FMPhos: Expanding the catalytic capacity of small-bite-angle bisphosphine ligands in regioselective alkene hydrofunctionalizations

Article abstract of DOI:10.1021/acscatal.0c04199

In contrast to the plethora of large-bite-angle bisphosphine ligands available to transition-metal catalysis, the development of small-bite-angle bisphosphine ligands has suffered from the limited structural variations accessible on their single-atom-containing backbones. Herein, we report the design and applications of a discrete very small bite-angle bisphosphine ligand, namely, FMPhos. Featuring a fluorene?methylene unit appended on the single-carbon linker, the ligand harbors an unusually rigid backbone that presumably stabilizes its complexation with transition metals during catalysis. Compared with the known dppm ligand, it exhibited superior reactivity and regioselectivity in a number of alkene hydrofunctionalization reactions, catalyzed by iridium and rhodium.

Full text of DOI:10.1021/acscatal.0c04199

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Research Article
FMPhos: Expanding the Catalytic Capacity of Small-Bite-Angle
Bisphosphine Ligands in Regioselective Alkene
Hydrofunctionalizations
Xiao-Yang Chen,† Xukai Zhou,† Jianchun Wang, and Guangbin Dong*
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ABSTRACT: In contrast to the plethora of large-bite-angle
bisphosphine ligands available to transition-metal catalysis, the
development of small-bite-angle bisphosphine ligands has suffered
from the limited structural variations accessible on their single-
atom-containing backbones. Herein, we report the design and
applications of a discrete very small bite-angle bisphosphine ligand,
namely, FMPhos. Featuring a fluorene−methylene unit appended
on the single-carbon linker, the ligand harbors an unusually rigid
backbone that presumably stabilizes its complexation with
transition metals during catalysis. Compared with the known
dppm ligand, it exhibited superior reactivity and regioselectivity in
a number of alkene hydrofunctionalization reactions, catalyzed by iridium and rhodium.
KEYWORDS: bite angle, bisphosphine ligand, regioselectivity, alkene hydrofunctionalization
could be equally important in the design and execution of new
transition-metal-catalyzed reactions. Nevertheless, the develop-
ment of these two classes of ligands has so far been highly
disproportionate.7 As depicted in Figure 1a, the backbone of
large bite-angle ligands typically contains multiple carbon
atoms, which gives plenty of space in incorporating a variety of
functional linkers to set the two phosphine units apart. Such
flexibility in ligand design accounts for the numerous privileged
large bite-angle ligands developed to date, not to mention that
many of them have been employed in enantioselective
catalysis. On the other hand, the most common small-bite-
angle ligand, bis(diphenylphosphino)methane (dppm), only
has a single-carbon-atom spacer between the two phosphine
units, leaving much less room for structural modifications
(Figure 1b). Besides, the large ring strain associated with the
four-member ring chelation could lead to dissociation of one of
the phosphino groups of dppm from the metal center, known
as “hemilability”, which significantly diminishes its efficiency
during catalysis.8 Consequently, only a few catalytically
competent small-bite-angle derivatives of dppm have been
described in the literature,9 stalling applications of this
INTRODUCTION
■
Ligands play an essential role in homogeneous catalysis
through modulating reactivity and selectivity of transition-
metal catalysts during the reactions.1 Phosphines are among
the most widely used ligands due to their robust σ-donating, π-
accepting L-type coordination, as well as the systematic and
predictable ways to alter their steric and electronic properties
by varying the substituents on the phosphorus.2 In particular,
chelating phosphines, e.g., bidentate phosphines or bi-
sphosphines, have found broad applications in chemical,
pharmaceutical, and agrochemical industries. One key
parameter for measuring steric and geometric properties of
bisphosphines is bite angle, i.e., the ligand−metal−ligand bond
angle of a coordination complex.3 The merits of using large-
bite-angle bisphosphine ligands in catalysis are well docu-
mented, such as acceleration of oxidative addition, migratory
insertion, and reductive elimination processes.4 Their
pronounced impact on controlling reaction regioselectivity
has also been recognized.5 For example, the Rh-catalyzed
alkene hydroformylation process,6 which represents one of the
largest volume applications with homogeneous catalysis and
produces 14 billion pounds of aldehydes annually, benefits
tremendously from using bisphosphines with extraordinarily
large bite angles, as nearly perfect linear selectivity can be
obtained with such ligands.
Received: September 28, 2020
Revised: November 10, 2020
In contrast, much less attention has been paid to the
advantages of using bisphosphines with very small bite angles.
Considering that large- and small-bite-angle bisphosphine
ligands may give complementary reactivity or selectivity, they
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Figure 1. FMPhos as a discrete small-bite-angle bisphosphine ligand.
important class of bisphosphine ligands in transition-metal
catalysis.
Scheme 1. Hypothesis on the Ligand Bite-Angle Effect in
the Regioselective Hydroalkenylation of Enamides
In this article, we wish to describe a full study of developing
a discrete small-bite-angle bisphosphine ligand, namely,
FMPhos, which contains a fluorene−methylene unit anchored
onto the single-carbon linker between two phosphino groups
(Figure 1c), as well as its applications in regioselective alkene
hydrofunctionalizations. FMPhos features a very small
calculated bite angle conferred by its unusually rigid backbone
when complexed with transition metals and displays
extraordinary reactivity and regioselectivity in three types of
alkene hydrofunctionalization reactions. While not explicitly
shown here, the incorporation of a fluorene moiety that
conjugates with two phosphino groups could also create useful
modification sites for fine-tuning the electronic property of the
ligand.
RESULTS AND DISCUSSION
■
Ligand Discovery. Our initial interest in exploring new
small-bite-angle structural motifs in bidentate phosphine
ligands was prompted by our previous research on the Ir(I)-
catalyzed, branched-selective hydroalkenylation of alkenes with
enamides as the coupling reagent, which provided an effective
approach to realize branched-selective ketone α-alkylation with
olefins.10 This study, along with pioneering works from the
groups of Shibata,11 Bower,12 Hartwig,13 Nishimura,14 and
others, capitalizes on the use of large bite-angle bisphosphine
ligands to achieve branched selectivity (Scheme 1). Based on
Huang and our mechanistic studies,15 the large bite angle of
the ligand promoted a rate-determining regioselective 1,2-Ir-C
migratory insertion of the C−H activation intermediate into
olefins, minimizing the steric interaction between the bulky
metal center and the alkene substituent.16 One intriguing
question is whether linear-selective alkene hydroalkenylation
could be realized using a small-bite-angle bisphosphine ligand,
which, in turn, should provide a useful entry to access linear
ketone-alkylation products. Our hypothesis is supported by a
recent computational study performed by Huang and Liu on
Ir-catalyzed hydroarylation of alkenes, which revealed that in
the absence of steric repulsions from large bite-angle ligands,
the linear/branched selectivity is predominantly controlled by
the electronic nature of the alkene.17 This implies that, using
aryl alkenes or alkyl alkenes with electron-withdrawing groups
(EWGs), high linear selectivityi.e., 2,1-insertionshould be
favorable due to the stabilization of the increasing negative
charge at the α carbon during the Ir−C bond formation.
To test this hypothesis, enamide S1 was used as the model
substrate and styrene was employed as the coupling partner
(Table 1). A preliminary screening showed that, when
Shibata’s Ir(COD)2BArF was used as the precatalyst,11
reducing the bite angle of bisphosphine ligands was indeed
accompanied by a great increase in linear selectivity. The use of
dppm with a bite angle of 72.0°, though displaying excellent
linear selectivity, resulted in a dramatic loss of reactivity (16%
yield, entry 2). In contrast, lower linear selectivity but better
yields were observed using dppe and dppbz, which have
medium-sized bite angles.
We questioned if the reduced reactivity of dppm was due to
the lack of stability of the resulting four-membered metallo-
cycle (Figure 2). With a flexible methylene linker, one can
imagine that the C−P bond could easily rotate away leading to
a more labile mono-coordinated complex (Figure 2a).8 Hence,
we envisioned that using a more rigid linker the C−P bond
rotation could be largely inhibited due to the buttressing effect,
and such a “locked” conformation should result in a more
stable catalyst (Figure 2b). Drawing inspiration from our prior
use of the 1,1-bis(diphenylphosphino)ethylene (L1) ligand in
the Ir-catalyzed deacylative transformations of ketones,18 we
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a
Table 1. Control Experiments
Figure 2. Linker effect in small-bite-angle ligands.
The synthesis of FMPhos is described in Scheme 2.
Treatment of 9-fluorenone with carbon tetrachloride and
Scheme 2. Synthesis of FMPhos
PPh3 under reflux in THF afforded 9-(dichloromethylene)-9H-
fluorene in 71% yield,19 which was subjected to a C−P cross-
coupling reaction that employed NiCl2(PPh3)2 as the catalyst,
Et3N as the base, Ph2PH as the coupling reagent, and DMF as
the solvent at 120 °C.20 FMPhos was obtained as a yellow
solid after column chromatography in 40% yield.
Crystal structures of L1 and FMPhos have been obtained,
and their corresponding bite angles with Ir have been
calculated via DFT studies (Figure 3; for details, see the
Supporting Information). Interestingly, the trend of bite angles
indeed correlates well with the linear-to-branched selectivity
(Figure 4), in which ligands with smaller bite angles give
variation from the standard
yield of I1
linear/branched
b
c
entry
condition
(%)
ratio
1
2
3
4
5
6
7
8
none
70
see above
50
21
35
68
65
76
67
27:1
other L instead of L3
DG2 instead of DG1
DG3 instead of DG1
no t-BuNHi-Pr
in CPME
in toluene
in DME
in MeTHF
at 110 °C
see above
d
n/d
n/d
d
19:1
27:1
24:1
25:1
24:1
24:1
20:1
27:1
9
10
11
12
69
70
54
at 130 °C
with 5 equiv of styrene
a
The reaction was performed with S1 (0.1 mmol), styrene (1.0
mmol), Ir(COD)2BArF (0.005 mmol), L3 (0.005 mmol), and t-
BuNHi-Pr (0.02 mmol) in 1,4-dioxane (0.1 mL) under a N2
b
1
atmosphere at 120 °C for 24 h. Determined by H NMR using
c
1
CH2Br2 as the internal standard. Determined by H NMR of the
d
crude products. Not determined. l:b = linear to branched ratio; DG
= directing group; BArF = tetrakis(3,5-bis(trifluoromethyl)phenyl)-
borate; COD = 1,5-cyclooctadiene; CPME = cyclopentyl methyl
ether; DME = 1,2-dimethoxyethane; and MeTHF = 2-methyltetrahy-
drofuran.
wondered whether such a ligand scaffold with a more rigid
backbone could deliver high linear-to-branched selectivity
without compromising the efficiency of the reaction. While the
use of simple methylene-bridged L1 ligand only gave a slightly
better yield with a decent linear/branched ratio (17:1),
significantly improved efficiency and excellent linear/branched
ratios were obtained with the ligands having substituents on
the methylene backbones (L2 and L3), which are expected to
inhibit the undesired C−P bond rotation. Particularly, the use
of FMPhos (L3), easily prepared in two steps from inexpensive
9-fluorenone, consistently provided a high yield and nearly
complete linear selectivity (entry 1).
Figure 3. X-ray crystal structures of ligands L1 (CCDC: 1992830)
and FMPhos (CCDC: 1992831) and their computed bite angles with
Ir via DFT studies.
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a
Scheme 3. Scope of Alkenes
Figure 4. Correlation between calculated bite angles (based on Ir(I)
complexes) and linear-to-branched selectivity in alkene hydro-
alkenylation.
higher linear selectivity and those with larger bite angles, as
observed previously,10−14 give higher branched selectivity
instead. This trend is clearly opposite to the one found in
the Rh-catalyzed hydroformylation of alkenes.6 Among all of
the ligands tested, FMPhos (L3) exhibits an equal or even
smaller calculated bite angle (71.7°) than those of L1 (72.3°)
and dppm (72.0°) based on their coordination with Ir(I)
complexes. This could likely be explained by the buttressing
effect of the rigid coplanar fluorene linker that pushes the two
phosphino groups closer to each other (Figure 3). Such an
effect is reflected by the relatively small [C···H] distance (2.45
Å) between the phenyl group on phosphine and fluorene linker
in the optimized structures (the sum of van der Waals radii of
C and H is 2.90 Å).
With an understanding of the ligand effect, control
experiments were subsequently conducted to probe the role
of other reactants. Among the three five-membered lactam-
derived enamide directing groups (DGs), isoindolin-1-one
(DG1) displayed the highest reactivity (entries 1, 3, and 4,
Table 1). A catalytic amount of t-BuNHi-Pr proved to be
critical as it prevents hydrolysis of the enamide by adventitious
water in the reaction (entry 5, Table 1).10 Among a series of
solvents evaluated, DME provided the highest reaction
efficiency, i.e., 75% yield and 25:1 selectivity (entries 6−9,
Table 1). The reaction was not improved when altering the
reaction temperature (entries 10 and 11, Table 1). Finally, the
reaction benefits from a high concentration of the alkene
coupling partner as the migratory insertion of the Ir−C
intermediate into the alkene is anticipated to be rate-
determining based on the prior mechanistic studies.15 Thus,
a reduced amount of styrene lowered the reaction efficiency
(entry 12, Table 1).
Scope of Linear-Selective Hydroalkenylation. With an
optimized catalytic condition in hand, the scope of this linear-
selective alkene hydroalkenylation was first investigated. It is
noteworthy that upon completion of the hydroalkenylation
reaction, a convenient one-pot enamide hydrolysis can be
performed to afford the corresponding linear α-alkylated
ketones.21 As depicted in Scheme 3, styrenes bearing various
electron-withdrawing groups, such as fluoro, chloro, trifluor-
omethyl, and ester groups, as well as electron-donating groups
including methyl, tert-butyl, and methoxy groups at the para
position, could all undergo the reaction smoothly to deliver the
desired linear alkylation products in moderate-to-good yields
with excellent linear-to-branched selectivity (1a−g). It was also
possible to introduce a diverse set of functional groups at the
a
Unless otherwise noted, all reactions were performed on a 0.2 mmol
1
scale; the linear/branched ratio was determined by H NMR of the
crude enamide products; and yields are isolated yields of the
b
corresponding ketones after hydrolysis. L2 was used as the ligand.
c
d
15 mol % Ir(COD)2BArF and FMPhos. 5 equiv of the alkene was
e
f
used. Toluene was used as the solvent. Yield was based on the
enamide product.
meta position of styrene, such as chloro, trifluoromethyl, and
methyl groups, without any erosion in the reaction perform-
ance (1h−j). This reaction was also amenable to an ortho-
substituted styrene as well as an indole-derived olefin, in which
cases consistently good yields and linear-to-branched selectiv-
ity were observed (1k, 1l).
The scope of functionalized alkenes was also explored.
Olefins containing a synthetically versatile functional group,
such as silyl and pinacol-boryl (Bpin) groups, turned out to be
excellent substrates, delivering the desired products in good
yields with complete linear-to-branched selectivity (1m, 1n).22
While attempts to use unfunctionalized aliphatic alkenes, i.e.,
1-octene, as the coupling reagent proved fruitless,23 moderate
reactivity and excellent linear-to-branched selectivity were
restored when alkenes bearing an electronegative N or O
substituent at the allylic position were employed (1o−q). It is
possible that the inductive effect caused by these EWGs
stabilizes the transition state of the 2,1-insertion, as predicted
by the prior DFT studies.16 Conjugated dienes were
competent for this reaction, albeit in a low yield (1r). Finally,
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a steroid-derived alkene could also be ligated with decent
reactivity and complete linear selectivity (1s).
Having shown that hydroalkenylation with various alkenes
was possible, we next sought to evaluate the performance of
structurally diverse enamides in this reaction (Scheme 4).
suitable substrates (2j−l). Finally, the reaction also accom-
modated several acyclic substrates, affording the desired mono-
alkylated acetone, acetophenone, and 5-phenylpentan-2-one in
moderate yields (2m−o). Notably, the ortho C−H bond of
acetophenone was untouched under the reaction conditions
(2n), a result that is complementary to Murai’s seminal study
on the ortho C−H alkylation of aromatic ketones.24 In all cases,
complete linear selectivity was observed.
a
Scheme 4. Scope of Enamides
Mechanistic Studies. To gain some insights into the
reaction mechanism, deuterated cyclopentanone-derived en-
amide (d-S1) was treated with a reduced amount of styrene in
toluene under the standard reaction condition for 7 h. As
shown in Scheme 5, the deuterium ratio at the vinyl hydrogen
of the recovered enamide substrate was significantly reduced.
Meanwhile, incorporation of deuterium at the α and β
positions of the recovered styrene was observed. These H/D
scrambling phenomena implied that (1) oxidative addition of
the Ir(I) species into the enamide vinyl C−H bond is
Scheme 5. Mechanistic Studies
b
Toluene was used as the solvent with 5 mol % mesitylenesulfonic
c
acid dihydrate as an additive. 15 mol % Ir(COD)2BArF and FMPhos.
d
e
72 h. The hydrolyzed crude product was treated with Pd/C under
a
H2 (balloon). Unless otherwise noted, all reactions were performed
on a 0.2 mmol scale; linear/branched ratio was determined by H
1
NMR of the crude enamide products; and yields are isolated yields of
the corresponding ketones after hydrolysis.
Typically, enamides were prepared via condensing DG1 with a
slight excess (1.3 equiv) of dimethyl ketals of the
corresponding ketones in excellent yields (with just a few
exceptions; see SI for details). While enamides derived from
cyclohexanones (2b) and cycloheptanones (2c) exhibited low
reactivity, substrates based on cyclopentanones generally gave
good yields of the corresponding linear alkylation products
following enamide hydrolysis. For example, mono- and di-β-
substituted cyclopentanones are good to excellent substrates
(2d−i), including those with a more acidic malonate moiety
(2i). Unsurprisingly, selective mono-alkylation occurred at the
less hindered side of cyclopentanones. In addition, benzo-fused
and bicyclic ketones with an oxygen or a carbon linker are also
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Scheme 6. Synthetic Utility
reversible and (2) Ir−H migratory insertion into styrene does
occur and is also reversible. Further analysis of the desired
hydroalkenylation product (d-I1) revealed that a significant
amount of deuterium was introduced at the benzylic position
(25% D). Moreover, a small amount of the alkenylation side
product (d-I2) was also isolated, in which the enamide alkene
was hydrogenated, with concomitant deuterium incorporation
at the α-nitrogen and allylic carbons.
Two pathways could possibly explain the formation of
product d-I2. Path a involves an Ir−H insertion into styrene
followed by C−C reductive elimination, and d-I2 is formed via
isomerization of the enamide alkene. Alternatively, if the
reaction proceeds via an Ir−C insertion mechanism (path b),
the hydroalkenylation product would be formed via a C−H
reductive elimination. However, if β-H elimination takes place
instead of C−H reductive elimination, the resulting Ir
dihydride could insert into the enamide alkene (likely directed
by the amide carbonyl) to give a stabilized π-allyl species,
which undergoes C−H reductive elimination to provide d-I2.25
Two control experiments were carried out to probe the Ir−
H vs Ir−C insertion pathway. First, the subjection of product
I1 to the standard reaction condition led to no alkene
isomerization to product I2 (Scheme 5). This indicates that
path a is less likely to be responsible for forming I2. Second,
while the reaction of d-S1 with α-methylstyrene did not give
the desired hydroalkenylation product (d-I3), deuterium was
incorporated at all of the three β positions of the recovered α-
methylstyrene. This result implied that Ir−H migratory
insertion likely occurred with α-methylstyrene but did not
lead to a successful C−C reductive elimination. Given the
success of coupling with simple styrene, the result of α-
methylstyrene is also inconsistent with the pathway of Ir−H
insertion/C−C reductive elimination (path a). Taken together
with the computational results from Huang and Liu,17 it is
reasonable to propose that the Ir−C migratory insertion into
styrene (path b) is the main productive reaction pathway.
Synthetic Utility. To highlight the utility of this hydro-
alkenylation process, a gram-scale reaction between S1 and
vinyl-Bpin was performed. Using a reduced loading of
Ir(COD)2BArF and FMPhos, the desired hydroalkenylation
product (1n) was isolated in a good yield (Scheme 6a). Most
importantly, the Bpin group can then be easily transformed
into a wide range of other functional moieties that would
otherwise be difficult to obtain through direct coupling
methods (Scheme 6b). For example, the boron moiety can
be converted to an alcohol (1t) or a protected amine (1u)
using Morken’s method,26 where the corresponding enol and
enamine are not suitable alkene partners for this reaction. In
addition, different coupling strategies could be adopted to
introduce a terminal alkene through Zweifel olefination27 or a
pyridine group under Aggarwal’s conditions28 (1v and 1w).
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a
Scheme 7. Ir-Catalyzed Linear-Selective Alkene Hydroarylation Reaction
b
c
d
10 mol % Ir(COD)2BArF and ligand at 155 °C. 4.5 Equiv of alkene and 10 mol % Ir(COD)2BArF and ligand in toluene (0.067 mL). 2.0 Equiv
e
f
of alkene and 10 mol % Ir(COD)2BArF and ligand without solvent. 4.5 Equiv of alkene. 4.5 Equiv of alkene and 10 mol % Ir(COD)2BArF and
a
1
ligand. Unless otherwise noted, all reactions were performed on a 0.1 mmol scale; the linear/branched ratio was determined by H NMR of the
crude products; yields are based on isolated yields of the corresponding arene; black color means dppm was used as the ligand; and blue color
means FMPhos was used as the ligand.
Linear-Selective Hydroarylation and Branched-Selec-
tive Hydroformylation. Having demonstrated that FMPhos
is an effective small-bite-angle ligand in the linear-selective
hydroalkenylation of alkenes with enamides, we next sought to
examine its performance in other alkene hydrofunctionaliza-
tion reactions. While FMPhos has a similar small bite angle to
dppm, the rigid 9-fluorenone backbone is expected to reinforce
and stabilize the chelating (κ2) coordination mode, presumably
preventing one phosphino group from slipping off the metal
center. Thus, we may anticipate that FMPhos could perform
better than dppm in either the reactivity or regioselectivity or
both in other mechanistically related alkene hydrofunctional-
ization processes. For example, in the case of Ir-catalyzed
alkene hydroarylation reaction, first discovered by Shibata,11
the control of its regioselectivity has not been trivial. In 2014,
Bower developed a novel large-bite-angle dFppb ligand to
achieve general high branched selectivity.12 However, the
corresponding general and efficient linear-selective alkene
hydroarylation with Ir catalysis has been elusive.
As depicted in Scheme 7, even though small-bite-angle
ligands were predicted to give predominantly the linear
hydroarylation product in this transformation,17 dppm failed
to induce high levels of linear-to-branched selectivity in many
cases (3b, 3c, 3h−j). By contrast, the use of FMPhos led to a
great increase in regioselectivity without any compromise in
reactivity. In cases where satisfactory linear-to-branched
selectivity was achieved with subpar reaction performance in
the presence of dppm (3a, 3d−g, 3k−o), the use of FMPhos
also raised the reaction efficiency to synthetically useful levels
(over 50% yields in most cases). Of particular note is the broad
substrate scope of this linear-selective hydroarylation process: a
variety of weakly coordinating functionalities can be used as
the DGs on the arene coupling partner, such as amides (3a, 3b,
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3l), lactams (3c), cyclic or acyclic ketones (3d−g, 3i−k, 3m−
o), and lactones (3h).
regiodivergent functionalizations of unactivated olefins. Efforts
on developing a chiral version of FMPhos for enantioselective
transformations are ongoing.
Finally, we evaluated the performance of FMPhos in the
venerable Rh-catalyzed alkene hydroformylation reaction.
Unlike the above hydroalkenylation and hydroarylation
processes, the hydroformylation reaction proceeds via a Rh−
H rather than a Rh−C insertion pathway.29 Hence, one would
expect that under the same ligand environment, the branched/
linear selectivity would be the opposite with respect to the two
Ir-catalyzed reactions. Using styrene as the substrate and large-
bite-angle Xantphos/DPEPhos as the ligand, the hydro-
formylation reaction took place with poor branched/linear
selectivity (b:l = 1.3:1/2.3:1) in the presence of catalytic
Rh(CO)2(acac) and pressurized syngas (150 psi) (Scheme 8).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acscatal.0c04199.
■
sı
Experimental procedures; spectral data; DFT calculation
data; and X-ray crystallographic data (PDF)
X-ray crystallographic data (CIF)
X-ray crystallographic data (CIF)
AUTHOR INFORMATION
Corresponding Author
■
Scheme 8. Small-Bite-Angle Effect in Rh-Catalyzed
a
Branched-Selective Hydroformylation of Styrene
Guangbin Dong − Department of Chemistry, The University
of Chicago, Chicago, Illinois 60637, United States;
orcid.org/0000-0003-1331-6015; Email: gbdong@
uchicago.edu
Authors
Xiao-Yang Chen − Department of Chemistry, The University
of Chicago, Chicago, Illinois 60637, United States;
orcid.org/0000-0003-3449-4136
Xukai Zhou − Department of Chemistry, The University of
Chicago, Chicago, Illinois 60637, United States
Jianchun Wang − Department of Chemistry, The University of
Chicago, Chicago, Illinois 60637, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/acscatal.0c04199
b
a
Isolated yield: 81%. Yields and the linear/branched ratio were
determined by 1H NMR of the crude products using tetrachloro-
ethane as the internal standard.
Author Contributions
†X.-Y.C. and X.Z. contributed equally to this work.
This observation is consistent with the experimental results
from van Leeuwen,5b who showed that even at elevated
temperatures, there was little improvement to the branched/
linear selectivity (b:l = 1:2.3) under similar reaction
conditions. By contrast, the reaction proceeded with high
efficiency (84% yield of the branched product) and excellent
branched/linear selectivity (b:l > 20:1) when employing
FMPhos as the bisphosphine ligand. As a sharp comparison,
the use of dppm again gave almost no reactivity in this reaction
(<1% combined yields). Taken together, these results
demonstrated that FMPhos can achieve highly efficient and
regioselective alkene hydrofunctionalization processes, com-
plementary to large-bite-angle bisphosphines, which would
otherwise be difficult with dppm.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the University of Chicago and the NSF (CHE-
1855556) for funding support. X.Z. thanks Dalian Institute of
Chemical Physics international talent training project for a
post-doctoral fellowship. Umicore AG & Co. KG is gratefully
acknowledged for a generous donation of the Ir and Rh salts
used in this study.
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■
In summary, a unique small-bite-angle bisphosphine ligand,
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