Direct synthesis of α-substituted phosphonates

Article abstract of DOI:10.1016/S0040-4039(01)00399-9

The α-substituted phosphonates (OCH₂CMe₂CH₂O)P(O)CH(X)(Ar) [X=Cl, OMe, NMe₂ and OSiMe₃], useful precursors for Horner-Wadsworth-Emmons reactions, are readily prepared by treating (OCH₂CMe₂CH₂O)PX with an aromatic aldehyde. In the reaction of (OCH₂CMe₂CH₂O)PCl with furfuraldehyde and cinnamaldehyde, the 5-chlorofurfurylphosphonate (OCH₂CMe₂CH₂O)P(O)CH₂ (5-Cl-C₄H₂O) and the γ-chlorophosphonate (OCH₂CMe₂CH₂O)P(O)CH=CH-CH(Cl)Ph, respectively, are formed in good yields.

Full text of DOI:10.1016/S0040-4039(01)00399-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3219–3221
Direct synthesis of a-substituted phosphonates
K. Praveen Kumar, C. Muthiah, Sudha Kumaraswamy and K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Received 23 October 2000; revised 19 February 2001; accepted 8 March 2001
Abstract—The a-substituted phosphonates (OCH2CMe2CH2O)P(O)CH(X)(Ar) [X=Cl, OMe, NMe2 and OSiMe3], useful precur-
sors for Horner–Wadsworth–Emmons reactions, are readily prepared by treating (OCH2CMe2CH2O)PX with an aromatic
aldehyde. In the reaction of (OCH2CMe2CH2O)PCl with furfuraldehyde and cinnamaldehyde, the 5-chlorofurfurylphosphonate
(OCH2CMe2CH2O)P(O)CH2(5-Cl-C4H2O) and the g-chlorophosphonate (OCH2CMe2CH2O)P(O)CHꢀCH-CH(Cl)Ph, respec-
tively, are formed in good yields. © 2001 Published by Elsevier Science Ltd.
Phosphonates are popular precursors in organic synthe-
sis for CꢁC bond forming reactions and, hence, new
reagents that will be useful for specific synthetic goals
are still being discovered.1–3 The a-substituted phospho-
nates (RO)2P(O)CH(X)Ar constitute a subclass of
phosphonates having the advantage of the additional
functional group ‘X’ already being incorporated. Two
general routes have been reported for the synthesis of
such phosphonates, where X is a halogen (cf. Scheme
1).2–4
and an aldehyde ArCHO, formed by a modified
Abramov reaction. Since the compound (OCH2CMe2-
CH2O)PX (7a: X=Cl) is conveniently prepared, cheap
and amenable to substitution (by OR, NRR%, etc.), we
felt that under suitable conditions, various a-substi-
tuted phosphonates may be directly accessible using this
as a precursor. The six-membered ring in 7 normally
remains intact and, hence, side reactions occur less
often when using these compounds. In this paper, we
report the use of 7 in the synthesis of various a-substi-
tuted phosphonates that have high potential for use in
Horner–Wadsworth–Emmons reactions (see Scheme 2
and Table 1).1h,8–10
For the synthesis of compounds (RO)2P(O)CH(X)Ar
(I), where X is a group other than a halogen, a proce-
dure that uses a common, readily accessible precursor is
not available.5–8 Species I can be regarded as an addi-
tion product of the corresponding phosphite (RO)2PX
The precursors 7 [X=Cl (a),11 OMe (b),12 NMe2 (c)13]
were prepared by literature procedures; compound 7d
Scheme 1.
Keywords: phosphonates; Abramov reaction.
* Corresponding author. Fax: +91-40-3012460; e-mail: kckssc@uohyd.ernet.in
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00399-9

3220
K. Pra6een Kumar et al. / Tetrahedron Letters 42 (2001) 3219–3221
2. The yield of a-chlorophosphonates 2 was only mod-
erate under the conditions employed. As explained
elsewhere,16 several products are possible in these
reactions, one of them being 2. Isolation of 2 is
facilitated in our case as they are stable solids.
3. In the reaction of 7a with furfuraldehyde and cin-
namaldehyde, we obtained the products 11 (65%
yield) and 12 (60% yield), respectively; these com-
pounds were recently prepared by us using a differ-
ent route.1h In these products, the incoming chlorine
goes to the 5-position of the furan ring or the
g-position of the cinnamyl residue instead of the
normal a-position. The formation of 11 and 12 also
contrasts with the isolation of the normal products
8d and 9e, respectively, in analogous reactions using
7b and 7c. A possible intermediate in these reactions
is (II); formation of the phosphoryl bond, as well as
the transfer of the X group, can occur subsequently
as shown in the structural diagram. This will explain
the formation of 2 and 8–10. For X=Cl, contribu-
tion by the ionic form (II%) could be significant;16 Cl−
may then attack at the available 5-position of the
furan ring or the g-position of the cinnamyl group
leading to 11 or 12, respectively.
Scheme 2.
[X=OSiMe3; bp 75°C/0.5 mmHg, l(P) 108.4] was pre-
pared in 94% yield by treating (OCH2CMe2-
CH2O)P(O)H with Me3SiCl/Et3N in toluene. Com-
pounds 7a–d were stirred with the respective aldehyde
at room temperature for 72 h to afford the phospho-
nates 8–12; for the synthesis of the chloro compounds
2, a mixture of 7a and the aldehyde was first heated at
60°C for 1 h and then stirred at room temperature for
72 h. Although the reactions worked well with aromatic
aldehydes, a pure phosphonate could not be isolated
when 7a–c were treated with the aliphatic alde-
hyde, Me2CHCHO; only 7d gave the phosphonate
(OCH2CMe2CH2O)P(O)CH(OSiMe3)(CHMe2) (10f) as
an isolable product.14
Important points to be noted are the following:
1. The present method offers an excellent route to
a-methoxy-, a-dimethylamino- and a-trimethylsily-
loxy-substituted phosphonates. The simplicity of the
method, coupled with the readily accessible starting
materials, makes this approach an elegant choice to
obtain synthetically useful phosphonates. In fact,
our preliminary results suggest that 8d is an excel-
lent precursor for 2-methoxy-1,3-dienes.15
Acknowledgements
The authors would like to thank the Council of Scien-
tific & Industrial Research (New Delhi) for financial
support and the University Grants Commission (New
Delhi; COSIST and SAP) for instrumental facilities.
Table 1. Data for a-substituted phosphonates 2 and 8–10 (cf. Scheme 2)
Compound
Ar
l(P) (ppm)
Yield (%)
Compound
Ar
l(P) (ppm)
Yield (%)
2 (X=Cl)
2aa
9 (X=NMe2)
Ph
8.1
8.4
8.4
7.5
8.6
45
55
60
45
40
9a
9b
9c
9d
9e
Ph
17.4
17.1
17.4
16.9
14.4
67
72
75
73
80
2ba
4-Me-C6H4
4-OMe-C6H4
4-Cl-C6H4
1-Naphthyl
4-Me-C6H4
4-OMe-C6H4
4-Cl-C6H4
Furfuryl
2c
2da
2ea
8: (X=OMe)
10: (X=OSiMe3)
8a
8b
8c
8d
Ph
9.8
9.9
10.2
10.0
92
88
86
85
10a
10b
10c
10d
10e
Ph
11.0
8.9
10.6
10.8
10.4
89
91
90
92
90
4-Me-C6H4
4-OMe-C6H4
PhCHꢀCH
2,4-Cl2-C6H3
4-Cl-C6H4
1-Naphthyl
4-Br-C6H4
a These compounds have been prepared by a different route by us before.1h,2

K. Pra6een Kumar et al. / Tetrahedron Letters 42 (2001) 3219–3221
3221
References
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3.97 (d, J=20 Hz, 1H, P-CH), 4.09–4.29 (m, 2H, OCH2),
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crystallized from toluene until a sharp melting point and
a single spot in TLC was obtained.
A similar procedure was adopted to synthesize 8b–d,
9a–e, 10a–e, 11 and 12; in the case of 10a–e the product
mixture was first washed with heptane and crystallized
from a mixture of CH2Cl2 and heptane. For the chloro
.
.