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this, the %Vbur values of the sub-
stituted biarylphosphines were
compared with that of CyJohn-
Phos, which has the smallest
%Vbur in the series (51.0% at
2.00 and 46.7% at 2.28 ).[35] In
this comparison, the %Vbur in-
creased in the order XPhos>
JohnPhos>SPhos (by ~13, ~9,
and ~6%, respectively, over Cy-
JohnPhos). DavePhos will likely
have a smaller %Vbur than XPhos,
but like the iPr group in XPhos,
DavePhos has a NMe2 group in
Table 1. Conditions tested for the reaction of 1 and PhB(OH)2.[a]
Entry
Catalyst
Ligand
[mol%]
Base, additive
Time
[h]
T
[8C]
Result[b]
[%]
1
2
3
4
5
6
7
8
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
none
XPhos (20)
XPhos (20)
XPhos (20)
XPhos (20)
SPhos (20)
SPhos (20)
SPhos (20)
SPhos (20)
SPhos (20)
SPhos (20)
SPhos (10)
SPhos (20)
SPhos (20)
SPhos (20)
none
Cs2CO3
Cs2CO3
Cs2CO3
Ag2O
Cs2CO3
Ag2O
CsF
K3PO4
14.5
24
18
22
5
22
18
24
22
1
RT
no reaction
54
RT to 50
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
no reaction
84
no reaction
incomplete[c]
incomplete[c]
incomplete[c]
88
a
similar location. Also, the
amino group could pose other
interactions with the metal
center. In contrast to DavePhos,
Ligand 1, which has a para-dime-
thylamino group, is expected to
be sterically similar to CyJohn-
Phos but with a more electron-
rich upper ring. Thus, it appears
9
K3PO4·H2O
10
11
12
13
14
15
16
17
18
19
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
0.2m aq Na2CO3
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
K3PO4+2 equiv. H2O
4
78
26
24
26
2
26
16
26
16
incomplete[c,d]
incomplete[c,e]
no reaction
83
Pd(PPh3)4
Pd(PPh3)4
Ni(cod)2
Ni(cod)2
Ni(cod)2
none
57[f]
PPh3 (30)
PCy3 (30)
SPhos (20)
no reaction
no reaction
no reaction
that
a
smaller %Vbur of the
biarylphos-
monocoordinating
phines may be more favorable
for the reactions considered
here, but the electron density in
the upper ring appears to have
less consequence, as seen from
the comparable reactions of Cy-
[a] Reactions were conducted with a 0.14m solution of 1 in PhMe with 10 mol% of the Pd or Ni catalyst,
2 equiv. of PhB(OH)2, and 2 equiv. of base. [b] If reported, the yield is of isolated and purified product. [c] Prod-
uct formation was observed by TLC but unreacted 1 was present. [d] Reaction was conducted with 1.2 equiv.
of PhB(OH)2. [e] Reaction was conducted in MeCN. [f] Aqueous Na2CO3 was degassed.
tions identified in entry 10 of Table 1. For this purpose, XPhos,
SPhos, 2-dicyclohexylphosphino-2’,6’-diisopropoxybiphenyl
(RuPhos), 2-(dicyclohexylphosphino)biphenyl (CyJohnPhos), (2-
biphenyl)di-tert-butylphosphine (JohnPhos), 2-dicyclohexyl-
phosphino-2’-(N,N-dimethylamino)biphenyl (DavePhos), as well
JohnPhos and Ligand 1. From this analysis, CyJohnPhos ap-
peared to be suitable for further analysis combined with cost
considerations (CyJohnPhos=$11.2 per mmol, SPhos=
$20.3 per mmol, and Ligand 1 has only become available com-
mercially recently at $56.40 per mmol).
as
2-dicyclohexylphosphino-4’-(N,N-dimethylamino)biphenyl
Next, a series of CÀC bond-forming reactions were evaluated
with three benzyloxy benzotriazoles; substrate 1 with an elec-
tron-rich aryl ring, substrate 2 with a heterocyclic ring, and
substrate 3 with an electron-deficient aryl ring. The study also
includes results from reduced catalyst loadings, and these data
are summarized in Table 2.
(Ligand 1) were selected for the second stage of the analysis.
We have shown that Ligand 1, an isomer of DavePhos, has
a different reactivity profile as well as interactions with
Pd(OAc)2 as compared to DavePhos.[33] The outcomes from the
use of these related biaryl ligands are represented graphically
in Scheme 3. In this analysis, catalysts supported by RuPhos
and JohnPhos were less effective than those from XPhos and
SPhos. DavePhos was comparable to XPhos, but CyJohnPhos
and Ligand 1 performed comparably and were superior.
Good to modest yields were obtained in most of these reac-
tions and some reactions progressed respectably at lower Pd
loadings as well (entries 7–10, 14–16). Yields of <40% were
obtained in the reactions of 1 and 3 with N-methylindole-5-
boronic acid and in the reaction of 3 with [(E)-2-phenylvinyl]-
boronic acid (entries 6, 14, and 21). However, the desired prod-
ucts were obtained in these cases. Reactions of p-nitrophenyl-
boronic acid were incomplete; with substrate 1 at a 2% Pd
loading (entry 9) and with substrate 4 at a 10% Pd loading
(entry 22) ꢀ30% yields were obtained. With furanyl substrate
3, a 54% product yield was obtained despite an incomplete re-
action (entry 13). Methylboronic acid underwent reaction with
substrate 1 at a 5% Pd loading (entry 10) to give the ethyl de-
rivative 12 in a respectable yield. This is a rare example of the
cross-coupling of an alkylboronic acid with benzylic electro-
As all the biarylphosphine ligands tested yielded product
with some notable differences, we wanted to rationalize their
effectiveness in light of their relative bulk. The Tolman cone
angle (q)[34] is a classical measure of ligand sterics and, more re-
cently, percent buried volume (%Vbur) has been evaluated for
a series of ligands, which includes the biarylphosphine li-
gands.[35] %Vbur indicates the spatial occupancy of a coordinated
ligand, that is, the overall steric influence, around a metal
center. As a result of the available data, we chose to compare
the %Vbur for the ligands in a series of similar AuCl complexes
(data for a uniform series of Pd complexes are unavailable). For
ChemCatChem 2015, 7, 4156 – 4162
4158
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