes,
B. U. W. Adv. Synth. Catal. 2008, 350, 465–470.
(11) The role of the type of base on the CÀH activation step is well-
documented, as exemplified by the importance of a “CO2” structural entity.
(a) Carboxylate: Ackermann, L. Chem. Rev. 2011, 111, 1315–1345. (b)
Carbonate: Garcia-Quadrado, D.; de Mendoza, P.; Braga, A. A. C.;
Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2007, 129, 6880–6886.
(12) For a study revealing the influence of the cation of the inorganic
base on the CÀH activation step, see: Theveau, L.; Verrier, C.; Lassalas,
P.; Martin, T.; Dupas, G.; Querolle, O.; van Hijfte, L.; Marsais, F.;
Hoarau, C. Chem.;Eur. J. 2011, 17, 14450–14463.
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 5. Pd-Catalyzed Auto-Tandem Synthesis of N1,N1-
Diethyl-N4-(1-methyl-1H-pyrido[2,3-b]indol-7, 6, and 8-yl)-
pentane-1,4-diamines (13aÀc)
Pd source/
ligand
yield
(%) 3a
yield (%)
8aÀca
yield (%)
13aÀca
entry
7
1
2
3
7ab
7bb
7cc
Pd(OAc)2/L1
Pd(OAc)2/L2
Pd(OAc)2/L1
7
6
62
65
47
52
Figure 2. Effect of base loading (K3PO4) on the direct arylation
reaction: 2.5 equiv versus 10 equiv of dry K3PO4.
a Isolated yield. b Pd/L: 5 mol %/10 mol %. c Pd/L:10mol%/20mol%.
step. Amine presumably acts as a proton shuttle from the
liquid to the solid phase of the reaction mixture, hereby
increasing the rate further.15 An experiment with 6 in the
presence of n-hexylamine (2 equiv) but without addition of
K3PO4 confirmed the proton shuttle hypothesis as no con-
version to 3 was observed in this case. To exclude any
assistance in the removal of remaining dba from the catalyst
by K3PO4 or amine, hereby influencing the rate of the
catalysis, both the loading of base and the effect of amines
were also tested starting from Pd(OAc)2 as the palladium
source (SI Figures 7, 8, and 16À20).16 The base effect of
K3PO4 and amine was still observed, ruling out a dba
removal by K3PO4 and amine.
study the base effect in the direct arylation on 6, which lacks
the chloro atom on the aniline, in more detail. The effect
observed on 7a was also present in this simplified substrate
(Figure 2). To exclude an effect of water, flame-dried base
was used. Both with dried and non-dried base, the effect was
observed. When 6 and its pentadeuterated analogue were
used, a significant KIE was observed (1.75), hereby revealing
that the CÀH bond cleavage is the rate-limiting step of the
direct arylation process and justifying the sensitivity of the
reaction for excess base (SI Figure 1).14 This points to an
interphase CÀH activation step which (at least partly) can
occur at the surface of the insoluble inorganic phosphate
base, hereby generating a rate increase.
In conclusion, we have developed an auto-tandem Pd-
catalyzed process consisting of intramolecular direct arylation
and aconsecutive intermolecularBuchwaldÀHartwigreaction
starting from easily accessible N-[3-chloro-1-methylpyridin-
2(1H)-ylidene]-3-, 4- and 2-chloroanilines (7aÀc) and amines
allowing the regioselective synthesis of respectively 7-, 6- and
8-amino-substituted 1-methyl-1H-R-carbolines, respectively.
A variety of amine classes can be used, making the synthetic
methodology suitable for library synthesis. Generally, (t-Bu)3P
is a good ligand for reactions involving secondary amines,
while Cy JohnPhos (L1) has to be used for primary amines. A
mechanistic study of the direct arylation reaction revealed a
base effect of K3PO4 and amine on the RDS (CÀH
activation).
Next, the effect of amine on the direct arylation was also
tested as in our tandem protocol amine is present as reagent.
Interestingly, when comparing the cyclization reaction of 6
with Pd2(dba)3/(t-Bu)3PandK3PO4 (10 equiv) (SI Figure 11)
with a similar experiment in the presence of 2 equiv of differ-
ent amine classes (Et3N, HexNH2, morpholine, Bu2NH)
(SI Figures 12À15), an additional acceleration of the cycliza-
tion was observed. No competitive BuchwaldÀHartwig
reaction occurred with primary and secondary amines. Re-
investigation of the primary kinetic isotope effect, using 6and
its pentadeuterated analogue, but this time in the presence of
n-hexylamine (2 equiv), gave a value of 1.93 (SI Figure 2).14
This shows that amine does not change the RDS (rate-
determining step) of the catalysis and therefore must play,
together with K3PO4, an active role in the CÀH activation
Acknowledgment. This work was financially supported
by the University of Antwerp (BOF), the Fund for Scien-
tific Research-Flanders (FWO-Flanders), and the Her-
cules Foundation.
(13) For reviews, see: (a) Seregin, I. V.; Gevorgyan, V. Chem. Soc.
Rev. 2007, 36, 1173–1193. (b) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174–238. (c) See ref 11a.
(14) (a) Simmons, E. M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012,
51, 3066–3072. (b) A noncompetive experiment was performed using
product ratios to determine the KIE. The KIE value is therefore an
underestimation of the actual value.
Supporting Information Available. Experimental pro-
cedures and full spectroscopic data for all new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(15) Pivalate has been reported to act as a proton shuttle for
carbonate bases in DMA as solvent: Lafrance, M.; Fagnou, K. J. Am.
Chem. Soc. 2006, 128, 16496–16497.
(16) For the interaction of dba with Pd0, see: Fairlamb, I. J. S. Org.
Biomol. Chem. 2008, 6, 3645–3656.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX