Hydrolysis of Cyclic Phosphites/Phosphoramidites and Its Inhibition-Reversible Cyclization of Acyclic Phosphonate Salts to Cyclic Phosphites

Article abstract of DOI:10.1021/op034058k

Hydrolysis of cyclic phosphites/phosphoramidites (OCH₂- CRR′CH₂O)PX [X = OPh (1), NMe₂ (2)] in the presence of intentionally added water is effectively inhibited by using simple additives such as KF, K₂CO₃, Et₃N, and molecular sieves. Among these, K₂CO₃ gave the best results. Cyclic H-phosphonates (OCH₂CRR′CH₂O)P(O)H (3), which are the tautomeric forms of the phosphites (OCH₂CRR′CH ₂O)P(OH), undergo facile hydrolysis in the presence of aqueous amines to give the acyclic phosphonate salts [H₂NMe₂] ⁺[(HOCH₂CRR′CH₂O)P(O)-(H)(O^-)] (4) that can be reverted back to 3 upon simple heating. Interestingly, competitive reactions of (OCH₂CRR′CH₂O)PX [X = Cl (I-III), NMe₂ (2)] with phenol and water in the presence of K ₂CO₃ led only to the phenoxy derivatives and not to the hydrolysis products.

Full text of DOI:10.1021/op034058k

Organic Process Research & Development 2003, 7, 925−928
Hydrolysis of Cyclic Phosphites/Phosphoramidites and Its Inhibition-Reversible
Cyclization of Acyclic Phosphonate Salts to Cyclic Phosphites
N. Satish Kumar, Sudha Kumaraswamy, Musa A. Said, and K. C. Kumara Swamy*
School of Chemistry, UniVersity of Hyderabad, Hyderabad-500046, A.P., India
Abstract:
cyclic phosphites/phosphoramidites (OCH2CRR′CH2O)PX
[X ) OPh (1), NMe2 (2)] in the presence of added water by
seVeral simple salts.7 Obviously, such a feature should be
common to a large number of other P(III) esters. We believe
that these observations can be put to practical use while
handling P(III) compounds.5
The first-stage hydrolysis products of 1 [(R, R′ ) Me
(a), R, R′ ) Et (b), R ) Me, R′ ) n-Pr (c)] or (OCH2-
CRR′CH2O)PCl [(R, R′ ) Me (I), R, R′ ) Et (II), R ) Me,
R′ ) n-Pr (III)], the hydroxy phosphites (OCH2CRR′CH2O)-
P(OH), exist essentially in the tautomeric phosphonate form
(OCH2CRR′CH2O)P(O)H (3a-c).1 ReVersible hydrolysis of
3a-c, examples of which are very rare, in the presence of
an amine base, is also reported herein.
Hydrolysis of cyclic phosphites/phosphoramidites (OCH2-
CRR′CH2O)PX [X ) OPh (1), NMe2 (2)] in the presence of
intentionally added water is effectively inhibited by using simple
additives such as KF, K2CO3, Et3N, and molecular sieves.
Among these, K2CO3 gave the best results. Cyclic H-phospho-
nates (OCH2CRR′CH2O)P(O)H (3), which are the tautomeric
forms of the phosphites (OCH2CRR′CH2O)P(OH), undergo
facile hydrolysis in the presence of aqueous amines to give the
acyclic phosphonate salts [H2NMe2]+[(HOCH2CRR′CH2O)P(O)-
(H)(O-)] (4) that can be reWerted back to 3 upon simple heating.
Interestingly, competitive reactions of (OCH2CRR′CH2O)PX
[X ) Cl (I-III), NMe2 (2)] with phenol and water in the
presence of K2CO3 led only to the phenoxy derivatives and not
to the hydrolysis products.
Results and Discussion
Normal hydrolysis of 1a-c leading to cyclic H-phospho-
nates 3a-c occurs upon addition of stoichiometric amounts
of water under neat conditions (Scheme 1).8 When 1a-c is
stirred with an excess of water (3 mol equiv) in tetrahydro-
furan for 12 h, 3a-c as well as further hydrolysis products
are observed [31P NMR]; an analogous reaction with water,
when conducted in the presence of K2CO3, afforded 1a-c
completely unaffected. This inhibition of hydrolysis was also
realized when KF, MgSO4, triethylamine, or molecular sieves
was used in place of K2CO3, but K2CO3 gave the best results.
EVen with 1:1:3 mole equiV of 1a, K2CO3, and H2O in THF
as the solvent, no hydrolysis was obserVed. The salts NaF
and KCl were ineffective in inhibiting the hydrolysis. Both
KF and K2CO3 are no doubt hygroscopic, but the effective-
ness of the latter in inhibiting hydrolysis is very impressive.
Hydrolysis of the phosphoramidites 2 [R, R′ ) Me (a); R,
Introduction
Although tervalent P(III) compounds of the type (RO)3P
or (RO)2PNR′R′′ are frequently used in the synthesis of a
large number of other phosphorus compounds including nu-
cleosides/glycosides, their high reactivity makes them sus-
ceptible to spontaneous oxidation and hydrolysis.1,2 In other
significant applications of P(III) esters as antioxidants3a-c
and heat stabilizers for synthetic polymers/plastics, hydrolysis
in particular is a commonly encountered hurdle during syn-
thesis, storage, and use of pure compounds.3d,e Unlike the
hydrolysis of phosphate esters,4 those of phosphites/phos-
phoramidites are much less investigated,3,5 although it is
known that the P-N bonds in P(III) compounds can be
readily cleaved under acid-catalyzed conditions.6 It is often
desirable that hydrolysis of the precursor P(III) derivatives
be prevented until reactions with the substrate are conducted.5
Herein we report the remarkable inhibition of hydrolysis of
(4) Selected references on the hydrolysis of phosphate esters: (a) Wroblewski,
A. E.; Verkade, J. G. J. Am. Chem. Soc. 1996, 118, 10168. (b) Gerratana,
B.; Sowa, G. A.; Cleland, W. W. J. Am. Chem. Soc. 2000, 122, 12615. (c)
Torres, R A.; Bruice, T. C. J. Am. Chem. Soc. 2000, 122, 781. (d) Kluger,
R.; Cameron, L. L. J. Am. Chem. Soc. 2002, 124, 3303. (e) Cassano, A.
G.; Anderson, V. E.; Harris, M. E. J. Am. Chem. Soc. 2002, 124, 10964.
(f) O’Brien, P. J.; Herschlag, D. Biochemistry 2002, 41, 3207. (g) Blasko,
A.; Bruice, T. C. Acc. Chem. Res. 1999, 32, 475. (h) Marian, M.; Anges,
M. M.; Tomasz, A. M. J. Chem. Soc., Chem. Commun. 1994, 1537. (i)
Oivanen, M.; Kuusela, S.; Lonnberg, H. Chem. ReV. 1998, 98, 961-1044.
(5) Goghova, M.; Karvas, M.; Durmis, J. Chem. Pap. 1989, 43, 421.
(6) (a) Emsley, J.; Hall, D. Chemistry of Phosphorus; Harper & Row: London,
1976; p 145. (b) Edmundson, R. S. In ComprehensiVe Organic Chemistry;
Barton, D. H. R., Ollis, W. D., Eds.; Sutherland, I. O., Vol. Ed.;
Pergamon: Exeter, 1979; Vol. 2, Chapter 10.3, pp 1189-1231.
(7) Said, M. A.; Vijjulatha, M.; Kumara Swamy, K. C. presented in part at the
symposium on Modern Trends in Inorganic Chemistry-VI, Hyderabad,
August 17-19, 1995. Abstract no. P-36.
* Address for correspondence: Prof. K. C. Kumara Swamy, School of
Chemistry, University of Hyderabad, Hyderabad-500046, A.P., India. Fax: +91-
40-3012460/3010120. E-mail: kckssc@uohyd.ernet.in.
(1) Stawinski, J.; Kraszewski, A. Acc. Chem. Res. 2002, 35, 952.
(2) Selected references: (a) Zhang, Z.; Wong, C.-H. Glycosylation methods:
Use of phosphites. In Carbohydrates in Chemistry and Biology; Ernst, B.,
Hart, G. W., Sinay, P., Eds.; Wiley-VCH: New York, 2000; p 117. (b)
Oka, N.; Wada, T.; Saigo, K. J. Am. Chem. Soc. 2002, 124, 4962. (c) Wilk,
A.; Grajkowski, A.; Phillips, L. R.; Beaucage, S. L. J. Am. Chem. Soc.
2000, 122, 2149. (d) Hayakawa, Y.; Kawai, R.; Hirata, A.; Sugimoto, J.-
i.; Kataoka, M.; Sakakura, A.; Hirose, M.; Noyori, R. J. Am. Chem. Soc.
2001, 123, 8165. (e) Burgess, K.; Cook, D. Chem. ReV. 2000, 100, 2047.
(3) (a) Bauer, I.; Ko¨rner, S.; Pawelke, B.; Al-Malaika, S.; Habicher, W. D.
Polym. Degrad. Stab. 1998, 62, 175. (b) Perez-Lamela, C.; Rijk, R.; Simal-
Gandara, J. J. Agric. Food Chem. 1998, 46, 687. (c) Chantara, T. R.;
Khairul, Z. Polym. Degrad. Stab. 1999, 65, 481. (d) Kleiner, H.-Jerg.;
Regnat, D.; Pfahler, G. U.S. Patent 6,013,706, 2000. (e) Quotschalla, U.;
Linhart, H. U.S. Patent 5,840,954, 1998.
(8) Compounds 1a and 2a are very well documented; see: (a) Brault, J. F.;
Savignac, P. J. Organomet. Chem. 1974, 66, 71. (b) Muthiah, C.; Praveen
Kumar, K.; Aruna Mani, C.; Kumara Swamy, K. C. J. Org. Chem. 2000,
65, 3733.
10.1021/op034058k CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/06/2003
Vol. 7, No. 6, 2003 / Organic Process Research & Development
•
925

Scheme 1
Figure 1. A diagram showing the hydrogen bonded dimeric
motif in 4d; only hydrogen bonded protons are shown. There
is a very weak hydrogen bond between HN(1) and O(3) which
is not shown in the picture. Selected hydrogen bond parameters
(Å, deg): O(4)-HO(4)‚‚‚O(1) 0.83 (5), 1.82 (5), 2.648 (4), 177-
(5); N(1)-HN(1)‚‚‚O(3) 0.95 (6), 1.73 (6), 2.658 (4), 168(5);
N(1)-HN(1)‚‚‚O(3) 0.95 (6), 2.56 (6), 3.215 (4), 126(4).
Table 1. Competitive Reaction of Phosphites with Phenol
and Water in THF
Scheme 2
P(III) compound
(1 mmol)
additive:H2O:phenola
(mmol)
entry
productb
1a
1b
1c
1a
1a
1a
1c
1
2
3
4
5
6
7
8
9
I
II
5:1:1
5:1:1
5:1:1
5:3:1
1:3:1
3:1c
III
2a
2a
2a
2c
2a
2a
2a
5:3:1
5:3:1 (2,6-Cl2-C6H3OH) 1d (2%)d
5:3:1 (2,6-Me2-C6H3OH) 1e (50%)d
10
3:1 (2,6-Cl2-C6H3OH)
1d
a In all cases except entry 10, K2CO3 was the additive; in entry 10, molecular
sieves (5 times the weight of the phosphite) were used. b No hydrolysis except
in entries 6 and 10, where 8% and 40% hydrolysis, respectively, occurred. c No
additive was used. d Rest was the starting phosphoramidite; (OCH2CMe2CH2O)-
P(OAr) [Ar ) 2,6-Cl2C6H3O (1d), 2,6-Me2C6H3O (1e)].
95% yield) [Scheme 2]. An X-ray structure of 4d [base )
N,N-(dimethylamino)pyridine (DMAP)] [Figure 1], which
exists as a hydrogen bonded dimer, confirms the identity of
these products.9,10 What is perhaps a lot more interesting is
that the salts 4a-c can be thermally conVerted back to the
cyclic phosphites 3a-c; this is readily confirmed by 31P NMR
as well as derivatization to the Pudovik products (OCH2-
CRR′CH2O)P(O)CH(OH)Ar [R ) R′ ) Me, Ar ) 4-Cl-
C6H4 (5a); R ) R′ ) Et, Ar ) Ph (5b); R ) Me, R′ ) n-Pr,
Ar ) Ph (5c)].11
Cyclization leading to a six-membered dioxaphosphori-
nane ring from an acyclic phosphate ester, to our knowledge,
is observed in two cases before: (a) formation of cyclic-
AMP from ATP in the presence of adenyl cyclase12 and (b)
formation of 3′,5′-cyclic phosphates from ribonucleoside-
5′-phosphates with DCC under the presence of a strong base
guanidine.13 In these cases, cleavage of an O-P or O-C
bond from the acyclic precursor is required in the formation
of the cyclic phosphate, while, in the formation of 3 from 4,
base elimination and dehydration are involved.
R′ ) Et (b); R ) Me, R′ ) n-Pr (c) ] and (OCH2CMe2-
CH2O)P(NH-cycl-C6H11) is also inhibited by KF and K2CO3.
We also conducted competitive reactions of (OCH2CMe2-
CH2O)PX [X ) Cl (I), NMe2 (2a)] with a mixture of water
and a phenol to ascertain whether any mechanistic contribu-
tion is there or not in the inhibition of hydrolysis by K2CO3
[Table 1]. Under these conditions, the phenol reacts prefer-
entially to give the phenoxy derivatives 1a-e. The stoichio-
metric reaction of 2a with H2O/phenol led to 1a with much
less hydrolysis (<10%); the inhibition of hydrolysis is most
likely due to the liberated dimethylamine. Use of molecular
sieves led to significant hydrolysis. These results suggest that
the basic nature of K2CO3 does have a role in inhibiting the
formation of a transition state species such as (A)6b by the
initial attack of the acidic proton on the phenol at the trivalent
phosphorus center, hence, the prevention of hydrolyzed
products.
(9) The hydrogen bonds here are only moderately strong. For comparison,
see: Kumara Swamy, K. C.; Kumaraswamy, S.; Kommana, P. J. Am. Chem.
Soc. 2001, 123, 12642.
(10) For more details on analogous derivatives, see: Said, M. A.; Kumara
Swamy, K. C.; Veith, M.; Huch, V. J. Chem. Soc., Perkin Trans. 1 1995,
2945.
(11) Kumaraswamy, S.; Selvi, R. S.; Kumara Swamy, K. C. Synthesis 1997,
207.
(12) Breslow, R. Acc. Chem. Res. 1995, 28, 146.
(13) Khorana, H. G. Chemical Biology- Selected Papers of H. G. Khorana;
World Scientific: Singapore, 2000; pp 80-95.
Compounds 3a-c undergo facile hydrolysis in the pres-
ence of aqueous amines to the acyclic phosphonates
[H2NMe2]+[(HOCH2CRR′CH2O)P(H)(O)(O-)] (4a-c) (90-
926
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Vol. 7, No. 6, 2003 / Organic Process Research & Development

Table 2. Details on the Hydrolysis Studies of 1a-c and 2a-c
An immediate application of the present results is in the
preservation of P(III) compounds. We could preserve 1a (no
solvent; 1.5 g, 6.6 mmol)) in the presence of 1 molar equiv
of K2CO3 and 3 molar equiv of water (stirred) for 3 days
without any apparent hydrolysis. Hydrolysis of the acyclic
phosphites P(OMe)3 and P(OPh)3 was also inhibited by using
K2CO3. In a similar way, hydrolysis of other aminophosphites
[e.g., (OCH2CMe2CH2O)P(NH-cyc-C6H11) (6)] could also be
prevented. The main limitation, however, is that a phosphite
bearing an aromatic diol residue like (1,2-C6H4O2)P(OPh)
[7; δ(P) 126.6] is still susceptible towards hydrolysis, even
in the presence of K2CO3.
entry
compound
additive
result
1
1a-c or 2a-c
KF
∼2% hydrolysis
(1 mmol) +
3 mmol of water)
2
3
4
5
a
a
a
a
K2CO3
Et3N
MgSO4
no hydrolysis
∼1% hydrolysis
∼2% hydrolysis
molecular ∼1% hydrolysis
sieves
6
7
a
a
KCl
NaF
complete hydrolysis
complete hydrolysis
a Same as that for entry 1.
Conclusions
In summary, we have presented the remarkable inhibition
of hydrolysis of cyclic phosphites/phosphoramidites 1 and 2
in the presence of added water by seVeral simple salts.
Competitive phosphorylation of phenols with phosphora-
midites in the presence of intentionally added water and
metals salts is also presented. We believe that these observa-
tions can be put to practical use while handling P(III)
compounds in laboratory and as well as in industrial
conditions.
dimethylamine solution (ca 20 mL) was added, and the
reaction mixture was stirred for 3 h. Compounds 4a-c were
obtained by removing excess dimethylamine solution in
vacuo at room temperature. The yields were essentially
quantitative.
4a. Yield: 2.04 g, 96%. 1H NMR: δ 0.69 (s, 6 H, CH3),
2.43 (s, 6 H, N(CH3)2, 3.13 (s, 2 H, OCH2), 3.40 (d, 3J(HH)
1
) 9.5 Hz, 2 H, OCH2), 6.57 (d, J(PH) ) 622.2 Hz, 1 H,
P(O)H). 13C NMR: δ 21.4 (s, CH3), 34.5 (s, N(CH3)2), 36.7
3
2
(d, J(PC) ) 3.9 Hz, C(CH3)2), 67.0, 68.6 (d, J(PC) ) 4.0
Hz, OCH2). 31P NMR: δ 4.6.
4b. Yield: 2.28 g, 95%. H NMR: δ 0.65 (t, J(HH) )
7.4 Hz, 6 H, CH2CH3), 1.05 (m, 4 H, CH2CH3), 2.47 (s, 6
Experimental Section
1
The H (200 MHz),13C (50 MHz), and 31P (80.9 MHz)
1
3
NMR spectra were recorded on a Bruker 200 MHz spec-
trometer in CDCl3. The chemical shifts reported are relative
to that of tetramethylsilane (1H, 13C, δ ) 0) and 31P NMR
with external standard 85% H3PO4 (31P, δ ) 0). The chloro
precursors I-III were prepared by the routes reported
before;14 compound I is very well-known and is now
available from Aldrich. Compounds 1a-c, 2a-c, and 3a-c
were prepared by standard routes. Spectroscopic data for
I-III and 1-3 are given in the Supporting Information.
Reactions of 1a-c and 2a-c with Water in the
Presence of Metal Salts or Et3N. To freshly distilled 1 or
2 (1 mmol) was added 5 mmol of KF or K2CO3 or MgSO4
or Et3N [or 1.5 g of molecular sieves] followed by dry THF
(8 mL) and water (3 mmol). The reaction mixture was stirred
continuously for 3 d. THF was removed by vacuum, the
residue was dissolved in CDCl3 (1 mL), and after ca. 0.5 h,
the solution was syringed out and submitted for spectroscopic
analysis (1H, 13C, 31P NMR; primarily 31P NMR was used
for analysis). Details are given in Table 2. The spectra in
the hydrolysis or its inhibition of 1a and 2a were also
checked in benzene-d6/THF or THF without any deuterated
solvent. The results were the same as that obtained using
CDCl3.
3
H, N(CH3)2), 3.16 (s, 2 H, OCH2), 3.45 (d, J(PH) ) 8.9
Hz, 2 H, OCH2), 6.58 (d, 1J(PH) ) 622.2 Hz, 1 H, P(O)H).
13C NMR: δ 6.8 (s, CH2CH3), 21.4 (s, CH2CH3), 34.5 (s,
N(CH3)2), 41.5 (br s, CEt2), 63.1, 65.0 (2 s, OCH2). 31P
NMR: δ 4.8.
4c. Yield: 2.31 g, 96%. 1H NMR: δ 0.78 (s, 3 H, CH3),
3
0.85 (t, J(HH) ) 6.9 Hz, 3 H, CH2CH2CH3), 1.17-1.23
(m, 4 H, CH2CH2CH3), 2.56 (s, 6 H, N(CH3)2), 3.29 (AB
2
qrt, J(HH) ≈ 8.5 Hz, 2 H, HOCH2), 3.58 (symmetrical m,
1
2 H, OCH2), 6.73 (d, J(PH) ) 626.1 Hz, 1H, P(O)H). 13C
NMR: δ 14.9 (s, CH3), 16.2, 18.3 (2 s, CH2CH2CH3), 34.5
(s, N(CH3)2), 36.3, 39.4 (s, C(CH3)(n-Pr)), 65.8 (2s, OCH2),
2
67.3 (d, J(PC) ) 3.5 Hz, OCH2). 31P NMR: δ 5.2.
[DMAPH]+[(HOCH2CMe2CH2O)P(H)(O)(O-)] (4d).
To a stirred solution of (OCH2C(CH3)2CH2O)P(O)H (1.50
g, 10.0 mmol) in dichloromethane (10 mL) water (0.18 g,
10.0 mmol) was added followed by DMAP (1.34 g, 11.0
mmol). The mixture was stirred for 3 h, the solution
concentrated to 2 mL, toluene (8 mL) added, and the solution
preserved at 0 °C. Crystals of 4d were obtained after 1 d
1
(Yield 2.7 g, 93.1%), mp 88-90 °C. H NMR (CDCl3): δ
0.78 (s, 6 H, CH3), 3.13 (s, 6 H, N(CH3)2), 3.25 (s, 2 H,
Hydrolysis of acyclic phosphites P(OMe)3 and P(OPh)3
in the absence of K2CO3 using similar experimental condi-
tions as those above occurred to an extent of 100% and 40%,
respectively. In the presence of K2CO3, the hydrolysis was
completely inhibited
Reversible Cyclization. (A) Preparation of the Salts
4a-c. To freshly distilled 3 (10 mmol) an excess of aq.
3
OCH2), 3.59 (d, J(PH) ) 11.1 Hz, 2 H, OCH2), 6.85 (d,
1J(PH) ) 621.3 Hz, 1 H, P(O)H), 6.70, 8.20 (2 d, 2J(HH) )
15.0 Hz each, 4 H, DMAP-H). 13C NMR (CDCl3): δ 21.5
(s, CH3), 37.1 (br s, C(CH3)2 ), 39.9 (s, N(CH3)2 ), 67.2,
68.5 (2 s, OCH2), 106.7, 139.9, 157.1 (DMAP-C). 31P NMR
(CDCl3): δ 5.6. The crystals were transferred using a
fluorocarbon liquid into a Lindemann capillary, and the data
were collected on an Enraf-Nonius MACH3 diffractometer
using Mo KR radiation at 293(2) K. The structure was solved
(14) Muthiah, C.; Praveen Kumar, K.; Aruna Mani, C.; Kumara Swamy, K. C.
J. Org. Chem. 2000, 65, 3733.
Vol. 7, No. 6, 2003 / Organic Process Research & Development
•
927

and refined using standard methods.15 Crystal data: a )
8.646(2) Å, b ) 8.761(3) Å, c ) 11.811(7) Å, R ) 109.19-
(7)°, â ) 105.72(3)°, γ ) 99.38(4)°, V ) 781.4(6) Å3, Z )
2, F ) 1.234 g cm-3, ) 0.187, F000 ) 312, data/restraints/
parameters 2750/0/189, R1 ) 0.0635, wR2 (all data) )
0.1968, S ) 1.184, residual electron density 0.564/-0.529
Å-3.
(B) Recyclization of the Salts 4a-c to the Cyclic
Phosphites 3a-c and Conversion of 3a-c to the Phos-
phonates (5a-c). The salts 4a-c (1.2-1.3 g) were heated
at 100 °C for 3 h, and the resulting 3a-c were distilled under
vaccum. The yields of 3a-c were in the range 60-85%;
however, in the conversion of these to the corresponding
hydroxyphosphonates by a literature procedure,11 no dif-
ficulties were encountered.
11.8 Hz, 1 H, P-CH-OH), 7.26-7.49 (m, 5 H, Ph-H).
3
13C NMR: δ 14.4, 16.3, 17.7, 34.8 (d, J(PC) ≈ 5.5 Hz,
C(Me)(n-Pr)), 36.1, 71.7 (d, 1J(PC) ) 160.0 Hz, P-CH(OH)),
75.9, 76.0, 76.4, 126.8, 126.9, 128.0, 128.2, 136.5. 31P
NMR: δ 13.6.
Hydrolysis of 6 and Its Inhibition. Compound 6
underwent ready hydrolysis in the presence of 3 molar equiv
of water in THF leading to [(HOCH2CMe2CH2O)P(O)(H)-
(O-)][H3NC6H11]+.10,16 In the presence of added KF, most
of the hydrolysis was inhibited and 31P NMR showed >95%
of 6; the slight hydrolysis perhaps occurred during transfer
of the CDCl3 solution to the NMR tube. Similarly, the
compound (OCH2CMe2CH2O)P(OCHMe2) (8) did not hy-
drolyze to any significant extent in THF/H2O/CsF.
Acknowledgment
5a. Yield: 60% (from cyclization route). The physical
We gratefully acknowledge financial support as well as
instrumental facilities provided by the Department of Science
and Technology (New Delhi). N.S.K. thanks the Council of
Scientific and Industrial Research (CSIR), New Delhi for a
fellowship.
data were identical to those reported by us before.11
1
5b. Yield: 85%. Mp: 130-133 °C. H NMR: δ 0.67,
3
0.76 (2 t, J(HH) ) 7.1 Hz for both, 6 H, CH2CH3), 1.05,
3
1.51 (2 qrt, J(HH) ) 7.1 Hz, 4 H, CH2CH3), 3.81-4.29
2
(m, 4 H, OCH2), 5.04 (d, J(PH) ) 12.3 Hz, 1 H, P-CH-
OH), 5.36 (br. s, 1 H, P-CH-OH), 7.14-7.52 (m, 5 H,
Supporting Information Available
Ph-H). 13C NMR: δ 6.9, 7.1 (2 s, CH2CH3), 22.5, 22.6 (2
X-ray crystallographic data as CIF file for 4d (base )
4-(dimethylamino)pyridine), an ORTEP drawing of 4d, and
routine experimental details with spectroscopic data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
3
s, CH2CH3), 37.1 (d, J(PC) ≈ 5.5 Hz, C(CH2CH3)2), 71.9
(d, 1J(PC) ) 157.6 Hz, P-CH(OH)), 75.1, 75.8 (2 d, 2J(PC)
) 6.9 Hz for both, OCH2), 126.9, 127.0, 127.8, 128.1, 137.3
(all C(Ar)). 31P NMR: δ 14.3.
5c. Yield: 75%. Mp: 168-170 °C. 1H NMR: δ 0.71 (s,
3
3 H, CH3), 0.91 (t, J(HH) ) 7.0 Hz, 3 H, CH2CH2CH3),
Received for review May 8, 2003.
OP034058K
1.21-1.45 (m, 4 H, CH2CH2CH3), 3.93-4.07 (m, 4 H,
2
OCH2), 4.35 (br s, 1 H, P-CH-OH), 5.12 (d, J(PH) )
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