Dephosphonylation of β-carbonyl phosphonates

Article abstract of DOI:10.1021/jo990221r

A new methodology has been developed for the P-C bond cleavage of β- carbonyl phosphonates. The α,α-disubstituted β-keto phosphonates and the α-carbamoyl phosphonates have been shown to undergo dephosphonylation by reaction of their lithium enolate with LiAlH₄, followed by quenching with aqueous H₂SO₄, affording regioselectively α,α-disubstituted ketone and α-substituted and α,α-disubstituted secondary amides.

Full text of DOI:10.1021/jo990221r

J . Org. Chem. 1999, 64, 7017-7022
7017
Dep h osp h on yla tion of â-Ca r bon yl P h osp h on a tes
Shi Yong Lee, Chi-Wan Lee, and Dong Young Oh*
Department of Chemistry, Korea Advanced Institute of Science and Technology, 373-1 Kusong Dong,
Yusong Gu, Taejon 305-701, Korea
Received February 5, 1999
A new methodology has been developed for the P-C bond cleavage of â-carbonyl phosphonates.
The R,R-disubstituted â-keto phosphonates and the R-carbamoyl phosphonates have been shown
to undergo dephosphonylation by reaction of their lithium enolate with LiAlH4, followed by
quenching with aqueous H2SO4, affording regioselectively R,R-disubstituted ketone and R-substituted
and R,R-disubstituted secondary amides.
Sch em e 1
In tr od u ction
There are a number of applications of â-keto esters1
and â-keto sulfones2 as synthetically useful intermediates
for preparation of regioselectively R-alkylated ketones by
alkylation with subsequent defunctionalization. On the
contrary, the method employing phosphonate as a tem-
porary activating group in the same manner has not been
studied yet due to the fact that dephosphonylation3 of
â-keto phosphonate is less known. Although various
methods or reagents4,5 have been used to reduce a C-PV
bond into a C-H bond, the known chemical methods for
C-PV bond cleavage are of limited generality due to the
unique substrate requirements. Moreover, there is only
one literature reference6 involving the C-P bond reduc-
tion of â-keto-1-phosphonato esters analogous to â-keto
phosphonates. Recently, we have reported a new utility
of â-keto phosphonate as a precursor to R-alkylated
ketones through dephosphonylation.7 The dephosphonyl-
ation could be accomplished by reaction of â-keto phos-
phonate sodium enolate with LiAlH4, followed by quench-
ing with aqueous H2SO4 (Scheme 1).
we present our efforts to generalize a new method for
the P-C bond cleavage of â-carbonyl phosphonates.
Resu lts a n d Discu ssion
In our previous paper, â-keto phosphonates were
dephosphonylated by successive treatment with NaH and
LiAlH4 to give the corresponding ketones in good yields,
after acidic quenching. To gain insight into the mecha-
nism of this reductive P-C bond cleavage, some experi-
ments were carried out side by side. Their results
suggested that dephosphonylation with LiAlH4 could
occur via metal enolate of â-keto phosphonate. Therein
at least one hydrogen atom at the R-position of â-keto
phosphonates was left unsubstituted for the enolate
formation.
We attempted dephosphonylation for a different kind
of â-keto phosphonates, which involve two substituents
at the R-position. These R,R-disubstituted â-keto phos-
phonates 1 under the reaction conditions similar to those
of the previous work were assumed to provide the
corresponding dephosphonylated ketones 3 via metal
enolate 2 utilizing a γ-hydrogen (Scheme 2).9
To expand the scope and utility of this dephosphonyl-
ation, we have examined various phosphonates including
â-enamino8 and â-carbamoyl phosphonates. In this paper,
* To whom correspondence should be addressed. Phone: 82-42-869-
2819. Fax: 82-42-869-2810. E-mail: dyoh@sorak.kaist.ac.kr.
(1) Krapcho, A. P. Synthesis 1982, 893.
(2) (a) Kinoshita, H.; Hori, I.; Oishi, T.; Ban, Y. Chem. Lett. 1984,
1517. (b) Kurth, M. J .; O’Brien, M. J . J . Org. Chem. 1985, 50, 3846.
(c) Fujii, M.; Nakamura, K.; Mekata, H.; Oka, S.; Ohno, A. Bull. Chem.
Soc. J pn. 1988, 61, 495.
Sch em e 2
(3) To distinguish between “dephosphorylation” and “dephosphonyl-
ation”, we use the term “dephosphonylation” as a limited meaning of
P-C bond cleavage in a compound bearing phosphonate groups.
(4) (a) Bestmann, H. J .; Schultz, H. Chem. Ber. 1962, 95, 2921. (b)
Okamoto, Y.; Iwamato, N.; Takamuku, S. J . Chem. Soc., Chem.
Commun. 1986, 1516. (c) Bestmann, H. J .; Graf, G.; Kolewa, S.;
Vilsmeier, E. Chem. Ber. 1970, 103, 2974. (d) Kondo, K.; Negishi, A.;
Tunemoto, D. Angew. Chem., Int. Ed. Engl. 1974, 13, 407.
(5) We reported that enamine phosphonates bearing R-stabilized
groups such as phenyl or thiophenyl gave the corresponding deoxy-
benzoin or â-keto sulfides during basic hydrolysis. Lee, K.; Oh, D. Y.
Bull. Kor. Chem. Soc. 1991, 12, 254.
(6) In this case, it was reported as a notable result that, during
attempted reductions of 2-oxo-1-phosphonato ester to corresponding
2-hydroxy-1-phosphonato ester with various reductants, only Li(t-
BuO)3AlH among them cleaved the P-C bond selectively to give the
corresponding â-keto ester. However, the mechanism and any applica-
tion of the dephosphonylation were not reported. Durrant, G.; Suth-
erland, J . K. J . Chem. Soc., Perkin Trans. 1 1972, 2582.
(7) Hong, J . E.; Shin, W. S.; J ang, W. B.; Oh, D. Y. J . Org. Chem.
1996, 61, 2199.
If successful, this approach would be well suited to the
synthesis of substituted ketones of the type 3 from the
R,R-disubstituted â-keto phosphonates 1 by LiAlH4-
mediated reduction of presumed metal enolates 2, which
(8) J ang, W. B.; Shin, W. S.; Hong, J . E.; Lee, S. Y.; Oh, D. Y. Synth.
Commun. 1997, 27, 3333.
10.1021/jo990221r CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/21/1999

7018 J . Org. Chem., Vol. 64, No. 19, 1999
Ta ble 1. Alk yla tion a n d Dep h osp h on yla tion of Su bstitu ted â-Keto P h osp h on a tes
Lee et al.
entry
R1
R2
R3
product 1, yield (%)a
product 3, yield (%)a,b
a
b
c
d
e
f
g
h
i
-(CH2)2-
-(CH2)3-
-(CH2)3-
cinnamyl
cinnamyl
allyl
cinnamyl
crotyl
cinnamyl
crotyl
cinnamyl
cinnamyl
1a , 84
1b, 74
1c, 67
1d , 72
1e, 87
1f, 81
1g, 71
1h , 80
1i, 74
3a , 53 (62)
3b, 46 (72)
3c, 58 (66)
3d , 88
3e, 71
3f, (73)
3g, 74
-CH2CH(CH3)CH2-
Me
Me
Me
Me
Et
Et
H
H
3h , 84
3i, 77
cinnamyl
Me
a
b
Yield of isolated product. Solvent was evaporated below 0 °C, and in parentheses is the yield using LDA instead of n-BuLi as a base.
in turn could be generated by treatment of 1 with n-BuLi.
The whole procedure including preparation of â-keto
phosphonates represents the use of phosphonate as a
temporary activating group for regioselective alkylation
of ketones. A test reaction with a representative R,R-
disubstituted â-keto phosphonate proved to be successful.
First, we performed alkylation of substituted â-keto
phosphonates10 at the R-position for preparation of R,R-
disubstituted â-keto phosphonates 1. The reaction of
sodium enolates of â-keto phosphonates, generated by
treatment with NaH, with excessive alkyl halides at room
temperature for 2-5 h gave the corresponding R-fully
substituted â-keto phosphonates in good yields, without
side products as shown in Table 1. Cyclic â-keto phos-
phonates required longer reaction time than acyclic ones.
Use of excessive alkyl halides is thought to bring about
short reaction times and high yields, which offers an
advantage over two literature examples11 reported until
now to our knowledge.
deuterium. On the other hand, in the case of using LiAlH4
and deuterated acid, the reaction afforded the ketone 3i′
containing two deuteriums at the R- and R′-positions,
respectively, as shown in Scheme 3. To investigate a
Sch em e 3
The prepared R,R-disubstituted â-keto phosphonates
1 were dephosphonylated to afford ketones 3. After 1 was
treated with n-BuLi or LDA, the reaction of the lithium
enolates with LiAlH4 at room temperature for 0.5-1 h
and then quenching with 5 N H2SO4 aqueous solution
provided the corresponding ketones in good yields along
with a small amount of alcohols resulting from overre-
duction as side products. In some cases, a small improve-
ment of yields was realized by the use of LDA in place of
n-BuLi as a base. Usually 3 equiv of LiAlH4 was used,
and use of less than 3 equiv necessitated longer reaction
times, leading to lower yields. In addition, using more
dilute H2SO4 in quenching caused increasing amounts
of alcohols as side products, which also resulted in lower
yields.
possibility of H-D exchange reaction between D3O+ and
ketone, a blank experiment was carried out in the
following manner. Product 3b was treated with 5 N
AcOD/D2O at room temperature for 1 h. As a result, no
deuterated ketone was observed, which makes it likely
that the proton exchange reaction of the product ketones
does not take place under our quenching conditions.
These results suggest that the cleavage of the P-C
bond is not caused by direct attack of hydride on the
R-carbon atom linked with the phosphorus atom as an
SN2 type reaction or the γ-carbon atom as an SN2′ type
reaction, and a possibility that acid might play a signifi-
cant role in dephosphonylation.
As another extension of dephosphonylation, we also
turned our attention to the question of whether R-car-
bamoyl phosphonates12,13 could be dephosphonylated. If
the dephosphonylation of R-carbamoyl phosphonates
could be accomplished by successive treatment with
n-BuLi and LiAlH4, then the corresponding secondary
To make the mechanism of dephosphonylation clear,
we carried out deuterium experiments as follows. When
the reaction of lithium enolate of â-keto phosphonate 1i
with LiAlD4 was followed by quenching with a diluted
H2SO4, the ketone product 3i did not contain any
(9) Some of our results described herein have been preliminarily
presented in a short communication. Lee, S. Y.; Hong, J . E.; J ang, W.
B.; Oh, D. Y. Tetrahedron Lett. 1997, 38, 4567.
(10) (a) Savignac, P.; Mathey, F. Tetrahedron Lett. 1976, 2829. (b)
Calogeropoulou, T.; Hammond, G. B.; Wiemer, D. F. J . Org. Chem.
1987, 52, 2, 4185. (c) Grieco, P. A.; Pogonowski, C. S. J . Am. Chem.
Soc. 1973, 95, 3071.
(12) Kem, K. M.; Nguyen, N. V.; Cross, D. J . J . Org. Chem. 1981,
46, 5188.
(11) (a) Clark, R. D.; Kozar, L. G.; Heathcock, C. H. Synthesis 1975,
635. (b) Ruder, S. M.; Kulkarni, V. R. Synthesis 1993, 945.
(13) Tay, M. K.; About-J audet, E.; Collignon, N.; Savignac, P.
Tetrahedron 1989, 45, 4415.

Dephosphonylation of â-Carbonyl Phosphonates
J . Org. Chem., Vol. 64, No. 19, 1999 7019
Sch em e 4
Sch em e 6
Ta ble 2. Dep h osp h on yla tion of â-Ca r bon yl
P h osp h on a tes
compound
R
R′
yield (%)a
6a
6b
6c
6d
6e
6f
6g
6h
6i
Me
Me
Me
allyl
PhS
PhS
PhS
Ph
benzyl
Ph
cyclohexyl
4-ClPh
benzyl
Ph
cyclohexyl
cyclohexyl
benzyl
66
52
70
83
72
81
79
56
47b
Also, compound 8b could be synthesized from R-methyl
homoallylphosphonate 9,15 prepared by allylation of
diethyl ethylphosphonate, through reaction of its anion
with isocyanate and dephosphonylation of the resulting
lithio complex 10 with LiAlH4 (Scheme 6). The strategy
using dephosphonylations like these is thought to be the
unique pathway accessible to R,R-disubstituted secondary
amides.
H
a
b
Yield of isolated products. Not to be isolated, the yield was
determined by NMR analysis.
amides14 would be obtained in good yields. To this end,
when we examined the reaction of R-lithio alkylphospho-
nates, derived from diethyl alkylphosphonates 4, with
isocyanates followed by addition of LiAlH4 and quenching
with aqueous H2SO4, dephosphonylation proved success-
ful. A variety of secondary amide products could be
obtained as solids (Scheme 4, Table 2).
Although R-carbamoyl phosphonates could be readily
prepared by quenching the metal complexes 5 with
aqueous acid solution,13 we carried out the whole proce-
dure without a stop in one pot.
Finally, to examine a possibility of geminal alkylation
of substituted secondary amides through this scheme, we
attempted to make dianion species. Treatment of lithio
complex 5 with 1 equiv of n-BuLi produced the presumed
dianion species 7, which then were alkylated with allyl
bromide and underwent subsequent dephosphonylation
with LiAlH4, affording the R,R-disubstituted secondary
amides 8 (Scheme 5). All the steps have proceeded not
Con clu sion
These studies have shown that the R,R-disubstituted
â-keto phosphonates and the R-carbamoyl phosphonates
undergo dephosphonylation by successive treatment with
n-BuLi and LiAlH4, yielding regioselectively R,R-disub-
stituted ketone and R-substituted and R,R-disubstituted
secondary amides. Also these results suggest that the use
of â-carbonyl phosphonates as precursors to R-alkylated
ketones and amides would be a complement of existing
methods to alkylate ketones regioselectively employing
â-keto esters and â-keto sulfones. In some cases isolated
yields were modest, and dephosphonylation has been
demonstrated to require rather severe conditions. Nev-
ertheless, this dephosphonylation offers a reasonable
route to geminal dialkylation of ketones and secondary
amides.
Sch em e 5
Exp er im en ta l Section
Gen er a l P r oced u r es. All reactions were conducted under
an atmosphere of nitrogen in oven-dried glassware with
magnetic stirring. THF was dried over and distilled from
sodium metal with benzophenone as the indicator. Melting
points were recorded in open capillary tubes and are uncor-
rected. 1H NMR and 13C NMR spectra were recorded in CDCl3
using TMS (0 ppm), residual CHCl3 (7.24 ppm), or solvent
resonance (77.0 ppm) as a standard. Some starting materials
were synthesized as described in the literature with minor
modification.10
Gen er a l P r oced u r e for th e Alk yla tion of â-Keto P h os-
p h on a tes. To a suspension of sodium hydride (0.060 g, 80%,
2.0 mmol) in dry THF (5 mL) at 0 °C was added the proper
â-keto phosphonate (2.0 mmol) in dry THF (5 mL) slowly, and
the mixture was allowed to warm to room temperature. After
the mixture was stirred for 1 h, alkyl bromide (4.0 mmol) in
dry THF (5 mL) was added, and the resulting reaction mixture
was stirred for 2-5 h at the same temperature. Aqueous H2-
SO4 solution (3.5 N, 5 mL) was added, and the resulting
solution extracted with diethyl ether (50 mL × 2). The
combined organic layers were washed with aqueous NaHCO3
solution (5%, 5 mL × 1) and distilled water (5 mL × 2), and
only in one pot but also in high yields from readily
available phosphonates and isocyanates.
(14) (a) Lebel, N. A.; Cherluck, R. M.; Curtis, E. A. Synthesis 1973,
678. (b) Schoenberg, A.; Heck, R. F. J . Org. Chem. 1974, 39, 3327. (c)
Mattingly, P. G.; Miller, M. J . J . Org. Chem. 1980, 45, 410. (d) Pfister,
J . R.; Wymann, W. E. Synthesis 1983, 38. (e) Zaloom, J .; Calandra,
M.; Roberts, D. C. J . Org. Chem. 1985, 50, 2601. (f) Blagbrough, I. S.;
Mackenzie, N. E.; Ortiz, C.; Scott, A. I. Tetrahedron Lett. 1986, 27,
1251.
(15) Balczewski, P.; Pietrzykowski, W. M.; Mikolajczyk, M. Tetra-
hedron 1995, 51, 7727.

7020 J . Org. Chem., Vol. 64, No. 19, 1999
Lee et al.
dried over MgSO4. After evaporation of ether, the residue was
chromatographed on a silica gel column using an EtOAc-
hexane mixture as eluent to provide the pure R-fully substi-
tuted â-keto phosphonate 1 as a colorless oil.
reaction time of 2 h after chromatography (EtOAc/hexane, 75/
25): 1H NMR (200 MHz, CDCl3) δ 0.87 (t, J ) 7.4 Hz, 3H),
1.29 (t, J ) 6.9 Hz, 6H), 1.42 (d, J ) 16.7 Hz, 3H), 1.48-1.64
(m, 2H), 2.51-2.64 (m, 1H), 2.65 (t, J ) 7.1 Hz, 2H), 3.01-
3.13 (m, 1H), 4.03-4.18 (m, 4H), 5.92-6.07 (m, 1H), 6.41 (d,
J ) 15.7 Hz, 1H), 7.15-7.30 (m, 5H); 13C NMR (50 MHz,
CDCl3) δ 13.6, 16.4 (d, J ) 5.7 Hz), 16.8 (d, J ) 4.8 Hz), 17.0,
36.9 (d, J ) 3.9 Hz), 41.8, 54.4 (d, J ) 127.1 Hz), 62.4-62.8
(m), 124.1 (d, J ) 13.7 Hz), 126.1, 127.3, 128.4, 133.9, 136.9,
207.8. Anal. Calcd for C19H29O4P: C, 64.76; H, 8.29. Found:
C, 64.35; H, 8.49.
Diet h yl 1-Cr ot yl-1-m et h yl-2-oxop r op ylp h osp h on a t e
(1g). Using the general procedure described above, the title
compound was obtained as a colorless oil (0.279 g, 71%) from
diethyl 1-methyl-2-oxopropylphosphonate10a (0.313 g, 1.5 mmol)
and crotyl bromide (0.477 g, 85%, 3.0 mmol) under a reaction
time of 3 h after chromatography (only EtOAc): 1H NMR (200
MHz, CDCl3) δ 1.23-1.36 (m, 9H), 1.57 (d, J ) 6.4 Hz, 3H),
2.26 (s, 3H), 2.31-2.55 (m, 1H), 2.76-2.91 (m, 1H), 3.99-4.14
(m, 4H), 5.06-5.22 (m, 1H), 5.38-5.59 (m, 1H); 13C NMR (50
MHz, CDCl3) δ 16.3-16.5 (m), 17.9, 28.1, 36.4 (d, J ) 4.2 Hz),
54.6 (d, J ) 127.3 Hz), 62.5-62.7 (m), 124.3 (d, J ) 14.4 Hz),
129.9, 206.0.
Diet h yl 1-Cin n a m yl-1-m et h yl-2-oxop r op ylp h osp h o-
n a te (1h ). Using the general procedure described above, the
title compound was obtained as a colorless oil (0.259 g, 80%)
from diethyl 1-methyl-2-oxopropylphosphonate (0.208 g, 1.0
mmol) and cinnamyl bromide (0.394 g, 2.0 mmol) under a
reaction time of 3 h after chromatography (only EtOAc): 1H
NMR (300 MHz, CDCl3) δ 1.34 (t, J ) 7.0 Hz, 6H), 1.45 (d, J
) 17.5 Hz, 3H), 2.36 (s, 3H), 2.55-2.66 (m, 1H), 3.05-3.15
(m, 1H), 4.10-4.20 (m, 4H), 5.95-6.06 (m, 1H), 6.46 (d, J )
15.7 Hz, 1H), 7.20-7.33 (m, 5H); 13C NMR (75 MHz, CDCl3) δ
16.4 (d, J ) 5.6 Hz), 16.9 (d, J ) 5.0 Hz), 28.2, 36.9 (d, J ) 3.8
Hz), 54.7 (d, J ) 127.3 Hz), 62.7-62.9 (m), 123.9 (d, J ) 13.7
Hz), 126.2, 127.4, 128.5, 134.1, 136.9, 205.9.
Diet h yl 1,1-Dicin n a m yl-2-oxobu t ylp h osp h on a t e (1i).
Using the general procedure described above, the title com-
pound was obtained as a colorless oil (0.652 g, 74%) from
diethyl 1-cinnamyl-2-oxobutylphosphonate11a (0.649 g, 2.0
mmol) and cinnamyl bromide (0.788 g, 4.0 mmol) under a
reaction time of 3 h after chromatography (EtOAc/hexane, 50/
50): 1H NMR (200 MHz, CDCl3) δ 1.08 (t, J ) 7.1 Hz, 3H),
1.30 (t, J ) 7.0 Hz, 6H), 2.77-2.96 (m, 6H), 4.06-4.21 (m, 4H),
6.14-6.28 (m, 2H), 6.47 (d, J ) 14.8 Hz, 2H), 7.15-7.32 (m,
10H).
Gen er a l P r oced u r e for th e Dep h osp h on yla tion of
R-F u lly Su bstitu ted â-Keto P h osp h on a tes. n-BuLi (0.69
mL of a 1.6 M solution in hexanes, 1.1 mmol) or LDA (0.55
mL of a 2.0 M solution in heptane/THF/ethylbenzene, 1.1
mmol) was added dropwise by syringe to a stirred solution of
R-fully substituted â-keto phosphonate (1, 1.0 mmol) in dry
THF (4 mL) under N2 at -78 °C. The mixture was allowed to
warm slowly to room temperature, and transferred into a
stirred solution of LiAlH4 (0.114 g, 3 mmol) in dry THF (6 mL)
at the same temperature. After the mixture was stirred for
30 min, aqueous H2SO4 solution (5 N, 5 mL) was added, and
the resulting solution extracted with diethyl ether (50 mL ×
2). The combined organic layers were washed with aqueous
NaHCO3 solution (5%, 5 mL × 1) and distilled water (5 mL ×
2), and dried over MgSO4. After evaporation of ether, the
residue was chromatographed on a silica gel column using an
EtOAc-hexane mixture as eluent to provide the pure R,R-
disubstituted ketone 3 as a colorless oil. The solvent was
evaporated below 0 °C in vacuo.
2-Cin n a m ylcyclop en ta n on e (3a ). Using the general pro-
cedure described above, the title compound was obtained as a
colorless oil (0.107 g, 53% for using n-BuLi as a base; 0.124 g,
62% for using LDA as a base) from diethyl 1-cinnamyl-2-
oxocyclopentylphosphonate (1a ; 0.336 g, 1.00 mmol) after
chromatography (EtOAc/hexane, 10/90): 1H NMR (200 MHz,
CDCl3) δ 1.52-1.85 (m, 2H), 1.88-2.06 (m, 2H), 2.14-2.30 (m,
4H), 2.57-2.73 (m, 1H), 6.14 (dt, J ) 15.7, 6.9 Hz, 1H), 6.41
(d, J ) 15.7 Hz, 1H), 7.15-7.36 (m, 5H); 13C NMR (50 MHz,
Dieth yl 1-Cin n am yl-2-oxocyclopen tylph osph on ate (1a).
Using the general procedure described above, the title com-
pound was obtained as a colorless oil (0.565 g, 84%) from
diethyl 2-oxocyclopentylphosphonate10b (0.44 g, 2.0 mmol) and
cinnamyl bromide (0.788 g, 4.0 mmol) under a reaction time
of 4 h after chromatography (EtOAc/hexane, 50/50): 1H NMR
(200 MHz, CDCl3) δ 1.34 (dt, J ) 1.6, 7.0 Hz, 6H), 1.75-1.99
(m, 1H), 2.07-2.21 (m, 3H), 2.43-2.66 (m, 3H), 2.70-2.91 (m,
1H), 4.08-4.24 (m, 4H), 5.95-6.11 (m, 1H), 6.44 (d, J ) 15.8
Hz, 1H), 7.18-7.34 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 16.3-
16.4 (m), 19.7, 29.6, 36.0, 39.2, 54.4 (d, J ) 133.2 Hz), 62.5-
62.9 (m), 124.1 (d, J ) 12.0 Hz), 126.1, 127.4, 128.5, 134.1,
136.9, 215.4; HRMS calcd for C18H25O4P 336.1491, found
336.1478.
Dieth yl 1-Cin n a m yl-2-oxocycloh exylp h osp h on a te (1b).
Using the general procedure described above, the title com-
pound was obtained as a colorless oil (0.259 g, 74%) from
diethyl 2-oxocyclohexylphosphonate10b (0.234 g, 1.0 mmol) and
cinnamyl bromide (0.394 g, 2.0 mmol) under a reaction time
of 4 h after chromatography (EtOAc/hexane, 50/50): 1H NMR
(200 MHz, CDCl3) δ 1.28-1.37 (m, 6H), 1.66-1.79 (m, 2H),
1.96-2.53 (m, 6H), 2.85-3.03 (m, 2H), 4.04-4.21 (m, 4H),
6.04-6.19 (m, 1H), 6.40 (d, J ) 15.9 Hz, 1H), 7.17-7.42 (m,
5H); 13C NMR (50 MHz, CDCl3) δ 16.3-16.5 (m), 21.5, 25.7,
31.8 (d, J ) 4.3 Hz), 36.6 (d, J ) 3.7 Hz), 41.2, 55.7 (d, J )
125.2 Hz), 62.7 (d, J ) 7.1 Hz), 125.3 (d, J ) 9.9 Hz), 126.1,
127.2, 128.4, 133.7, 137.2, 208.4.
Dieth yl 1-Allyl-2-oxocycloh exylp h osp h on a te (1c).11b
Using the general procedure described above, the title com-
pound was obtained as a colorless oil (0.368 g, 67%) from
2-oxocyclohexylphosphonate (0.468 g, 2.0 mmol) and allyl
bromide (0.484 g, 4.0 mmol) under a reaction time of 5 h after
chromatography (EtOAc/hexane, 70/30): 1H NMR (200 MHz,
CDCl3) δ 1.22-1.32 (m, 6H), 1.58-1.71 (m, 2H), 1.92-2.39 (m,
6H), 2.68-2.92 (m, 2H), 3.97-4.18 (m, 4H), 4.96-5.05 (m, 2H),
5.55-5.71 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 16.2-16.4
(m), 21.4 (d, J ) 2.4 Hz), 25.6, 31.5 (d, J ) 4.3 Hz), 37.3 (d, J
) 4.0 Hz), 41.1, 55.2 (d, J ) 125.4 Hz), 62.5-62.7 (m), 118.6,
133.6 (d, J ) 9.8 Hz), 208.2.
Diet h yl 1-Cin n a m yl-5-m et h yl-2-oxocycloh exylp h os-
p h on a te (1d ). Using the general procedure described above,
the title compound was obtained as a colorless oil (0.262 g,
72%) from 5-methyl-2-oxocyclohexylphosphonate10b (0.248 g,
1.0 mmol) and cinnamyl bromide (0.394 g, 2.0 mmol) under a
reaction time of 5 h after chromatography (EtOAc/hexane, 50/
50): 1H NMR (200 MHz, CDCl3) δ 0.92 (d, J ) 6.6 Hz, 3H),
1.33 (t, J ) 7.1 Hz, 6H), 1.18-1.59 (m, 2H), 1.88-1.99 (m, 1H),
2.13-2.29 (m, 1H), 2.35-2.52 (m, 3H), 2.90-3.05 (m, 2H),
3.99-4.23 (m, 4H), 5.99-6.13 (m, 1H), 6.37 (d, J ) 15.8 Hz,
1H), 7.17-7.36 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 16.4 (t,
J ) 5.6 Hz), 21.6, 27.8, 34.1, 36.8 (d, J ) 3.4 Hz), 40.3, 41.2,
55.4 (d, J ) 122.2 Hz), 62.8 (d, J ) 7.2 Hz), 125.4 (d, J ) 10.6
Hz), 126.1, 127.2, 128.5, 133.8, 137.3, 208.3.
Dieth yl 1-Cr otyl-1-m eth yl-2-oxopen tylph osph on ate (1e).
Using the general procedure described above, the title com-
pound was obtained as a colorless oil (0.505 g, 87%) from
diethyl 1-methyl-2-oxopentylphosphonate10a (0.452 g, 2.0 mmol)
and crotyl bromide (0.635 g, 85%, 4.0 mmol) under a reaction
time of 2 h after chromatography (EtOAc/hexane, 80/20): 1H
NMR (200 MHz, CDCl3) δ 0.83 (t, J ) 7.4 Hz, 3H), 1.21-1.36
(m, 9H), 1.43-1.60 (m, 2H), 1.56 (d, J ) 7.2 Hz, 3H), 2.21-
2.47 (m, 1H), 2.52-2.63 (m, 2H), 2.74-2.93 (m, 1H), 3.97-
4.12 (m, 4H), 5.04-5.20 (m, 1H), 5.38-5.54 (m, 1H); 13C NMR
(50 MHz, CDCl3) δ 13.5, 16.3-16.5 (m), 17.0, 17.8, 30.4, 36.4,
41.7, 54.2 (d, J ) 127.2 Hz), 62.4-62.7 (m), 124.5 (d, J ) 14.5
Hz), 129.7, 207.9.
Diet h yl 1-Cin n a m yl-1-m et h yl-2-oxop en t ylp h osp h o-
n a te (1f). Using the general procedure described above, the
title compound was obtained as a colorless oil (0.570 g, 81%)
from diethyl 1-methyl-2-oxopentylphosphonate (0.452 g, 2.0
mmol) and cinnamyl bromide (0.788 g, 4.0 mmol) under a

Dephosphonylation of â-Carbonyl Phosphonates
J . Org. Chem., Vol. 64, No. 19, 1999 7021
CDCl3) δ 20.6, 28.9, 33.0, 38.1, 48.9, 126.0, 127.0, 127.6, 128.4,
131.7, 137.3, 220.3; HRMS calcd for C14H16O 200.1201, found
200.1206.
3H), 2.22-2.32 (m, 1H), 2.52-2.62 (m, 1H), 2.63-2.73 (m, 1H),
6.09-6.19 (m, 1H), 6.42 (d, J ) 15.8 Hz, 1H), 7.20-7.36 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 16.0, 28.4, 36.1, 47.1, 126.0,
127.2, 127.3, 128.5, 132.1, 137.3, 211.8.
1,1-Dicin n a m ylbu ta n -2-on e (3i). Using the general pro-
cedure described above, the title compound was obtained as a
colorless oil (0.117 g, 77% for using n-BuLi as a base) from
diethyl 1,1-dicinnamyl-2-oxobutylphosphonate (1i; 0.220 g,
0.50 mmol) employing LiAlD4 (0.063 g, 1.5 mmol) in place of
LiAlH4 after chromatography (EtOAc/hexane, 20/80): 1H NMR
(200 MHz, CDCl3) δ 1.01 (t, J ) 7.2 Hz, 3H), 2.30-2.60 (m,
6H), 2.80 (quintet, J ) 7.1 Hz, 1H), 6.03-6.18 (m, 2H), 6.40
(d, J ) 15.9 Hz, 2H), 7.16-7.34 (m, 10H).
r,r′-d 2-1,1-Dicin n a m ylbu ta n -2-on e (3i′). Using the gen-
eral procedure described above, the title compound was
obtained as a colorless oil from 1i employing AcOD/D2O (5 N,
5 mL) in place of aqueous H2SO4 solution as a quenching
agent: 1H NMR (200 MHz, CDCl3) δ 1.01 (d, J ) 7.2 Hz, 3H),
2.35-2.52 (m, 5H), 6.11 (dt, J ) 15.8, 7.2 Hz, 2H), 6.41 (d, J
) 15.9 Hz, 2H), 7.18-7.35 (m, 10H).
2-Cin n a m ylcycloh exa n on e (3b). Using the general pro-
cedure described above, the title compound was obtained as a
colorless oil (0.049 g, 46% for using n-BuLi as a base; 0.077 g,
72% for using LDA as a base) from diethyl 1-cinnamyl-2-
oxocyclohexylphosphonate (1b; 0.175 g, 0.50 mmol) after
chromatography (EtOAc/hexane, 10/90): 1H NMR (300 MHz,
CDCl3) δ 1.32-1.47 (m, 1H), 1.58-1.75 (m, 2H), 1.77-1.92 (m,
1H), 1.98-2.21 (m, 3H), 2.25-2.51 (m, 3H), 2.61-2.72 (m, 1H),
6.13-6.23 (m, 1H), 6.37 (d, J ) 15.8 Hz, 1H), 7.15-7.35 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 25.0, 27.9, 33.0, 33.5, 42.1,
50.7, 126.0, 126.9, 128.3, 128.4, 131.6, 137.5, 212.4.
2-Allylcycloh exa n on e (3c).16 Using the general procedure
described above, the title compound was obtained as a colorless
oil (0.080 g, 58% for using n-BuLi as a base; 0.091 g, 66% for
using LDA as a base) from diethyl 1-allyl-2-oxocyclohexylphos-
phonate (1c; 0.274 g, 1.0 mmol) after chromatography (EtOAc/
hexane, 10/90): 1H NMR (200 MHz, CDCl3) δ 1.24-1.39 (m,
1H), 1.53-2.13 (m, 6H), 2.21-2.37 (m, 3H), 2.43-2.55 (m, 1H),
4.90-5.01 (m, 2H), 5.61-5.81 (m, 1H); 13C NMR (50 MHz,
CDCl3) δ 24.9, 27.8, 33.3, 33.7, 41.9, 50.1, 116.1, 136.4, 212.3.
2-Cin n a m yl-4-m eth ylcycloh exa n on e (3d ). Using the
general procedure described above, the title compound was
obtained as a colorless oil (0.100 g, 88% for using n-BuLi as a
base) from diethyl 1-cinnamyl-5-methyl-2-oxocyclohexylphos-
phonate (1d ; 0.182 g, 0.50 mmol) after chromatography
(EtOAc/hexane, 10/90): 1H NMR (200 MHz, CDCl3) δ 0.97 (d,
J ) 6.3 Hz, 3H), 1.06-1.26 (m, 1H), 1.29-1.46 (m, 1H), 1.80-
2.18 (m, 4H), 2.33-2.58 (m, 3H), 2.61-2.77 (m, 1H), 6.11-
6.26 (m, 1H), 6.38 (d, J ) 15.9 Hz, 1H), 7.17-7.37 (m, 5H);
13C NMR (50 MHz, CDCl3) δ 21.2, 32.0, 32.7, 35.8, 41.5, 41.7,
49.5, 125.9, 126.0, 126.9, 128.4, 131.5, 137.5, 212.4.
2-Cr otylh exa n -3-on e (3e). Using the general procedure
described above, the title compound was obtained as a colorless
oil (0.110 g, 71% for using n-BuLi as a base) from diethyl
1-crotyl-1-methyl-2-oxopentylphosphonate (1e; 0.290 g, 1.0
mmol) after chromatography (EtOAc/hexane, 10/90): 1H NMR
(200 MHz, CDCl3) δ 0.88 (t, J ) 7.3 Hz, 3H), 1.02 (d, J ) 6.9
Hz, 3H), 1.50-1.63 (m, 5H), 1.95-2.02 (m, 2H), 2.34-2.41 (t,
J ) 7.1 Hz, 2H), 2.51 (q, J ) 6.9 Hz, 1H), 5.22-5.56 (m, 2H);
13C NMR (50 MHz, CDCl3) δ 13.8, 16.0, 17.0, 17.8, 36.0, 43.3,
46.4, 127.3, 128.2, 214.3.
2-Cin n a m ylh exa n -3-on e (3f). Using the general procedure
described above, the title compound was obtained as a colorless
oil (0.157 g, 73% for using LDA as a base) from diethyl
1-cinnamyl-1-methyl-2-oxopentylphosphonate (1f; 0.352 g, 1.0
mmol) after chromatography (EtOAc/hexane, 10/90): 1H NMR
(200 MHz, CDCl3) δ 0.90 (t, J ) 7.3 Hz, 3H), 1.11 (d, J ) 6.9
Hz, 3H), 1.50-1.68 (m, 2H), 2.14-2.28 (m, 1H), 2.42 (t, J )
7.6 Hz, 2H), 2.47-2.57 (m, 1H), 2.57-2.73 (m, 1H), 6.11 (dt, J
) 15.8, 6.9 Hz, 1H), 6.39 (d, J ) 15.9 Hz, 1H), 7.15-7.34 (m,
5H); 13C NMR (50 MHz, CDCl3) δ 13.7, 16.1, 16.9, 36.1, 43.2,
46.1, 125.9, 127.0, 127.4, 128.4, 131.9, 137.2, 213.7. Anal. Calcd
for C15H20O: C, 83.28; H, 9.32. Found: C, 83.24; H, 9.30.
3-Cr ot ylbu t a n -2-on e (3g). Using the general procedure
described above, the title compound was obtained as a colorless
oil (0.093 g, 74% for using n-BuLi as a base) from diethyl
1-crotyl-1-methyl-2-oxopropylphosphonate (1g; 0.262 g, 1.0
mmol) after chromatography (EtOAc/hexane, 10/90): 1H NMR
(200 MHz, CDCl3) δ 1.05 (d, J ) 6.9 Hz, 3H), 1.58-1.63 (m,
3H), 1.95-2.07 (m, 1H), 2.11 (s, 3H), 2.18-2.32 (m, 1H), 2.43-
2.58 (m, 1H), 5.24-5.52 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
15.8, 17.0, 23.3, 35.9, 47.2, 127.4, 127.9, 211.8.
Gen er a l P r oced u r e for th e Dep h osp h on yla tion of
r-Ca r ba m oyl P h osp h on a tes. To a stirred solution of the
proper phosphonate (4; 1.0 mmol) in dry THF (5 mL) under
N2 at -78 °C was added n-BuLi (0.66 mL of a 1.6 M solution
in hexanes, 1.05 mmol) dropwise, and the mixture was allowed
to warm slowly to -30 °C. Addition of the proper isocyanate
(1.0 mmol) was followed by warming slowly to room temper-
ature, and LiAlH4 (3.0 mL of a 1.0 M solution in THF) was
added. After the mixture was stirred for 1 h, aqueous H2SO4
solution (5 N, 5 mL) was added, and the resulting solution
extracted with diethyl ether (30 mL × 3). The combined
organic layers were washed with aqueous NaHCO3 solution
(5%, 5 mL × 1) and distilled water (5 mL × 2), and dried over
MgSO4. After evaporation of ether, the residue was chromato-
graphed on a silica gel column using an EtOAc-hexane
mixture as eluent to provide the pure amide 6 as a white solid.
N-Ben zylp r op a n a m id e (6a ).18 Using the general proce-
dure described above, the title compound was obtained as a
white solid (0.108 g, 66%) from diethyl ethylphosphonate
(0.166 g, 1.0 mmol) and benzyl isocyanate (0.14 mL, 1.1 mmol)
after chromatography (EtOAc/hexane, 50/50): mp 49-50 °C;
1H NMR (300 MHz, CDCl3) δ 1.15 (t, J ) 7.6 Hz, 3H), 2.22 (q,
J ) 7.6 Hz, 2H), 4.40 (d, J ) 0.5.7 Hz, 2H), 5.86 (br s, 1H),
7.22-7.34 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 9.8, 29.6, 43.5,
127.4, 127.8, 128.6, 138.4, 173.6. Anal. Calcd for C10H13NO:
C, 73.59; H, 8.03; N, 8.58. Found: C, 73.52; H, 8.16; N, 8.43.
N-P h en ylp r op a n a m id e (6b). Using the general procedure
described above, the title compound was obtained as a white
solid (0.078 g, 52%) from diethyl ethylphosphonate (0.166 g,
1.0 mmol) and phenyl isocyanate (0.12 mL, 1.1 mmol) after
1
chromatography (EtOAc/hexane, 30/70): mp 103-105 °C; H
NMR (300 MHz, CDCl3) δ 1.22 (t, J ) 7.5 Hz, 3H), 2.37 (q, J
) 7.5 Hz, 2H), 7.07 (t, J ) 7.4 Hz, 1H), 7.24-7.51 (m, 5H); 13
C
NMR (75 MHz, CDCl3) δ 9.7, 30.7, 119.7, 124.1, 129.0, 137.9,
172.0.
N-Cycloh exylp r op a n a m id e (6c).19 Using the general
procedure described above, the title compound was obtained
as a white solid (0.109 g, 70%) from diethyl ethylphosphonate
(0.166 g, 1.0 mmol) and cyclohexyl isocyanate (0.14 mL, 1.1
mmol) after chromatography (EtOAc/hexane, 50/50): mp 89-
1
91 °C; H NMR (300 MHz, CDCl3) δ 0.99-1.17 (m, 3H), 1.13
(t, J ) 7.5 Hz, 3H), 1.26-1.40 (m, 2H), 1.53-1.70 (m, 3H),
1.64-1.90 (m, 2H), 2.14 (q, J ) 7.5 Hz, 2H), 3.66-3.79 (m,
1H), 5.35 (br s, 1H); 13C NMR (75 MHz, CDCl3) δ 10.0, 24.6,
25.5, 29.9, 33.2, 48.0, 172.7. Anal. Calcd for C9H17NO: C, 69.63;
H, 11.04; N, 9.02. Found: C, 69.62; H, 10.95; N, 9.02.
3-Cin n a m ylbu ta n -2-on e (3h ).17 Using the general proce-
dure described above, the title compound was obtained as a
colorless oil (0.079 g, 84% for using n-BuLi as a base) from
diethyl 1-cinnamyl-1-methyl-2-oxopropylphosphonate (1h ; 0.162
g, 0.50 mmol) after chromatography (EtOAc/hexane, 20/80):
1H NMR (300 MHz, CDCl3) δ 1.16 (d, J ) 7.0 Hz, 3H), 2.18 (s,
N-(4-Ch lor op h en yl)-4-p en ten a m id e (6d ). Using the gen-
eral procedure described above, the title compound was
obtained as a white solid (0.174 g, 83%) from diethyl 3-bute-
nylphosphonate (0.166 g, 1.0 mmol) and 4-chlorophenyl iso-
(18) (a) Koziara, A.; Zawadzki, S.; Zwierzak, A. Synthesis 1979, 527.
(b) Kita, Y.; Akai, S.; Ajimura, N.; Yoshigi, M.; Tsugoshi, T.; Yasuda,
H.; Tamura, Y. J . Org. Chem. 1986, 51, 4150.
(16) Araujo, H. C.; Mahajan, J . R. Synthesis 1978, 228.
(17) Shibata, I.; Nishio, M.; Baba, A.; Matsuda, H. Chem. Lett. 1993,
1953.
(19) Zhang, Z.; Scheffold, R. Helv. Chim. Acta 1993, 76, 2602.

7022 J . Org. Chem., Vol. 64, No. 19, 1999
Lee et al.
cyanate (0.169 g, 1.1 mmol) after chromatography (EtOAc/
hexane, 25/75): mp 86-87 °C; H NMR (300 MHz, CDCl3) δ
2.40-2.47 (m, 4H), 5.01-5.12 (m, 2H), 5.77-5.90 (m, 1H),
7.22-7.45 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 29.3, 36.7,
116.0, 121.1, 128.9, 129.2, 136.3, 136.6, 170. 6.
mmol) was added. The mixture was warmed to room temper-
ature, and LiAlH4 (3.0 mL of a 1.0 M solution in THF) was
added. After the mixture was stirred for 1 h, aqueous H2SO4
solution (5 N, 5 mL) was added, and the resulting solution
extracted with diethyl ether (30 mL × 3). The combined
organic layers were washed with aqueous NaHCO3 solution
(5%, 5 mL × 1) and distilled water (5 mL × 2), and dried over
MgSO4. After evaporation of ether, the residue was chromato-
graphed on a silica gel column (EtOAc/hexane, 15/85) to
provide the pure amide product as a white solid (0.184 g,
65%): mp 59-63 °C; 1H NMR (300 MHz, CDCl3) δ 2.60-2.87
(m, 2H), 3.82-3.86 (m, 2H), 5.13-5.22 (m, 2H), 5.83-5.94 (m,
1H), 7.07-7.45 (m, 10H), 8.37 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 36.5, 53.4, 115.1, 118.5, 119.9, 124.6, 127.7, 129.0,
129.4, 130.8, 133.2, 137.3, 166.8; HRMS calcd for C17H17NOS
283.1031, found 283.1049. Anal. Calcd for C17H17NOS: C,
72.05; H, 6.05; N, 4.94. Found: C, 72.09; H, 6.07; N, 4.94.
N-(4-Ch lor oph en yl)-2-m eth yl-4-pen ten am ide (8b). Meth -
od A. Using a procedure similar to that described above for
the synthesis of 8a except that diethyl ethylphosphonate (0.166
g, 1.0 mmol) and 4-chlorophenyl isocyanate (0.169 g, 1.1 mmol)
were used, the title compound was obtained as a white solid
(0.136 g, 61%) after purification by chromatography (EtOAc/
hexane, 15/85).
Meth od B. Using the general procedure described above
for the synthesis of 7, the title compound was obtained as a
white solid (0.141 g, 63%) from diethyl R-allylethylphosphonate
9 (206 g, 1.0 mmol) and 4-chlorophenyl isocyanate (0.169 g,
1.1 mmol) after chromatography: mp 79-82 °C; 1H NMR (300
MHz, CDCl3) δ 1.22 (d, J ) 6.7 Hz, 2H), 2.17-2.25 (m, 1H),
2.36-2.50 (m, 2H), 5.03-5.12 (m, 2H), 5.71-5.84 (m, 1H),
7.22-7.27 (m, 2H), 7.32 (s, 1H), 7.43-7.46 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 17.4, 38.3, 42.0, 117.3, 121.3, 128.9, 129.2,
135.4, 136.4, 174.3; HRMS calcd for C12H14ClNO 223.0764,
found 223.0775. Anal. Calcd for C12H14ClNO: C, 64.43; H, 6.31;
N, 6.26. Found: C, 64.36; H, 6.42; N, 6.34.
Dieth yl 2-Meth yl-3-bu ten ylp h osp h on a te (9).15 To a
stirred solution of diethyl ethylphosphonate (0.332 g, 2.0 mmol)
in dry THF (6 mL) under N2 at -78 °C was added n-BuLi (1.31
mL of a 1.6 M solution in hexanes, 2.10 mmol) dropwise, and
the solution was stirred for 1 h. Allyl bromide (0.190 mL, 2.2
mmol) was added, and the mixture was warmed to room
temperature. After the mixture was stirred for 3 h, saturated
NH4Cl solution (2 mL) was added, and the resulting solution
extracted with diethyl ether (30 mL × 3). The combined
organic layers were washed with distilled water (3 mL × 2),
dried over MgSO4, and evaporated. The crude product was
purified by chromatography (EtOAc/hexane, 75/25) to afford
the title compound as a colorless oil (0.379 g, 92%): 1H NMR
(300 MHz, CDCl3) δ 1.10 (dd, J ) 7.1, 18.5 Hz, 3H), 1.73-
1.90 (m, 1H), 1.96-2.07 (m, 1H), 2.46-2.56 (m, 1H), 4.01-
4.11 (m, 4H), 4.99-5.06 (m, 2H), 5.64-5.78 (m, 1H); 13C NMR
(75 MHz, CDCl3) δ 12.7, 16.4 (d, J ) 5.8 Hz), 30.6 (d, J ) 140.6
Hz), 61.5 (d, J ) 7.3 Hz), 116.9, 135.7 (d, J ) 15.4 Hz).
1
N-Ben zyl-2-p h en ylth ioa ceta m id e (6e). Using the general
procedure described above, the title compound was obtained
as a white solid (0.185 g, 72%) from diethyl phenylthiometh-
ylphosphonate (0.260 g, 1.0 mmol) and benzyl isocyanate (0.14
mL, 1.1 mmol) after chromatography (EtOAc/hexane, 25/75):
mp 56-57 °C; 1H NMR (200 MHz, CDCl3) δ 3.62 (s, 2H), 4.38
(d, J ) 5.8 Hz, 2H), 7.03-7.29 (m, 10H); 13C NMR (50 MHz,
CDCl3) δ 37.1, 43.5, 126.4, 127.2, 127.3, 128.1, 128.4, 129.1,
134.4, 137.6, 167.6.
N-P h en yl-2-p h en ylth ioa ceta m id e (6f).20 Using the gen-
eral procedure described above, the title compound was
obtained as a white solid (0.197 g, 81%) from diethyl phe-
nylthiomethylphosphonate (0.260 g, 1.0 mmol) and phenyl
isocyanate (0.12 mL, 1.1 mmol) after chromatography (EtOAc/
1
hexane, 25/75): mp 73-76 °C; H NMR (300 MHz, CDCl3) δ
3.75 (s, 2H), 7.10 (t, J ) 7.4 Hz, 1H), 7.17-7.47 (m, 10H), 8.56
(br s, 1H); 13C NMR (50 MHz, CDCl3) δ 38.4, 119.9, 124.8,
127.1, 128.4, 129.0, 129.5, 134.1, 137.2, 165.9. Anal. Calcd for
C
14H13NOS: C, 69.10; H, 5.39; N, 5.76. Found: C, 69.45; H,
5.51; N, 5.77.
N-Cycloh exyl-2-p h en ylth ioa ceta m id e (6g). Using the
general procedure described above, the title compound was
obtained as a white solid (0.197 g, 79%) from diethyl phen-
ylthiomethylphosphonate (0.260 g, 1.0 mmol) and cyclohexyl
isocyanate (0.14 mL, 1.1 mmol) after chromatography (EtOAc/
1
hexane, 25/75): mp 86-88 °C; H NMR (200 MHz, CDCl3) δ
0.92-1.37 (m, 5H), 1.47-1.62 (m, 3H), 1.69-1.77 (m, 2H), 3.55
(s, 2H), 3.60-3.76 (m, 1H), 6.67 (br s, 1H), 7.12-7.25 (m, 5H);
13C NMR (50 MHz, CDCl3) δ 24.4, 25.2, 32.5, 37.4, 48.2, 126.5,
128.1, 129.1, 134.6, 166.5.
N-Cycloh exyl-2-p h en yla ceta m id e (6h ). Using the gen-
eral procedure described above, the title compound was
obtained as a white solid (0.122 g, 56%) from diethyl ben-
zylphosphonate (0.228 g, 1.0 mmol) and cyclohexyl isocyanate
(0.14 mL, 1.1 mmol) after chromatography (EtOAc/hexane, 30/
70): mp 124-128 °C; 1H NMR (300 MHz, CDCl3) δ 0.92-1.14
(m, 3H), 1.23-1.36 (m, 2H), 1.48-1.63 (m, 3H), 1.78-1.84 (m,
2H), 3.52 (s, 2H), 3.65-3.76 (m, 1H), 5.22 (br s, 1H), 7.20-
7.38 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 24.6, 25.4, 32.9,
44.0, 48.1, 127.2, 128.9, 129.3, 135.1, 169.9.
N-Ben zyla ecta m id e (6i).18b Using the general procedure
described above, the title compound was obtained from diethyl
methylphosphonate (0.152 g, 1.0 mmol) and benzyl isocyanate
(0.14 mL, 1.1 mmol), but cannot be isolated purely even after
chromatography (EtOAc/hexane, 50/50). The yield was deter-
mined by 1H NMR analysis (47%): 1H NMR (200 MHz, CDCl3)
δ 2.19 (s, 3H), 4.54 (d, J ) 5.6 Hz, 2H) 7.17-7.38 (m, 5H),
9.71 (br s, 1H); 13C NMR (50 MHz, CDCl3) δ 25.4, 44.5, 127.2,
127.4, 128.6, 137.3, 175.2.
N-P h en yl-2-p h en ylth io-4-p en ten a m id e (8a ). To a stirred
solution of diethyl phenylthiomethylphosphonate (0.260 g, 1.0
mmol) in dry THF (5 mL) under N2 at -78 °C was added
n-BuLi (0.66 mL of a 1.6 M solution in hexanes, 1.05 mmol)
dropwise, and the solution was stirred for 1 h. Phenyl
isocyanate (0.12 mL, 1.1 mmol) was added, and the mixture
was warmed slowly to -30 °C. n-BuLi (0.66 mL of a 1.6 M
solution in hexanes, 1.05 mmol) was added dropwise, and the
mixture was warmed to 0 °C. After the mixture was stirred
for 1 h at the same temperature, allyl bromide (0.087 mL, 1.0
Ack n ow led gm en t. This research was supported by
a grant from the Korea Advanced Institute of Science
and Technology.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra of all compounds described in the Experimental
Section and HRMS data for compounds 1a , 3a , 8a , and 8b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(20) Roblot, G.; Wylde, R.; Martin, A.; Parello, J . Tetrahedron 1993,
49, 6381.
J O990221R