The carbonyl group tuned electron-deficient phosphorus ligands and their application in Rhodium catalyzed arylation to aldehydes

Article abstract of DOI:10.1016/j.tetlet.2015.08.076

Acylphosphines, which could be efficiently prepared from acid chlorides and secondary phosphines, were developed as a type of carbonyl group tuned electron-deficient phosphorus ligand. They were found to be a kind of efficient ligand in Rhodium catalyzed arylation to aldehydes through accelerating the transmetalation process. Chiral acylphosphine ligands could be generated from carboxylic acids bearing the chiral framework correspondingly.

Full text of DOI:10.1016/j.tetlet.2015.08.076

Tetrahedron Letters 56 (2015) 5673–5675
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The carbonyl group tuned electron-deficient phosphorus ligands
and their application in Rhodium catalyzed arylation to aldehydes
⇑
Jiefang Yang, Xingyu Chen, Zhiqian Wang
State Key Laboratory of Chemical Resource Engineering, College of Science, Beijing University of Chemical Technology, Beijing 100029, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Acylphosphines, which could be efficiently prepared from acid chlorides and secondary phosphines, were
developed as a type of carbonyl group tuned electron-deficient phosphorus ligand. They were found to be
a kind of efficient ligand in Rhodium catalyzed arylation to aldehydes through accelerating the transmet-
alation process. Chiral acylphosphine ligands could be generated from carboxylic acids bearing the chiral
framework correspondingly.
Received 14 July 2015
Revised 23 August 2015
Accepted 26 August 2015
Available online 29 August 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Acylphosphines
Electron-deficient phosphorus ligands
Rhodium catalysis
Aldehydes addition
Transition metal catalyzed reactions are playing an essential
role in modern organic synthesis. Numerous chemical transforma-
tions could be realized by number-limited transition metals, which
were endowed by ligands with divers catalyzing ability through an
electronic and sterically hindered effect on the metal center.
Various ligands based on hetero atoms or coordinative functional
groups have been designed and prepared with the development
of organic synthesis methodology,1 among which the phosphorus
ligands have taken an essential place in homogenous catalysis
and organometallic chemistry.2 The electronic property of phos-
phorus ligands, which could be tuned by the adjacent functional
group, would greatly affect the reactivity of the catalyst.1e,3
Comparing to the electron-rich phosphorus ligands which would
usually enhance catalysts’ reactivity in hydrogenation and
hydroformylation reactions, electron-deficient phosphorus
ligands, such as DIFLUORPHOS developed by Jean-Pierre Genet
and the phosphoramidite ligands by Feringa, have also been
found to be good ligands in a broad range of reactions.1e,3a,4
Except tuned by aryl groups adjacent to phosphorus atom, the
electron-deficient phosphorus ligands are still much less
developed with a new type of electron tuning group (Fig. 1).
Carbonyl group, a fundamental functional group, is an impor-
tant electron withdrawing group which could efficiently reduce
synthesis of polymerization photoinitiators, acylphosphine
oxides.5 Comparing to the wide use in polymerization, their triva-
lent phosphine structure was much less regarded as a potential
electron-deficient ligand in transition metal catalyzed reactions.6
The character of the carbonyl group decreasing
r
-donor and
increasing
p
-acceptor abilities of phosphine ligands would be just
essential to accelerate the transmetalation process,3a for example,
in Rhodium catalyzed arylation of organoboronic reagents.
Herein we would like to report a type of electron-deficient
phosphorus ligand, acylphosphines, and their first successful
application in Rhodium catalyzed arylation to aldehydes.7
The acylphosphines L1–L5 could be efficiently prepared from
commercial available acid chlorides 1 and secondary phosphines
2 in ethers as shown in Scheme 1.6f,g Only a few researches
showed that the acylphosphines could form stable complexes
through coordinating with transition metals, such as Ruthenium,
Rhodium, and Iridium, and some of these complexes have tried
to be used as ligands in the catalysts for organic reactions.6 In
our study, the pre-catalyst for arylation of organoboronic reagents,
[RhCl(coe)2]2 (Chlorobis(cyclooctene)Rhodium(I)), was found to be
able to undergo a ligand exchange with acylphosphines. By mixing
benzoyldiphenylphosphine L1 and [RhCl(coe)2]2, a fast coordina-
tion would be detected from the changing of chemical shifts on
the 31P NMR spectrum. Even with the Wilkinson’s Catalyst, RhCl
(PPh3)3, a ligand exchange on the Rhodium center could also take
place very fast, which indicated the acylphosphines have success-
fully inherited the coordinative ability from traditional trivalent
phosphines. Initial studies for the acylphosphines’ application in
Rhodium catalyzed arylation were carried out with the reaction
the electron density of its
a-atoms. Acylphosphines or phospho-
mides (L in Scheme 1), in which the phosphine is adjacent to a car-
bonyl group, have been prepared as key intermediates for the
⇑
Corresponding author.
E-mail address: wangzhq@mail.buct.edu.cn (Z. Wang).
http://dx.doi.org/10.1016/j.tetlet.2015.08.076
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

5674
J. Yang et al. / Tetrahedron Letters 56 (2015) 5673–5675
Table 1
Rhodium-acylphosphine catalyzed arylation to benzaldehydea
P
O
P
P
OH
C
X
1% mol Rh
B(OH)2
O
X= O, N
[RhCl(coe)2]2/L
+
GWE
This work
solvent, additive
Figure 1. Electron-withdrawing groups on phosphorus ligands.
3a
4a
5a
Entry
L.
Sol./ratio to H2O
Add.
Temp (°C)
Yieldb (%)
of benzaldehyde 3a, 2.5 equiv of PhB(OH)2 4a, and 2.5 equiv of base
Na2CO3 in toluene/H2O (1:1.5) in the presence of 0.5 mol % of [RhCl
(coe)2]2 and 1 mol % of acylphosphine L1. After 24 h at room tem-
perature, the reaction would afford the addition product 5a in 65%
yield (Table 1, entry 1), while the triphenylphosphine could only
achieve 29% yield under the same conditions (Table 1, entry 3).
This result indicated the acylphosphine L1 performed as an elec-
tron-deficient phosphorus ligand and enhanced the reactivity of
Rhodium catalyzed arylation by accelerating the transmetalation
process.3a
We investigated different bases as adducts in the addition to
benzaldehyde 3a, and found relatively weaker bases, such as
Na2CO3 and KF, would give better yield than stronger bases
(Table 1, entries 5–7), while a dramatical shift of yield, from 65%
to 95%, was found when the ratio of toluene and water was opti-
mized from 1:1.5 to 1:0.5 (Table 1, entry 8). Variations of solvent
with water at this ratio were tested and toluene was found to be
the best solvent of all, while dichloromethane could give a similar
high yield but DME was found to draw down the yield greatly
(Table 1, entries 9–11). Further optimization of reaction conditions
showed that a slight heating of the reaction mixture to 60 °C would
enhance reactivity and shorten the reacting time to 4 h with 99%
yield (Table 1, entry 12) at a low catalyst loading (1 mol % Rh).
Under this condition, the derivatives of the acylphosphines,
L2–L5, were found to work as the ligands in this reaction as well
(Table 1, entries 13–16), in which L2 and L5 showed a moderate
to good reactivity. But not quite such an obvious electronic effect
could be observed in the variation of the substitution on the
benzoyl group, which may be due to the overwhelming electron-
withdrawing effect of the carbonyl group comparing to the sub-
stances on the benzoyl group.
1
2
3
4
5
6
7
8
L1
No
L1
PPh3
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
Tol/1:1.5
Tol/1:1.5
Tol/1:1.5
Tol/1:1.5
Tol (1:1.5)
Tol (1:1.5)
Tol (1:1.5)
Tol (1:0.5)
Diox/1:0.5
DME/1:0.5
DCE/1:0.5
Tol/1:0.5
Tol/1:0.5
Tol/1:0.5
Tol/1:0.5
Tol/1:0.5
Na2CO3
Na2CO3
Na2CO3
Na2CO3
KF
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
60
60
60
60
60
65
N.R.c
13d
29
60
Trace
11
95
40
<5
92
99
36
KOH
K3PO4
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
9
10
11
12
13
14
15
16
78
50
85
a
Reaction condition unless otherwise noted: aldehyde (0.3 mmol, 1.0 equiv),
phenylboronic acid (2.5 equiv), solvent (1 mL), base (2.5 equiv), 0.5 mol % of [RhCl
(coe)2]2 and 1 mol % of acylphosphine L1.
b
Isolated yield.
No ligand employed.
2 mol % of acylphosphine L1 was used.
c
d
Table 2
Rhodium-acylphosphine L1 catalyzed arylation to aldehydesa
1% mol Rh
[RhCl(coe)2]2/L
OH
Ar B(OH)2
+
R
O
R
Ar
Toluene/H2O (2:1)
Na2CO3, 60oC
3
4
5
Entry
3 (R=)
4 (Ar=)
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (3a)
C6H5 (4a)
99 (5a)
95 (5b)c
82 (5c)c
73 (5d)
96 (5e)c
53 (5f)c
53 (5g)c
31 (5h)
41 (5i)
4-MeC6H5 (4b)
3-MeC6H5 (4c)
2-MeC6H5 (4d)
2-Naphthyl (4e)
1-Naphthyl (4f)
4-CF3C6H5 (4g)
4-MeOC6H5 (4h)
4-ClC6H5 (4i)
C6H5 (4a)
C6H5 (4a)
C6H5 (4a)
C6H5 (4a)
C6H5 (4a)
With the optimized reaction condition, the reactions of various
arylboronic acids 4 and aldehydes 3 were tested, and the results
are shown in Table 2. Several arylboronic acids reacting with
benzaldehyde 3 would afford the desired product 5 in good to
excellent yields (Table 2, entries 1–5). Sterically hindered aryl-
boronic acids would give a relatively lower yield (Table 2, entry
6), while not quite such an obvious electronic effect was observed
in some cases (Table 2, entries 7–9). As for the aldehydes 3, most
substituted benzaldehydes with arylboronic acid could afford the
corresponding diarylmethanols in good to excellent yield, showing
9
C6H5 (3a)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4-MeOC6H5 (3b)
4-MeC6H5 (3c)
4-BrC6H5 (3d)
4-ClC6H5 (3e)
2-MeOC6H5 (3g)
2-ClC6H5 (3h)
2-MeC6H5 (3i)
2-Naphthyl (3j)
1-Naphthyl (3k)
n-C4H9 (3l)
n-C4H9 (3l)
n-C4H9 (3l)
n-C4H9 (3l)
2-ClC6H5 (3h)
99 (5h)
74 (5b)
81 (5j)
85 (5i)
68 (5k)
94 (5l)d
62 (5d)
74 (5e)
83 (5f)
64 (5m)
77 (5n)
62 (5o)
73 (5p)
85 (5q)d
C6H5 (4a)
C6H5 (4a)
C6H5 (4a)
C6H5 (4a)
O
O
Et3N, Et2O
r.t.
+
HPPh2
Ar
PPh2
Ar
Cl
C6H5 (4a)
2
1
L
4-MeC6H5 (4b)
3-MeC6H5 (4c)
2-Naphthyl (4e)
4-MeOC6H5 (4h)
O
O
O
PPh2
PPh2
O
Ph
PPh2
24
C6H5 (4a)
50 (5r)
(3m)
H
Ph
L3
L1
L2
O
O
a
Reaction condition unless otherwise noted: aldehyde (0.3 mmol, 1.0 equiv),
phenylboronic acid (2.5 equiv), solvent (1 mL), base (2.5 equiv), 0.5 mol % of [RhCl
PPh2
PPh2
(coe)2]2 and 1 mol % of acylphosphine L1, reactions were monitored by TLC.
b
Isolated yield.
3 mol % of Rhodium catalyst was employed.
5 mol % of Rhodium catalyst was employed.
Me
Cl
L4
L5
c
d
Scheme 1. The synthesis of acylphosphines L1–L5.

J. Yang et al. / Tetrahedron Letters 56 (2015) 5673–5675
5675
1. Tf2O, DIPEA
DCM, 0°C
Pd(OAc) 2/dppp
DIPEA
OH
OH
OTf
OMe
DMSO, methanol
CO,80°C
2. MeI, K2CO3
acetone
60% yield
54% yield
6
S-BINOL
1. KOH
Et3N
EtOH/ H2O
COOMe
OMe
COCl
OMe
COPPh2
OMe
2. SOCl2
DMF
89% yield
THF
23% yield
7
8
L6
1% mol Rh
[RhCl(coe)2]2/L6
OH
+ PhB(OH)2
O
Toluene/H2O (2:1)
Na2CO3, 60oC
3k
4a
5f
Scheme 2. Synthesis of a chiral acylphosphine L6 and application as a chiral ligand in Rhodium catalyzed arylation to 1-naphthylaldehyde 3k.
the sterical and electrical effect of substitution on benzaldehyde
had a less affection on the reactivity (Table 2, entries 10–18, 23).
For the less reactive aliphatic aldehydes, this condition with
acylphosphine L1 as the ligand for Rhodium catalyst could afford
products 5m–5p in good yield as well (Table 2, entries 19–22). In
the presence of a potential 1,4-addition competition (Table 2, entry
24), the 1,2-addition would take place as the main reaction and
afford the corresponding alcohol product 5r, just as the selectivity
of traditional phosphine ligands would have done.8
Acylphosphines could also be decorated into chiral ligands by
connecting the phosphine with chiral carboxylic acid.9 An
acylphosphine ligand L6 bearing axial chiral binaphthyl skeleton
could be synthesized from (S)-BINOL generated acid chloride 8
and diphenylphosphine 2 as shown in Scheme 2.10 In the Rhodium
catalyzed arylation to 1-naphthylaldehyde 3k with phenylboronic
acid 4a, the chiral acyphosphine L6 performing as the chiral
ligands for Rhodium could afford the product 5f in a nearly quan-
titative yield, even much higher than L6, but unfortunately with a
poor enantioselectivity. Though the enantioselectivity in the alde-
hyde addition is not satisfying, the chiral ligands’ decoration and
application in other asymmetric synthesis could be carried on in
future.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.08.
076.
References and notes
1. (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori,
R. J. Am. Chem. Soc. 1980, 102, 7932; (b) Noyori, R.; Takaya, H. Acc. Chem. Res.
1990, 23, 345; (c) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029; (d) Zhang,
W.; Chi, Y.; Zhang, X. Acc. Chem. Res. 2007, 40, 1278; (e) Xie, J.; Zhou, Q. Acc.
Chem. Res. 2008, 41, 581; (f) Zhu, S.; Zhou, Q. Acc. Chem. Res. 2012, 45, 1365; (g)
Genet, J.; Ayad, T.; Ratovelomanana-Vidal, V. Chem. Rev. 2014, 114, 2824; (h)
Defieber, C.; Grützmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47,
4482; (i) Chen, M. S.; White, C. M. J. Am. Chem. Soc. 2004, 126, 1346; (j) Chen, J.;
Chen, J.-M.; Lang, F.; Zhang, X.-Y.; Cun, L.-F.; Zhu, J.; Deng, J.-G.; Liao, J. J. Am.
Chem. Soc. 2010, 132, 4552; (k) Velazquez, E. D.; Verpoort, F. Chem. Soc. Rev.
2012, 41, 7032–7060; (l) Visbal, R.; Gimeno, M. C. Chem. Soc. Rev. 2014, 43,
3551–3574.
2. Kamer, P. C. J.; Leeuwen, P. W. N. M. Phosphorus(III) Ligands in Homogeneous
Catalysis: Design and Synthesis; Wiley, 2012.
3. (a) Tian, P.; Dong, H.; Lin, G.-Q. ACS Catal. 2012, 2, 95–119; (b) Korenaga, T.;
Maenishi, R.; Hayashi, K.; Sakai, T. Adv. Synth. Catal. 2010, 352, 3247.
4. (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346; (b) Harutyunyan, S. R.; den
Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008, 108, 2824;
(c) Teichert, J. F.; Feringa, B. L. Angew. Chem., Int. Ed. 2010, 49, 2486.
5. (a) Kunzek, H.; Braun, M.; Nesener, E.; Rühlmann, K. J. Organomet. Chem. 1973,
49, 149–156; (b) Lindner, E.; Frey, G. Chem. Ber. 1980, 113, 3268–3274; (c)
Lindner, E.; Hübner, D. Chem. Ber. 1983, 116, 2574–2590; (d) Corrales, T.;
Catalina, F.; Peinado, C.; Allen, N. S. J. Photochem. Photobiol., A 2003, 159, 103–
114; (e) Leca, D.; Fensterbank, L.; Lacôte, E.; Malacria, M. Chem. Soc. Rev. 2005,
34, 858–865.
6. (a) Whittemore, S. M.; Yoder, R. J.; Stambuli, J. P. Organometallics 2012, 31,
6124–6130; (b) Whittemore, S. M.; Gallucci, J.; Stambuli, J. P. Organometallics
2011, 30, 5273–5277; (c) Nesterov, V.; Duan, L.; Schnakenburg, G.; Streubel, R.
Eur. J. Inorg. Chem. 2011, 567–572; (d) Vedejs, E.; Donde, Y. J. Am. Chem. Soc.
1997, 119, 9293–9294; (e) Gowrisankar, S.; Neumann, H.; Spannenberg, A.;
Beller, M. Organometallics 2014, 33, 94–99; (f) Gowrisankar, S.; Federsel, C.;
Neumann, H.; Ziebart, C.; Jackstell, R.; Spannenberg, A.; Beller, M.
ChemSusChem 2013, 6, 85–91; (g) Kumar, P.; Siddiqui, M. M.; Reddi, Y.;
Mague, J. T.; Sunoj, R. B.; Balakrishna, M. S. Dalton Trans. 2013, 42, 11385.
7. (a) Jagt, R. B. C.; Toullec, P. Y.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J. Org.
Biomol. Chem. 2006, 4, 773; (b) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.;
Zhou, Q.-L. Org. Lett. 2006, 8, 1479; (c) Nishimura, T.; Kumamoto, H.; Nagaosa,
M.; Hayashi, T. Chem. Commun. 2009, 5713; (d) Morikawa, S.; Michigami, K.;
Amii, H. Org. Lett. 2010, 12, 2520; (e) Ma, Q.-S.; Ma, Y.-D.; Liu, X.; Duan, W.-Z.;
Qu, B.; Song, C. Tetrahedron: Asymmetry 2010, 21, 292; (f) Xing, C.-H.; Liao, Y.-
X.; He, P.; Hu, Q.-S. Chem. Commun. 2010, 3010; (g) Liao, Y.-X.; Xing, C.-H.; He,
P.; Hu, Q.-S. Org. Lett. 2008, 10, 2509–2512.
Conclusion
In summary, we found the easily prepared acylphosphines
could be successfully used as a new type of electron-deficient
ligands in Rhodium catalyzed arylation to aldehydes. The experi-
mental studies showed that the acylphosphine ligands have a good
coordinative ability inherited from tradition trivalent phosphines
and a positive ability of the accelerating transmetalation process
tuned by the adjacent carbonyl group. The acylphosphines could
be generated into chiral ligands based on (S)-BINOL framework.
Studies of chiral acylphosphine ligands’ decoration and application
in asymmetric synthesis would be taken under investigation.
Acknowledgements
We thank the National Natural Science Foundation of China
(NSFC 21302010) and the Fundamental Research Funds for the
Central Universities (YS1406) for their generous support. We
acknowledge the support from the ‘Public Hatching Platform for
Recruited Talents of Beijing University of Chemical Technology’.
8. Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65, 4450.
9. Shintani, R.; Inoue, M.; Hayashi, T. Angew. Chem., Int. Ed. 2006, 45, 3353.
10. Zhu, S.; Wang, C.; Chen, L.; Liang, R.; Yu, Y.; Jiang, H. Org. Lett. 2011, 13, 1146–
1149.