Palladium-catalyzed allylation of pronucleophiles with alkynes at 50°C - Remarkable effect of 2-(dicyclohexylphosphanyl)-2′-(dimethylamino) biphenyl as ligand

Article abstract of DOI:10.1002/ejoc.200600337

The allylation of various pronucleophiles 1a-i with 1-phenylprop-1-yne (2) proceeded very smoothly at 50°C in the presence of catalytic amounts of Pd₂(dba)₃·CHCl₃ (5 mol-%) and 2-(dicyclohexylphosphanyl)-2′-(dimethylamino)

Full text of DOI:10.1002/ejoc.200600337

FULL PAPER
DOI: 10.1002/ejoc.200600337
Palladium-Catalyzed Allylation of Pronucleophiles with Alkynes at 50 °C –
Remarkable Effect of 2-(Dicyclohexylphosphanyl)-2Ј-(dimethylamino)biphenyl
as Ligand
Nitin T. Patil,[a] Dschun Song,[a] and Yoshinori Yamamoto*[a]
Keywords: Palladium / Alkynes / Pronucleophiles / Allylation / Biphenyl ligands / Lower temperatures
The allylation of various pronucleophiles 1a–i with 1-phen-
CHCl3/PPh3 were used, the reaction needed 100 °C for com-
ylprop-1-yne (2) proceeded very smoothly at 50 °C in the pletion.
presence of catalytic amounts of Pd2(dba)3·CHCl3 (5 mol-%)
and 2-(dicyclohexylphosphanyl)-2Ј-(dimethylamino)biphenyl
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
(I; 20 mol-%) in toluene, whilst when Pd(PPh3)4 or Pd2(dba)3· Germany, 2006)
allylation reactions, reasoning that suitable tuning of li-
Introduction
gands attached to palladium might speed up the formation
of the presumed π-allylpalladium complexes generated from
alkynes, which would then be attacked by pronucleophiles,
allowing us to perform the allylation at a lower temperature.
We thus undertook a search for a suitable ligand and, after
studying various ligands, found that the best results were
given by the biphenyl ligand I in combination with Pd2-
(dba)3·CHCl3, allowing us to allylate pronucleophiles at
50 °C. The detailed results of the work are reported here.
Palladium-catalyzed carbon–carbon and carbon–hetero-
atom bond-forming reactions are one of the most impor-
tant research areas in organic synthesis, one example of
these processes being the treatment of substrates with allylic
compounds in the presence of Pd0 and a stoichiometric
amount of a base (Tsuji–Trost reaction).[1] All of these reac-
tions are considered to be nucleophilic substitutions. In ge-
neral, addition reactions[2] are preferable to substitution re-
actions because they can be performed with 100% atom
efficiency,[3] without any waste formation. With this in
mind, we have recently been investigating the allylation of
carbon[4] and heteroatom[5] pronucleophiles with alkynes
with the aid of a combined Pd0/carboxylic acid catalytic
system. Since the products of this process were obtained
through formal addition of pronucleophiles to alkynes, no
waste elements were produced and, moreover, no base was
needed, though a relatively high temperature (100 °C) was
necessary in order to drive the reaction to completion. As
a partial solution to this problem we later reported the al-
lylation of some pronucleophiles with alkynes under micro-
wave irradiation conditions in the absence of any solvent.[6]
As the reaction was carried out without any solvent, at least
one substrate had to be a liquid in order for the reaction to
be performed under homogeneous condition, so the
method was not applicable when both substrates (pronu-
cleophiles and alkynes) were solids. In the hope of finding
milder and superior reaction conditions, we thus decided to
pursue the search for alternative catalytic systems in these
Results and Discussion
The results for various ligands are summarized in
Table 1. Treatment of 1a with 1-phenylprop-1-yne (2) at
50 °C in the presence only of Pd(PPh3)4 as catalyst did not
yield any product, with the starting material being reco-
vered (Table 1, Entry 1). The combination of Pd2(dba)3·
CHCl3 and PPh3 at various stoichiometries at 50 °C also
did not result in any product formation (Entries 2 and 3).
Gratifyingly though, when ligand I was employed, the reac-
tion proceeded smoothly and the desired product 3a was
obtained in an isolated yield of 90% (Entry 4). The use of
its congener, biphenyl ligand II, also proved satisfactory,
giving the product in 89% yield (Entry 5), but in the case
of ligand III the yield was considerably lower (Entry 6). The
optimal temperature for the reaction to occur is 50 °C; any
further decrease in the reaction temperature results in lower
yields.
After the unique role of 2-(dicyclohexylphosphanyl)-2Ј-
(dimethylamino)biphenyl (I) had been established, a few
representative pronucleophiles were tested in this allylation
reaction with 1-phenylprop-1-yne (2) as a standard alkyne.
The results are summarized in Table 2. Treatment of 2-ace-
tylcyclopentanone (1b) with 2 in the presence of Pd2(dba)3·
[a] Department of Chemistry, Graduate School of Science, Tohoku
University,
Sendai 980-8578, Japan
E-mail: yoshi@mail.tains.tohoku.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2006, 4211–4213
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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N. T. Patil, D. Song, Y. Yamamoto
FULL PAPER
Table 1. Allylation of 1a with 1-phenylprop-1-yne (2) at 50 °C.[a]
Table 2. Allylation of various pronucleophiles with 2 at 50 °C.[a]
[a] Treatment of 1a with alkyne 2 (1.1 equiv.) in the presence of
Pd2(dba)3·CHCl3 (5 mol-%), ligands (as specified in the table), and
benzoic acid (10 mol-%) was carried out at 50 °C in toluene for
48 h. [b] Yields were determined by 1H NMR spectroscopy with
dibromomethane as an internal standard. [c] The starting material
was recovered. [d] Isolated yields are shown in parentheses.
CHCl3 (5 mol-%)/I (20 mol-%)/PhCOOH (10 mol-%) in tol-
uene (1 ) at 50 °C gave the desired allylation product 3b
in 93% yield (Table 2, Entry 1). Similarly, the sterically con-
strained 1,3-diketones 1c and 1d reacted with 2 under stan-
dard reaction conditions to afford the corresponding al-
lylation products 3c and 3d in 81% and 79% yields, respec-
tively (Entries 2 and 3). Aldehyde 1e was found to be a good
substrate for this catalytic system, also undergoing smooth
allylation (Entry 4).
We next turned out attention to the allylation of amines.
As shown in Entries 5–9, anilines containing either elec-
tron-donating or electron-withdrawing groups on their aro-
matic rings smoothly underwent reaction with 2 to give the
desired products in high yields. In the case of p-chloroani-
line (Entry 10) only a 52% yield of product was obtained,
unlike in our previously reported catalytic system,[4d] in
which the allylation had proceeded with quantitative forma-
tion of product, perhaps because of a side reaction in which
oxidative insertion of the L–Pd complex into the Ar–Cl
bond competes with the desired reaction.[7] Indoline (1g)
and tetrahydroquinoline (1h) also underwent smooth al-
[a] The reactions of pronucleophiles 1 with 1-phenylprop-1-yne (2,
1.1 equiv.) in the presence of Pd2dba3·CHCl3 (0.05 mmol), I
(0.2 equiv.), and benzoic acid (0.1 equiv.) were carried out at 50 °C
in toluene (1 ) until the disappearance of the starting material 1
was observed. [b] All products obtained were identified as (E) iso-
1
mers by H NMR spectroscopy. [c] Isolated yields.
lylation, giving the corresponding products 3g and 3h in 91 system are not completely understood: several structural
and 99% yields, respectively (Entries 11–12). Dibenzyl- features of biphenyl–Pd complexes may contribute to their
amine (1i) reacted with 2 quite sluggishly, giving the prod- effectiveness.[8]
uct 3i in only 61% yield, indicating that bulky amines are
The catalytic cycle for the allylation reactions is presum-
not good nucleophiles in this catalytic system (Entry 13). ably similar to that reported previously and depicted in Fig-
The reasons for the high reactivity of this present catalytic ure 1. Although the reasons for the high reactivity of the
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Eur. J. Org. Chem. 2006, 4211–4213

Palladium-Catalyzed Allylation of Pronucleophiles with Alkynes at 50 °C
FULL PAPER
Supporting Information (see footnote on the first page of this arti-
current catalytic system are not completely understood, we
cbelieve that the main reason for the rate enhancement
might be acceleration of the β-elimination.[9] Palladium
metal coordinated to a bulky ligand should act as good
leaving group in the β-elimination process to form phenyl-
allene (6) and subsequently π-allylpalladium complex 7.
The rate of transformation of 5 to 7 should thus increase,
which should in turn enhance the overall reaction rate.
cle). Experimental details, characterization data for newly synthe-
1
sized compounds 3g and 3h, H NMR spectra of all compounds.
Acknowledgments
N. T. P. thanks the Japan Society for the Promotion of Science
(JSPS) for a postdoctoral research fellowship.
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Figure 1. Plausible mechanism.
Conclusion
We have discovered a remarkable effect of 2-(dicyclohex-
ylphosphanyl)-2Ј-(dimethylamino)biphenyl as a ligand in
the palladium-catalyzed allylation of various pronucleo-
philes with alkynes at 50 °C and are now in a position to
allylate various pronucleophiles at 50 °C instead of 100 °C.
Potential applications of biphenyl ligands for cross-coupling
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Experimental Section
General Procedure: 1-Phenylprop-1-yne (2, 0.21 mmol) and 2-(dicy-
clohexylphosphanyl)-2Ј-(dimethylamino)biphenyl (I, 20 mol-%)
were added under argon to a toluene solution (1 ) of the pronu-
cleophile 1 (0.2 mmol), Pd2(dba)3·CHCl3 (5 mol-%), and benzoic
acid (10 mol-%). The solution was stirred at 50 °C in a screw-
capped vial until the disappearance of the starting material was
observed, the reaction mixture was cooled to room temperature,
filtered through a short silica gel pad, and concentrated, and the
residue was purified by column chromatography (silica gel, hexane/
AcOEt) to afford the allylation product 3 in good yield.
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Received: April 17, 2006
Published Online: July 19, 2006
Eur. J. Org. Chem. 2006, 4211–4213
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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