Palladium(II)-catalyzed conjugate phosphination of electron-deficient acceptors

Article abstract of DOI:10.1021/ol8028466

A general protocol for the conjugate transfer of diphenyl-, dicyclohexyl-, and di-tert-butylphosphinyl groups from silylphosphines to cyclic and acyclic electron-deficient acceptors employing a bench-stable palladium(II) catalyst is reported. Several Eand

Full text of DOI:10.1021/ol8028466

ORGANIC
LETTERS
2009
Vol. 11, No. 5
1091-1094
Palladium(II)-Catalyzed Conjugate
Phosphination of Electron-Deficient
Acceptors
Verena T. Trepohl,† Susumu Mori,‡ Kenichiro Itami,*,‡ and Martin Oestreich*,†
Organisch-Chemisches Institut, Westfa¨lische Wilhelms-UniVersita¨t, Corrensstrasse 40,
D-48149 Mu¨nster, Germany, and Department of Chemistry, Graduate School of
Science, Nagoya UniVersity, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
martin.oestreich@uni-muenster.de; itami@chem.nagoya-u.ac.jp
Received December 17, 2008
ABSTRACT
A general protocol for the conjugate transfer of diphenyl-, dicyclohexyl-, and di-tert-butylphosphinyl groups from silylphosphines to cyclic
and acyclic electron-deficient acceptors employing a bench-stable palladium(II) catalyst is reported. Several E and Z configured r,ꢀ-unsaturated
carbonyl and carboxyl acceptors (including imides) as well as nitroalkenes participate in this palladium(II)-catalyzed process in high chemical
yields.
The area of transition-metal-catalyzed conjugate element transfer
onto R,ꢀ-unsaturated carbonyl and carboxyl acceptors is cur-
rently witnessing tremendous growth.1 Prior to the C-element
bond forming event, an interelement linkage is usually activated
by a ligand-stabilized transition metal either through oxidative
addition of the element-element bond to the low-valent metal
center2,3 or through element-to-metal transmetalation.3 In-
dicators for the recent substantial progress are several novel
(asymmetric) C-B (B-B bond activation4), C-Si (B-Si5
or Si-Si bond activation6), as well as C-P bond forming
(4) Rhodium(I) catalysis: (a) Kabalka, G. W.; Das, B. C.; Das, S.
Tetrahedron Lett. 2002, 43, 2323–2325. Copper(I) catalysis: (b) Ito, H.;
Yamanaka, H.; Tateiwa, J.-i.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821–
6825. (c) Mun, J.; Lee, J.-E.; Yun, J. Org. Lett. 2006, 8, 4887–4889. (d)
Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008, 47, 145–147. Nickel(0)
catalysis: (e) Hirano, K.; Yorimitsu, H.; Ohshima, K. Org. Lett. 2007, 9,
5031–5033. Platinum(0) catalysis: (f) Lawson, Y. G.; Lesley, M. J. G.;
Marder, T. B.; Norman, N. C.; Rice, C. R. Chem. Commun. 1997, 2051–
2052. (g) Bell, N. J.; Cox, A. J.; Cameron, N. R.; Evans, J. S. O.; Marder,
T. B.; Duin, M. A.; Elsevier, C. J.; Baucherel, X.; Tulloch, A. A. D.; Tooze,
R. P. Chem. Commun. 2004, 1854–1855.
† Universita¨t Mu¨nster.
‡ Nagoya University.
(1) Suginome, M.; Matsuda, T.; Ohmura, T.; Seki, A.; Murakami, M.
In ComprehensiVe Organometallic Chemistry III; Mingos, D. M. P.,
Crabtree, R. H., Ojima, I., Eds.; Elsevier: Oxford, 2007, Vol. 10, pp
725-787.
(5) Rhodium(I) catalysis: (a) Walter, C.; Auer, G.; Oestreich, M. Angew.
Chem., Int. Ed. 2006, 45, 5675–5677. (b) Walter, C.; Oestreich, M. Angew.
Chem., Int. Ed. 2008, 47, 3818–3820.
(2) Han, L.-B.; Tanaka, M. Chem. Commun. 1999, 395–402
.
(3) Burks, H. E.; Morken, J. P. Chem. Commun. 2007, 4717–4725
.
10.1021/ol8028466 CCC: $40.75
Published on Web 02/03/2009
2009 American Chemical Society

reactions (Si-P bond activation7). Our contribution is the
disclosure of a rhodium(I)-catalyzed activation of interelement
compounds in basic aqueous media,5,7 a process believed to
hinge upon a hydroxyrhodium(I) complex as the active cata-
lyst. Its Lewis basic oxygen will interact chemoselectively
with the more electronegative element of the interelement
reagent, thereby weakening the element-element bond
eventually resulting in transmetalation of the less electro-
negative element. This general strategy for the conjugate
element transfer was inspired and guided by the related 1,4-
addition of arylboronic acids8 and its mechanism of action.9
Scheme 1
.
Conjugate Phosphination Using Bench-Stable
Palladium(II) Complex 1
As the logical next step, we reasoned that palladium(II)-
catalyzed protocols for conjugate arylation,10 which are
tantamount to the aforementioned rhodium(I) catalysis,8,9
might also qualify for our purposes.5,7 Accordingly, a
transmetalation mechanism involving a hydroxypalladium(II)
complex was verified.11 As we had elaborated an efficient
rhodium(I)-catalyzed 1,4-addition of phosphinyl groups yet
limited in substrate scope,7 we decided to investigate its
unprecedented palladium(II)-catalyzed counterpart. In this
Letter, we report a robust method for the conjugate phos-
phination of electron-deficient acceptors12 using silylphos-
phines7,13 as a source of nucleophilic trivalent phosphorus.14
(2a)7,16 to cyclic acceptor 4 (Scheme 1). Variation of reaction
conditions (only a selection is shown) led to a straightforward
procedure, affording the adduct in high chemical yield.
Catalyst identification commenced with bench-stable palla-
dium(II) catalyst 1 developed by Itami et al. for the hydroary-
lation of fullerene with arylboronic acids.15 This work also
included examples of conjugate arylation of cyclic and acyclic
R,ꢀ-unsaturated carbonyls. We were then delighted to see that
1 also facilitated the phosphinyl transfer from t-BuMe2Si-PPh2
Table 1. Ligand [Pd(OAc)2·L] and Additive Screeninga
entry
ligand L
mol %
C6F5CO2H (mol %)
yield (%)
(6) Palladium(0) catalysis: (a) Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am.
Chem. Soc. 1988, 110, 5579–5581. Copper(I) catalysis: (b) Ito, H.; Ishizuka,
T.; Tateiwa, J.-i.; Sonoda, M.; Hosomi, A. J. Am. Chem. Soc. 1998, 120,
11196–11197. Rhodium(I) catalysis: (c) Nakao, Y.; Chen, J.; Imanaka, H.;
Hiyama, T.; Ichikawa, Y.; Duan, W.-L.; Shintani, R.; Hayashi, T. J. Am.
Chem. Soc. 2007, 129, 9137–9143.
1
2
3
4
5
6
7
8
Ph3P
L1
L2
L3
Ph3P
L1
L2
L3
Ph3P
L1
L2
20
20
20
-
-
-
-
-
-
-
-
10
10
10
10
45
76
64
55
36
74
66
58
41
80
71
63
20
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
(7) Rhodium(I) catalysis: (a) Trepohl, V. T.; Oestreich, M. Chem.
Commun. 2007, 3300–3302. (b) For a related example, see: Hayashi, M.;
Matsuura, Y.; Watanabe, Y. J. Org. Chem. 2006, 71, 9248–9251.
(8) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229–4231.
9
(9) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052–5058.
10
11
12
(10) (a) Phosphine ligand:Nishikata, T.; Yamamoto, Y.; Miyaura, N.
Angew. Chem., Int. Ed. 2003, 42, 2768–2770. (b) Bipyridine ligand:Lu,
X.; Lin, S. J. Org. Chem. 2005, 70, 9651–9653. (c) Carbene ligand:Zhang,
T.; Shi, M. Chem.-Eur. J. 2008, 14, 3759–3764.
L3
a Conjugate phosphinations of 4 were conducted using Pd(OAc)2 and
an equimolar amount of the indicated ligand L1-L3 (twice the amount in
the case of Ph3P) as well as 2a (2.5 equiv) in 1,4-dioxane:H2O ) 10:1
(0.20 M) at 60 °C. Yields after oxidation and flash chromatography.
(11) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organometallics 2004,
23, 4317–4324.
(12) For an authoritative summary of conjugate phosphorus(III) and
phosphorus(V) transfer, see: Enders, D.; Saint-Dizier, A.; Lannou, M.-I.;
Lenzen, A. Eur. J. Org. Chem. 2006, 29–49.
(13) For thermal as well as fluoride-mediated conjugate addition of
R3Si-PR2, see: (a) Couret, C.; Escudie, J.; Satge, J.; Anh, N. T.; Soussan,
G. J. Organomet. Chem. 1975, 91, 11–30. (b) Hayashi, M.; Matsuura, Y.;
To ascertain whether 1 () Pd(O2CC6F5)2·L1) is the ideal
counteranion-ligand combination, we surveyed four different
ligandssPh3P and L1-L3swith Pd(OAc)2 as the palla-
dium(II) source with or without C6F5CO2H as additive15a
(Table 1). Independent of the catalyst loading and the
presence of added acid, a clear trend was observed: Ph3P10a
performed poorly, while all nitrogen-based ligands10b were
superior in the order L1 > L2 > L3. Any further decrease
in the amount of Pd(OAc)2 gave lower yields.
Watanabe, Y. Tetrahedron Lett. 2004, 45, 9167–9169
.
(14) Selected examples of 1,4-addition of R2P groups: (a) Thermal
addition of R2PH: Zabotina, E. Y.; de Kanter, F. J. J.; Bickelhaupt, F.;
Wife, R. L. Tetrahedron 2001, 57, 10177–10180. (b) Thermal addition of
R2PH·BH3: Join, B.; Delacroix, O.; Gaumont, A.-C. Synlett 2005, 1881–
1884. (c) Addition of metalated, borane-protected R2PH: Imamoto, T.;
Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J. Am. Chem. Soc. 1990,
112, 5244–5252. (d) For the Conant reaction (transfer of P(V) nucleophile
generated from R2PCl/glacial acetic acid), see: Conant, J. B.; Braverman,
J. B. S.; Hussey, R. E. J. Am. Chem. Soc. 1923, 45, 165–171.
(15) (a) Mori, S.; Nambo, M.; Chi, L.-C.; Bouffard, J.; Itami, K. Org.
Lett. 2008, 10, 4609–4612. (b) For a complementary Rh(I) catalysis, see:
Nambo, M.; Noyori, R.; Itami, K. J. Am. Chem. Soc. 2007, 129, 8080–
8081.
(16) Hayashi, M.; Matsuura, Y.; Watanabe, Y. Tetrahedron Lett. 2004,
45, 1409–1411
.
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Org. Lett., Vol. 11, No. 5, 2009

Table 2. Conjugate Phosphination of Cyclic R,ꢀ-Unsaturated
Carbonyl Compounds
Table 4. Conjugate Phosphination of R,ꢀ-Unsaturated Imides
entry silylphosphine Si-P acceptor
R
adduct yield (%)
entry silylphosphine Si-P acceptor
n
adduct yield (%)
1
2
3
4
5
4
5
6
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
E-15
Z-15
E-16
Z-16
E-15
Z-15
E-16
Z-16
Ph
Ph
n-Bu
n-Bu
Ph
17a
17a
18a
18a
17b
17b
62
73
58
64
51
55
63
82
1
2
3
4
5
6
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
3
4
5
3
4
5
1
2
3
1
2
3
6a
7a
8a
6b
7b
8b
94
84
90
72
80
88
Ph
n-Bu 18b
n-Bu 18b
We then continued to apply this procedure to conventional
cyclic R,ꢀ-unsaturated carbonyl compounds 3-5 using both
t-BuMe2Si-PPh2 (2a) and Me2PhSi-PCy2 (2b) representa-
tive for diaryl- and dialkylphosphinyl groups (Table 2). As
in all preceding and subsequent examples, phosphinylfphos-
phinoyl oxidation with H2O2 or sulfurization with S8 allowed
facile purification by flash chromatography on silica gel. The
yields obtained with substrates 3-5 compare well with those
of the rhodium(I)-catalyzed variant.7a
the door for auxiliary-based, diastereoselective 1,4-additions.17
Again, Z alkenes performed better than E alkenes. Maleimide
19 afforded even higher yields (Scheme 2).
Scheme 2. Conjugate Phosphination of a Maleimide
Table 3. Conjugate Phosphination of Acyclic R,ꢀ-Unsaturated
Carbonyl Compounds
Being aware of the fact that R,ꢀ-unsaturated carboxyls are
intrinsically less reactive than carbonyl compounds, we were
nevertheless surprised to learn these were reluctant to
participate in this reaction.18 Conversely, both fumaric (E-
21) and maleic ester (Z-21) gave the desired products in
chemical yields expected for the respective double bond
isomer (Scheme 3).
entry silylphosphine Si-P acceptor
R
adduct yield (%)
1
2
3
4
5
6
7
8
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
t-BuMe2Si-PPh2 (2a)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
Me2PhSi-PCy2 (2b)
E-9
Z-9
E-10
E-11
E-9
Z-9
E-10
E-11
Ph
Ph
Me
n-Bu
Ph
Ph
Me
n-Bu 14b
12a
12a
13a
14a
12b
12b
13b
78
91
84
71
74
80
85
65
Scheme 3
.
Conjugate Phosphination of Fumaric and Maleic
Esters
Acyclic R,ꢀ-unsaturated carbonyl compounds, e.g., acceptors
9-11, had emerged as unreactive with the rhodium(I) catalytic
system but reacted cleanly under the palladium(II) catalysis
(Table 3). We note that isolated yields were invariably higher
for Z than for E configured precursors (vide infra).
Gratifyingly, R,ꢀ-unsaturated imides 15 and 16 with E and
Z double bond geometry extended the scope (Table 4), opening
Org. Lett., Vol. 11, No. 5, 2009
1093

The range of conceivable substrates for this reaction was
completed with nitroalkene E-23, furnishing the 1,4-adduct
in good isolated yield (Scheme 4).
Scheme 4. Conjugate Phosphination of a Nitroalkene
Figure 1
Me2PhSi-Pt-Bu2 (2c).
. Selected examples of conjugate Pt-Bu2 transfer using
After identification of all these acceptors, we tested
Me2PhSi-Pt-Bu2 (2c) to realize the transfer of the electron-
rich di-tert-butylphosphinyl group (Figure 1). Although
chemical yields were somewhat lower, conjugate phosphi-
nation worked except for R,ꢀ-unsaturated imides, thereby
rounding off the scope of this palladium(II) catalysis.
In summary, we elaborated a general method for the
conjugate phosphinyl transfer employing easy-to-handle
silylated diaryl- and dialkylphosphines 2a-c7 (Figure 2).
This novel palladium(II) catalysis for interelement bond
activation is superior to the rhodium(I)-catalyzed process
previously reported by us.7 Future work will be devoted to
mechanistic investigations and the development of enantio-
selective19 and substrate-controlled17,20 variants.
Figure 2.
Silylphosphines surveyed in this work.7,16
Acknowledgment. The research was supported by the
International Research Training Group Mu¨nster-Nagoya
(GRK 1143) (predoctoral fellowship to V.T.T., 2007-2009),
the Aventis Foundation (Karl Winnacker fellowship to M.O.,
2006-2008), the PRESTO program of the Japan Science
and Technology Agency (to K.I.), and a Grant-in-Aid for
Scientific Research from MEXT and JSPS (to K.I.). Generous
donation of chemicals from Wacker AG (Burghausen/
Germany) is gratefully acknowledged.
(17) (a) Conjugate addition of lithiated R2PH·BH3: Le´autey, M.; Castelot-
Deliencourt, G.; Jubault, P.; Pannecoucke, X.; Quirion, J.-C. Tetrahedron
Lett. 2002, 43, 9237–9240. (b) Conjugate addition of lithiated or sodiated
(EtO)2P(O)H: Castelot-Deliencourt, G.; Pannecoucke, X.; Quirion, J.-C.
Tetrahedron Lett. 2001, 42, 1025–1028.
(18) There is precedence for the conjugate phosphination of R,ꢀ-
unsaturated esters using alkali metal or “naked” phosphinides. See for
example refs 13b and 14c.
(19) For organocatalytic conjugate phosphination of R,ꢀ-unsaturated
aldehydes, see: (a) Carlone, A.; Bartoli, G.; Bosco, M.; Sambri, L.;
Melchiorre, P. Angew. Chem., Int. Ed. 2007, 46, 4504–4506. (b) Ibrahem,
I.; Rios, R.; Vesely, J.; Hammar, P.; Eriksson, L.; Himo, F.; Cordova, A.
Angew. Chem., Int. Ed. 2007, 46, 4507–4510.
Supporting Information Available: General procedure,
characterization data, as well as 1H, 13C, and 31P NMR spectra
for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(20) A remarkable reagent-contolled 1,4-addition of a metalated P-
stereogenic phosphine oxide is known: Haynes, R. K.; Lam, W. W.-L.;
Yeung, L.-L. Tetrahedron Lett. 1996, 37, 4729–4732
.
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