New allylphosphonates derived from (OCH2CMe2CH2O)PCl and Baylis-Hillman adducts - Stereochemistry and utility

Article abstract of DOI:10.1055/s-2002-34899

New allylphosphonates have been prepared; an X-ray structural proof for the major Z-isomer has been given for phosphonate 3. Horner-Wadsworth-Emmons reaction of 3 or 6 (Z isomer) with aromatic aldehydes leads to carbomethoxy/ cyano substituted butadienes. In the reaction using cyanoallylphosphonate 6, use of either Z or E isomer leads to the same E,Z product; stereochemistry of one such cyano product is confirmed by X-ray crystallography. In the reaction of 3 with 4-nitrobenzaldehyde stereochemistry for the (E,E) isomer is confirmed by X-ray crystallography.

Full text of DOI:10.1055/s-2002-34899

LETTER
1787
New Allylphosphonates Derived from (OCH2CMe2CH2O)PCl and
Baylis–Hillman Adducts – Stereochemistry and Utility
A
llylphosphonate
.
s
D
erived fr
M
om Baylis–Hillman A
d
u
ducts thiah,a K. Senthil Kumar,a J. J. Vittal,b K. C. Kumara Swamy*a
a
School of Chemistry, University of Hyderabad, Hyderabad- 500046, A. P., India
Fax +91(40)3012460; E-mail: kckssc@uohyd.ernet.in
b
Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543 Singapore
Received 2 September 2002
Abstract: New allylphosphonates have been prepared; an X-ray
structural proof for the major Z-isomer has been given for phospho-
nate 3. Horner–Wadsworth–Emmons reaction of 3 or 6 (Z isomer)
with aromatic aldehydes leads to carbomethoxy/ cyano substituted
butadienes. In the reaction using cyanoallylphosphonate 6, use of
either Z or E isomer leads to the same E,Z product; stereochemistry
of one such cyano product is confirmed by X-ray crystallography.
In the reaction of 3 with 4-nitrobenzaldehyde stereochemistry for
the (E,E) isomer is confirmed by X-ray crystallography.
Key words: allylphosphonates, Baylis–Hillman adducts, 2-substi-
tuted butadienes, Horner–Wadsworth–Emmons reaction
Scheme 1
Synthesis of the phosphonates is accomplished by using
allylic type rearrangement of the allylphosphites 2
[Scheme 2; Table 1].6–8 In the case of 2-carbomethoxy
compounds 3–5, the Z-isomer is obtained as the most pre-
dominant/ exclusive isomer; the stereochemistry has been
proven by an X-ray structure determination for the major
isomer of 3 (Figure 1). In the case of 2-cyanoallylphos-
phonates 6–8, both Z and E isomers are obtained in com-
parable quantities when the corresponding allylphosphite
was heated under neat conditions. In the case of 6 we have
isolated both the E and Z isomers as crystalline solids.
The enormous synthetic utility of organophosphonates as
Horner–Wadsworth–Emmons (HWE) reagents has been
abundantly exploited in synthetic organic chemistry and
hence there is always scope for developing new phospho-
nates or improving the existing methodology for their syn-
thesis.1 In view of the ease of synthesis, cost-effectiveness
and stability (towards oxidation) of the cyclic chlorophos-
phite (OCH2CMe2CH2O)PCl (1),2 we became interested
in utilizing this compound to obtain synthetically useful
phosphonates. In one approach we utilized the Pudovik
product of the phosphite (OCH2CMe2CH2O)P(O)H
(readily obtained from the hydrolysis of 1) with an alde-
hyde and in the second one, we directly used the reaction
of 1 and its substituted products [P-Cl or P(O)H P-OR
or P-NMe2] with suitable aldehydes (Scheme 1).2–4 Here-
in we report (i) the synthesis of phosphonates derived
from 1 and the Baylis–Hillman adducts of an aldehyde
with acrylonitrile or methylacrylate5 and (ii) utility of
these phosphonates in HWE reactions. We also give the
structural proof for the stereochemistry of one of the phos-
phonates and two of the HWE products, thus facilitating
structural assignment in future work. The phosphonates
synthesized here can be attractive reagents for further re-
actions in view of their facile and economic synthesis cou-
pled with the presence of functional groups.
Scheme 2
We have also isolated the intermediate allylphosphites 2
[R = H; X = CO2Me, Ar = Ph (a) or C6H4-4-Me (b), X =
CN, Ar = Ph (c) or C6H4-4-Me (d); (P) for these 120.7
0.1)] in a spectroscopically pure state. The rearrangement
of 2c in toluene at 70 °C is essentially complete in 1 h and
no intermediate could be detected [31P NMR]. Interesting-
ly, the intensity of the downfield isomer relative to the up-
field one increases with time.
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1787,1790,ftx,en;D16002ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1788
C. Muthiah et al.
LETTER
Table 1 Phosphonates 3–8 Isolated in the Present Study (cf Scheme 2)a
Compd
Ar
X
R
Z/E
95:5
Yield (%)
(P)
3
4
5
6
7
8
Ph
CO2Me
CO2Me
CO2Me
CN
H
90
89
87
80
81
96
21.1, 18.2
21.3
C6H4-4-Me
C6H4-4-OMe
Ph
H
100:0
100:0
50:50
60:40
40:60
H
21.3
H
17.8, 17.6
18.0, 17.7
17.0, 15.8
C6H4-4-Me
Ph
CN
H
CN
CO2Et
a Chemical shifts are referenced to ext. 85% H3PO4. We observed a dependence of (P) value for the phosphonates on the concentration to an
extent of 1 ppm.
The Z isomer of allylphosphonate 3 (X-ray; Figure 111,12
and the E isomer of 6 (assignment tentative; see below)
were employed to prepare 2-substituted-1,3-butadienes
11a–d and 12a–e by the HWE reaction (Scheme 4;
Table 2).13 The stereochemistry at the newly formed dou-
ble bond was essentially E, with 5% of a second isomer
)
1
in the case of 11a, 11b, 11d and 12e, based on the H
NMR spectra of the reaction mixtures. The 3J(H-H) value
16–18 Hz for the protons at the newly formed double bond
is also consistent with this. For 11d the stereochemistry is
proven by X-ray structural analysis.11,12 The E stereo-
chemistry at the newly formed double bond and the Z con-
figuration at the existing double bond for the cyano
system is convincingly proven by an X-ray structure de-
termination of 12b.11,12
Figure 1 An ORTEP drawing of 3 [Z isomer]. Selected bond di-
stances: P-O(1) 1.544(2), P-O(2) 1.554(2), P-O(3) 1.433(3), P-C(6)
1.777(3), C(6)-C(7) 1.488(4), C(7)-C(8) 1.326(4).
In view of a recent report on the facile conversion of allyl
alcohols I to cinnamyl alcohols II,9 we felt that substituted
cinnamyl phosphite 9 derived from II (Ar = Ph) also can
lead to phosphonates 10 (Scheme 3).10 However, under
the conditions analogous to those used to prepare 3–8, this
rearrangement did not take place, probably because of
greater steric factors at the terminal CH(Ph) end of the
double bond and the non-availability of a convenient
transition state. Upon heating 9 at 170 °C, however, for-
mation of a mixture of phosphonates [31P NMR] was
noticed and 10 could be isolated in low yields.
Scheme 4
In the case of 6, from the HWE reaction using the second
isomer (assigned Z stereochemistry) and 4-chlorobenzal-
dehyde, we again obtained 12b as the only isolable prod-
Scheme 3
1
uct [IR, TLC, mp, H and 13C NMR]. This result is
different from that reported before by Janecki.14 There is
Synlett 2002, No. 11, 1787–1790 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Allylphosphonates Derived from Baylis–Hillman Adducts
1789
Table 2 Details on the Synthesis of 2-Substituted-1,3-butadienesa
(11d and 12b). The use of NaH by us, in place of LDA
used by Janecki and Bodalski,14 has probably avoided
the formation of other phosphonate side products. In
addition (as noted above), since the precursor
(OCH2CMe2CH2O)PCl (1) is readily prepared and more
convenient to handle than (EtO)2PCl, our phosphonates
are relatively easier to prepare and are cost effective; the
yields are also quite high. Given the synthetic potential of
both Baylis–Hillman and HWE reactions, we believe that
the results reported here are quite significant and useful.
Entry
R
R′
Product
11a
Yield (%)
1
2
3
4
5
6
7
8
9
H
H
Cl
H
H
H
H
Cl
H
H
80
80
85
90
92
94
90
94
90
Cl
11b
11c
Cl
NO2
H
11d
12a
Cl
12b
12c
Acknowledgement
OMe
Cl
We thank the Council of Scientific and Industrial Research for
financial support and Department of Science and Technology for
setting up of the National Single Crystal Diffractometer Facility at
the University of Hyderabad.
12d
12e
CH3
a Isolated yields after column chromatography.
References
(1) Selected references: (a) Arai, T.; Sasai, H.; Yamaguchi, K.;
Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 441. (b) Arai,
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(e) Tullis, J. S.; Vares, L.; Kann, N.; Norrby, P.-O.; Rein, T.
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Sun, J. J. Chem. Soc., Perkin Trans. 1 1999, 509. (g) Iorga,
B.; Eymery, F.; Savignac, P. Synthesis 2000, 576. (h) Tago,
K.; Kogen, H. Org. Lett. 2000, 2, 1975. (i) Sun, S.; Turchi,
I. J.; Xu, D.; Murray, W. V. J. Org. Chem. 2000, 65, 2555.
(j) Vaes, L.; Rein, T. Org. Lett. 2000, 2, 2611. (k) Reiser,
U.; Jauch, J. Synlett 2001, 90. (l) Crist, R. M.; Reddy, P. V.;
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possibly a delocalization of the negative charge in the
phosphonate anion [cf. structures III and IV (Figure 2),
which are the extreme resonance canonicals]. Although
this feature is possible for carbomethoxy derivatives also,
we were not able to verify this because the second isomer
is not formed in significant quantities. However, as re-
gards the synthesis of 2-substituted-1,3-butadienes that
may be valuable precursors for Diels–Alder reactions, our
phosphonates appear to be better than those available pre-
viously in view of the ease of preparation.13
(2) Muthiah, C.; Praveen Kumar, K.; Aruna Mani, C.; Kumara
Swamy, K. C. J. Org. Chem. 2000, 65, 3733.
Figure 2
(3) Kumaraswamy, S.; Selvi, R. S.; Kumara Swamy, K. C.
Synthesis 1997, 207.
(4) Praveen Kumar, K.; Muthiah, C.; Kumarswamy, S.; Kumara
Swamy, K. C. Tetrahedron Lett. 2001, 42, 3219.
(5) Selected references: (a) Review: Basavaiah, D.; Rao, P. D.;
Hyma, R. S. Tetrahedron 1996, 52, 8001. (b) Basavaiah,
D.; Pandiaraju, S. Tetrahedron 1996, 52, 2261.
An analogous reaction of phosphonate 8 (E/Z 1:1) with p-
chlorobenzaldehyde gave 13 (Figure 3) as a mixture of
(EE/EZ) isomers in 1:1 ratio. This result is in consonance
with that described above assuming that the stereochem-
istry at the newly formed double bond is E.
(c) Aggarwal, V. K.; Mereu, A.; Tarver, G. J.; McCague, R.
J. Org. Chem. 1998, 63, 7183. (d) Hayase, T.; Shibata, T.;
Soai, K.; Wakatsuki, Y. Chem. Commun. 1998, 1271.
(e) Shi, M.; Jiang, J.-K.; Feng, Y.-S. Org. Lett. 2000, 2,
2397. (f) Basavaiah, D.; Kumaragurubaran, N.; Sharada, D.
S. Tetrahedron Lett. 2001, 42, 85.
(6) Janecki, T.; Bodalski, R. Synthesis 1990, 799.
(7) The Baylis–Hillman adducts ArC(R)(OH)-C(X)=CH2 were
prepared by literature methods.5a
Figure 3
(8) Typical procedure for 6: To a stirred solution of
(Ph)CH(OH)-C(CN)=CH2 (1.50 g, 9.5 mmol) and Et3N
(0.96 g, 9.5 mmol) in toluene (50 mL),
In a previous study, Janecki noted that it was not possible
to make unambiguous configurational assignments based
on the spectroscopic data for the mixtures of 2-cyano-
butadienes. In our case, using a pure isomer of phospho-
nate, the configurational assignment of the products has
been made based on the X-ray structure determination of
the carbomethoxy phosphonate (3) and the HWE products
(OCH2CMe2CH2O)PCl(1) (1.6 g, 9.5 mmol) was added
dropwise at 0 °C under nitrogen; stirring was continued for
30 min. The precipitate was filtered off, washed with diethyl
ether, and the washings added to the filtrate. The combined
filtrate was evaporated to dryness and the residue was heated
at 110 °C under nitrogen for 3 h by which time rearrange-
Synlett 2002, No. 11, 1787–1790 ISSN 0936-5214 © Thieme Stuttgart · New York

1790
C. Muthiah et al.
LETTER
Hz, 2 H, OCH2), 4.13 [d, 3J(PH) ~ 20.0 Hz, 1 H, OCH2],
ment had taken place. The isomers of compound 6 (~1:1;
total yield 80%) so obtained were separated by column
chromato-graphy (hexane–ethyl acetate). Isomer a (higher
Rf): mp 114–116 °C; IR (cm–1) 2212, 1604; 1H NMR 1.05,
1.14 (2 s, 6 H, 2 CH3), 3.08 [d, 2J(PH) = 22.2 Hz, 2 H, PCH2],
3.89–4.30 (m, 4 H, OCH2), 7.39–7.54 (m, 6 H, olefinic-H +
Ar-H); 13C NMR 21.4, 21.5, 27.0 [d, 1J(PC) = 139.0 Hz],
32.6 [d, 3J(PC) = 6.2 Hz], 75.7 [d, 2J(PC) = 6.2 Hz], 104.5,
4.15–4.30 (~m, 2 H, OCH2), 6.20 and 6.41 (2 d, 2J ~ 1.5 Hz,
CH2=C), 7.25–7.55 (m, 5 H, 5 H, Ar-H); 13C NMR 21.3,
21.5, 32.6 [d, 3J(PC) = 6.0 Hz], 47.7 [d, 1J(PC) = 137.0 Hz,
CHPh], 76.2 [d, 2J(PC) = 20.5 Hz], 117.7 (d, J = 10.0 Hz),
118.9, 128.5, 129.0, 129.4, 129.6, 132.9 (J = 6.5 Hz), 134.8
(J = 8.0 Hz); 31P NMR 14.6.
(11) X-ray data were collected on an Enraf-Nonius-MACH3 at
293 K (3, 12b) or Bruker AXS SMART diffractometer at
296 K(11d) using Mo-K ( = 0.71073 Å) radiation and
capillary mounting. The structures were solved by direct
methods;12 all non-hydrogen atoms were refined
anisotropically. The quality of data of 11d was only
moderate but the stereochemistry is unambiguous.
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 190318 – 190320. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax:
+44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
ORTEP drawings of 11d and 12b are available from the
authors.
104.8, 119.5, 128.8, 129.1, 130.0, 132.9, 148.1, 148.3; 31
NMR 17.6. Anal. Calcd for C15H18NO3P: C, 61.84; H,
P
6.24; N, 4.81. Found: C, 61.76; H, 6.18; N, 4.74. Isomer b
(lower Rf): Mp 128–130 °C; 1H NMR 1.03, 1.07 (2 s, 6 H,
2 CH3), 3.01 [d, 2J(PH) = 21.3 Hz, 2 H, PCH2], 3.85–4.22
(m, 4 H, OCH2), 7.10–7.90 (m, 6 H, olefinic-H + Ar-H); 13
C
NMR 21.4, 31.6 [d, 1J(PC) = 138.0 Hz], 32.5 [d, 3J(PC) =
6.2 Hz], 75.6 [d, 2J(PC) = 6.2 Hz], 100.1, 100.3, 118.0,
128.8, 130.6, 133.1, 148.0, 148.2; 31P NMR 17.8. Anal.
Calcd for C15H18NO3P: C, 61.84; H, 6.24; N, 4.81. Found: C,
61.66; H, 6.16; N, 4.70. The HWE reactions of the
phosphonates with the aldehydes were conducted in THF
using NaH as the base (supplementary material is available
from the authors).
(9) Basavaiah, D.; Kumaragurubaran, N.; Padmaja, K. Synlett
1999, 1630.
(12) Sheldrick, G. M. SHELX-97; University of Göttingen:
Germany, 1997.
(10) Spectral data for compound 9 (mp 70–72 °C): 1H NMR
0.78, 1.28 (2s, 6 H, 2 CH3), 3.40 (~t, 2J ~ 3J ~ 10.2 Hz, 2 H,
OCH2), 4.24 (d, 3J ~ 10.2 Hz, 2 H, OCH2), 4.56 [dd, 3J(PH)
~ 10.2 Hz, 4J(HH) ~ 1.0 Hz, 2 H, OCH2], 7.21 [s, 1 H,
CH=C(CN)], 7.41–7.82 (m, 5 H, Ar-H); 13C NMR 22.3,
22.7, 32.7 [d, 2J(PC) = 5.0 Hz], 64.2 [d, 2J(PC) = 20.5 Hz],
69.2, 108.6, 117.4, 128.2, 128.9, 129.0, 130.8, 132.8, 144.7;
31P NMR 121.7. Compound 10 (mp: 168–170 °C). 1H
NMR 0.95, 1.05 (2 s, 6 H, 2 CH3), 3.75 (~t, 2J ~ 3J ~ 12.0
(13) Other reports on the synthesis of 2-substituted-1,3-
butadienes: (a) Nakano, M.; Okamoto, Y. Synthesis 1983,
917. (b) Shen, Y.; Ni, J. J. Chem. Res. Synop. 1997, 358.
(c) Lee, B. S.; Gil, J. M.; Oh, D. Y. Tetrahedron Lett. 2001,
42, 2345.
(14) (a) Janecki, T. Synthesis 1991, 167. (b) Janecki, T.;
Bodalski, R. Synthesis 1989, 506.
Synlett 2002, No. 11, 1787–1790 ISSN 0936-5214 © Thieme Stuttgart · New York