Palladium-catalyzed dehydrogenative cis double phosphorylation of alkynes with H-phosphonate leading to (Z)-bisphosphoryl-1-alkenes

Article abstract of DOI:10.1021/ja7108272

Dehydrogenative cis double phosphorylation of terminal alkynes with H-phosphonate took place efficiently in the presence of a divalent palladium catalyst to afford (Z)-bisphosphoryl-1-alkenes selectively. Copyright

Full text of DOI:10.1021/ja7108272

Published on Web 02/08/2008
Palladium-Catalyzed Dehydrogenative Cis Double Phosphorylation of Alkynes
with H-Phosphonate Leading to (Z)-Bisphosphoryl-1-alkenes
Li-Biao Han,* Yutaka Ono, and Shigeru Shimada
National Institute of AdVanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan
Received December 26, 2007; E-mail: libiao-han@aist.go.jp
Table 1. Pd-Catalyzed Dehydrogenative Double Phosphorylation
of H-Phosphonate 1 with 1-Octynea
We disclose a palladium-catalyzed dehydrogenative cis double
phosphorylation of terminal alkynes with H-phosphonate 1 affording
(Z)-bisphosphoryl-1-alkenes 2 (eq 1).1 Metal-mediated additions of
hydrogen phosphonates (RO)2P(O)H to carbon-carbon unsaturated
bonds, so far reported, all are hydrophosphorylation reactions (i.e.,
the addition of the P(O)-H bond).2 A dehydrogenative cis double
phosphorylation reaction has never been recognized.3 Although,
synthetic and biological applications of (Z)-bisphosphoryl-1-alkenes
2 as precursors for bidentate ligands and antibiotics4 are readily
expected, there is no general method for their preparation and only
a very limited number of these compounds are known.5
% yieldb
entry
catalyst
olefin (equiv)
2a
3ac
4a
1
2
3
4
5
6
7
8
9
PdCl2
none
none
none
none
none
none
none
49
21
7
28
55
59
30
27
48
30
10
14
12
13
15
13
4
0
7
8
1
7
2
1
1
2
9
Pd(OAc)2
PdCl
2/4.0 Ph3P
PdCl2(PhCN)2
PdCl2(COD)
Pd(PPh3)4
53
56
10
51
69
72
74
(η3-allylPdCl)2
CH2dCHPh (3)
CH2dCHCN (3)
CH2dCHCO2Me (3)
CH2dCHCO2Me (1)
CH2dCMeCO2Me (3) 67
10
11
12
77(75)d
a Reaction conditions: 1 (0.25 mmol), 1-octyne (0.25 mmol), (η3-
allylPdCl)2 (3 mol % based on Pd), olefin, toluene (1 mL), 100 °C, 16-22
h. b Determined by 31P NMR. Yields are based on H-phosphonae 1 used.
c Total yields of the R and â regioisomers. d Yield in parentheses is an
isolated yield.
We accidentally found this reaction during an ongoing study on
the palladium-catalyzed hydrophosphorylation of alkynes.6 As
previously reported, when PdCl2 was employed as a catalyst, no
addition took place with a mixture of (MeO)2P(O)H and 1-octyne
in toluene at 100 °C for 16 h. Remarkably, however, under similar
reaction conditions an addition did proceed when the more reactive
five member H-phosphonate 16b was employed to give, to our
surprise, not the expected hydrophosphorylation product 3a but a
cis double phosphorylation product bis(phosphinoyl)alkene 2a as
the main product, stereoselectively (eq 2).7 The formation of a 1,2-
bis(phosphoryl)alkane 4a was also detected with a ratio of 2a/
3a(regioisomer ratio R/â)/4a ) 49:28(14/11):13 (entry 1, Table 1).8
As shown in Table 1, this double phosphorylation can be
catalyzed by divalent palladium(II) complexes, especially the
chloropalladium(II) complexes, but is poorly catalyzed by zerovalent
palladium(0) complexes which predominantly produces the hydro-
phosphorylation adduct 3a rather than the double phosphorylation
product 2a. Thus, Pd(PPh3)4 afforded 3a in 48% yield, and produced
only trace amount of 2a. As expected palladium(II) complexes that
are easily reducible to zerovalent palladium species are not good
catalysts for this double phosphorylation either. Thus, Pd(OAc)2
only gave 2a in 21% yield (entry 2). The addition of Ph3P also
dramatically suppressed the formation of 2a (entry 3). On the other
hand, other divalent phosphine-free chloropalladium complexes such
as PdCl2(PhCN)2, PdCl2(COD), and (η3-allylPdCl)2 could catalyze
the dehydrogenative double phosphorylation as efficiently as PdCl2,
giving 2a in good yields.
the formation of 4a but also the formation of 3a was significantly
suppressed by the addition of styrene. While the sterically crowed
methyl methacrylate worked less effectively (entry 12), other
electron-deficient olefins such as acrylonitrile and methyl acrylate
can further improve the yield of 2a to 72% and 77%, respectively
(entries 9 and 11).
By employing a similar reaction condition used for the reaction
of 1 with 1-octyne (entry 11, Table 1), the palladium catalyzed
dehydrogenative double phosphorylation of 1 with other alkynes
was investigated thoroughly (Table 2). Like 1-octyne, other aliphatic
terminal alkynes including the bulky t-butylacetylene (entries 1 and
2) could undergo the dehydrogenative double phosphorylation to
give the corresponding bis(phosphinoyl)alkenes. In addition, func-
tionalized alkynes with cyano, chloro, carboxyl, and silyl groups
all could be used as the substrates in the reaction to generate the
corresponding products. Terminal aromatic alkynes also gave good
yields of the corresponding dehydrogenative double phosphorylation
products (entries 8-11). Both arylacetylenes having an electron-
donating (entries 9 and 10) and an electron-withdrawing (entry 11)
group gave similar results to phenylacetylene, which may indicate
that an electronic effect of a substituent is small in this reaction.
Ferrocenylacetylene also produced the corresponding double phos-
phorylation adduct in a moderate yield.
Since the formation of 4a may be due to the reduction of 2a
with an hydrogen in situ generated,8 we assumed that its formation
should be suppressed by the addition of an olefin serving as an
hydrogen scavenger to favor the formation of 2a. This did work
well. Thus, the yield of 2a increased to 69% when the same reaction
of 1 with 1-octyne catalyzed by (η3-allylPdCl)2 was carried out in
the presence of 3 equiv of styrene (entry 8). Interestingly, not only
Compound 1 readily reacted with (η3-allylPdCl)2 (1:Pd ) 2:1,
THF, 25 °C, 0.5 h) to give 5 in 95% isolated yield (Scheme 1).
Furthermore, a stoichiometric reaction of 5 with 1-octyne (5:1-
9
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J. AM. CHEM. SOC. 2008, 130, 2752-2753
10.1021/ja7108272 CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Palladium-Catalyzed Dehydrogenative Cis Double
Phosphorylation of Alkynes with H-Phosphonate 1a
an alkyne to give 6 via a selective cis addition of the P(O)-Pd
bond to the carbon-carbon triple bond. Intramolecularly and/or
intermolecularly via a reaction with 1, complex 6 gave a hydri-
dopalladium complex 7, which reacts with 1 to release hydrogen,
produce 2, and regenerate the palladium(II) species. Although,
currently a firm evidence for the generation of the hydrogen is not
available, the formation of 6 from 5 as well as 2 from 6 were
strongly evidenced by related reactions found accidently during the
course of other studies (eq 3).9 Thus, complex 8 (an analogue of
5) reacted with 1-octyne (8:1-octyne ) 1:2.5) in CD2Cl2 in a sealed
tube at 50 °C to give quantitatively a new complex 9 (an analogue
of 6) via a cis insertion of the Pd-P(O) bond of 8 to 1-octyne with
P(O) bonding to the terminal carbon and Pd bonding to the internal
carbon. Furthermore heating 9 at 80 °C resulted in the formation
of 2a in 75% yield, which may be rationalized to take place via
intermediates 10 and 11.10
In summary, we have successfully revealed the first dehydro-
genative cis double phosphorylation of H-phosphonate with alkynes
forming (Z)-bisphosphoryl-1-alkenes. Further studies on the reaction
mechanism and applications to other H-phosphorus compounds are
now in progress.
Acknowledgment. This work was supported by New Energy
and Industrial Technology Development Organization (NEDO) of
Japan (Industrial Technology Research Grant Program).
Supporting Information Available: Characterization data of new
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
References
a Reaction conditions: 1 (1 mmol), alkyne (1 mmol), CH2dCHCO2Me
(1 mmol), (η3-allylPdCl)2 (3 mol % as Pd), toluene (4 mL), 100 °C, 16 h.
(1) Part of this work was presented at the 87th Spring Meeting of the Chemical
Society of Japan, 3D3-13, March 2007.
(2) Han, L.-B.; Zhang, C.; Yazawa, H.; Shimada, S. J. Am. Chem. Soc. 2004,
126, 5080, and references cited therein.
b
Yields based on 1 used. [P] ) P(O)(OCMe2-Me2CO).
Scheme 1. A Simplified Sketch for the Dehydrogenative Double
Phosphorylation of Alkynes with 1 ([P] ) P(O)(OCMe2-Me2CO),
for Clarity, Ligands on Palladium were Omitted).
(3) For an analogy, the dehydrogenative double silylation is well recognized.
(a) Tamao, K.; Miyake, N.; Kiso, Y.; Kumada, M. J. Am. Chem. Soc.
1975, 97, 5603. A related metal-mediated dehydrogenative coupling of
phosphines: (b) Han, L.-B.; Tilley, T.D. J. Am. Chem. Soc. 2006, 128,
13698. Although in a preliminary mechanistic study, we found the
formation of (E)-[(MeO)2P(O)]CHdCPh[P(O)(OMe)2] by the reaction of
phenylacetylene with [(MeO)2P(O)]2Pd(PPh2Me)2. However, it should be
noted that this compound was not generated via a similar dehydrogenative
double phospholylation but via the normal hydrophosphorylation of PhCt
CP(O)(OMe)2 with (MeO)2P(O)H. (c) Han, L.-B.; Tanaka, M. Chem.
Commun. 1999, 395. (d) Han, L.-B.; Tanaka, M. Shokubai 1999, 41, 577.
(4) (a) Green, J. R. J. Organomet. Chem. 2005, 690, 2439. (b) Blackburn, G.
M.; Forster, A. R.; Guo, M.-J.; Taylor, G. E. J. Chem. Soc., Perkin Trans.
1 1991, 2867. (c) Christensen, B. G.; Beattie, T. R.; Graham, D. W. French
Patent 2034480; CAN 75:88759.
(5) Only the simplest (Z)-[(RO)2P(O)] R1CdCR2[P(O)(OR)2] (R1 ) R2
)
H) and a limited number of others having functionalities [R1 (R2) ) CN,
F, or CHE2 (E ) CO2R, CN)] are known. Compounds such as 2 where
R1 (R2) is a simple alkyl (aryl) group are not known. (a) Timofeeva, T.
N.; Ignat’ev, V. M.; Ionin, B. I.; Petrov, A. A. Doklady Akade. Nauk
SSSR 1969, 189, 1052; CAN 72:67041. (b) Honig, M. L.; Martin, D. J.
Phosphorus Relat. Group V Elem. 1974, 4, 63-4. (c) Kadyrov, A. A.;
Rokhlin, E. M.; Galakhov, M. V. IzV. Akadi Nauk SSSR, Ser. Khim. 1988,
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72703. (e) Shekhadeh, A.; Didkovskii, N. G.; Dogadina, A. V.; Ionin, B.
I. J. Gen. Chem. USSR 2005, 75, 9.
(6) (a) Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1996, 118, 1571. (b) Han,
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(7) The trans isomer of 2a could not be detected by 31P NMR spectroscopy
of the crude reaction mixture. The structure of 2a was readily determined
on the bases of its 1H and 31P NMR spectra (see Supporting Information
for details).
(8) Two ways for the formation of 4a are possible: reduction of 2a by
hydrogen and hydrophosphorylation of 3a with 1. Allen, A., Jr.; Manke,
D. R.; Lin, W. Tetrahedron Lett. 2000, 41, 151.
(9) Structures of complexes 8 and 9 were all unambiguously determined by
X-ray crystallography (see Supporting Information for detailed data).
(10) The formation of 2,3-dimethyl-3-buten-2-ol (81% yield) was detected by
1H NMR spectroscopy.
octyne ) 1:2, toluene, 50 °C, 16 h) gave 76% yield of 2a. Moreover,
5 catalyzed the dehydrogenative double phosphorylation of 1 with
1-octyne, as efficiently as (η3-allylPdCl)2, to give 2a in 75% yield.
Although a detailed reaction mechanism remains to be clarified,
we feel that a Pd(II)/Pd(IV) catalytic cycle, rather than a conven-
tional Pd(0)/Pd(II) catalytic cycle,3 as shown in Scheme 1 should
be suitable for explaining the reaction. Thus first, 5 reacted with
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