Synthesis of (E)- and (Z)-alkenylphosphonates using vinylboronates

Article abstract of DOI:10.1021/ol027515a

(Matrix presented) (E)- and (Z)-alkenylphosphonates have been prepared stereospecifically via the reaction of vinylboronate esters with triethyl phosphite in the presence of palladium acetate.

Full text of DOI:10.1021/ol027515a

ORGANIC
LETTERS
2003
Vol. 5, No. 5
729-731
Synthesis of (E)- and (Z)-
Alkenylphosphonates Using
Vinylboronates
George W. Kabalka* and Sankar K. Guchhait
Departments of Chemistry and Radiology, The UniVersity of Tennessee,
KnoxVille, Tennessee 37996-1600
kabalka@utk.edu
Received December 20, 2002
ABSTRACT
(E)- and (Z)-alkenylphosphonates have been prepared stereospecifically via the reaction of vinylboronate esters with triethyl phosphite in the
presence of palladium acetate.
Alkenylphosphonates are routinely used to prepare biologi-
cally active molecules,1 flame retardants,2 polymer additives,3
and other transformations4 such as Michael additions,4a
aminohydroxylations,4b, dihydroxylations,4c aziridinations,4d,e
epoxidations,4e C-glycosylations,4f Horner-Wadsworth-
Emmons reactions,4g and hydrogenations.4h (E)- and (Z)-
alkenylphosphonates exhibit different biological activities in
nucleotide derivatives1c,e and produce stereoisomeric inter-
mediates in asymmetric reactions.4a-e Thus, the development
of stereoselective methods to prepare (E)- and (Z)-alkenyl-
phosphonates has become important in organic synthesis. A
survey of the literature5 reveals that most synthetic methods
produce either (E)- or a mixture of (E)- and (Z)-vinylphos-
phonates. Coupling of dialkyl phosphites with vinyl bromides
does produce (E)- and (Z)-vinylphosphonates stereoselec-
tively,6,7 but it is difficult to prepare stereochemically pure
vinyl bromides. Recently, Srebnik reported a method for the
synthesis of (Z)-vinylphosphonates.8
(1) (a) Raboisson, P.; Baurand, A.; Cazenave, J.-P.; Gachet, C.; Schutz,
D.; Spiess, B.; Bourguigon, J.-J. J. Org. Chem. 2002, 67, 8063. (b) Holstein,
S. A.; Cermak, D. M.; Wiemer, D. F.; Lewis, K.; Hohl, R. J. Bioorg. Med.
Chem. 1998, 6, 687. (c) Lazrek, H. B.; Rochdi, A.; Khaider, H.; Barascut,
J. L.; Imbach, J. L.; Balzarini, J.; Witvrouw, M.; Pannecouque, C.; De Clerq,
E. Tetrahedron 1998, 54, 3807. (d) Smith, P. W.; Chamiec, A. J.; Cobley,
K. N.; Duncan, K.; Howes, P. D.; Whittington, A. R.; Wood, M. R. J.
Antibiot. Tokyo 1995, 48, 73. (e) Harnden, M. R.; Parkin, A.; Parratt, M.
J.; Perkins, R. M. J. Med. Chem. 1993, 36, 1343. (f) Megati, S.; Phadtare,
S.; Zemlicka, J. J. Org. Chem. 1992, 57, 2320. (g) Smeyers, Y. G.; Romero-
Sanchez, F. J.; Hernandez-Laguna, A.; Fernandez-Ibanez, N.; Galvez-Ruano,
E.; Arias-Perez, S. J. Pharm. Sci. 1987, 76, 753. (h) Chance, L. H.; Moreau,
J. P. U.S. Patent 3910886, 1975.
(5) Hydrophosphorylation of terminal alkynes: (a) Zhao, C.-Q.; Han,
L. B.; Goto, M.; Tanaka, M. Angew Chem., Int. Ed. 2001, 40, 1929. (b)
Han, L. B. Tanaka, M. J. Am. Chem. Soc. 1996, 118, 1571. Zirconation of
alkynylphosphonates: (c) Quntar, A. A. A.; Melman, A.; Srebnik, M. J.
Org. Chem. 2002, 67, 3769. Carbocupration: (d) Gil, J. M.; Oh, D. Y. J.
Org. Chem. 1999, 64, 2950. Catalytic hydrogenation of alkynylphos-
phonates: (e) Cristau, H.-J.; Mbianda, X. Y.; Beziat, Y.; Gasc, M. B. J.
Organomet. Chem. 1997, 529, 301. Radical trapping: (f) Jiao, X.-Y.;
Bentrude, W. G. J. Am. Chem. Soc. 1999, 121, 6088. Allylic rearrange-
ment: (g) Muthiah, C.; Kumar, K. P.; Mani, C. A.; Swamy, K. C. K. J.
Org. Chem. 2000, 65, 3733. Triflation: (h) Okauchi, T.; Yano, T.;
Fukamachi, T.; Ichikawa, J.; Minami, T. Tetrahedron Lett. 1999, 40, 5337.
Wittig: (i) Xu, Y.; Flavin, M. T.; Xu, Z. Q. J. Org. Chem. 1996, 61, 7697.
Peterson olefination: (j) Washbusch, R.; Carran, J.; Savignac, P. Tetra-
hedron 1996, 52, 14199.
(2) Welch, C. M.; Gozalez, E. J.; Guthrie, J. D. J. Org. Chem. 1961, 26,
3270.
(3) Jin, J. I. U.S. Patent 74-496233; Chem. Abstr. 1979, 90, 153010m.
(4) For reviews, see: Minami, T.; Motoyoshiya, J. Synthesis 1992, 333.
(a) Enders, D.; Wahl, H.; Papadopoulos, K. Tetrahedron 1997, 53, 12961.
(b) Cristau, H.-J.; Pirat, J.-L.; Drag, M.; Kafarski, P. Tetrahedron Lett. 2000,
41, 9781. (c) Yokomatsu, T.; Yamagishi, T.; Suemune, K.; Yoshida, Y.;
Shibuya, S. Tetrahedron 1998, 54, 767. (d) Kim, D. Y.; Rhie, D. Y.
Tetrahedron 1997, 53, 13603. (e) Cristau, H.-J.; Mbianda, X. Y.; Geze,
A.; Beziat, Y.; Gasc, M. B. J. Organomet. Chem. 1998, 571, 189. (f) Junker,
H.-D.; Fessner, W.-D. Tetrahedron Lett. 1998, 39, 269. (g) Inoue, H.;
Tsubouchi, H.; Nagaoka, Y.; Tomioka, K. Tetrahedron 2002, 58, 83. (h)
Ranu, B. C.; Guchhait, S. K.; Ghosh, K. J. Org. Chem. 1998, 63, 5250.
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10.1021/ol027515a CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/13/2003

the reaction in the absence of solvents. When pinacolato (E)-
1-octenylboronate was heated with triethyl phosphite and
palladium acetate at 95 °C under nitrogen, diethyl (E)-1-
octenylphosphonate was formed in 60% yield. Carrying out
the reaction in the presence of oxygen improved the yield
to 85%.12
A survey of various catalysts (Table 1) revealed that
palladium acetate was the most effective. Addition of Ph3P
to the Pd(OAc)2 (or the use of Pd(dppf)Cl2) did not improve
the yield. In general, an excess of P(OEt)3 was required to
attain the highest yields.
Table 1. Survey of Catalysts Used in the Reaction of
Pinacolato (E)-1-Octenylboronate with P(OEt)3
a
catalyst
reaction time (h)
yieldb (%)
Pd(OAc)2
PdCl2
NiCl2 (anhy)c
Pd(OAc)2, PPh3
Pd(dppf)Cl2
8
8
25
12
40
84
75
43
55
d
incomplete reaction
a Reaction conditions: pinacolato (E)-1-octenylboronate (1 mmol),
P(OEt)3 (2 mmol), catalyst (4 mol %), 95 °C under O2. b Isolated yields.c 6
mol %. d PPh3 (4 equiv) was added.
We then examined the reactions of various (E)- and (Z)-
vinylboronates (Table 2). The Pd(OAc)2-catalyzed reaction
of vinylboronates with P(OEt)3 at 95 °C under an oxygen
atmosphere furnished vinylphosphonates in good to high
yield.13 Significantly, (E)- and (Z)-vinylboronates (entries
1-6) were stereospecifically converted to corresponding (E)-
and (Z)-alkenylphosphonates, respectively. The method is
suitable for both aryl- and alkyl-substituted vinylboronates.
Halogen functionalities (entries 3, 4, and 7) were unaffected
under the reaction conditions. An R-substituted vinylboronate
also underwent the reaction to afford a moderate yield of
expected product, although the reaction was slow (entry 8).
The reaction does not appear to require a boronate ester since
boronic acids also react, although an excess of P(OEt)3 is
required to solubilize the boronic acid. The use of P(OMe)3
required a longer reaction time but produced the desired
product.
Since (E)- and (Z)-vinylboronates9,10 can be prepared
stereospecifically, they are ideal precursors for the stereo-
specific formation of (E)- and (Z)-alkenylphosphonates. We
decided to explore the preparation of (E)- and (Z)-alkenyl-
phosphonates from vinylboronates as a part of an ongoing
research program focused on reactions of boronic acids and
their esters.11 Herein, we wish to report the results of this
study (Scheme 1).
Scheme 1
In conclusion, we have developed an improved method
for preparing (E)- and (Z)-alkenylphosphonates stereo-
specifically from vinylboronates. To the best of our knowl-
edge, this is the first report of the conversion of vinylboronic
esters and their acids to 1-alkenylphosphonates. The new
method has the advantage that (E)- and (Z)-vinylphos-
phonates can be prepared stereospecifically in good yields
using readily accessible starting materials. Further investiga-
tions are in progress.
We first examined the reaction of pinacolato (E)-1-
octenylboronate with P(OEt)3 in the presence of Pd(OAc)2
in refluxing EtOH. Diethyl (E)-1-octenylphosphonate was
formed in 54% yield in 35 h. Acetonitrile, tetrahydrofuran,
and toluene were ineffective as solvents. We then examined
Table 2. Pd(OAc)2-Catalyzed Conversion of Vinylboronates to Alkenylphosphonates,a Scheme 1
entry
1
R
R′
stereochemistry
time (h)
9
product
yieldb (%)
78
refc
5i, 6
Ph
Ph
H
E
PhCHdCHP(O)(OEt)2
E
2
3
4
5
6
7
8
H
Z
E
Z
E
Z
E
E
7
9
PhCHdCHP(O)(OEt)2
75
79
60
84
63
81
55
5e,i, 6, 8
5i
Z
p-Cl-C6H4
p-Cl-C6H4
n-C6H13
n-C6H13
p-F-C6H4
Ph
H
p-Cl-C6H4CHdCHP(O)(OEt)2
E
H
6
p-Cl-C6H4CHdCHP(O)(OEt)2
5i
Z
H
8
n-C6H13CHdCHP(O)(OEt)2
5b
E
H
6
n-C6H13CHdCHP(O)(OEt)2
13a
13b
13c
Z
H
9
p-F-C6H4CHdCHP(O)(OEt)2
E
CH3
120
PhCHdC(CH3)P(O)(OEt)2
E
a Reaction conditions: vinylboronate (1 mmol), P(OEt)3 (2 mmol), and Pd(OAc)2 (4 mmol %), 95 °C, O2. b Isolated yields. c Literature reference.
730
Org. Lett., Vol. 5, No. 5, 2003

Acknowledgment. We thank the Department of Energy
and the Robert H. Cole Foundation for support of this
research.
for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL027515A
Supporting Information Available: General experimen-
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T.; Satoh, T.; Pivsa-Art, S.; Normura, M. J. Org. Chem. 1998, 63, 5211.
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