Differentially Substituted Phosphines via Decarbonylation of Acylphosphines

Article abstract of DOI:10.1021/acs.orglett.7b00579

A new route to phosphines was developed by a method that features a "pre-join and transform" process that proceeds via acylphosphine intermediates that may be readily prepared from carboxylic acids and disubstituted phosphines. The efficient decarbonylations of these acylphosphines using a nickel catalyst delivered the corresponding phosphines. This method shows that the carboxyl group can play a role similar to halides or triflates for introducing a substituted phosphorus atom on an aromatic ring.

Full text of DOI:10.1021/acs.orglett.7b00579

Letter
pubs.acs.org/OrgLett
Differentially Substituted Phosphines via Decarbonylation of
Acylphosphines
Rongrong Yu,† Xingyu Chen,† Stephen F. Martin,‡ and Zhiqian Wang*,†
†State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, College of Science, Beijing University
of Chemical Technology, Beijing 100029, China
‡Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States
S
* Supporting Information
ABSTRACT: A new route to phosphines was developed by a method
that features a “pre-join and transform” process that proceeds via
acylphosphine intermediates that may be readily prepared from
carboxylic acids and disubstituted phosphines. The efficient decarbon-
ylations of these acylphosphines using a nickel catalyst delivered the
corresponding phosphines. This method shows that the carboxyl group
can play a role similar to halides or triflates for introducing a substituted phosphorus atom on an aromatic ring.
ransition-metal (TM)-catalyzed carbon−phosphorus cou-
corresponding acylphosphine may be conveniently realized by
a straightforward acylation.6 We reasoned that this intermediate
acylphosphine might undergo a “transform” sequence of C−P
bond activation, decarbonylation, and reductive elimination.
Some precedent for the initial C−P bond activation step is found
in the pioneering work of Garg and Houk, who used amides as
novel substrates for various transition-metal-catalyzed coupling
and ester-forming reactions via a “C−N” bond activation
process.7 Other methods featuring a C−P bond activation
process as a key step in new C−P or C−C bond formation have
been recently disclosed.8
T
pling reactions have been widely used to prepare
substituted phosphines,1 especially chiral phosphines, that are
commonly used in a variety of important catalytic processes.2 In
these reactions, the aryl halides (−X), triflates (−OTf), and their
derivatives are typically employed as the electrophilic partners for
carbon−phosphorus bond formation (Figure 1a).3 Although
In order to assess the feasibility of the overall process set forth
in Figure 1, we conducted an exploratory study in which the
acylphosphine 1a was converted to the triarylphosphine 2a in the
presence of several transition metal catalysts (Table 1). Use of 5
mol % of Pd(OAc)2 and Pd2(dba)3 afforded the desired product
2a in 10−20% yield (entries 1, 2). Varying the phosphine ligands
on the catalyst afforded little improvement in yield (data not
shown). When rhodium(I) catalysts that perform well in C−C
and C−H activation reactions were used,9 no conversion of the
substrate was observed (entries 3, 4). However, use of
homogeneous nickel complexes10 led to significant improve-
ments in yield. For example, when the acylphosphine 1a was
heated in toluene at 140 °C in the presence of NiCl2(dppp) and
NiCl2(dppf), the phosphine 2a was obtained in yields of 56% and
67%, respectively (entries 5, 6). Simply changing the solvent to
xylenes and increasing the temperature to 150 °C offered further
improvements, and 2a was isolated in 92% yield when
NiCl2(dppp) was used as the catalyst.
Figure 1. “Pre-join and transform” process.
carboxylic acids have recently emerged as attractive starting
materials for decarboxylative bond formation reactions,4 they
have rarely been employed as a coupling partner in TM-catalyzed
C−P bond forming reactions.5 It is thus notable that we
envisioned a novel two-step approach for the facile synthesis of a
variety of trivalent phosphines using a “pre-join and transform”
pathway that employs carboxylic acids as the electrophilic
coupling partner (Figure 1b). In this procedure, a disubstituted
phosphine is first coupled with a carboxylic acid to form an
acylphosphine, which is then subjected to a decarbonylative C−P
bond activation and reductive elimination to afford a trivalent
phosphine.
In optimization studies to probe the effects of the phosphine
ligand, we found that use of dppp, dppf, dppe, and PPh3
uniformly provided good yields of 2a (entries 7−10). Even
NiCl2·6H2O catalyzed the transformation of 1a into 2a in 80%
We have previously shown that the “pre-join” step merging a
carboxylic acid and a secondary phosphine to form the
Received: February 25, 2017
© XXXX American Chemical Society
A
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Table 1. Condition Optimization for Decarbonylation
Table 2. Scope of the Process
entry
catalyst
solvent
temp (°C)
yield (%)
1
Pd(OAc)2
toluene
toluene
toluene
toluene
toluene
toluene
xylene
xylene
xylene
xylene
xylene
xylene
C6H5Cl
DMF
140
140
140
140
140
140
150
150
150
150
150
140
150
150
150
150 (air)
20
10
>5
>5
56
67
2
Pd2(dba)3
3
RhCl(PPh3)3
[RhCl(coe)2]2
NiCl2(dppp)
NiCl2(dppf)
NiCl2(dppp)
NiCl2(dppf)
NiCl2(dppe)
NiCl2(PPh3)2
NiCl2·6H2O
Ni(COD)2
4
5
6
a
7
92 (83 )
8
84
58
88
80
91
69
6
9
10
11
12
13
14
15
16
NiCl2(dppp)
NiCl2(dppp)
NiCl2(dppp)
NiCl2(dppp)
DMSO
xylene
<5
b
30
Reaction conditions: 1a (0.2 mmol), catalyst (5% mol), solvent (0.5
a
b
mL), in N2, yield determined by 31P NMR. Isolated yield. Reaction
performed in air.
yield, perhaps because either the acylphosphine or triarylphos-
phine 2a served as the ligands (entry 11), whereas anhydrous
NiCl2 was not as effective with a yield of 44%. The
decarbonylation of 1a could also be achieved by Ni(COD)2 at
140 °C in a yield of 91% (entry 12). Though Ni(COD)2 showed
relatively higher activity, we still preferred to use NiCl2(dppp)
considering its better practicability. Varying the solvent revealed
that nonpolar arenes were better than polar aprotic solvents
(entries 13−15), and the reaction does not proceed efficiently in
the presence of atmospheric oxygen (entry16). From a
preparative perspective, it is notable that the reaction can be
easily scaled up as evidenced by the decarbonylation of 1a (20
mmol) using NiCl2(dppp) (5 mol %) in xylenes at 150 °C and
delivering 2a in 83% yield.
Having optimized the reaction conditions, we examined the
scope of the process (Table 2). A variety of substituted
acylphosphines derived from naphthalene were converted into
phosphines in very good yields (Table 2, 2a−d) although the
presence of a 2-ethoxy group appears to be detrimental (Table 2,
2c). Substituted aryl and cycloalkyl acylphoshines were also
converted in good yields into their corresponding phosohines
(Table 2, 2e,f). It is also possible to vary the acyl moiety as
substituted phenyl and pyridyl acylphosphines were good
substrates (Table 2, 2g−j). Even acylphosphines derived from
aliphatic carboxylic acids can be converted into trivalent
phosphines in good yields (Table 2, 2k,l). Bisphosphines and
chiral binaphthyl-derived phosphines are also readily available
(Table 2, 2m−o).
Reaction conditions for preparation of acylphosphines see Supporting
Information and ref 6. Reaction conditions for decarbonylation: 1 (0.2
mmol), NiCl2(dppp) (5% mol), xylene (0.5 mL), in N2, at 150 °C,
a
isolated yield. Crude acylphosphine 1 was used. Yield determined by
31P NMR, isolated yield as phosphine oxide shown in parentheses,
characterized by phosphine oxide.
(Schemes 1 and 2) and bis-phosphorus derivatives (Scheme 3).11
For example, the iodide and carboxylic ester groups of 3 are sites
for sequential cross-coupling reactions. Namely, the iodide
moiety in 3 may serve as the first reactive center in a Suzuki-
coupling to give the biaryl 4,12 and the carboxylic ester group can
Scheme 1. Sequential Cross-Coupling with Iodide and Ester
The previous experiments clearly demonstrate that C−P
activation of various acylphosphines followed by decarbonylation
and reductive elimination represents a novel and viable entry to
trivalent phosphines. It is thus now apparent that carboxylic acids
can serve as an alternative to the more traditional use of triflates
and halides in cross-coupling reactions to generate phosphines.
The potential of our new method can be nicely exemplified by its
application to the syntheses of several novel triaryl phosphines
B
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group for the synthesis of differentially substituted phosphines.
Other applications of this chemistry are under current
investigation and will be reported in due course.
Scheme 2. Sequential Cross-Coupling with Triflate and ester
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b00579.
Experimental procedures and characterization data for all
new compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wangzhq@mail.buct.edu.cn.
ORCID
Scheme 3. Example for Bis-phosphorus Derivative
Stephen F. Martin: 0000-0002-4639-0695
Zhiqian Wang: 0000-0001-9831-649X
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(NSFC 21302010, 21571015) and the Fundamental Research
Funds for the Central Universities (YS1406, buctrc 201321,
PT1613-07) for their generous support. We acknowledge
support from the “Public Hatching Platform for Recruited
Talents of Beijing University of Chemical Technology”.
then provide a functional handle for the introduction of a
phosphino group (Scheme 1). Similarly, the triflate in 7 can be
transformed into aryl groups via a Suzuki reaction, whereupon
the remaining ester group is converted into the final phosphines
10 (Scheme 2). Alternatively, the triflate group in 11 can be
converted into a phosphine oxide,13 and the ester to a phosphine
to generate 14 (Scheme 3).
Although the mechanism for converting acylphosphines into
trivalent phosphines is not fully understood, the catalytic cycle
outlined in Figure 2 seems plausible in light of known
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