Organic Letters
Letter
moieties. Indeed, cataCXium PCy with an N-phenylpyrrole
scaffolddeveloped by Beller’s group for cross-couplings of
4ha in 75% yield. CataCXium PInCy with the N,N-
phenylindole scaffold 1j was bisalkenylated on the phenyl
unit to provide phosphine−bisalkene 4ja in 78% yield. Bis-
C−H bond alkenylations of 1a were also carried out with other
symmetrical para-substituted diarylacetylenes (i.e., R = Br, Me,
OMe), affording 4ab−ad in 73−75% yield.
1
5
aryl chlorides is alkenylated on the phenyl ring to provide
phosphine−alkene 3ha in 77% yield. CM-Phosdeveloped by
16
Kwong for cross-coupling reactions with aryl mesylates
undergoes indolinyl C3−H bond alkenylation to afford 3ia in
moderate yield.
To estimate the coordination ability of phosphine 4aa, we
prepared palladium(II) complex 5a (Scheme 3). Mixing ligand
Next, we investigated the reactivity of other internal alkynes.
The functionalization of DavePhos (1f) with 1,2-bis(4-
bromophenyl)ethyne afforded phosphine 3fb in 77% yield
without cleavage of the C−Br bonds, which could be further
employed to generate more diversity via cross-coupling
reactions. Hydroarylation of 1,2-bis(4-bromophenyl)ethyne,
Scheme 3. Stabilization of Pd(II) with Bulky Phosphine
1
,2-di-p-tolylethyne, 1,2-bis(4-methoxyphenyl)ethyne, and 1,2-
bis(4-(trifluoromethyl)phenyl)ethyne with JohnPhos (1a)
efficiently occurred to produce 3ab−ae in good yields. Less
reactive hex-3-yne (2f) and dec-5-yne (2g) were also suitable
substrates in C−H bond alkenylation, affording the novel
phosphine−alkene ligands 3bf, 3hf, 3ag, and 3bg in good
yields. However, the use of nonsymmetrical alkynes (e.g., ethyl
3
-phenylpropiolate or 1-phenyl-1-propyne) led to nonharve-
stable mixtures of isomers.
We then explored the difunctionalization of biarylphosphine
ortho′-C−H bonds using an excess amount of internal alkyne
and 4 mol % [Rh(OAc)(COD)] with 50 mol % KOAc in
2
toluene at 120 °C (Scheme 2). The steric factor of the
Scheme 2. Scope of Rhodium(I)-Catalyzed Twofold
ortho′,ortho′-C−H Bond Alkenylation of Biarylphosphines
with Alkynes
4
aa and PdCl (PhCN) in CH Cl at room temperature led to
2 2 2 2
3
1
1
the complete formation of complex 5a, as indicated by P{ H}
NMR spectroscopy with a downfield shift of the phosphorus
atom from δ = −7.7 ppm for the free phosphine to δ = 67.0
ppm for the complex. In the X-ray crystallographic structure,
complex 5a was found to have a dimeric structure with a
chloro bridge unit and a distorted square-planar coordination
geometry. The Pd−Pd distance of 3.50 Å was somewhat longer
than that in the corresponding SPhos−palladium compound
(
2.24 Å), and the Pd−P distance of 2.26 Å was similar to that
in the SPhos−palladium compound (2.25 Å). In contrast to
17
JohnPhos and SPhos, which adopted a closed conformation,
a presents an open conformation, i.e., the secondary aryl ring
5
points away from the metal center, avoiding a metal−arene
interaction. This conformation switch might be due to the
introduction of the very bulky 1,2-diphenylvinyl substituents.
Finally, we demonstrated the positive effect of the
introduction of the alkenyl group on biarylphosphines by
comparing the catalytic activities of a couple of these novel
(
bis)alkenylated (dialkyl)biarylphosphines with their parent
phosphines that are often used in Pd-catalyzed cross-coupling
reactions. Aryl chlorides are much less reactive substrates in
Pd-catalyzed cross-coupling reactions, but they are more
abundant and less expensive than the bromide or iodide
equivalents. Their cross-coupling with amides remains
challenging, as specific phosphine ligands have to be designed
to promote the oxidative addition to the aryl chloride and
reductive elimination of an amidate ligand from the Pd(II)
phosphorus substituent appears to be critical. The diphenyl-
phosphino and diisopropylphosphino groups were efficient
directing groups in the bis-ortho′-alkenylation, affording 4ba
and 4ca in 60% and 74% yield, respectively. In contrast, the
reaction with tBu-JohnPhos (1d) failed to deliver the
difunctionalized phosphine 4da, and we observed only the
formation of monofunctionalized phosphine 3da in 54% yield.
The introduction of a strong electron-donating group such as
2
center, which can generate κ -amidate palladium intermediate
complexes (A in Scheme 4), resulting in inhibition of the
18
reductive elimination and thus the catalytic efficiency. We
selected electron-rich and sterically hindered 2-chlorotoluene
and acetamide as model substrates to evaluate the potential of
our bifunctional biarylphosphines in Pd-catalyzed amidation
NMe did not affect the reactivity, as the dialkenylated product
2
4
ga was isolated in 70% yield. The twofold C−H bond
activation/functionalization of cataCXium PCy (1h) afforded
C
Org. Lett. XXXX, XXX, XXX−XXX
Zhang, Zhuan
