Cationic Alkynyl Heck Reaction toward Substituted Allenes Using BobCat: A New Hybrid Pd(0)-Catalyst Incorporating a Water-Soluble dba Ligand

Article abstract of DOI:10.1021/jacs.8b11759

The cationic alkynyl Heck reaction between aryl triflates and alkynes to give substituted allenes is described. Key to the success of this method was the discovery and development of a new hybrid Pd(0)-catalyst, BobCat, that incorporates a water-soluble dba-ligand and biaryl phosphine ligand to provide substituted allenes in good yields under mild reaction conditions.

Full text of DOI:10.1021/jacs.8b11759

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Communication
The Cationic Alkynyl Heck Reaction Towards
Substituted Allenes Using BobCat: A New Hybrid Pd(0)-
Catalyst Incorporating a Water-Soluble dba Ligand
Robynne K. Neff, and Doug E. Frantz
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b11759 • Publication Date (Web): 06 Dec 2018
Downloaded from http://pubs.acs.org on December 6, 2018
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Journal of the American Chemical Society
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The Cationic Alkynyl Heck Reaction Towards Substituted Allenes
Using BobCat: A New Hybrid Pd(0)-Catalyst Incorporating a Water-
Soluble dba Ligand
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Robynne K. Neff and Doug E. Frantz*
Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249
Supporting Information Placeholder
a) Original report by Heck for the isolation of an allene from the cross-coupling bewteen an aryl
ABSTRACT: The cationic alkynyl Heck reaction between
aryl triflates and alkynes to give substituted allenes is de-
scribed. Key to the success of this method was the discov-
ery and development of a new hybrid Pd(0)-catalyst, Bob-
Cat, that incorporates a water-soluble dba-ligand and
biaryl phosphine ligand to provide substituted allenes in
good yields under mild reaction conditions.
iodide and 3-hexyne
I
Pd(OAc)
2 3
, PPh
2
CO Me
+
2
CO Me
Et N, 100 ºC
3
•
4% yield
ref. 14)
!
only one example with multiple by-products
(
b) Report from Miura on the Pd-catalyzed cross-coupling between aryl bromides and alkynes
towards allenes
Br
R1
Pd(OAc)
, PPh
R
R1
2
3
+
R
R1
Cs
2
CO , DMF
3
1
30 ºC
•
R
1
27-71% yields
!
narrow scope - ortho substitution required for good yields
(ref. 15)
The Heck (or Mizoroki-Heck) reaction is arguably the
most synthetically versatile method of all Pd(0)-catalyzed
cross-coupling reactions in the organic chemist’s
c) Intramolecular Heck reaction between aryl chlorides and alkynes reportd by Hamblett
Cl
Pd(OAc)
phosphine ligand
0 mol%
2
15 mol%
N
N
N
3
+
3
1
toolbox. Since the seminal independent reports from
CF3
CF
3
CF
2 3
Cs CO , EtOAc
2
3
•
both Mizoroki and Heck, this transformation has been
exploited by academic labs in countless elegant synthetic
strategies towards complex natural products and biologi-
MW, 140 ºC
Ph
Ph
Ph
ligand = X-Phos 4:1 allene/diene 79%
ref. 16)
(
! mixtures of allene/diene unavoidable in all cases
4
d) Substituted allenes from aryl bromides and alkynes through a non-Heck base-assisted
deprotonation mechanism
cally active small molecules. The Heck reaction has also
Pd
phosphine ligand
0 mol%
2 3
dba 2.5 mol%
R
been employed in numerous industrial applications in-
O
Br
P
R1
1
+
R1
O
4
cluding Merck’s commercial production of its LTD re-
R
R1
•
R
1
2 3
Cs CO ,PivOH
5
ligand
ceptor antagonist Singulair, Albemarle’s large-scale pro-
toluene, 120 ºC
51-92% yields
6
● Heck-type β-hydride elimination ruled out as pathway
(ref. 17)
duction of naproxen, Dow’s production of 2- and 4-vi-
7
Figure 1. (a) Original report by Heck for the isolation of an
allene from the cross-coupling between an aryl iodide and 3-
hexyne. (b) Report from Miura on the Pd-catalyzed cross-
coupling between aryl bromides and alkynes towards al-
lenes. (c) Intramolecular Heck reaction between aryl chlo-
rides and alkynes reported by Hamblett. (d) Substituted al-
lenes from aryl bromides and alkynes through a non-Heck
base-assisted deprotonation mechanism.
nyltoluenes co-monomers for polystyrene and in the
8
manufacturing of the herbicide Prosulfuron on ton scale.
But what makes the Heck reaction ultimately so useful
is its ability to inspire creative bond connections that go
beyond traditional cross-couplings with olefins. For ex-
ample, innovative variations including the heteroatomic-
9
10
Heck, oxidative/dehydrogenative-Heck,
reductive-
11
12
Heck and decarboxylative-Heck reactions have all pi-
oneered new avenues of olefin functionalization. In ad-
dition, significant effort has been invested in the discov-
ery and development of new Pd-catalysts that impart im-
proved reactivity and/or selectivity that has evolved the
substrate scope of the Heck reaction dramatically over the
originally reported by Heck himself over 25 years ago
and then rediscovered almost 10 years later by Miura
1
4,15
(Figure 1).
In spite of these early reports, we are only
aware of two subsequent examples including an intramo-
lecular reaction between aryl chlorides and alkynes to
1
6
13
yield a mixture of exocyclic allenes and dienes and an
intermolecular reaction between aryl bromides and al-
kynes to access allenes that proceeds via a base-assisted
deprotonation rather than a Heck-like Pd-mediated b-hy-
years.
Yet despite the numerous diverse applications of olefins in
the Heck reaction, it is somewhat surprising that it has rarely
been applied to alkynes where the direct products would be
1
7
dride elimination.
substituted
allenes.
The
first
example
was
Since 2013, our group has become captivated with ex-
ploiting b-hydride eliminations from catalytically gener-
ated vinyl metal complexes as a practical approach to
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Journal of the American Chemical Society
Page 2 of 6
1
8,19
substituted allenes.
In particular, our focus has cen-
Unfortunately, we were plagued by irreproducible
yields and various side products that hindered purification
when we attempted to apply these initial optimized reac-
tion conditions to a broad range of substrates. Upon closer
inspection, we determined that our commercial sources of
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
tered on accessing cationic vinyl Pd(II) complexes where
b-hydride eliminations are facile due to enhanced agostic
interactions with the electrophilic metal center. From this
perspective, we envisioned that the extension of the Heck
reaction between alkynes and aryl triflates (the “cationic
alkynyl Heck reaction”) would not only provide a con-
venient route to substituted allenes but may also provide
opportunity for new catalyst discovery. We report here
our preliminary results on the cationic alkynyl Heck reac-
tion and the design of a new Pd(0)-catalyst crucial for suc-
cess of this catalytic method.
2 3
Pd dba were contaminated with excess dba ligand (up to
25 mol %) and ascertained that this could be the culprit
for our irreproducibility and the source of inseparable im-
20
purities. To confirm our suspicion, we implemented dba
itself as a substrate under our reaction conditions with
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
aryl triflate 1 and observed the formation of dieneone 4 in
21
addition to other more complex products (eq 1). In an
attempt to minimize the negative impacts of excess dba
ligand, we purified commercial Pd dba to give the previ-
2 3
Our screening efforts began using an aryl triflate (1)
and 4-octyne (2) using commercial sources of Pd(0) and
various phosphine-based ligands (Table 1). Based on our
previous experiences in this area, we hypothesized that
the interplay between ligand and base would be key to
identifying optimal reaction conditions to favor allene
formation while minimizing isomerization to thermody-
namically more stable diene-based products. Initial
proof-of-concept was achieved through the use of Pd[P(o-
MeO
OTf
O
2
Pd dba3 (5 mol %)
+
(1)
Ph
L4 (15 mol%)
O
Ph
Ph
Na
THF/H
5 ºC
3
PO
4
(1.5 equiv)
OMe
Ph
2
O (4:1)
4
+
1
dba
6
complex mixture
2 3
ously unreported THF solvate Pd dba •THF (<2% excess
1
dba by H NMR). While the yields became more con-
sistent, the impurity profile of these reactions still suf-
fered due to Heck-like byproducts derived from the ob-
ligatory dba inherent with this Pd(0)-source (eq 2). Fur-
thermore, relatively long reaction times (18 h) were
needed for complete consumption of aryl triflate 1 impli-
cating the inhibitory role that dba continued to play with
this Pd(0)-source.
tol)
allene 3 was obtained in 21% assay yield (Table 1, entry
). Further refinement of reaction parameters led to the
identification of phosphine ligand L4 and Na PO as base
in a mixed THF/H O solvent system to give 3 in 99%
3 2
] as catalyst and Hünig’s base where trisubstituted
1
3
4
2
HPLC assay yield (Table 1, entry 9).
Table 1. Preliminary Optimization Data for the Alkyyl
Heck Reaction Between Aryl Triflate 1 and 4-Octyne (2).
OTf
OMe
Pd(0)-catalyst
•
+
OTf
ligand, base
solvent
Pd
2
dba
3
!THF (5 mol%)
OMe
•
OMe
+
(< 2% excess dba)
(2)
1
2
(±)-3
L4 (15 mol %)
(1 equiv)
(2.5 equiv)
OMe
Na PO4 (1.5 equiv)
3
1
2
THF/H
2
O (4:1)
(±)-3
6
5 ºC, 18 h
consistent isolated yields ~83-87%
isolated purity <95%
iPr
OMe
PCy2
OMe
P
i
Pr
PMeO
MeO
P MeO
Discouraged but not deterred by this result, we em-
barked on systematically designing several new Pd(0)-
catalysts to either further reduce or completely remove
iPr
L1
MeO
L3
L2
L4
2
2
dba altogether. A brief summary of our efforts is delin-
eated in Table 2. The hybrid dba/L4 catalyst C1 proved
superior to any prior catalysts generated in situ with re-
spect to both purity and yield yet the dba-derived byprod-
ucts persisted enough to negatively impact final product
yield
entry
Pd(0)-catalyst
liganda
base
%)b
(
1c
2c
3f
4
Pd[P(o-tol)
Pd[P(t-Bu)
]
d
-
-
Hünig’se
Hünig’se
21
<5
16
56
71
49
75
31
99
3 2
d
3
)
2
23
yield (Table 2, entry 1). We also independently synthe-
g
g
g
g
g
g
g
h
Pd
Pd
Pd
Pd
Pd
Pd
Pd
2
2
2
2
2
2
2
dba
dba
dba
dba
dba
dba
3
3
3
3
3
3
3
PPh
PCy
3
Na
Na
Na
Na
Na
Na
Na
3
3
3
3
3
3
3
PO
PO
PO
PO
PO
PO
PO
4
4
4
4
4
4
4
sized homoleptic Pd(0)-catalyst C2 that removed the lia-
bilities associated with dba and provided 3 in good yield
and purity but unfortunately brought on new liabilities of
its own due to poor stability upon storage even at -20 °C
h
h
h
h
h
h
3
5
PPhCy
2
6
L1
(Table 2, entry 2). In an attempt to simultaneously ad-
7
L2
dress both the complete removal of dba while maintaining
reactivity, we synthesized hybrid catalyst C3 with a mod-
ified 4-CO Na-dba ligand using the rationale that under
2
basic biphasic reaction conditions, the water-soluble dba
ligand would be extracted into the aqueous layer leaving
the punitive mono-ligated Pd(0)-complex in the organic
layer free to react. After several iterations of optimization
with this new catalyst, we identified reaction parameters
8
L3
9
dba
L4
a
b
With 15 mol %. Determined by quantitative HPLC anal-
c
d
ysis. Toluene as solvent at 80 ºC for 18 h. With 10 mol %.
e
f
With 3.0 equiv. THF/H
2
O (4 : 1) as solvent at 65 ºC for 18
g
h
h. With 5 mol %. With 1.5 equiv.
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Journal of the American Chemical Society
Table 3. Preliminary Scope of the Cationic Alkynyl Heck
that consistently gave reproducible kinetics, good yields
1
2
3
4
5
6
7
8
9
a
Reaction
and high purity of the allene product 3 (Table 2, entry 8).
We call this new hybrid catalyst “BobCat” and its discov-
ery was crucial to the generality of the cationic alkynyl
Heck reaction.
R1
OTf
BobCat
1
0 mol %
H
•
+
R1
R1
Hünig’s/water
(
6
4 : 1)
5 ºC
3-12 h
R
R
R1
Table 2. Optimization with Newly Designed Pd(0)-Catalysts
(1 equiv)
(2.5 equiv)
MeO
OTf
OMe
H
OMe
Pd(0)-catalyst
•
H
+
•
H
•
base
solvent
65 ºC
•
OMe
1
2
(±)-3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1 equiv)
(2.5 equiv)
(±)-5, 92%
(±)-6, 92%
(±)-7, 91%
Cy Cy
P
Cy Cy
P
2
CO Na
Cy Cy
P
OMe
OTBDMS
•
H
OMe
OMe
Pd
•
H
H
OMe
Pd
Pd
OMe
O
•
O
P
MeO
Cy
(±)-8, 88%
(±)-9, 87%
(±)-10, 86%
Cy
2
NaO C
C1
C2
C3
BobCat
OMe
F
OMe
H
H
H
•
•
•
OHC
OBn
yield
OBn
entry
Pd-cat.
solvent
base
time
(
%)a
82
91
86
85
(±)-11, 86%
(±)-12, 83%
(±)-13, 80%
OBn
OBn
1
2
3
4
C1
C2
C3
C3
THF/H
THF/H
THF/H
2
2
2
Ob
Ob
Ob
Na
3
3
3
3
PO c
PO c
PO c
PO c
4
18 h
15 h
5 h
MeO
OMe
OMe
H
Na
4
H
H
•
O
O
•
•
Na
4
OBn
MeO
OBn
2-MeTHF/H
2-MeTHF
2
Ob Na
4
3 h
(±)-14, 79%
(±)-15, 73%
OBn
(±)-16, 34%
OBn
•
5
6
7
C3
C3
C3
C3
Hünig’sd 8 h
Ob Hünig’sd 3 h
79
84
79
91
NO
2
NC
H
Cl
H
2-MeTHF/H
2
H
•
•
Hünig’s
-
-
6 h
3h
(±)-17, 70%b
(±)-18, 61%b
(±)-19, 60%
Ob
8
Hünig’s/H
2
a
b
c
Isolated yield. Solvent ratio = 4 : 1 With 1.5 equiv.
With 3.0 equiv.
O
H
H
d
B
O
H
•
•
•
The preliminary scope of the alkynyl Heck reaction be-
±)-20, 55%b
(±)-21, 61%
(±)-22, 98%
(
tween aryl triflates and symmetrical alkynes to access tri-
substituted allenes was then explored using BobCat in a
mixed solvent system of Hünig’s base and water at 65 °C
Table 3). A broad spectrum of aryl triflates perform well
in the reaction including both electron-rich (i.e., 7, 9, and
0) and electron-poor substrates (i.e., 17 and 18) utilizing
symmetrical alkynes. One limitation we have encoun-
tered, however, is competing hydrolysis to the corre-
sponding phenol with electron-deficient aryl triflates that
obviated the use of water as co-solvent. This, in turn, lead
to slower kinetics and slightly lower isolated yields of the
corresponding allene. Nonetheless, the ability to access
functionalized trisubstituted allenes such as boronic ester
a
b
Isolated yields are reported. Water was omitted as co-
solvent due to competing hydrolysis of the aryl triflate.
(
goal are highlighted in Scheme 1. Alkynes with slight
steric bias (as in 24) provided modest regioselectivity (2 :
) favoring the tetrasubstituted allene 26. Alkynes with
1
1
directing groups to potentially bias the regiochemistry of
the carbopalladation step have shown mixed results thus
far. For example, alkyne 27 yields a promising 79:21 mix-
ture of regioisomeric allenes 28 and 29, respectively. In-
terestingly, phthalimide-derived alkyne 30 provided al-
lene 31 as the only isolatable allene product. Gratify-
ingly, the intramolecular alkynyl Heck with unsymmet-
rical alkyne 32 provided exocyclic allene 33 in good iso-
lated yield. In contrast, unsymmetrical alkyne 34 that in-
corporates the proven picolinamide directing group from
the Engle group was unproductive in the alkynyl Heck re-
action yielding no detectable amounts of allene-derived
2
0 exemplifies the utility of this method towards valuable
synthetic building blocks that have yet to be reported.
Our attention then turned towards the use of unsymmet-
rical alkynes in an attempt to identify electronic or steric
bias that may promote regioselectivity in the alkynyl
Heck reaction. Our initial results towards this
2
4
products. An additional limitation with respect to un-
symmetrical alkynes we would like to divulge includes
the lack of productive reactivity of phenylacetylenes (i.e.,
2
5
3
5) at this stage of development.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Scheme 1. Preliminary Results with Unsymmetrical
Page 4 of 6
BobCat
20 mol %
H
MeO
+
OMe
•
(3)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2-MeTHF/water
(4 : 1)
Alkynes.
OTf
23
1 equiv)
65 ºC
24 h
no base
(±)-6, 24%
(
(2.5 equiv)
MeO
MeO
H
OTf
BobCat
10 mol %
OTBDMS
TBDMSO
2
2-MeTHF/H O solvent mixture. The corresponding al-
•
•
+
Hünig’s/water
(4 : 1)
OMe
lene 6 was isolated in 24% yield after 24 hours that rein-
forces our hypothesis that a Heck-type mechanism via a
Pd-mediated b-hydride elimination is operable rather than
an outer-sphere base-assisted deprotonation/elimination.
However, we concur that a more thorough mechanistic in-
vestigation is warranted and is currently in progress to
further substantiate our hypothesis.
TBDMSO
86%
25 : 26
(1 : 2)
2
3
24
65 ºC
17 h
2
5
(±)-26
(1 equiv)
(2.5 equiv)
dr = 2 : 1
OMe
MeO
H
OMe
BobCat
10 mol %
•
O
+
2
3
+
Hünig’s/water
(4 : 1)
(
1 equiv)
2
7
•
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(2.5 equiv)
65 ºC
H
O
1
7 h
MeO
(±)-28
O
(±)-29
8
9%
2
8 : 29
In conclusion, the direct synthesis of substituted allenes
via the alkynyl Heck reaction between aryl triflates and
alkynes has been realized. Key to the success of this
method was the development of a new hybrid Pd(0)-cat-
alyst, BobCat, that incorporates a water-soluble dba lig-
and that simultaneously reduces Heck-derived byprod-
ucts while providing straightforward access to the reac-
tive monoligated Pd(0)-complex. We believe that ioniza-
ble dba ligands, like the one incorporated into BobCat,
will find broad application in a multitude of Pd(0)-cata-
lyzed processes. Ongoing studies within our laboratories
include the use of aryl halides and the development of a
catalytic, asymmetric alkynyl Heck reaction towards en-
antioenriched allenes.
(
79 : 21)
OMe
23
1 equiv)
BobCat OMe
0 mol %
H
(
O
O
•
O
BobCat
1
10 mol %
N
O
O
OTf
•
Hünig’s/water
4 : 1)
Hünig’s/water
(4 : 1)
N
H
(
6
1
5 ºC
7 h
O
65 ºC
17 h
3
2
(±)-33, 64%
30
2.5 equiv)
(
±)-31, 53%
(
2
3
23
(1 equiv)
(1 equiv)
BobCat
10 mol %
O
BobCat
10 mol %
N
N
H
no detectable
Hünig’s/water allene formation
Hünig’s/water
(4 : 1)
3
4
(4 : 1)
65 ºC
1
35
(
2.5 equiv)
65 ºC
(2.5 equiv)
7 h
17 h
A plausible mechanism for the alkynyl Heck reaction
between aryl triflates and alkynes is proposed in Scheme
. We propose that the water-soluble 4-CO Na-dba lig-
2
and incorporated into BobCat allows for a dynamic equi-
librium under the biphasic reaction conditions that allows
2
ASSOCIATED CONTENT
Supporting Information
-
26
facile access to the monoligated 12 e Pd(0)-complex.
Subsequent oxidative addition into the aryl triflate pro-
vides a cationic aryl Pd(II)-species (A) that undergoes a
carbopalladation with the alkyne to provide vinyl Pd(II)-
complex B. We believe the cationic nature
The Supporting Information is available free of charge on the ACS
Publications website at DOI: ( )
1
Experimental procedures, full characterization data, copies of H,
1
3
31
Scheme 2. Proposed Mechanism for the Cationic Al-
kynyl Heck Reaction
C, and P NMR spectra for all products and catalysts reported
(PDF)
Hünig’s + H+
Cy
Cy
AUTHOR INFORMATION
R
Hünig’s
P
OMe
H
OTf
R1
TfO
Corresponding Authors
•
Pd
extractive removal
R
PdL
Pd(II)-hydride
H
of 4-CO Na-dba
2
* doug.frantz@utsa.edu
R1
oxidative
addition
Cy Cy
CO2Na
β-hydride
P
elimination
OMe Pd
ORCID
OTf
R
O
OTf
PdL
H
n
2
NaO C
BobCat
Doug E. Frantz: 0000-0002-4509-4579
Notes
LPd
R
H
R1
aryl palladium
intermediate
A
R1
R1
cationic vinyl
Pd(II)-complex
B
R1
carbopalladation
The authors declare no competing interest
of complex B promotes a relatively low-barrier b-hy-
ACKNOWLEDGMENT
dride elimination to provide the allene and a Pd(II)-
hydride that undergoes base-assisted reductive elimina-
tion to regenerate the Pd(0)-catalyst. In support of the
punitive Pd-mediated b-hydride elimination step, we
have performed a reaction in the absence of base using 20
mol% BobCat (eq. 3) between aryl triflate 22 and 5-
decyne in
We would like to thank the National Science Foundation (CHE-
1362953 and MRI-1625963) for supporting this work. High-reso-
lution mass spectrometry data at UTSA were obtained through sup-
port from the National Institute of Minority Health and Health Dis-
parities (G12MD007591) within the NIH. D.E.F. would also like
to thank the Max and Minnie Tomerlin Voelcker Fund for provid-
ing unrestricted support.
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Journal of the American Chemical Society
1
32, 13981-13983. (f) Delcamp, J. H.; Brucks, A. P.; White,
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018, 118, 6026-6052.
0. (a) Amatore, C.; Jutand, A. Role of dba in the Reactivity of
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11-528. (b) Zalesskiy, S. S.; Ananikov, V. P. Pd
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cursor of Soluble Metal Complexes and Nanoparticles: Deter-
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Journal of the American Chemical Society
Page 6 of 6
Complexes with an Additional, Weak Agostic Interaction. J.
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
2
2. The use of various Pd(II)-catalysts with L4 as ligand in avoid
dba altogether was met with only limited success (see Support-
ing Information).
3. For related hybrid Pd-catalysts, see: Yin, J.; Rainka, M. P.;
Zhang, X. –X.; Buchwald, S. L. A Highly Active Suzuki Cata-
lyst for the Synthesis of Sterically Hindered Biaryls: Novel
Ligand Coordination. J. Am. Chem. Soc. 2002, 124, 1162-
25. We believe that the lack of reactivity with phenylacetylenes
may be due to the regiochemical preference for the carbopal-
ladation step to place the Pd-center adjacent to the aromatic
ring precluding any catalytic turnover with BobCat.
26. We would like to thank a reviewer who suggested that the ion-
izable dba ligand may serve as a ligand through the carboxylate
groups that may lead to a neutral or anionic pathway to help
rationalize the unique reactivity observed with BobCat.
1
163.
2
4. Liu, Z.; Derosa, J.; Engle, K. M. Palladium(II)-Catalyzed Re-
gioselective syn-Hydroarylation of Disubstituted Alkynes
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Cy Cy
R1
CO2Na
OTf
BobCat
P
10 mol %
H
•
OMe
+
R1
R1
Pd
Hünig’s/water
(4 : 1)
O
R
R1
R
6
5 ºC
22 examples
4-98% yield
NaO2C
3
R
BobCat
OTf
PdLn
H
β-hydride
elimination
carbopalladation
R1
H
R1
cationic vinyl
Pd(II)-complex
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