Synthesis and Synthetic Utilization of α-Functionalized Vinylphosphonates Bearing β-Oxy or β-Thio Substituents

Article abstract of DOI:10.1021/jo980467g

The β-hetero-substituted vinylphosphonates la-c on treatment with LDA or LTMP were readily lithiated at the α-position of the phosphono group, and the resulting α-lithiovinylphosphonates were trapped with various electrophiles to afford the corresponding α-functionalized vinylphosphonates 2-14 in 55-96% yields. The Friedel-Crafts reaction of α-(silyl)- or a-(germyl)-phosphonoketene dithioacetals 2, 9, or 4 with acid chlorides gave α-acylated phosphonoketene dithioacetals 15-19 in 53-91% yields. The palladium-catalyzed cross-coupling reaction of β-ethoxy-α-(tributylstannyl)vinylphosphonate 13 with a variety of organic halides (R = acyl, allyl, aryl, etc.) provided β-ethoxy-α-substituted vinylphosphonates 21-26 in good to moderate yields. The palladium-mediated cross-coupling reaction of α-(iodo)vinylphosphonates 7 and 14 with terminal acetylenes afforded α-alkynylated vinylphosphonates 41-44 in 69-83% yields. Several α-functionalized β-hetero-substituted vinylphosphonates were applied to the synthesis of pyrazoles and an isoxazole possessing a phosphono function.

Full text of DOI:10.1021/jo980467g

J . Org. Chem. 1998, 63, 6239-6246
6239
Syn th esis a n d Syn th etic Utiliza tion of r-F u n ction a lized
Vin ylp h osp h on a tes Bea r in g â-Oxy or â-Th io Su bstitu en ts
Ryoji Kouno, Tatsuo Okauchi, Mitsuharu Nakamura, J unji Ichikawa, and Toru Minami*,†
Department of Applied Chemistry, Kyushu Institute of Technology, Sensui-cho, Tobata,
Kitakyushu 804-8550, J apan
Received March 11, 1998
The â-hetero-substituted vinylphosphonates 1a -c on treatment with LDA or LTMP were readily
lithiated at the R-position of the phosphono group, and the resulting R-lithiovinylphosphonates
were trapped with various electrophiles to afford the corresponding R-functionalized vinylphos-
phonates 2-14 in 55-96% yields. The Friedel-Crafts reaction of R-(silyl)- or R-(germyl)-
phosphonoketene dithioacetals 2, 9, or 4 with acid chlorides gave R-acylated phosphonoketene
dithioacetals 15-19 in 53-91% yields. The palladium-catalyzed cross-coupling reaction of â-ethoxy-
R-(tributylstannyl)vinylphosphonate 13 with a variety of organic halides (R ) acyl, allyl, aryl, etc.)
provided â-ethoxy-R-substituted vinylphosphonates 21-26 in good to moderate yields. The
palladium-mediated cross-coupling reaction of R-(iodo)vinylphosphonates 7 and 14 with terminal
acetylenes afforded R-alkynylated vinylphosphonates 41-44 in 69-83% yields. Several R-func-
tionalized â-hetero-substituted vinylphosphonates were applied to the synthesis of pyrazoles and
an isoxazole possessing a phosphono function.
Ta ble 1. Syn th esis of r-F u n ction a lized
Vinylphosphonates containing various functional groups
have been widely studied due to their synthetic and
biological usefulness.1 We have recently reported the
generation of R-carbanions of phosphonoketene dithio-
acetals and their synthetic application to dithioallenes.2
These results have intrigued us to develop R-functional-
ization of vinylphosphonates via R-phosphono-stabilized
vinyl anions, which have not, to our knowledge, been
explored so far despite their potential usefulness and
wide applicability.3,4 We report here a new convenient
synthesis of various vinylphosphonates containing syn-
thetically useful substituents such as organometallic
groups and halogens on the R-carbon. They are new
homologues of vinylphosphonates and expected to show
various reactivities similar to those of vinylphosphonates,
vinyl ethers, heteroatom-substituted olefins, etc. We also
describe the synthesis of a new class of vinylphospho-
nates, which are not readily accessible, via functional
group transformation of the resulting R-functionalized
vinylphosphonates and synthetic applications of several
new vinylphosphonates for the preparation of hetero-
cycles.
Vin ylp h osp h on a tesa
† Tel: +81-(0)93-884-3304. Fax: +81-(0)93-884-3300.
(1) For a review on synthetic uses of vinylphosphonates, see, (a)
Minami, T.; Motoyoshiya, J . Synthesis 1992, 333. For biological uses,
see, for example: (b) Kawamoto, A. P.; Campbell, M. M. J . Chem. Soc.,
Perkin Trans. 1 1997, 1249. (c) Gao, J .; Martichonok, V.; Whitesides,
G. M. J . Org. Chem. 1996, 61, 9538.
Resu lts a n d Discu ssion
Syn t h esis of r-F u n ct ion a lized Vin ylp h osp h o-
n a tes. To synthesize R-functionalized vinylphosphonates
which serve as versatile synthetic intermediates, we
examined the reaction of R-phosphonovinyl anions with
various electrophiles. The 2,2-(ethylenedithio)-1-phospho-
novinyl anion was generated by addition of a THF
solution of lithium 2,2,6,6-tetramethylpiperidide (LTMP)
to phosphonoketene dithioacetal 1a at -78 °C for 1.0 h5
and was subsequently treated with chlorotrimethylsilane
(1.5 equiv) to give an R-silylated phosphonoketene dithio-
acetal 2 in 81% yield (eq 1) (entry 1 in Table 1). Similar
treatment of the R-phosphonovinyl anion with chloro-
triphenylsilane, chlorotrimethylgermane, or chlorotri-
phenyltin also produced the corresponding R-triorgano-
(2) For the synthesis and synthetic application of phosphonoketene
dithioacetals, see: Minami, T.; Okauchi, T.; Matsuki, H.; Nakamura,
M.; Ichikawa, J .; Ishida, M. J . Org. Chem. 1996, 61, 8132.
(3) â-Alkyl-R-phosphonio- or phosphonovinyl anion easily isomerizes
to the corresponding allyl anion. See: (a) Minami, T.; Shikita, S.; So,
S.; Nakayama, M.; Yamamoto, I. J . Org. Chem. 1988, 53, 2937. (b)
Kiddle, J . J .; Babler, J . H. J . Org. Chem. 1993, 58, 3572.
(4) For the synthesis and synthetic application of R-phosphonoallenyl
anion, see: (a) Macomber, R. S.; Hemling, T. C. J . Am. Chem. Soc.
1986, 108, 343. For â-aryl-R-phosphonovinyl anion, see: (b) Mimouni,
N.; About-J audet, E.; Collignon, N.; Savignac, Ph. Phosphorus, Sulfur
Silicon 1993, 75, 99.
(5) A related 1-lithio ketene dithioacetal has been reported to be
generated by halogen/Li exchange of the corresponding bromoketene
dithioacetal with t-BuLi at much lower temperature (at -120 °C),
see: Chamberlin, A. R.; Nguyen, H. J . Org. Chem. 1986, 51, 940.
S0022-3263(98)00467-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/13/1998

6240 J . Org. Chem., Vol. 63, No. 18, 1998
Kouno et al.
Ta ble 2. F r ied el-Cr a fts Acyla tion of
Vin ylp h osp h on a tes 1a , 2, 4, a n d 9 w ith Acid Ch lor id esa
metal-substituted phosphonoketene dithioacetals 3, 4, or
5 in 69-78% yields (entries 2-4). In addition, the
R-phosphonovinyl anion was similarly trapped with elec-
trophiles such as dimethyl disulfide and halogens (I2, Br2)
to lead to the desired phosphonoketene dithioacetals
bearing the methylthio and halogeno group on the
R-carbon in good to moderate yields (entries 5-7).
In the case of acyclic dithioacetal 1b instead of the
cyclic dithioacetal 1a , a THF solution of LTMP was
inversely added dropwise to the mixture of 1b and an
electrophile (Me3SiCl or Bu3SnCl) at -78 °C to prevent
elimination of a thiolate anion.6 As expected, R-trimeth-
ylsilyl- and R-tributyltin-substituted phosphonoketene
dithioacetals 9 and 10 were provided in 64% and 83%
yields, respectively (eq 2) (entries 8 and 9).
These results have indicated that R-phosphonovinyl
anions as well as various R-hetero-substituted vinyl
anions can serve as important intermediates in organic
synthesis.10
F u n ction a l Gr ou p Tr a n sfor m a tion s a t th e r-P osi-
tion of r-F u n ction a lized Vin ylp h osp h on a tes. The
vinylphosphonates bearing electron-withdrawing sub-
stituents, such as ester and cyano groups at the R-posi-
tion, have been widely used in organic synthesis.1 These
studies prompted us to develop multipurpose vinylphos-
phonates via the above prepared R-functionalized vi-
nylphosphonates.
Our first attempt was to introduce an acyl group at
the R-position of the phosphonoketene dithioacetals. The
Friedel-Crafts reaction of 1a with acetyl chloride (4
equiv)/AlCl3 (4 equiv) in CH2Cl2 at 0 °C for 3.0 h gave
the desired R-(acetyl)phosphonoketene dithioacetal 15 in
modest yield (38%) (eq 4) (entry 1 in Table 2). To
Furthermore, we examined the generation of â-ethoxy-
R-phosphonovinyl anion from â-(ethoxy)vinylphosphonate
1c7 and its reactivities toward electrophiles.8 Treatment
of 1c with lithium diisopropylamide (LDA) in THF at -78
°C followed by addition of an electrophile such as chlo-
rotrimethylsilane, tert-butylchlorodimethylsilane, chlo-
rotributyltin, or iodine led to the successful formation of
R-substituted-â-(ethoxy)vinylphosphonates 11, 12, 13, or
14, respectively, in 75-96% yields (eq 3) (entries 10-
13). All compounds 11-14 have the trans-configuration
between the ethoxy and the phosphono group, which was
determined on the basis of the phosphorus-cis-vinyl
proton NMR coupling constants (3J P-H ) 7.6-17.1 Hz).9
(6) 1,2-Migration of the ethylthio group has been found to take place
when acyclic dithioacetal 1b is added to a LTMP solution. See ref 2.
(7) For the addition of phosphorus dithio acid to 1c, see: Kutyrev,
G. A.; Kashina, N. V.; Ishmaeva, E. A.; Cherkasov, R. A.; Pudovic, A.
N. Zh. Obshch. Khim. 1977, 47, 2460; Chem. Abstr. 1978, 88, 445.
(8) For the preparation of (Z)-2-(ethoxy)vinyllithium via halogen/
metal exchange between (Z)-2-(ethoxy)vinyl bromide and butyllithium,
and reaction with carbonyl compounds, see: Lau, K. S. Y.; Schlosser,
M. J . Org. Chem. 1978, 43, 1595.
(10) For the preparation of R-hetero (B, Si, O, S, Se, Te)-substituted
vinyl carbanions and their synthetic application, for R2B, see: (a)
Pelter, A.; Smith, K.; J ones, K. D. J . Chem. Soc. Perkin Trans. 1 1992,
747. For R3Si: (b) Grobel, B.-Th.; Seebach, D. Chem. Ber. 1977. 110,
867. For RO (c) see ref 8. For RS, see: (d) Takeda, T.; Furukawa, H.;
Fujimori, M.; Suzuki, K.; Fujiwara, T. Bull. Chem. Soc. J pn. 1984,
57, 1863. For a review of synthesis and synthetic application of R-seleno
and R-telluro vinyl carbanions, see: (e) Kauffmann, T. Angew. Chem.,
Int. Ed. Engl. 1982, 21, 410.
(9) For the effects of stereochemistry on 1H NMR parameters in
substituted vinylphosphonates, see: (a) Xu, Y.; Flavin, M. T.; Xu, Z.-
Q. J . Org. Chem. 1996, 61, 7697 and references therein. (b) Galvez-
Ruano, E.; Bellanato, J .; Fernandez-Ibanez, M.; Sainz-Diaz, C. I.; Arias-
Perez, M. S. J . Mol. Struct. 1986, 142, 397. (c) Williamson, M. P.;
Castellano, S.; Griffin, C. E. J . Phys. Chem. 1968, 72, 175. Also see
ref 2.

Utilization of R-Functionalized Vinylphosphonates
J . Org. Chem., Vol. 63, No. 18, 1998 6241
Ta ble 3. P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g Rea ction
of Vin ylp h osp h on a te 13 w ith Or ga n ic Ha lid esa
Sch em e 1
banion from 1c with acid chlorides,14 we next applied the
Stille cross-coupling15 to â-ethoxy-R-(tributylstannyl)-
vinylphosphonate 13. The reaction of 13 with benzoyl
chloride in the presence of Pd(PPh3)4 (4 mol %) and CuCN
(9 mol %)16 gave the desired R-benzoylated â-(ethoxy)-
vinylphosphonate 21 in 87% yield (eq 5) (entry 1 in Table
3). Similar treatment of 13 with a wide variety of organic
circumvent the low reactivity of 1a toward an acetyl
cation, R-silylated phosphonoketene dithioacetal 2 was
used in this reaction instead of 1a . This modification
improved the yield of 15 up to 89% (entry 2). Similar
treatment of 2 with various acid chlorides (2 equiv)/AlCl3
(2 equiv) also led to the corresponding R-acylated phospho-
noketene dithioacetals 16-18 in satisfactory yields (68-
89%) (entries 4, 6, and 8).11 The R-silylated acyclic
dithioacetal 9 was also treated with benzoyl chloride (4
equiv)/AlCl3 (4 equiv) to afford the expected benzoylated
derivative 19 in a rather low yield (53%) (entry 10). To
investigate an effect of R- and â-substituents of vi-
nylphosphonates, the reaction of R-germylated dithioac-
etal, â-ethoxy- or â-ethylthio-R-silylated vinylphospho-
nates 4, 11, or 20 with acid chlorides was carried out.
The dithioacetal 4, as well as 2 and 9, was treated with
various acid chlorides under the conditions similar to
those above to afford the corresponding R-acylated
phosphonoketene dithioacetals 15-18 in comparably
good yields (entries 3, 5, 7, and 9). On the other hand,
the reaction of 11 or 20 with acid chlorides (acetyl or
benzoyl chlorides) did not give the corresponding acylated
products and starting 11 and 20 were recovered in all
cases.
On the basis of these results, we have found that an
R-silyl (or R-germyl) substituent and â,â-dithio substit-
uents were required to achieve reasonable yields in the
acylation of vinylphosphonates. This could be rational-
ized by the stability of the intermediates in these reac-
tions. Cations A, arising from R-(silyl)- or R-(germyl)-
phosphoketene dithioacetals 2, 9, or 4, have higher
stability than cations B from â-oxy (or â-thio) vinyl
derivatives 11 (or 20), because of â-silyl12 (or germyl) and
two R-thio13 cation-stabilizing effects (Scheme 1).
To achieve the synthesis of R-acylated â-(ethoxy)-
vinylphosphonates, which are not accessible by the
Friedel-Crafts reaction or direct acylation of the R-car-
halides such as ethyl chloroformate, allyl bromide, and
aryl halides successfully produced the corresponding
cross-coupling products 22-26 in 47-97% yields (entries
2-7).17 Thus, a new class of R-triorganometal-substitut-
ed vinylphosphonates was found to be utilized as a
powerful tool for the synthesis of R-acyl-, aryl-, and ester-
substituted vinylphosphonates.
F u n ction a l Gr ou p Tr a n sfor m a tion s a t th e â-P osi-
tion of r-Silyla ted Vin ylp h osp h on a te. Next, we
examined the functional group transformation at the
â-position of the R-silylated vinylphosphonate 11. The
Michael addition of an ethanethiolate anion with 11
followed by elimination of an ethoxide anion gave a 3.8:1
mixture of (E)- and (Z)-â-ethylthio-R-(trimethylsilyl)-
vinylphosphonate (E)-20 and (Z)-20 in 96% yield (Scheme
2).18 The structures of (E)-20 and (Z)-20 are assignable
from their phosphorus-cis- and trans-vinyl proton cou-
pling constant (see Experimental Section).9a Further-
more, R-(trimethylsilyl)vinylphosphonate 28,19 which is
a versatile synthetic reagent serving as not only vi-
nylphosphonate but also vinylsilane, was readily pre-
(15) For reviews, see: (a) Stille, J . K. Angew. Chem., Int. Ed. Engl.
1986, 25, 508. (b) Mitchell, T. N. Synthesis 1992, 803.
(16) For the effect of the Cu(I) salt cocatalyst on Stille cross-coupling
reactions, see: Liebeskind, L. S.; Fengl, R. W. J . Org. Chem. 1990,
55, 5359.
(11) Compound 18 was alternatively produced by direct acylation
of the vinyl carbanion, generated from 1a and LTMP in THF at -78
°C, with benzoyl chloride (2.0 equiv) in rather low yield (43%).
(12) See, for examples: (a) Lambert, J . B. Tetrahedron 1990, 46,
2677. (b) J arview, A. W. P. Organomet. Chem. Rev., Sect. A 1970, 6,
153. (c) Colvin, W. E. Silicon in Organic Synthesis; Butterworth:
London, 1981; Chapter 3.
(13) See, for example; Price, C. C.; Oae, S. Sulfur Bonding; The
Ronald Press Company: New York, 1962; Chapter 2.
(14) A direct acylation of the R-carbanion from 1c with benzoyl
chloride in THF at -78 °C were unsuccessful to give the compound
21, since the product 21 underwent the Michael addition of the
R-carbanion.
(17) Compound 23 was alternatively produced in 94% yield by the
reaction of R-carbanion from 1c with allyl bromide in the presence of
CuBr-SMe2 (1.2 equiv) in THF at -78 °C to room temperature.
(18) A direct synthesis of 20 by the reaction of an R-carbanion of
â-(ethylthio)vinylphosphonate with chlorotrimethylsilane cannot be
achieved, since treatment of the vinylphosphonate with LDA generates
a â-carbanion, but not the R-carbanion. See ref 2.
(19) For an alternative synthesis of 28, see: Hong, S.; Chang, K.;
Ku, B.; Oh, D. Y. Tetrahedron Lett. 1989, 30, 3307.

6242 J . Org. Chem., Vol. 63, No. 18, 1998
Kouno et al.
Sch em e 2
yields (30-64%) (entries 2-4). To test the synthetic
usefulness of the functionalized vinylphosphonates, the
2-stannylated 1,2-(dithio)vinylphosphonate 34 analogous
to the 1-stannylated vinylphosphonate 13 was subjected
to the palladium-catalyzed cross-coupling reaction with
several organic halides to give the corresponding 2-sub-
stituted 1,2-(dithio)vinylphosphonates 32, 35, and 36 in
66-86% yields (eq 7) (Table 5).
Ta ble 4. Syn th esis of â-F u n ction a lized
Vin ylp h osp h on a tesa
Syn th esis of Heter ocyclic Com p ou n d s. Some of
R-acyl-â-hetero-substituted vinylphosphonates prepared
above were tried to be utilized for the synthesis of
phosphono group-containing heterocyclic compounds.
R-Acylated vinylphosphonates 19 and 21 were trans-
formed into phosphono-containing pyrazoles 3720 and 3821
in 82% and 83% yields, respectively, by refluxing with
hydrazine monohydrate in EtOH (eq 8 and Scheme 3).
Ta ble 5. P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g Rea ction
of Vin ylp h osp h on a te 34 w ith Or ga n ic Ha lid esa
Sch em e 3
pared via 11. Hydrogenation of 11 over Pd/C at atmo-
spheric pressure gave 27, followed by treatment of 27
with NaOEt (0.2 equiv) producing the desired 28 in 80%
yield.
Syn t h esis of â-F u n ct ion a lized Vin ylp h osp h o-
n a tes. We have also explored the possibility of func-
tionalization at the â-position of 1,2-dithio-substituted
vinylphosphonates 29 and 30.2 The â-(phosphono)vinyl
anion,2 generated from 1,2-bis(ethylthio)vinylphospho-
nate 29 and n-butyllithium at -78 °C, reacted with
benzoyl chloride to give the expected â-benzoylated
vinylphosphonate 31 in modest yield (44%)(eq 6) (entry
1 in Table 4). Similar treatment of the 1,2-(trimethyl-
The reaction of 21 with hydroxylamine proceeded under
reflux to give 4-(phosphono)isoxazole 39 in 61% yield
(Scheme 3). Interestingly, the use of 25 in the reaction
with hydroxylamine under mild conditions (room tem-
perature, 60 h) resulted in 4-(phosphono)isoquinoline
N-oxide 40 in 85% yield (eq 9).22 These results have
shown that R-keto-â-hetero-substituted vinylphospho-
nates can be utilized for the synthesis of phosphono-
containing heterocyclic compounds.
(20) For the cyclization of ketene dithioacetals to thiopyrazoles,
see: (a) Taylor, E. C.; Purdum, W. R. Heterocycles 1977, 6, 1865. (b)
Singh, G.; Deb, B.; Ila, H.; J unjappa, H. Synthesis 1987, 286.
(21) For an alternative synthesis of 38, see: Aboujaoude, E. E.;
Collignon, N.; Savignac, P. Tetrahedron 1985, 41, 427.
(22) It is well-known that oximes undergo intramolecular Michael
addition to electronegative olefins to give cyclic nitrones, see, for
example; Minami, T.; Isonaka, T.; Okada, Y.; Ichikawa, J . J . Org.
Chem. 1993, 58, 7009 and references therein. The spectral data of 40
were consistent with the structure described for eq 9 (see Experimental
Section).
enedithio)-2-phosphonovinyl anion with electrophiles
such as benzoyl chloride, trimethylsilyl triflate, and
tributyltin chloride led to the corresponding â-function-
alized vinylphosphonates 32-34 in low to moderate

Utilization of R-Functionalized Vinylphosphonates
J . Org. Chem., Vol. 63, No. 18, 1998 6243
Ta ble 6. P a lla d iu m -Med ia ted Cr oss-Cou p lin g Rea ction
of 7 a n d 14 w ith Ter m in a l Acetylen esa
Syn th esis of r-Alk yn ylvin ylp h osp h on a tes. The
development of new classes of enyne systems has at-
tracted considerable attention from organic chemists
because the enynes show interesting chemical reactivi-
ties23 and biological reactivities.24 From this point of
view, we have proposed the synthesis a novel kind of
enyne compound containing phosphorus and hetero
functional groups. The palladium-mediated cross-cou-
pling reaction25 of iodo-substituted vinylphosphonates 7
and 14 with phenylacetylene in THF at room tempera-
ture afforded the desired enyne compounds 41 and 44 in
73% and 79% yields, respectively (eq 10) (entries 1 and
4 in Table 6).
Sch em e 4
Similar palladium-mediated reaction of 7 with (tri-
methylsilyl)acetylene or 3-(tetrahydro-2-pyranyloxy)pro-
pyne at room temperature also produced the correspond-
ing enyne products 42 or 43, respectively, in good yields
(entries 2 and 3). Furthermore, oxidative homo-coupling
of terminal alkyne 45 derived from 42 produced the
expected diene-diyne derivative 46 in excellent yield
(93%) (Scheme 4).26
Con clu sion . We note the following results from this
investigation: (1) R- and â-(phosphono)vinyl anions were
successfully trapped with various electrophiles to give R-
and â-functionalized vinylphosphonates in good yields;
(2) a new class of R- and â-(triorganometal)-substituted
vinylphosphonates were applied to the Friedel-Crafts
acylation, palladium-mediated cross-coupling reaction,
etc., to lead to versatile functional group-containing
vinylphosphonates which are not easily accessible; (3)
functionalized heterocyclic compounds bearing the phos-
phono group were synthesized.
(TMP), and triethylamine (Et3N) were refluxed with CaH2 and
then distilled. A commercial solution of n-BuLi (3.04, 1.68,
1.64, or 1.60 M in hexane) was used. The starting materials
1a , 1b, 29, and 30 were prepared according to the established
procedures.2 Diethyl phosphonoacetaldehyde diethyl acetal
was prepared in 89% yield by the Arbuzov reaction of bro-
moacetaldehyde diethyl acetal with triethyl phosphite at 160-
165 °C.
Gen er a l. 1H and 13C NMR spectra were obtained in CDCl3,
operating 1H NMR at 59.8 or 500.00 MHz, and 13C NMR at
15.0 or 125.65 MHz, with Me4Si as an internal standard.
Melting points were measured in open capillary tubes and are
uncorrected.
P r ep a r a tion of Dieth yl (E)-2-(Eth oxy)vin ylp h osp h o-
n a te (1c). To a solution of LDA, generated in situ from DIA
(2.7 g, 27 mmol) and n-BuLi (3.04 M in hexane, 7.8 mL, 24
mmol) in THF (50 mL) at -78 °C for 45 min, was added
dropwise diethyl phosphonoacetaldehyde diethyl acetal (6.0 g,
24 mmol) in THF (10 mL), and the reaction mixture was
stirred at this temperature for 1.0 h. The reaction was
quenched by the addition of phosphate buffer (pH ) 7), and
the organic layer was extracted with AcOEt, washed with
brine, dried over Na2SO4, and concentrated in vacuo. The
residue was distilled under reduced pressure (bp 100 °C/1
mmHg) to give 1c (4.8 g, 97%) as a colorless oil; IR (neat) 1610,
1240 cm-1; 1H NMR δ 1.33 (6 H, t, J ) 7.0 Hz), 1.34 (3 H, t, J
Exp er im en ta l Section
Ma ter ia ls. Dichloromethane was distilled from P2O5. THF
was distilled from sodium benzophenone ketyl in a recycling
still. Diisopropylamine (DIA), 2,2,6,6-tetramethylpiperidine
3
) 7.0 Hz), 3.91 (2 H, q, J ) 7.0 Hz), 4.08 (4 H, dq, J P-H ) 2.5
(23) See, for examples, (a) Danishefsky, S. J .; Shair, M. D. J . Org.
Chem. 1996, 61, 16. (b) Nicolaou, K. C.; Dai, W.-M. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1387.
(24) Ishida, N.; Miyazaki, K.; Kumagai, K.; Rikimaru, M. J . Antibiot.
1965, 18, 68.
(25) For palladium-mediated cross-coupling reactions between alk-
enyl halides and terminal alkynes, see, for example; Sonogashira, K.;
Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 50, 4467.
(26) Sonogashira, K. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, Chapter 2.4, p 521.
2
Hz, J ) 7.0 Hz), 4.71 (1 H, dd, J ) 13.7 Hz, J P-H ) 10.1 Hz),
3
7.21 (1 H, dd, J ) 13.7 Hz, J P-H ) 11.6 Hz); 13C NMR δ 14.4,
16.4 (d, 3J P-C ) 6.2 Hz), 61.5 (d, 2J P-C ) 5.2 Hz), 66.3, 88.0 (d,
1J P-C ) 201.5 Hz), 163.3 (d, 2J P-C ) 21.6 Hz); MS m/z 208 (M+).
Anal. Calcd for C8H17O4P: C, 46.15; H, 8.23. Found: C, 46.27;
H, 8.34.
Gen er a l P r oced u r e for th e Syn th esis of r-F u n ction -
a lized P h osp h on ok eten e Dith ioa ceta ls 2-8. To a solution

6244 J . Org. Chem., Vol. 63, No. 18, 1998
Kouno et al.
of LTMP, generated in situ from TMP (0.18 g, 1.3 mmol) and
n-BuLi (1.64 M in hexane, 0.73 mL, 1.2 mmol) in THF (3 mL)
at -78 °C for 40 min, was added dropwise 1a (0.25 g, 1.0 mmol)
in THF (1.5 mL) at -78 °C, and the mixture was stirred for
50 min. An electrophile in THF (1.5 mL) was added dropwise
to the mixture, and the reaction mixture was stirred for 1.0-
3.0 h at this temperature. After similar workup, the residue
was chromatographed on silica gel (AcOEt:hexane ) 4:1) to
give 2-8. The reaction conditions and yields of 2-8 were
summarized in Table 1. The compounds 2 and 4-7 have the
following properties. The properties for compounds 3 and 8
are provided in the Supporting Information.
1.44-1.59 (6 H, m), 2.88-2.95 (4 H, m), 4.02-4.13 (4 H, m);
13C NMR δ 13.8, 14.3, 14.5, 14.8, 16.5 (d, 3J P-C ) 6.2 Hz), 27.4,
29.0, 30.2, 30.4, 61.3 (d, 2J P-C ) 6.2 Hz), 140.9 (d, 1J P-C ) 133.5
Hz), 159.5. Anal. Calcd for C22H47O3PS2Sn: C, 46.08; H, 8.26.
Found: C, 45.72; H, 8.05.
Gen er a l P r oced u r e for th e Syn th esis of r-F u n ction -
a lized Vin ylp h osp h on a tes 11-14. To a solution of LDA (6.0
mmol) in THF (8.0 mL) was added dropwise at -78 °C a
solution of 1c (1.0 g, 5.0 mmol) in THF (4.0 mL), and the
mixture was stirred for 1.0 h. An electrophile was added
dropwise to the mixture, and the reaction mixture was stirred
for 1.5-13.0 h at -78 °C to room temperature. After similar
workup, the residue was chromatographed on silica gel (AcO-
Et:hexane ) 1:1) to give 11-14. The reaction conditions and
yields of 11-14 are summarized in Table 1. The compounds
11, 13, and 14 have the following properties. The properties
for compound 12 are provided in the Supporting Information.
Dieth yl (E)-2-eth oxy-1-(tr im eth ylsilyl)vin ylp h osp h o-
Diet h yl 1-(t r im et h ylsilyl)-1-(1,3-d it h iola n -2-ylid en e)-
m eth ylp h osp h on a te (2): colorless oil; IR (neat) 1460, 1235
1
cm-1; H NMR δ 0.31 (9 H, s), 1.31 (6 H, t, J ) 7.0 Hz), 3.37
(4 H, brs), 4.04 (4 H, dq, J ) 7.0, 7.0 Hz); 13C NMR δ 0.8, 16.2
3
2
(d, J P-C ) 6.0 Hz), 37.6, 38.2, 61.0 (d, J P-C ) 5.2 Hz), 109.3
1
2
(d, J P-C ) 145.2 Hz), 172.1 (d, J P-C ) 3.5 Hz); MS m/z 326
(M+). Anal. Calcd for C11H23O3PS2Si: C, 40.47; H, 7.10.
Found: C, 40.45; H, 7.19.
1
n a te (11): colorless oil; IR (neat) 1600, 1420, 1225 cm-1; H
NMR δ 0.18 (9 H, s), 1.30 (9 H, t, J ) 7.1 Hz), 3.71-4.26 (4 H,
3
Dieth yl 1-(tr im eth ylger m yl)-1-(1,3-d ith iola n -2-ylid en -
e)m eth ylp h osp h on a te (4): colorless crystal; mp 42.5-44.5
m), 4.03 (2 H, q, J ) 7.1 Hz), 7.47 (1 H, d, J
) 16.4 Hz);
P-H
2
13C NMR δ 0.5, 15.1, 16.2 (d, J P-C ) 6.0 Hz), 60.6 (d, J P-C
)
3
°C; IR (KBr) 1475, 1235 cm-1; 1H NMR δ 0.46 (9 H, s), 1.30 (6
5.1 Hz), 69.6, 98.8 (d, 1J P-C ) 155.1 Hz), 170.1 (d, 2J P-C ) 15.5
Hz); MS m/z 280 (M+). Anal. Calcd for C11H25O4PSi: C, 8.99;
H, 47.12. Found: C, 8.75; H, 46.92.
3
H, t, J ) 7.0 Hz), 3.27-3.51 (4 H, m), 4.04 (4 H, dq, J P-H
)
7.0 Hz, J ) 7.0 Hz); 13C NMR δ 1.0, 16.2 (d, J P-C ) 6.2 Hz),
3
2
1
37.3, 38.5, 60.9 (d, J P-C ) 4.9 Hz), 110.4 (d, J P-C ) 153.0
Diet h yl (Z)-1-(t r ib u t ylst a n n yl)-2-(et h oxy)vin ylp h os-
2
Hz), 168.9 (d, J P-C ) 6.2 Hz). Anal. Calcd for C11H23O3PS2-
p h on a te (13): colorless oil; IR (neat) 2925, 1590, 1200 cm-1
;
Ge: C, 35.61; H, 6.25. Found: C, 35.72; H, 6.21.
1H NMR δ 0.89 (9 H, t, J ) 7.4 Hz), 0.92-1.07 (5 H, m), 1.26-
1.35 (16 H, m) 1.41-1.57 (6 H, m), 3.94-4.06 (6 H, m), 7.51 (1
Dieth yl 1-(tr ip h en ylsta n n yl)-1-(1,3-d ith iola n -2-ylid en -
e)m eth ylp h osp h on a te (5): colorless crystal; mp 137.5-138.5
°C; IR (KBr) 1470, 1240 cm-1; 1H NMR δ 1.02 (6 H, t, J ) 7.0
Hz), 2.88-3.48 (4 H, m), 3.52-4.08 (4 H, m), 7.04-7.76 (15
3
3
H, d, J P-H ) 15.0 Hz); 13C NMR δ 10.7 (d, J P-C ) 2.1 Hz),
13.7, 15.3, 16.4 (d, 3J P-C ) 7.2 Hz), 27.3, 28.9, 60.7 (d, 2J P-C
5.2 Hz), 68.9, 98.0 (d, 1J P-C ) 157.2 Hz), 167.8 (d, 2J P-C ) 18.6
Hz). Anal. Calcd for 20H43O4PSn: C, 48.31; H, 8.72.
Found: C, 48.38; H, 8.72.
)
3
H, m); 13C NMR δ 15.9 (d, J P-C ) 6.9 Hz), 38.1, 39.4, 61.2 (d,
C
2J P-C ) 5.2 Hz), 107.7 (d, 1J P-C ) 156.4 Hz), 128.2, 128.7, 136.9,
3
139.5 (d, J P-C ) 1.5 Hz); MS m/z 603 (M+). Anal. Calcd for
Dieth yl (Z)-2-eth oxy-1-(iod o)vin ylp h osp h on a te (14):
1
C
26H29O3PS2Sn: C, 51.76; H, 4.84. Found: C, 51.42; H, 4.97.
yellow oil; IR (neat) 1610, 1395, 1215 cm-1; H NMR δ 1.35-
Diet h yl
1-(m et h ylt h io)-1-(1,3-d it h iola n -2-ylid en e)-
1.41 (9 H, m), 4.01-4.15 (4 H, m), 4.21 (2 H, q, J ) 7.0 Hz),
m eth ylp h osp h on a te (6): colorless oil; IR (neat) 1470, 1240
cm-1; 1H NMR δ 1.35 (3 H, t, J ) 7.2 Hz), 1.36 (3 H, t, J ) 7.0
Hz), 3.14 (3 H, s), 3.38-3.40 (2 H, m), 3.59-3.62 (2 H, m),
7.38 (1 H, d, 3J P-H ) 7.6 Hz); 13C NMR δ 15.3, 16.2 (d, 3J P-C
)
1 2
7.3 Hz), 55.4 (d, J P-C ) 205.86 Hz), 62.4 (d, J P-C ) 5.2 Hz),
70.8, 164.2 (d, 2J P-C ) 29.0 Hz); MS m/z 334 (M+). Anal. Calcd
for C8H16O4PI: C, 28.76; H, 4.83. Found: C, 28.81; H, 4.86.
Gen er a l P r oced u r e for th e F r ied el-Cr a fts Acyla tion
of Vin ylp h osp h on a tes 1a , 2, 4, a n d 9. To a suspension of
AlCl3 (0.27 g, 2.0 mmol) in CH2Cl2 (10 mL) was added dropwise
an acid chloride (2.0 mmol) at 0 °C, and the mixture was
stirred at this temperature for 0.5 h. A solution of a vi-
nylphosphonate 1a , 2, 4 or 9 in CH2Cl2 (5 mL) was added to
the mixture, and the reaction mixture was stirred for 1-3 h.
After similar workup as above, the residue was chromato-
graphed on silica gel (AcOEt:hexane ) 4:1 or 1:1) to give 15-
19. The reaction conditions and yields of 15-19 are sum-
marized in Table 2. The compound 19 has the following
properties. The properties for compounds 15-18 are provided
in the Supporting Information.
3
4.06-4.17 (4 H, m); 13C NMR δ 16.3 (d, J P-C ) 6.2 Hz), 18.7,
2
1
36.3, 41.0, 62.2 (d, J P-C ) 6.3 Hz), 102.1 (d, J P-C ) 203.7
2
Hz), 175.3 (d, J P-C ) 24.8 Hz). Anal. Calcd for C9H17O3PS3:
C, 35.98; H, 5.70. Found: C, 36.03; H, 5.74.
Dieth yl 1-iod o-1-(1,3-d ith iola n -2-ylid en e)m eth ylp h os-
p h on a t e (7): yellow crystal; mp 82-84 °C; IR (KBr) 1480,
1220 cm-1; 1H NMR δ 1.36 (6 H, t, J ) 7.0 Hz), 3.46 (2 H, dd,
J ) 6.5 Hz, J ) 6.0 Hz), 3.86 (2 H, dd, J ) 6.5 Hz, J ) 6.0
3
Hz), 4.03-4.18 (4 H, m); 13C NMR δ 16.2 (d, J P-C ) 7.2 Hz),
37.2, 42.5, 59.3 (d, 1J P-C ) 200.5 Hz), 62.7 (d, 2J P-C ) 5.2 Hz),
2
167.4 (d, J P-C ) 16.5 Hz). Anal. Calcd for C8H14O3PS2I: C,
25.27; H, 3.71. Found: C, 25.28; H, 3.72.
Gen er a l P r oced u r e for th e Syn th esis of r-F u n ction -
a lized P h osp h on ok eten e Dith ioa ceta ls 9 a n d 10.
A
solution of LTMP (1.2 mmol) in THF (3 mL) was added
dropwise to a solution of 1b (0.28 g, 1.0 mmol) and an
electrophile (1.5 mmol) in THF (3 mL) via cannula at -78 °C,
and the reaction mixture was stirred for 1.5 h at this
temperature. After similar workup, the residue was chro-
matographed on silica gel (AcOEt:hexane ) 1:1) to give 9 or
10. The reaction conditions and yields of 9 and 10 are
summarized in Table 1. The compounds 9 and 10 have the
following properties.
Diet h yl 1-b en zoyl-1-[b is(et h ylt h io)m et h ylen e]m et h -
ylp h osp h on a te (19): colorless crystal; mp 66.5-68.0 °C; IR
1
(KBr) 1670, 1520, 1250 cm-1; H NMR δ 1.04 (3 H, t, J ) 7.4
Hz), 1.20 (6 H, t, J ) 7.0 Hz), 1.38 (3 H, t, J ) 7.4 Hz), 2.74 (2
H, q, J ) 7.4 Hz), 2.94 (2 H, q, J ) 7.4 Hz), 4.01-4.16 (4 H,
m), 7.45-7.48 (2 H, m), 7.55-7.59 (1 H, m), 7.99-8.00 (2 H,
3
m); 13C NMR δ 14.7, 14.9, 16.0 (d, J P-C ) 6.2 Hz), 28.9, 62.7
2
1
(d, J P-C ) 6.2 Hz), 128.5, 129.4, 133.4, 136.5, 138.1 (d, J P-C
2
2
) 175.9 Hz), 153.2 (d, J P-C ) 7.3 Hz), 192.2 (d, J P-C ) 10.3
Hz); MS m/z 388 (M+). Anal. Calcd for C17H25O4PS2: C, 52.56;
H, 6.49. Found: C, 52.70; H, 6.51.
Dieth yl 1-[bis(eth ylth io)m eth ylen e]-1-(tr im eth ylsilyl)-
m eth ylp h osp h on a te (9): colorless oil; IR (neat) 1460, 1240
1
cm-1; H NMR δ 0.25 (9 H, d, J ) 4.3 Hz), 1.19-1.30 (12 H,
Gen er al P r ocedu r e for th e P alladiu m -Catalyzed Cr oss-
Cou p lin g Rea ction of Vin ylp h osp h on a te 13 w ith Or -
ga n ic Ha lid es. To a solution of 13 (0.40 g, 0.80 mmol) and
an organic halide in toluene (12 mL) were added Pd(PPh3)4
(38 mg, 4 mol %) and CuCN (6.8 mg, 9 mol %) at room
temperature, and the reaction mixture was refluxed for 1.5-
24 h. The reaction was quenched by the addition of phosphate
buffer (pH ) 7), filtrated through a Celite pad. The organic
layer was extracted with AcOEt, washed with brine, dried over
Na2SO4, and concentrated in vacuo. The residue was chro-
m), 2.75-2.93 (4 H, m), 3.98-4.10 (4 H, m); 13C NMR δ 2.3,
14.1, 14.2, 16.2 (d, 3J P-C ) 7.2 Hz), 30.1, 30.4, 61.1 (d, 2J P-C
6.2 Hz), 134.3 (d, J P-C ) 136.6 Hz), 164.7. Compound 9 was
used without further purification in the next step due to its
instability.
)
1
Dieth yl 1-(tr ibu tylsta n n yl)-1-[bis(eth ylth io)m eth ylen -
e]m eth ylp h osp h on a te (10): colorless oil; IR (neat) 2950,
1
1460, 1230 cm-1; H NMR δ 0.90 (9 H, t, J ) 7.4 Hz), 1.01-
1.17 (6 H, m), 1.26-1.37 (12 H, m), 1.32 (6 H, t, J ) 7.0 Hz),

Utilization of R-Functionalized Vinylphosphonates
J . Org. Chem., Vol. 63, No. 18, 1998 6245
3
1
matographed on silica gel (AcOEt:hexane ) 4:1) to give 21-
26. The reaction conditions and yields of 21-26 are summa-
rized in Table 3. The compounds 21, 22, and 25 have the
following properties. The properties for compounds 23, 24, and
26 are provided in the Supporting Information.
16.4 (d, J
) 7.0 Hz), 28.1 (d, J P-C ) 125.0 Hz), 61.0 (d,
P-C
2J P-C ) 4.1 Hz), 66.1, 67.1 (d, J P-C ) 4.1 Hz).
2
To a solution of 27 (0.83 g, 3.0 mmol) in THF (5 mL) was
added NaOEt (40 mg, 0.59 mmol) in THF (10 mL) at room
temperature. After the reaction mixture was stirred for 10
min at this temperature, the reaction was quenched by the
addition of phosphate buffer (pH ) 7). After usual workup,
the residue was chromatographed on silica gel (AcOEt:hexane
) 2:1) to give a colorless oil (0.56 g, 80%), whose structure
was identified as 28 by comparison of spectral data with those
of an authentic sample:19 IR (neat) 1250, 1030 cm-1; 1H NMR
δ 0.20 (9 H, s), 1.32 (3 H, t, J ) 7.0 Hz), 4.07 (2 H, q, J ) 7.0
Hz), 6.34 (1 H, dd, 3J P-H ) 58.9 Hz, J ) 3.4 Hz), 6.79 (1 H, dd,
Dieth yl (E)-1-ben zoyl-2-(eth oxy)vin ylph osph on ate (21):
1
colorless oil; IR (neat) 1600, 1250 cm-1; H NMR δ 1.15 (3 H,
t, J ) 7.3 Hz), 1.29 (6 H, t, J ) 7.0 Hz), 4.01 (2 H, q, J ) 7.0
2
Hz), 4.13 (4 H, dq, J ) 7.0 Hz, J P-H ) 7.0 Hz), 7.42-7.45 (2
H, m), 7.47 (1 H, d, 3J P-H ) 11.5 Hz), 7.53-7.56 (1 H, m), 7.89
3
(2 H, m); 13C NMR δ 15.0, 16.1 (d, J P-C ) 7.3 Hz), 62.2 (d,
2J P-C ) 5.2 Hz), 71.4, 106.3 (d, 1J P-C ) 188.1 Hz), 128.1, 129.2,
3
2
132.9, 137.5 (d, J P-C ) 4.1 Hz), 163.3 (d, J P-C ) 20.6 Hz),
192.2 (d, J P-C ) 4.1 Hz); MS m/z 312 (M+). Compound 21
was used in the reaction with hydrazine or hydroxylamine
without further purification.
3J P-H ) 34.5 Hz, J ) 3.4 Hz); 13C NMR δ -1.3 (d, J P-C ) 8.5
2
3
3
2
Hz), 16.3 (d, J P-C ) 7.3 Hz), 61.3 (d, J P-C ) 5.2 Hz), 142.1
1 2
(d, J P-C ) 135.5 Hz), 143.9 (d, J P-C ) 4.2 Hz): MS m/z 236
Eth yl (2E)-3-eth oxy-2-(d ieth ylp h osp h on o)p r op en oa te
(22): colorless oil; IR (neat) 1720, 1605, 1190 cm-1; 1H NMR δ
1.30 (3 H, t, J ) 7.0 Hz), 1.33 (6 H, t, J ) 7.0 Hz), 1.41 (3 H,
t, J ) 7.0 Hz), 4.04-4.17 (4 H, m), 4.23 (2 H, q, J ) 7.0 Hz),
(M+).
Gen er a l P r oced u r e for th e Syn th esis of â-F u n ction -
a lized Vin ylp h osp h on a tes 31-34. To a solution of 29 or
30 (0.51 mmol) in THF (10 mL) was added dropwise n-BuLi
(1.68 M in hexane, 0.30 mL, 0.51 mmol) at -78 °C, and then
the mixture was stirred at this temperature for 0.5 h. After
an electrophile (0.77 mmol) in THF (1.0 mL) was added to the
mixture, the reaction mixture was stirred for 0.17-4.0 h at
this temperature. After similar workup, the residue was
purified by preparative TLC (AcOEt:hexane ) 2:1) to give 31-
34. The reaction conditions and yields of 31-34 are sum-
marized in Table 4. The compound 32 and 34 have the
following properties. The properties for compounds 31 and
33 are provided in the Supporting Information.
3
4.25 (2 H, q, J ) 7.0 Hz), 7.58 (1 H, d, J P-H ) 11.0 Hz); 13C
NMR δ 14.1, 15.2, 16.2 (d, 3J P-C ) 6.2 Hz), 60.3, 62.1 (d, 2J P-C
2
1
) 5.3 Hz), 73.0, 98.1 (d, J P-C ) 194.4 Hz), 129.5 (d, J P-C
)
2
261.5 Hz), 170.3 (d, J P-C ) 22.6 Hz). Anal. Calcd for
11H21O6P: C, 47.14; H, 7.55. Found: C, 47.25; H, 7.47.
C
Dieth yl (E)-2-eth oxy-1-(2′-for m ylp h en yl)vin ylp h osp h o-
n a te (25): yellow oil; IR (neat) 1695, 1620, 1220 cm-1; 1H NMR
δ 1.23 (3 H, t, J ) 7.5 Hz), 1.26 (6 H, t, J ) 7.0 Hz), 4.04 (2 H,
q, J ) 7.5 Hz), 4.05-4.11 (4 H, m), 7.35-7.44 (3 H, m), 7.53-
3
7.60 (1 H, m), 7.95 (1 H, d, J P-H ) 8.0 Hz), 10.08 (1 H, s); 13
C
NMR δ 15.2, 16.2 (d, 3J P-C ) 7.3 Hz), 61.9 (d, 2J P-C ) 6.3 Hz),
Diet h yl 3-b en zoyl-6,7-d ih yd r o-5H -1,4-d it h iep in -2-yl-
1
4
1
70.7, 101.7 (d, J P-C ) 198.4 Hz), 127.3, 127.9 (d, J P-C ) 2.1
p h osp h on a te (32): yellow oil; IR (neat) 1670, 1250 cm-1; H
Hz), 130.9 (d, 3J P-C ) 3.1 Hz), 133.7, 134.0 (d, 2J P-C ) 6.2 Hz),
NMR δ 1.19 (6 H, t, J ) 7.2 Hz), 2.28 (2 H, tt, J ) 5.8, 5.8 Hz),
3.42 (2 H, t, J ) 5.8 Hz), 3.47 (2 H, t, J ) 5.8 Hz), 3.93-4.07
(4 H, m), 7.46 (2 H, t, J ) 8.0 Hz), 7.54-7.57 (1 H, m), 7.92-
3
2
136.1 (d, J P-C ) 5.2 Hz), 160.0 (d, J P-C ) 26.8 Hz), 192.2;
MS m/z 312 (M+). Compound 25 was used in the reaction with
hydroxylamine without further purification.
7.93 (2 H, m); 13C NMR δ 16.1 (d, J P-C ) 6.2 Hz), 30.5, 32.1,
3
3
2
Rea ction of 11 w ith Lith iu m Eth a n eth iola te. A solu-
tion of lithium ethanethiolate, generated in situ from ethaneth-
iol (40 mg, 0.64 mmol) in THF (3.0 mL) and n-BuLi (1.60 M
in hexane, 0.40 mL, 0.64 mmol) at -78 °C for 1.0 h, was added
dropwise to a solution of 11 (0.15 g, 0.53 mmol) in THF (2.0
mL) via cannula. After being stirred for 10 min at this
temperature, the mixture was then allowed to warm to room
temperature and stirred for 3.0 h. After similar workup, the
residue was purified by preparative TLC (AcOEt:hexane ) 2:1)
to give diethyl (E)- and (Z)-2-(ethylthio)-1-(trimethylsilyl)-
vinylphosphonates [(E)-20 (0.12 g, 76%) and (Z)-20 (33 mg,
20%)].
32.7 (d, J P-C ) 5.2 Hz), 63.0 (d, J P-C ) 5.2 Hz), 126.4 (d,
1J P-C ) 184.1 Hz), 128.5, 129.6, 133.3, 135.0, 150.2 (d, J P-C
2
) 17.6 Hz), 191.4 (d, 3J P-C ) 6.3 Hz); MS m/z 372 (M+). Anal.
Calcd for C16H21O4PS2: C, 51.60; H, 5.68. Found: C, 51.40;
H, 5.84.
Dieth yl 3-(tr ibu tylsta n n yl)-6,7-d ih yd r o-5H-1,4-d ith i-
ep in -2-ylp h osp h on a te (34): yellow oil; IR (neat) 2950, 1230
cm-1; 1H NMR δ 0.90 (9 H, t, J ) 7.3 Hz), 1.01-1.15 (6 H, m),
1.32 (6 H, tt, J ) 7.3, 7.3 Hz), 1.35 (6 H, t, J ) 7.0 Hz), 1.45-
1.65 (6 H, m), 2.18 (2 H, tt, J ) 6.1, 6.1 Hz), 3.50 (2 H, t, J )
6.1 Hz), 3.61 (2 H, t, J ) 6.1 Hz), 4.01-4.11 (4 H, m); 13C NMR
3
δ 13.7, 14.9, 16.3 (d, J P-C ) 6.2 Hz), 27.4, 28.9, 29.1, 32.3,
3
2
(E)-20: colorless oil; Rf 0.43 (AcOEt:hexane ) 5:1); IR (neat)
1243, 1025 cm-1; 1H NMR δ 0.27 (9 H, s), 1.30 (6 H, t, J ) 7.0
Hz), 1.35 (3 H, t, J ) 7.4 Hz), 2.87 (2 H, q, J ) 7.4 Hz), 3.97-
34.4 (d, J P-C ) 4.1 Hz), 62.1 (d, J P-C ) 5.2 Hz), 119.5 (d,
1J P-C ) 203.6 Hz), 163.8 (d, 2J P-C ) 36.2 Hz); MS m/z 557 (M+).
Anal. Calcd for C21H43O3PS2Sn: C, 45.25; H, 7.78. Found:
C, 45.01; H, 7.60.
3
4.07 (4 H, m), 8.11 (1 H, d, J P-H ) 31.8 Hz); 13C NMR δ -0.7
3
3
(d, J P-C ) 3.1 Hz), 15.6, 16.4 (d, J P-C ) 6.2 Hz), 29.6, 61.2
(d, 2J P-C ) 5.2 Hz), 122.1 (d, 1J P-C ) 138.6 Hz), 162.1 (d, 2J P-C
) 4.1 Hz).
Gen er al P r ocedu r e for th e P alladiu m -Catalyzed Cr oss-
Cou p lin g Rea ction of Vin ylp h osp h on a te 34 w ith Or -
ga n ic Ha lid es. The reaction of 34 (0.57 g, 1.0 mmol) with
an organic halide (1.5 mmol) was performed in the presence
of Cl2Pd(PPh3)2 (29 mg, 4 mol %) and CuCN (13 mg, 14 mol
%) in toluene (17 mL) with stirring at 50 °C for 1.0-1.5 h,
After workup similar to that described in the reaction of 13
with organic halides, the residue was purified by preparative
TLC (AcOEt:hexane ) 2:1) to give 32, 35, and 36. The reaction
conditions and yields of 32, 35, and 36 are summarized in
Table 5. Compound 32 has physical data identical with those
of 32 obtained in the above experiment, and the properties
for compound 35 and 36 are provided in the Supporting
Information.
Rea ction of 25 w ith Hyd r oxyla m in e. The reaction was
carried out at room temperature for 60 h with 25 (82 mg, 0.26
mmol), hydroxylamine hydrochloride (36 mg, 0.52 mmol), and
Et3N (52 mg, 0.52 mmol) in EtOH (5.0 mL). After similar
workup, the residue was purified by preparative TLC (AcOEt:
MeOH ) 15:1) to give 4-(diethylphosphono)isoquinoline N-
oxide (40) (62 mg, 85%) as a yellow oil: IR (neat) 1330, 1230
cm-1; 1H NMR δ 1.37 (6 H, t, J ) 7.1 Hz), 4.18-4.30 (4 H, m),
7.68-7.73 (2 H, m), 7.78-7.80 (1 H, m), 8.44-8.46 (1 H, m),
(Z)-20: colorless oil; Rf 0.64 (AcOEt:hexane ) 5:1); IR (neat)
1245, 1027 cm-1;1H NMR δ 0.19 (9 H, s), 1.32-1.35 (9 H, m),
2.81 (2 H, q, J ) 7.7 Hz), 4.08 (4 H, q, J ) 7.0 Hz), 7.35 (1 H,
3
3
d, J P-H ) 55.6 Hz); 13C NMR δ 0.6 (d, J P-C ) 2.0 Hz), 15.3,
3
2
16.4 (d, J P-C ) 7.3 Hz), 29.8, 61.2 (d, J P-C ) 6.2 Hz), 123.8
1
2
(d, J P-C ) 143.6 Hz), 157.9 (d, J P-C ) 5.2 Hz); MS m/z 296
(M+). Compounds (E)- and (Z)-20 gave no satisfactory elemen-
tal analysis data due to their high viscosity.
Syn th esis of Dieth yl 1-(Tr im eth ylsilyl)vin ylp h osp h o-
n a te (28) via 11. Hydrogenation of 11 (1.0 g, 3.6 mmol) was
accomplished under a hydrogen atmosphere (balloon) at room
temperature for 48 h in MeOH (8.0 mL) containing palladium
on activated carbon (10%, 0.50 g). After removal of the catalyst
by filtration and concentration of the filtrate in vacuo, the
residue was distilled under reduced pressure to give 27 (1.0
g, 99%) as a colorless oil; bp 95-98 °C/0.6 mmHg; IR (neat)
1245, 1030 cm-1; 1H NMR δ 0.16 (9 H, s), 1.18 (3 H, t, J ) 7.0
2
Hz), 1.31 (6 H, t, J ) 7.0 Hz), 1.59 (1 H, dt, J P-H ) 23.8 Hz,
J ) 6.7 Hz), 3.45 (2 H, q, J ) 7.0 Hz), 3.62-3.79 (2 H, m),
3
4.02-4.12 (4 H, m); 13C NMR δ -0.8 (d, J P-C ) 3.1 Hz), 15.1,

6246 J . Org. Chem., Vol. 63, No. 18, 1998
Kouno et al.
3
8.64 (1 H, dd, J ) 2.0 Hz, J P-H ) 12.0 Hz), 8.87 (1 H, s,); 13
C
mg, 0.37 mmol) in 3.0 mL of dry pyridine/EtOH (1:1) was
added a solution of 45 (24 mg, 0.086 mmol) in THF (1.5 mL)
at room temperature, and the reaction mixture was stirred at
70 °C for 30 min. After usual workup, the residue was purified
by preparative TLC (AcOEt:MeOH ) 15:1) to give 46 (22 mg,
93%) as a yellow crystal: mp 151.5-152.5 °C; IR (KBr) 1470,
1230 cm-1; 1H NMR δ 1.36 (12 H, t, J ) 7.0 Hz), 3.45-3.49 (4
H, m), 3.55-3.58 (4 H, m), 4.08-4.20 (8 H, m); 13C NMR δ
16.3 (d, J P-C ) 7.5 Hz), 37.2, 40.6 62.9 (d, J P-C ) 6.3 Hz),
82.1 (d, 3J P-C ) 5.2 Hz), 82.2 (d, 2J P-C ) 8.3 Hz), 94.1 (d, 1J P-C
) 201.7 Hz), 175.9 (d, 2J P-C ) 14.5 Hz); MS m/z 554 (M+). Anal.
Calcd for C20H28O6P2S4: C, 43.31; H, 5.09. Found: C, 43.19;
H, 5.09.
NMR δ 16.2 (d, 3J P-C ) 6.2 Hz), 63.3 (d, 2J P-C ) 6.2 Hz), 124.7
1
2
(d, J P-C ) 184.0 Hz), 125.6, 125.6, 127.8 (d, J P-C ) 7.3 Hz),
2
129.9, 123.0, 130.1, 139.1, 142.1 (d, J P-C ) 15.6 Hz); MS m/z
281 (M+). The compound 40 gave no satisfactory elemental
analysis data due to its high viscosity.
Gen er al P r ocedu r e for th e P alladiu m -Mediated Cr oss-
Cou p lin g Rea ction of Vin ylp h osp h on a te 7 w ith Ter m i-
n a l Acetylen es. After a solution of PdCl2 (10 mg, 18 mol %)
and PPh3 (38 mg, 46 mol %) in THF (3 mL) was stirred at
room temperature for 10 min, CuI (74 mg, 0.39 mmol), Et3N
(0.37 g, 3.7 mmol), 7 (0.12 g, 0.31 mmol) in THF (1 mL), and
a solution of an acetylene (0.69 mmol) in THF (2 mL) was
added to the solution in turn. The reaction mixture was stirred
at this temperature for 24-60 h. The reaction was quenched
by the addition of phosphate buffer (pH ) 7), filtrated through
a Celite pad. The organic layer was extracted with AcOEt,
washed with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by preparative TLC (AcOEt:
hexane ) 2:1) to give 41-43. The reaction conditions and
yields of 41-43 are summarized in Table 6. Compound 42
has the following properties. The properties for compounds
41 and 43 are provided in the Supporting Information.
Diet h yl 3-(t r im et h ylsilyl)-1-(1,3-d it h iola n -2-ylid en e)-
2-p r op yn ylp h osp h on a te (42): colorless crystal; mp 47.5-
48.5 °C; IR (KBr) 2130, 1480, 1240 cm-1; 1H NMR δ 0.21 (9 H,
3
2
Ack n ow led gm en t. We are grateful for financial
support of this work by a Grant-in-Aid for Scientific
Research on Priority Areas (07216256) from the J apan
Ministry of Education, Science and Culture and by the
C.O.E. Research Fund of KIT. We also thank the Center
for Instrumental Analysis KIT for the use of their
facilities.
Su p p or tin g In for m a tion Ava ila ble: Spectral and ana-
lytical data for compounds 3, 8, 12, 15-18, 23, 24, 26, 31, 33,
35-39, 41, and 43-45 (36 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
s), 1.35 (6 H, t, J ) 7.0 Hz), 3.41-3.57 (4 H, m), 4.13 (4 H, dq,
3J P-H ) 7.3 Hz, J ) 7.0 Hz); 13C NMR δ 0.2, 16.1 (d, J P-C
)
)
3
2
1
6.8 Hz), 36.8, 40.5, 62.5 (d, J P-C ) 6.1 Hz), 95.0 (d, J P-C
193.4 Hz), 101.7 (d, 3J P-C ) 8.6 Hz), 102.6 (d, 2J P-C ) 6.9 Hz),
173.4 (d, J P-C ) 13.8 Hz); MS m/z 350 (M+); HRMS calcd for
2
C
13H23O3SiPS2 350.0595, found 350.0602.
Tetr aeth yl 1,6-Bis(1,3-dith iolan -2-yliden e)-2,4-h exadiyn -
1,6-d iyld ip h osp h on a te (46). To a solution of Cu(OAc)2 (67
J O980467G