Preparation of 1,5-disubstituted pyrrolidin-2-ones

Article abstract of DOI:10.1021/jo000219w

1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5- (benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2,5-dimethoxy-2,5-dihydrofuran(7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.

Full text of DOI:10.1021/jo000219w

4364
J . Org. Chem. 2000, 65, 4364-4369
P r ep a r a tion of 1,5-Disu bstitu ted P yr r olid in -2-on es
Alan R. Katritzky,* Shamal Mehta, Hai-Ying He, and Xilin Cui
Center for Heterocyclic Chemistry, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received February 16, 2000
1,5-Disubstituted pyrrolidin-2-ones 18a -g, 19a -h , and 20a -f were synthesized in good to excellent
yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with
allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-
2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from
2,5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically
with nucleophiles.
Sch em e 1
In tr od u ction
Pyrrolidin-2-ones possess varied biological activity and
have been used as pharmaceuticals.1,2 Consequently,
there has been an ongoing interest in the synthesis of
substituted pyrrolidin-2-ones. They are also effective
intermediates for the synthesis of pyrrolidine alkaloids
and γ-amino acids.3 Although the preparation of pyr-
rolidin-2-ones has been much studied,4 it remains of
considerable interest to explore new synthetic routes. We
now report the novel synthesis of 1,5-disubstituted
pyrrolidin-2-ones via benzotriazole methodology.5
Typical routes to 1,5-disubstituted pyrrolidin-2-ones
can be classified as follows (Scheme 1): (A) treatment of
carbinolamide (1) with CF3COOH gave a ring-closure
product 4 [R1, R2 ) -CH(CH2CH2CH3)CH2CH(O2CCF3)-
CH2-];6 (B) reductive ring-contraction of pyridazin-3-ones
2 by Zn in AcOH formed 4 (R1 ) H, R2 ) aryl);7 (C)
ring-closure reactions of (i) dimethyl 3-oxohexanedioate
(3) with primary amines to 4 (R1 ) H or alkyl, R2
)
CH2CO2CH3),8 (ii) γ,δ-unsaturated hydrazide (5) with
active MnO2 to 4 (R1 ) NHCO2Et, R2 ) CHdCHCH3),9
and (iii) γ-amino-R,â-unsaturated carboxylate 6 with
magnesium in methanol to 4 (R1 ) H, R2 ) alkyl);10
(D) reaction of 2,5-dimethoxy-2,5-dihydrofuran (7) and
primary amines in refluxing acetic acid produced 4 (R2 )
alkoxy) (Scheme 1).11,12
The reported methods generally introduce R2 (alkyl or
aryl) group into the pyrrolidin-2-one ring directly from
the starting material. Because of the strong C-C bond,
it is difficult to replace such R2 groups substituted by any
other functionality. The weaker C-N bond of N-substi-
tuted benzotriazoles should allow easy replacement of a
Bt group via nucleophilic substitution, elimination, re-
duction, and cyclization, etc.5 We report herein the
synthesis of 5-benzotriazolyl-1-substituted-pyrrolidin-2-
ones as versatile synthons and their novel reactions with
allylsilanes, organozinc reagents, and phosphorus com-
pounds to generate 1,5-disubstituted pyrrolidin-2-ones.
(1) Harrison, T. Contemp. Org. Synth. 1995, 209.
(2) (a) Lin, N. H.; Carrera, G. M., J r.; Anderson, D. J . J . Med. Chem.
1994, 37, 3542. (b) Shih, N. Y.; Lupo, A. T., J r.; Aslanian, R.; Orlando,
S.; Piwinski, J . J .; Green, M. J .; Ganguly, A. K.; Clark, M. A.; Tozzi,
S.; Kreutner, W.; Hey, J . A. J . Med. Chem. 1995, 38, 1593. (c) Elliott,
R. L.; Kopecka, H.; Lin, N. H.; He, Y.; Garvey, D. S. Synthesis 1995,
772.
(3) (a) Castelhano, A. L.; Krantz, A. J . Am. Chem. Soc. 1984, 106,
1877. (b) Hiemstra, H.; Fortgens, H. P.; Speckamp, W. N. Tetrahedron
Lett. 1984, 25, 3115. (c) Huang, P. Q.; Wang, S. L.; Ye, J . L.; Ruan, Y.
P.; Huang, Y. Q.; Zheng, H.; Gao, J . X. Tetrahedron 1998, 54, 12547.
(d) Banziger, M.; McGarrity, J . F.; Meul, T. J . Org. Chem. 1993, 58,
4010. (e) Wei, Z. Y.; Knaus, E. E. Synlett 1993, 295.
(4) (a) Polniaszek, R. P.; Belmont, S. E. J . Org. Chem. 1991, 56,
4868. (b) Meyers, A. I.; Seefeld, M. A.; Lefker, B. A.; Blake, J . F.;
Williard, P. G. J . Am. Chem. Soc. 1998, 120, 7429. (c) Burgess, L. E.;
Meyers, A. I. J . Org. Chem. 1992, 57, 1656. (d) Fehn, S.; Burger, K.
Tetrahedron: Asymmetry 1997, 8, 2001. (e) Ma, D.; Ma, J .; Ding, W.;
Dai, L. Tetrahedron: Asymmetry 1996, 7, 2365. (f) Burgess, L. E.;
Meyers, A. I. J . Am. Chem. Soc. 1991, 113, 9858. (g) Koot, W. J .; Ginkel,
R.; Kranenburg, M.; Hiemstra, H. Tetrahedron Lett. 1991, 32, 401.
(5) Katritzky, A. R.; Lan, X.; Yang J . Z.; Denisko, O. V. Chem. Rev.
1998, 98, 409.
Resu lts a n d Discu ssion
P r epar ation of 5-Ben zotr iazolyl-1-su bstitu ted-pyr -
r olid in -2-on es 9 a n d 10. The reaction of 2,5-dimethoxy-
(6) Hart, D. J .; Tsai, Y. M. Tetrahedron Lett. 1981, 22, 1567.
(7) Brown, G. R.; Foubister, A. J .; Wright, B. J . Chem. Soc., Chem.
Commun. 1984, 1373.
(8) Celerier, J . P.; Marx, E.; Lhommet, G. J . Heterocycl. Chem. 1988,
25, 1275.
(10) Wei, Z. Y.; Knaus, E. E. Tetrahedron Lett. 1993, 34, 4439.
(11) Baussanne, I.; Chiaroni, A.; Husson, H. P.; Riche C.; Royer, J .
Tetrahedron Lett. 1994, 35, 3931.
(12) Poli, G.; Baffoni, S. C.; Giambastiani, G.; Reginato, G. Tetra-
hedron 1998, 54, 10403.
(9) Vedejs, E.; Meier, G. P. Tetrahedron Lett. 1979, 43, 4185.
10.1021/jo000219w CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/17/2000

Preparation of 1,5-Disubstituted Pyrrolidin-2-ones
J . Org. Chem., Vol. 65, No. 14, 2000 4365
Ta ble 1. Isola ted Yield s of 9-11
Sch em e 2
a
b
No detectable amount of the product was isolated. HOCH2-
CH2NH2 was used, but 9f and 10f were obtained as esters due to
the presence of CH3COOH. c (S)-PhCH(CH2OH)NH2 was used, but
9j, 10j, and 11j were obtained as esters due to the presence of
d
CH3COOH. Yields estimated by 1H NMR spectrum.
forms the same transient iminium cation 15, which
immediately reacts with BtH to produce 5-benzotriazolyl-
1-substituted-pyrrolidin-2-ones 9 and 10.13 No conjugated
pyrrolinone 17 was detected in our reaction. In addition,
the intramolecular condensation of the formyl group and
the secondary amine in the transient 12 generates the
intermediate iminium cation 13, which reacts with BtH
and subsequently eliminates AcOH to afford the minor
product R-(benzotriazol-1-yl)pyrrole 11.
2,5-dihydrofuran (7), benzotriazole, and primary amine
8 in refluxing AcOH for 24 h gave 5-(benzotriazol-1-yl)-
1-substituted-pyrrolidin-2-one 9 and 5-(benzotriazol-2-yl)-
1-substituted-pyrrolidin-2-one 10, along with a minor
byproduct 1-(1-substituted-1H-pyrrol-2-yl)-1H-1,2,3-benzo-
triazole 11 (Scheme 2). Bt1 isomer 9 and Bt2 isomer 10
were separated by column chromatography (silica gel),
with the Bt1 isomer as the major constituent. Although
some of the intermediates, e.g., 9a ,c,f,g,i-k and 10b,f-k ,
were not fully characterized possibly due to easy oxida-
Our previous work14 has demonstrated that (i) Bt1 and
Bt2 groups are both good leaving groups and can be
replaced by a nucleophile, and (ii) the mechanism of
nucleophilic substitution of the Bt group from the adduct
X involves a planar iminium salt Y as intermediate
(Scheme 2). Therefore, the position at which the sub-
stituent is attached to the benzotriazole ring is not
important. Thus, the mixture of intermediates 9 and 10
could be used for the subsequent nucleophilic substitu-
tions with allylsilanes, organozinc reagents and phos-
phorus compounds.
1
tion, they had clear H and 13C NMR spectra, and their
nucleophilic reactions with allylsilanes, organozinc re-
agents, and phosphorus compounds also afforded the
fully characterized expected 1,5-disubstituted pyrrolidin-
2-ones. The total yields for 9 and 10 are from good to
excellent (Table 1). Methyl (2S)-2-amino-3-phenylpro-
panoate gave the expected intermediate 9i, which indi-
cates that easily obtained chiral amino acid esters could
be used for the preparation of 1,5-disubstituted pyrroli-
din-2-ones, although no expected product was isolated
using (2S)-2-amino-3-phenylpropanoic acid. From chiral
primary amines, the intermediates 9h -j and 10h -j were
obtained with little chiral control at the 5-position as
Su bstitu tion of th e Ben zotr ia zole Gr ou p fr om 9
Usin g Allylsila n es. Initially, it was desired to confirm
that there was no difference in the reactivity of the Bt1
isomer 9 and the Bt2 isomer 10. Hence, 9b (R1 ) PhCH2),
9c (R1 ) PhCH2CH2), and 10b (R1 ) PhCH2), 10c (R1 )
PhCH2CH2) were each separately used to react with allyl-
(trimethyl)silane in the presence of BF3‚Et2O. The yields
of 18a , generated from 9b and 10b, were 90% and 87%,
respectively, while the yields of 18b, generated from 9c
and 10c, were 90% and 90%, respectively (Scheme 3).
These examples prove that the Bt1 isomer and Bt2 isomer
have no significant difference in their reactivities and
1
shown by the H and 13C NMR spectra.
The mechanism for the reaction of 7 and R1NH2 was
previously supposed to involve a competitive R- and
γ-tautomerization of the transient 2-hydroxypyrrole (14),
leading to the formation of 5-methoxypyrrolidin-2-one 16
and the conjugated pyrrolinone 17, respectively (Scheme
2).12 We believe, in our reaction, 2-hydroxypyrrole (14)
(13) (a) Katritzky, A. R.; Yannakopoulou, K.; Lue, P.; Rasala, D.;
Urogdi, L. J . Chem. Soc., Perkin Trans. 1 1989, 225. (b) Katritzky, A.
R.; Chang, H. X.; Wu, J . Synthesis 1994, 907.
(14) (a) Katritzky, A. R.; Fan, W. Q. J . Org. Chem. 1990, 55, 3205.
(b) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron 1991,
47, 2683. (c) Katritzky, A. R.; Qiu, G.; Yang, B.; Steel, P. J . J . Org.
Chem. 1998, 63, 6699.

4366 J . Org. Chem., Vol. 65, No. 14, 2000
Katritzky et al.
Sch em e 3
Sch em e 4
Sch em e 5
lead to the same products in very similar yields. To
compare and discuss different reactions, the same experi-
ments were carried out by using the pure Bt1 isomer 9
as the starting material.
Treatment of intermediates 9b-e,i with 4 equiv of
trimethylallyl- or trimethyl(2-methylallyl)silane in the
presence of BF3‚Et2O at 0 °C furnished 1-substituted-5-
allylpyrrolidin-2-ones 18a -f in 80-90% yield and 18g
in 49% yield (Scheme 3). The structures of 18a -g were
1
confirmed by the H, 13C NMR spectra and high-resolu-
tion mass spectra (HRMS). The Bt group of 9 serves as
a good leaving group and is easily eliminated in the
presence of BF3‚Et2O to generate iminium cation Y,
which is subsequently attacked by the nucleophile allyl-
silane to afford the 1-substituted-5-allylpyrrolidin-2-ones
18a -g. Thus, by using benzotriazole methodology, an
allyl group is easily introduced into the 5-position of
the pyrrolidin-2-one ring. However, 18g was obtained
as diastereoisomers with no control by the N-(chiral)-
substituted group of the 5-position chiral center.
triethyl- or trimethyl phosphite.15 In our reaction, avoid-
ing the use of potassium cyanide, the treatment of 9d -
g,i,j in dry THF with triethyl phosphite in the presence
of 1 equiv of ZnBr2 produced diethyl 1-substituted-5-oxo-
2-pyrrolidinylphosphonates 20a -f in moderate to good
yields (Scheme 5). The Bt groups of 9d -g,i,j are readily
replaced with a phosphono group. The intermediates 9f
and 9j, as esters, were hydrolyzed during the reaction;
thus, 20a and 20e were obtained as primary alcohols.
Su bstitu tion of th e Ben zotr ia zole Gr ou p fr om 9
Usin g Or ga n ozin c Rea gen ts. Grignard reagents can-
not be directly used for the nucleophilic substitution of
9, since they react with carbonyl groups. Treatment of
9b and 9e with 3 equiv of organozinc reagent, generated
by the reaction of the Grignard reagents and zinc
chloride, in reflux THF gave 1,5-disubstituted pyrrolidin-
2-ones 19a -g in moderate to excellent yields, while
treatment of 9e with 3 equiv of 2-bromomalonate and
zinc powder in reflux THF afforded 19h in 67% yield
(Scheme 4). The structures of 19a -h were determined
1
The structures of 20a -f are determined by H and 13C
NMR, and the 13C NMR spectra show that phosphorus
has the coupling splitting effect on some carbon peaks.
Again, a chiral group at 1-position [R1 ) (S)-PhCH(CH2-
OH) or (S)-PhCH2CH(CO2Me)] did not control the chiral
center at 5-position, as 20e and 20f were obtained as
diastereoisomers.
In conclusion, we have described a simple and novel
route to 1,5-disubstituted pyrrolidin-2-ones via the benzo-
triazole methodology. Several advantages for this reac-
tion include the following: (1) the intermediates 9a -k
and 10a -k could be obtained in one step; (2) the total
yield for Bt1 and Bt2 isomers is from good to excellent
1
by the H, 13C NMR as well as HRMS. The nucleophilic
substitution of 9 with organozinc reagents thus allows
the introduction of various substituents, e.g., propynyl,
vinyl, propenyl, benzyl, cyclopentyl, pentyl, and ester,
into the 5-position of the pyrrolidin-2-one rings.
Su bstitu tion of th e Ben zotr ia zole Gr ou p fr om 9
by P h osp h or u s Nu cleop h iles. In 1997, Maury et al.
reported that the cyano group of (3R,5S,8aR)-3-phenyl-
hexahydrooxazolo[3,2-a]pyridine-5-carbonitrile, gener-
ated from the double condensation of (R)-phenylglycinol
and glutaraldehyde in the presence of potassium cyanide,
could be replaced by a phosphono group using either
(15) Maury, C.; Wang, Q.; Gharbaoui, T.; Chiadmi, M.; Tomas, A.;
Royer, J .; Husson, H. Tetrahedron 1997, 53, 3627.

Preparation of 1,5-Disubstituted Pyrrolidin-2-ones
J . Org. Chem., Vol. 65, No. 14, 2000 4367
1H), 7.20-7.29 (m, 5H), 7.40-7.43 (m, 2H), 7.80-7.90 (m, 2H);
13C NMR δ 25.9, 29.0, 44.4, 77.8, 118.4, 126.9, 127.8, 128.5,
128.6, 135.3, 144.4, 175.1.
(70% to 84%) and there is no difference for the reactivity
of Bt1 and Bt2 isomer; (3) the compounds 9a -k and 10a -
k , as versatile synthons, can be further transformed to
new 1,5-disubstituted pyrrolidin-2-ones via the nucleo-
philic substitution of benzotriazole group with allylsi-
lanes, organozinc reagents and phosphorus compounds.
5-(2H -1,2,3-Ben zot r ia zol-2-yl)-1-[(1S)-1-p h en ylet h yl]-
p yr r olid in -2-on e (10h ). Obtained as diastereoisomers in the
1
ratio 53:47 (minor isomer in the parentheses): yellow oil; H
NMR δ 0.79 (d, J ) 7.2 Hz, 3H), 2.13-2.28 (m, 1H), 2.37-
2.63 (m, 2H), 3.15-3.35 (m, 1H), 5.52-5.65 (m, 1H), 6.09-
6.15 (m, 1H), 7.25-7.51 (m, 7H), 7.83-7.95 (m, 2H); 13C NMR
δ 15.3 (14.6), 27.3 (27.1), 29.1 (28.6), 50.1 (50.8), 76.5 (76.1),
118.3 (118.2), 126.7 (126.5), 127.4 (127.2), 127.9, 128.7, 138.9,
144.2 (144.7), 175.3 (175.0).
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of 5-(Ben zo-
tr iazol-1-yl)-1-su bstitu ted-pyr r olidin -2-on es 9 an d 5-(Ben -
zotr ia zol-2-yl)-1-su bstitu ted -p yr r olid in -2-on es 10. An ap-
propriate primary amine (25 mmol), 2,5-dimethoxy-2,5-
dihydrofuran (7) (3.2 g, 25 mmol), and 1H-1,2,3-benzotriazole
(6.5 g, 55 mmol) were dissolved in acetic acid (25 mL) and
refluxed under N2 for 24 h. After the reaction mixture was
cooled, CH2Cl2 (50 mL) was added. The organic layer was
washed with 2 M NaOH and dried over Na2SO4. The solvent
was evaporated in vacuo, and the residue was separated by
flash chromatography (silica gel) with hexanes-EtOAc (7:3)
as eluent to give 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-
2-ones 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-
ones 10, together with a byproduct 1-(1-substituted-1H-pyrrol-
2-yl)-1H-1,2,3-benzotriazole 11.
Meth yl (2S)-2-[2-(2H-1,2,3-Ben zotr ia zol-2-yl)-5-oxo-1-
p yr r olid in yl]-3-p h en ylp r op a n oa te (10i). Obtained as dia-
stereoisomers in the ratio 54:46 (minor isomer in the paren-
1
theses): brown oil; H NMR δ 2.30-2.67 (m, 3H), 2.90-3.19
(m, 2H), 3.33 (d, J ) 8.1 Hz, 1H), 3.41 (s, 3H) [3.66 (s, 3H)],
4.79-4.87 (m, 1H) [4.34-4.41 (m, 1H)], 5.98 (d, J ) 6.9 Hz,
1H) [6.56 (d, J ) 8.4 Hz, 1H)], 6.92-7.10 (m, 3H), 7.12-7.25
(m, 3H), 7.25-7.51 (m, 2H), 8.01 (d, J ) 8.4 Hz, 1H); 13C NMR
δ 25.1 (24.2), 28.7 (30.3), 34.1 (33.2), 51.6 (52.9), 55.9 (54.9),
72.0 (70.9), 109.1, 119.6 (2), 123.8 (123.7), 126.4 (126.2), 127.4
(126.5), 127.8 (127.5), 127.9 (2), 128.1 (128.0), 128.6, 131.1
(130.6), 136.1 (135.6), 145.7 (145.6), 169.2 (168.8), 174.5
(174.2).
5-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-ben zylp yr r olid in -2-on e
(9b): brown powder; mp 169.5-170.0 °C; 1H NMR δ 2.40-
2.55 (m, 1H), 2.70-2.85 (m, 2H), 3.00-3.15 (m, 1H), 3.53, 4.91
(AB, J ) 15.0 Hz, 2H), 6.34 (d, J ) 6.6 Hz, 1H), 7.04-7.06 (m,
2H), 7.20-7.22 (m, 4H), 7.37-7.49 (m, 2H), 8.07 (d, J ) 8.1
Hz, 1H); 13C NMR δ 25.2, 29.4, 44.3, 71.4, 109.0, 120.4, 124.3,
127.9, 128.0, 128.3, 128.6, 131.4, 134.8, 146.3, 174.2. Anal.
Calcd for C17H16N4O2: C, 69.85; H, 5.52; N, 19.16. Found: C,
69.63; H, 5.66; N, 18.93.
(2S)-2-[2-(2H -1,2,3-Ben zot r ia zol-2-yl)-5-oxo-1-p yr r oli-
d in yl]-2-p h en yleth yl Aceta te (10j). Obtained as diastereo-
isomers in the ratio 52:48 (minor isomer in the parentheses):
1
yellow oil; H NMR 1.66 (s, 3H) [1.87 (s, 3H)], 2.35-2.75 (m,
3H), 3.17-3.42 (m, 1H), 3.90-4.12 (m, 1H), 4.48-4.62 (m, 1H)
[5.01-5.17 (m, 1H)], 5.24-5.40 (m, 1H) [5.55-5.67 (m, 1H)],
6.22 (d, J ) 7.0 Hz, 1H) [6.46 (d, J ) 6.9 Hz, 1H)], 6.80-6.95
(m, 1H), 7.01-7.15 (m, 1H), 7.24-7.51 (m, 5H), 7.60-7.75 (m,
1H), 7.81-7.95 (m, 1H); 13C NMR δ 20.2 (20.5), 27.3 (26.7),
29.3 (29.4), 54.9 (53.9), 61.9 (61.5), 77.4 (76.8), 118.3 (118.1),
126.6, 127.1, 127.3, 127.6, 127.7, 127.9, 128.6, 128.9, 134.7,
134.9, 144.3 (144.0), 170.6 (171.6), 176.1 (175.9).
5-(1H -1,2,3-Ben zot r ia zol-1-yl)-1-[(1S)-1-p h en ylet h yl]-
p yr r olid in -2-on e (9h ). Obtained as diastereoisomers in the
1
ratio 57:43 (minor isomer in the parentheses): yellow oil; H
NMR δ 0.79 (d, J ) 7.2 Hz, 3H), 2.26-2.38 (m, 1H), 2.53-
2.77 (m, 2H), 3.12-3.30 (m, 1H), 5.50-5.65 (m, 1H), 6.05-
6.15 (m, 1H), 7.03 (d, J ) 8.0 Hz, 1H), 7.15-7.25 (m, 2H),
7.30-7.53 (m, 5H), 8.10 (d, J ) 7.6 Hz, 1H); 13C NMR δ 15.8
(15.1), 26.8 (27.0), 29.7 (29.4), 50.2 (50.5), 69.9 (69.6), 109.3
(109.1), 120.4 (120.1), 124.3 (124.2), 127.6 (127.5), 127.8
(127.6), 128.2 (127.9), 128.9, 131.3, 138.5, 146.1 (147.2), 174.9
(175.2). Anal. Calcd for C18H18N4O: C, 70.57; H, 5.92; N, 18.29.
Found: C, 70.23; H, 6.02; N, 18.46.
Gen er a l P r oced u r e for th e Rea ction of 9 w ith Allyl-
sila n es. To an ice-cold solution of 9 (0.7 mmol) in dry CH2Cl2
(10 mL) under N2 was added an appropriate allylsilane (2.8
mmol) and the mixture stirred for 10 min. BF3‚Et2O (4.2 mmol)
in dry CH2Cl2 (10 mL) was added dropwise, and the mixture
was stirred at 0 °C for 24 h. Then 2 M NaOH (10 mL) was
added to quench the reaction. The aqueous phase was ex-
tracted with CH2Cl2, and the combined extracts were dried
over Na2SO4. After removal of solvents in vacuo, the residue
was separated by column chromatography (silica gel) with
hexanes/EtOAc (3:2) as eluent to give 18.
Meth yl (2S)-2-[2-(1H-1,2,3-Ben zotr ia zol-1-yl)-5-oxo-1-
p yr r olid in yl]-3-p h en ylp r op a n oa te (9i). Obtained as dia-
stereoisomers in the ratio 59:41 (minor isomer in the paren-
5-Allyl-1-ben zyl-p yr r olid in -2-on e (18a ): yellow oil; 1H
NMR δ 1.72-1.90 (m, 1H), 2.03-2.11 (m, 1H), 2.14-2.30 (m,
1H), 2.36-2.65 (m, 3H), 3.51-3.56 (m, 1H), 4.02 (d, J ) 14.7
Hz, 1H), 5.02-5.17 (m, 3H), 5.60-5.73 (m, 1H), 7.20-7.48 (m,
5H); 13C NMR δ 23.1, 30.0, 37.0, 44.1, 56.2, 118.7, 127.4, 127.8,
128.5, 132.4, 136.3, 175.4; HRMS calcd for C14H18NO 216.1388
(M + 1), found 216.1390.
1
theses): yellow oil; H NMR δ 2.34-2.90 (m, 3H), 2.93-3.15
(m, 2H), 3.49 (d, J ) 8.1 Hz, 1H), 3.66 (s, 3H) [3.41 (s, 3H)],
4.79-4.87 (m, 1H), 6.06 (d, J ) 5.7 Hz, 1H) [6.30 (d, J ) 6.6
Hz, 1H)], 7.00-7.10 (m, 4H), 7.23 (t, J ) 6.6 Hz, 2H), 7.46 (t,
J ) 6.9 Hz, 1H), 7.56 (d, J ) 8.4 Hz, 1H), 8.06 (d, J ) 7.8 Hz,
1H); 13C NMR δ 26.1 (25.2), 28.7 (28.6), 34.1 (32.9), 52.3 (51.5),
55.9 (54.6), 78.3 (76.3), 103.4, 110.0 (112.8), 117.9 (117.8), 119.4
(120.2), 123.5 (121.9), 126.4 (126.2), 126.8 (126.5), 127.9
(127.8), 128.3 (128.2), 135.3 (132.2), 136.1 (135.8), 143.8
(145.4), 169.7 (169.1), 175.2 (175.3).
5-Allyl-1-p h en eth ylp yr r olid in -2-on e (18b): yellow oil; 1H
NMR δ 1.65-1.89 (m, 1H), 1.97-2.53 (m, 5H), 2.75-3.07 (m,
2H), 3.10-3.28 (m, 1H), 3.45-3.67 (m, 1H), 3.85-4.05 (m, 1H),
5.05-5.30 (m, 2H), 5.55-5.80 (m, 1H), 7.15-7.45 (m, 5H); 13
C
(2S)-2-[2-(1H -1,2,3-Ben zot r ia zol-1-yl)-5-oxo-1-p yr r oli-
d in yl]-2-p h en yleth yl Aceta te (9j). Obtained as diastereo-
isomers in the ratio 54:46 (minor isomer in the parentheses):
yellow oil; 1H NMR δ 1.95 (s, 3H) [1.75 (s, 3H)], 2.25-2.45 (m,
1H), 2.60-2.87 (m, 2H), 3.07-3.32 (m, 1H), 4.00-4.18 (m, 1H)
[3.70-3.83 (m, 1H)], 4.48-4.57 (m, 1H) [5.05-5.18 (m, 1H)],
5.20-5.31 (m, 1H) [5.48-5.60 (m, 1H)], 6.67 (J ) 6.3 Hz, 1H)
[6.25 (d, J ) 6.4 Hz, 1H)], 6.80-7.05 (m, 2H), 7.10-7.55 (m,
6H), 7.89 (d, J ) 8.2 Hz, 1H) [8.08 (d, J ) 8.2 Hz, 1H)]; 13C
NMR δ 20.6 (20.3), 25.8 (26.3), 29.6 (29.5), 54.6 (54.2), 61.8
(61.3), 70.7 (71.0), 109.3 (109.2), 120.1 (120.5), 123.9, 124.3,
126.9 (127.4), 127.7, 127.8, 128.0 (128.7), 129.0, 130.8 (130.9),
134.2 (134.6), 146.3 (146.1), 170.0 (170.6), 175.2 (175.1).
5-(2H-1,2,3-Ben zotr ia zol-2-yl)-1-ben zylp yr r olid in -2-on e
(10b): yellow oil; 1H NMR δ 2.50-2.67 (m, 3H), 3.08-3.25 (m,
1H), 3.60, 4.94 (AB, J ) 14.7 Hz, 2H), 6.22 (d, J ) 6.6 Hz,
NMR δ 23.4, 30.0, 33.7, 37.4, 41.9, 57.2, 118.7, 126.4, 128.4,
128.6, 132.7, 138.8, 175.0; HRMS calcd for C15H20NO 230.1545
(M + 1), found 230.1546.
5-(2-Meth yl-2-p r op en yl)-1-p h en eth ylp yr r olid in -2-on e
1
(18c): yellow oil; H NMR δ 1.66 (s, 3H), 1.83-2.10 (m, 2H),
2.25-2.61 (m, 4H), 2.75-3.00 (m, 2H), 3.12-3.30 (m, 1H),
3.45-3.60 (m, 1H), 3.87-4.05 (m, 1H), 4.71 (s, 1H), 4.83 (s,
1H), 7.10-7.50 (m, 5H); 13C NMR δ 22.4, 23.8, 29.8, 33.9, 41.4,
42.1, 56.4, 113.6, 126.4, 128.5, 128.6, 138.7, 140.9, 175.4;
HRMS calcd for C16H22NO 244.1701 (M + 1), found 244.1688.
1-(4-Meth oxyben zyl)-5-(2-m eth yl-2-pr open yl)pyr r olidin -
2-on e (18d ): yellow oil; 1H NMR δ 1.64 (s, 3H), 1.70-1.80 (m,
1H), 1.91-2.10 (m, 2H), 2.30-2.60 (m, 3H), 3.50-3.60 (m, 1H),
3.80 (s, 3H), 3.94, 4.93 (AB, J ) 14.7 Hz, 2H), 4.87 (d, J )
14.5 Hz, 2H), 6.85 (d, J ) 8.4 Hz, 2H), 7.17 (d, J ) 8.4 Hz,
2H); 13C NMR δ 22.9, 24.1, 30.3, 41.7, 44.0, 55.5, 55.6, 113.9,

4368 J . Org. Chem., Vol. 65, No. 14, 2000
Katritzky et al.
114.3, 114.4, 118.8, 127.3, 129.2, 129.7, 130.4, 141.7, 159.4,
175.3; HRMS calcd for C16H22NO2 260.1651 (M + 1), found
260.1659.
2.70-3.00 (m, 2H), 3.00-3.30 (m, 1H), 3.50-3.65 (m, 1H), 3.76
(s, 3H), 3.85-4.00 (m, 1H), 4.30-4.50 (m, 1H), 6.83 (d, J )
8.5 Hz, 2H), 7.02-7.20 (m, 3H), 7.20-7.40 (m, 4H); 13C NMR
δ 23.6, 24.6, 28.6, 29.6, 32.9, 33.0, 39.2, 42.0, 42.1, 55.0, 58.8,
68.1, 89.0, 113.7, 126.5, 127.5, 127.7, 128.4, 129.0, 129.4, 129.5,
130.7, 130.8, 136.8, 158.0, 174.8; HRMS calcd for C20H24NO2
310.1807 (M + 1), found 310.1806.
5-Cyclop en t yl-1-(4-m et h oxyp h en et h yl)p yr r olid in -2-
on e (19f): yellow oil; 1H NMR δ 1.40-1.80 (m, 8H), 1.80-
2.00 (m, 1H), 2.00-2.40 (m, 2H), 2.40-2.60 (m, 1H), 2.70-
2.90 (m, 2H), 3.10-3.35 (m, 1H), 3.60-3.80 (m, 1H), 3.78 (s,
3H), 3.80-3.90 (m, 1H), 4.64 (d, J ) 5.9 Hz, 1H), 6.84 (d, J )
8.4 Hz, 2H), 7.12 (d, J ) 8.2 Hz, 2H); 13C NMR δ 23.1, 25.9,
28.7, 32.3, 33.1, 33.2, 42.1, 55.1, 78.6, 88.5, 113.8, 129.5, 131.0,
158.1, 174.6; HRMS calcd for C18H26NO2 288.1964, found
288.1961.
1-(4-Meth oxyph en eth yl)-5-pen tylpyr r olidin -2-on e (19g):
colorless oil; 1H NMR δ 0.90 (br s, 3H), 1.22-1.38 (m, 4H),
1.50-1.63 (m, 2H), 1.90-2.00 (m, 2H), 2.20-2.40 (m, 1H),
2.40-2.60 (m, 1H), 2.70-2.90 (m, 2H), 3.20-3.40 (m, 3H),
3.60-3.80 (m, 1H), 3.85 (s, 3H), 4.67-4.69 (m, 1H), 6.83 (d,
J ) 7.9 Hz, 2H), 7.12 (d, J ) 7.8 Hz, 2H); 13C NMR δ 13.9,
22.3, 24.6, 28.3, 28.9, 29.3, 33.1, 42.1, 55.1, 65.9, 89.5, 113.8,
129.5, 131.0, 158.1, 174.8; HRMS calcd for C18H28NO2 290.2120
(M + 1), found 290.2101.
To freshly cleaned and dried Zn powder (1.56 g, 23.9 mmol)
in THF (20 mL) was added diethyl 2-bromomalonate (0.75 g,
3.1 mmol) and the mixture allowed to reflux at 80 °C for 1 h.
A solution of 9e (0.35 g, 1.04 mmol) in THF (20 mL) was then
added dropwise over a period of 10 min. The solution was
allowed to reflux for 48 h, cooled, and quenched by 2 M NaOH
(20 mL). The mixture was extracted with three portions of
CH2Cl2 and dried over Na2SO4. After removal of solvents in
vacuo, the residue was separated by column chromatography
(silica gel) with hexanes/EtOAc (3:1) as eluent to give 19h .
Dieth yl 2-(5-oxo-1-p h en eth yl-2-p yr r olid in yl)m a lon a te
(19h ): yellow oil; 1H NMR δ 1.20-1.39 (m, 6H), 2.10-2.48
(m, 4H), 2.70-2.86 (m, 1H), 2.86-3.12 (m, 2H), 3.68 (d, J )
5.2 Hz, 1H), 3.90-4.05 (m, 1H), 4.10-4.30 (m, 5H), 7.10-7.40
(m, 5H); 13C NMR δ 13.9, 21.5, 29.4, 33.3, 42.2, 53.5, 56.8, 61.7,
61.8, 126.4, 128.4, 128.6, 138.4, 166.9, 167.0, 175.1. Anal. Calcd
for C19H25NO5: N, 4.03. Found: N, 4.50.
Gen er a l P r oced u r e for th e Rea ction of 9 w ith P h os-
p h or u s Com p ou n d s. To a solution of 9 (1.3 mmol) in dry
CH2Cl2 (20 mL) under N2 at 0 °C was added triethyl phosphite
(0.36 mL, 2.1 mmol) and ZnBr2 (0.30 g, 1.3 mmol). The reaction
mixture was stirred at 0 °C for 20 h and then quenched with
2 M NaOH (10 mL). The aqueous phase was extracted with
CH2Cl2. The combined organic extracts were washed with
brine and dried over anhydrous Na2SO4. After removal of
solvent in vacuo, the residue was separated by column chro-
matography (silica gel) with hexanes/EtOAc (4:1) as eluent to
afford 20.
Dieth yl 1-(2-h yd r oxyeth yl)-5-oxo-2-p yr r olid in ylp h os-
p h on a te (20a ): yellow oil; 1H NMR δ 1.30-1.50 (m, 6H), 2.05
(s, 2H), 2.20-2.45 (m, 2H), 2.45-2.60 (m, 1H), 3.40-3.60 (m,
1H), 4.00-4.30 (m, 7H), 4.30-4.50 (m, 1H); 13C NMR δ 16.3
(J ) 5.4 Hz), 20.4 (J ) 32.3 Hz), 29.3, 40.9, 52.9, 55.1, 60.9,
62.3 (J ) 7.1 Hz), 62.9 (J ) 7.0 Hz), 170.6, 175.4 (J ) 3.3 Hz);
HRMS calcd for C10H21NO5P 266.1157 (M + 1), found 266.1162.
Dieth yl 1-(4-m eth oxyben zyl)-5-oxo-2-pyr r olidin ylph os-
p h on a te (20b): yellow oil; 1H NMR δ 1.35 (t, J ) 8.1 Hz,
6H), 2.00-2.50 (m, 3H), 2.55-2.70 (m, 1H), 3.63 (d, J ) 9.6
Hz, 1H), 3.80 (s, 3H), 4.10-4.30 (m, 5H), 5.17 (d, J ) 14.4 Hz,
1H), 6.82 (d, J ) 8.7 Hz, 2H), 7.20 (d, J ) 8.4 Hz, 2H);
13C NMR δ 16.2 (J ) 5.5 Hz), 16.3 (J ) 5.3 Hz), 29.5, 44.4,
51.2, 53.4, 55.0, 55.3, 62.2 (J ) 7.3 Hz), 62.9 (J ) 7.1 Hz),
113.8, 127.7, 129.5, 158.9, 174.9 (J ) 2.9 Hz); HRMS calcd for
5-Ally l-1-(4-m e t h o x y p h e n e t h y l)-p y r r o lid in -2-o n e
(18e): yellow oil; 1H NMR δ 1.61-1.78 (m, 1H), 1.95-2.10 (m,
1H), 2.10-2.25 (m, 1H), 2.25-2.47 (m, 3H), 2.65-2.90 (m, 2H),
3.00-3.20 (m, 1H), 3.45-3.55 (m, 1H), 3.77 (s, 3H), 3.75-4.00
(m, 1H), 5.05-5.20 (m, 2H), 5.60-5.77 (m, 1H), 6.83 (d, J )
8.5 Hz, 2H), 7.13 (d, J ) 8.5 Hz, 2H); 13C NMR 23.2, 29.9,
32.6, 37.3, 41.9, 55.0, 57.0, 113.7, 118.5, 129.4, 130.6, 132.6,
158.0, 174.7; HRMS calcd for C16H22NO2 260.1651 (M + 1),
found 260.1676.
1-(4-Met h oxyp h en et h yl)-5-(2-m et h yl-2-p r op en yl)p yr -
r olid in -2-on e (18f): yellow oil; 1H NMR δ 1.68 (s, 3H), 1.68-
1.80 (m, 1H), 1.90-2.10 (m, 2H), 2.20-2.50 (m, 3H), 2.70-
2.90 (m, 2H), 3.00-3.20 (m, 1H), 3.40-3.60 (m, 1H), 3.70 (s,
3H), 3.80-4.00 (m, 1H), 4.73 (d, J ) 8.5 Hz, 1H), 4.85 (d, J )
8.4 Hz, 1H), 6.82 (d, J ) 8.7 Hz, 2H), 7.10 (d, J ) 8.7 Hz, 2H);
13C NMR δ 22.4, 23.8, 29.7, 33.0, 41.5, 42.0, 56.0, 56.1, 113.4,
113.7, 113.9, 129.5, 129.6, 141.1, 158.1, 174.7; HRMS calcd
for C17H24NO2 274.1807 (M + 1), found 274.1802.
Meth yl (2S)-2-(2-a llyl-5-oxo-1-p yr r olid in yl)-3-p h en yl-
p r op a n oa te (18g): yellow oil; 1H NMR δ 1.50-1.90 (m, 2H),
2.00-2.60 (m, 4H), 2.70-2.90 (m, 1H), 3.30-3.50 (m, 2H), 3.76
(s, 3H), 4.05-4.20 (m, 1H), 5.00-5.20 (m, 2H), 5.40-5.80 (m,
1H), 7.10-7.50 (m, 5H); 13C NMR δ 23.7, 29.5, 34.8, 37.8, 37.9,
52.4, 57.7, 59.6, 118.3, 126.7, 128.4, 129.1, 133.2, 170.3, 174.9;
HRMS calcd for C17H22NO3 288.1600 (M + 1), found 288.1588.
Gen er a l P r oced u r e for th e Rea ction of 9 w ith Or ga n o-
zin c Rea gen ts. To an ice-cold solution of Grignard reagent
(8.0 mmol) in dry THF (10 mL) under N2, was added ZnCl2
(8.5 mmol) and the solution allowed to warm to room temper-
ature over 0.5 h. A solution of 9b or 9e (2.7 mmol) in dry THF
(10 mL) was then added, and the reaction mixture was
refluxed for 48 h. After cooling, CH2Cl2 (20 mL) and 2 M NaOH
(10 mL) were added. The aqueous phase was extracted with
CH2Cl2, and the combined extracts were dried over Na2SO4.
After removal of solvents in vacuo, the residue was separated
by column chromatography (silica gel) with hexanes/EtOAc
(3:2) as eluent to give 19a -g.
1-Ben zyl-5-(1-p r op yn yl)p yr r olid in -2-on e (19a ): yellow
oil; 1H NMR δ 1.84 (s, 3H), 2.00-2.18 (m, 1H), 2.20-2.33 (m,
1H), 2.35-2.50 (m, 1H), 2.50-2.71 (m, 1H), 4.00-4.09 (m, 2H),
5.04 (d, J ) 14.6 Hz, 1H), 7.26-7.31 (m, 5H); 13C NMR δ 26.2,
30.0, 44.3, 48.6, 81.6, 127.4, 128.4, 128.5, 136.4, 174.0; HRMS
calcd for C14H16NO 214.1232 (M + 1), found 214.1215.
1-(4-Met h oxyp h en et h yl)-5-(1-p r op yn yl)p yr r olid in -2-
1
on e (19b): yellow oil; H NMR δ 1.83 (s, 3H), 1.90-2.10 (m,
1H), 2.15-2.30 (m, 1H), 2.30-2.40 (m, 1H), 2.40-2.55 (m, 1H),
2.70-2.90 (m, 2H), 3.20-3.35 (m, 1H), 3.77 (s, 3H), 3.80-3.90
(m, 1H), 4.05-4.15 (m, 1H), 6.82 (d, J ) 7.7 Hz, 2H), 7.14 (d,
J ) 7.7 Hz, 2H); 13C NMR δ 3.5, 26.8, 30.1, 32.8, 42.5, 49.9,
55.3, 76.9, 81.3, 114.0, 129.7, 130.9, 158.2, 174.2; HRMS calcd
for C16H20NO2 258.1494 (M + 1), found 258.1490.
1-(4-Meth oxyph en eth yl)-5-vin yl-pyr r olidin -2-on e (19c):
colorless crystalline; mp 63-64 °C (from CHCl3/hexane);
1H NMR δ 1.60-1.80 (m, 1H), 2.10-2.20 (m, 1H), 2.20-2.50
(m, 2H), 2.60-2.90 (m, 2H), 3.00-3.20 (m, 1H), 3.78 (s, 3H),
3.70-3.90 (m, 2H), 5.16 (d, J ) 17.0 Hz, 1H), 5.19 (d, J ) 8.4
Hz, 1H), 5.50-5.70 (m, 1H), 6.82 (d, J ) 8.4 Hz, 2H), 7.10 (d,
J ) 8.4 Hz, 2H); 13C NMR δ 25.5, 30.0, 32.7, 42.2, 55.1, 61.7,
113.7, 117.9, 129.7, 131.0, 137.8, 158.1, 174.8. Anal. Calcd for
C
15H19NO2: N, 5.71. Found: N, 5.82.
1-(4-Met h oxyp h en et h yl)-5-(1-p r op en yl)p yr r olid in -2-
1
on e (19d ): yellow oil; H NMR δ 1.50-1.90 (m, 4H), 2.00-
2.20 (m, 1H), 2.20-2.50 (m, 2H), 2.60-2.85 (m, 2H), 3.00-
3.20 (m, 1H), 3.60-3.80 (m, 1H), 3.77 (s, 3H), 4.20-4.40 (m,
1H), 5.10-5.30 (m, 1H), 5.50-5.80 (m, 1H), 6.82 (d, J ) 8.7
Hz, 2H), 7.10 (d, J ) 8.3 Hz, 2H); 13C NMR δ 12.8, 25.6, 30.3,
32.8, 42.4, 54.8, 55.1, 113.7, 128.0, 129.5, 130.1, 130.9, 158.0,
174.7; HRMS calcd for C16H22NO2 260.1651 (M + 1), found
260.1643.
C
16H25NO5P 342.1470 (M + 1), found 342.1470.
Dieth yl 1-(3,4-d im eth oxyben zyl)-5-oxo-2-p yr r olid in yl-
1
p h osp h on a te (20c): yellow oil; H NMR δ 1.36 (t, J ) 6.9
Hz, 6H), 2.00-2.50 (m, 3H), 2.55-2.77 (m, 1H), 3.68 (d, J )
9.4 Hz, 1H), 3.86 (s, 6H), 4.10-4.30 (m, 5H), 5.16 (d, J ) 14.7
Hz, 1H), 6.80-6.88 (m, 3H); 13C NMR δ 16.2 (J ) 5.5 Hz), 16.3
(J ) 5.2 Hz), 20.1, 29.7, 44.9, 51.3, 53.5, 55.7 (J ) 8.2 Hz),
5-Be n zyl-1-(4-m e t h oxyp h e n e t h yl)p yr r olid in -2-on e
(19e): yellow oil; 1H NMR δ 1.60-1.75 (m, 1H), 1.80-1.90 (m,
1H), 1.90-2.10 (m, 1H), 2.10-2.20 (m, 1H), 2.40-2.60 (m, 1H),

Preparation of 1,5-Disubstituted Pyrrolidin-2-ones
J . Org. Chem., Vol. 65, No. 14, 2000 4369
62.5 (J ) 7.3 Hz), 63.1 (J ) 7.2 Hz), 110.8 (J ) 38.7 Hz), 120.7,
128.0, 148.5 (J ) 38.7 Hz), 175.1 (J ) 2.9 Hz); HRMS calcd
for C17H27NO6P 372.1576 (M + 1), found 372.1597.
(J ) 3.1 Hz). Anal. Calcd for C16H24NO5P: C, 56.30, H, 7.09,
N, 4.10. Found: C, 55.83, H, 7.28, N, 4.49.
Meth yl (2S)-2-[2-(d ieth oxyp h osp h or yl)-5-oxo-1-p yr r oli-
d in yl]-3-p h en ylp r op a n oa te (20f): yellow oil; 1H NMR δ
1.20-1.50 (m, 6H), 1.70-2.30 (m, 2H), 2.45-2.60 (m, 1H),
3.25-3.40 (m, 1H), 3.60-3.70 (m, 1H), 3.73 (s, 3H), 3.95-4.30
(m, 6H), 4.90-5.10 (m, 1H), 7.10-7.30 (m, 5H); 13C NMR δ
16.2 (J ) 6.6 Hz), 16.4 (J ) 5.6 Hz), 20.6 (J ) 2.6 Hz), 24.8
(J ) 5.3 Hz), 29.5 (J ) 12.5 Hz), 33.8, 34.6, 52.2, 52.6, 54.8,
55.0, 56.3, 57.2, 59.1, 62.0 (J ) 7.1 Hz), 62.8 (J ) 4.8 Hz),
63.1 (J ) 4.6 Hz), 68.2, 70.4, 126.4, 126.8, 128.3, 128.5, 128.6,
129.0, 137.1, 137.8, 169.6, 170.3, 174.8, 176.7 (J ) 5.0 Hz);
HRMS calcd for C18H27NO6P 384.1576 (M + 1), found 384.1574.
Dieth yl 1-(4-m eth oxyp h en eth yl)-5-oxo-2-p yr r olid in yl-
p h osp h on a te (20d ): yellow oil; 1H NMR δ 1.33 (t, J ) 6.9
Hz, 6H), 2.00-2.35 (m, 3H), 2.40-2.60 (m, 1H), 2.70-2.85
(m, 1H), 2.85-3.00 (m, 1H), 3.35-3.50 (m, 1H), 3.50-3.60 (m,
1H), 3.80 (s, 3H), 4.00-4.10 (m, 1H), 4.10-4.25 (m, 4H), 6.82
(d, J ) 8.7 Hz, 2H), 7.10 (d, J ) 8.7 Hz, 2H); 13C NMR δ 16.3
(J ) 5.6 Hz), 16.4 (J ) 5.2 Hz), 20.3, 29.5, 32.3, 43.5, 53.2,
55.0, 55.3, 62.0 (J ) 7.0 Hz), 62.7 (J ) 7.3 Hz), 113.7, 129.5,
130.4, 158.0, 174.9 (J ) 3.0 Hz); HRMS calcd for C17H27NO5P
356.1627 (M + 1), found 356.1627.
Dieth yl 1-[(1S)-2-h yd r oxy-1-p h en yleth yl]-5-oxo-2-p yr -
1
r olid in ylp h osp h on a te (20e): yellow oil; H NMR δ 1.30-
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C NMR spec-
tra and CHN analyses or HRMS for compounds 9a ,c-g,k ,
10a ,c-g,k , and 11a -c,h ,j. This material is available free of
charge via the Internet at http://pubs.acs.org.
1.40 (m, 6H), 2.00-2.40 (m, 2H), 2.43-2.65 (m, 1H), 2.70-
3.10 (m, 2H), 3.40-3.60 (m, 3H), 4.00-4.30 (m, 4H), 7.20-
7.45 (m, 5H); 13C NMR δ 16.2 (J ) 5.2 Hz), 16.3 (J ) 5.1 Hz),
20.2, 29.5, 33.1, 43.3, 50.1, 53.1, 55.3, 62.1 (J ) 7.3 Hz), 62.8
(J ) 7.0 Hz), 126.3, 128.3, 128.5, 138.4 (J ) 4.1 Hz), 175.0
J O000219W