Triphenylphosphoranylidene substituted heterocycles as versatile intermediates

Article abstract of DOI:10.3987/COM-08-S(F)12

N-Cbz-(α-aminoacyl)benzotriazoles 5a-e reacted with (stabilized-methylene)triphenylphosphoranes 6 and 13 to give the corresponding esters 7a-e (66-91%) or nitriles 14a-e (63-85%). Deprotection of N-Cbz-γ-amino-β-oxo-α-triphenylphosphoranylidene esters 7a-

Full text of DOI:10.3987/COM-08-S(F)12

HETEROCYCLES, Vol. 76, No. 2, 2008
1401
HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 1401 - 1423. © The Japan Institute of Heterocyclic Chemistry
Received, 19th April, 2008, Accepted, 23rd June, 2008, Published online, 26th June, 2008. COM-08-S(F)12
TRIPHENYLPHOSPHORANYLIDENE SUBSTITUTED
HETEROCYCLES AS VERSATILE INTERMEDIATES
Alan R. Katritzky,*1 Adam S. Vincek,1 and Peter J. Steel2
1Center for Heterocyclic Compounds, University of Florida, Department of
Chemistry,
Gainesville,
Florida
32611-7200,
USA,
(E-mail:
2
katritzky@chem.ufl.edu) Department of Chemistry, University of Canterbury,
Christchurch, New Zealand
Abstract
(stabilized-methylene)triphenylphosphoranes 6 and 13 to give the corresponding
esters 7a–e (66–91%) or nitriles 14a–e (63–85%). Deprotection of
–
N-Cbz-(α-aminoacyl)benzotriazoles
5a–e reacted with
N-Cbz-γ-amino-β-oxo-α-triphenylphosphoranylidene esters 7a–d induced
cyclization to form 2,4-dioxo-3-triphenylphosphoranylidene pyrrolidines 9a–c
(20–98%) and 1,3-dioxo-2-triphenylphosphoranylidene tetrahydropyrrolizine 9d
(79%). N-Cbz-δ-amino-β-oxo-α-triphenylphosphoranylidene ester 7e cyclized
to form 2,4-dioxo-3-triphenylphosphoranylidene piperidine 9e (60%).
Deprotection of N-Cbz-γ-amino-β-oxo-α-triphenylphosphoranylidene nitriles
14a–d similarly formed 5-amino-4-triphenylphosphonio-2,4-dihydropyrrol-3-one
bromides 15a–c (70–72%) and 3-ammonio-2-triphenylphosphoniotetrahydro-
pyrrolizin-1-one dibromide 15d (66%).
N-Methyl pyrrolidine 11 was
transformed into 3,3-dibromopyrrolidin-2,4-dione 16 (79%), 3,3-dibromo-5-
hydroxypyrrolidin-2,4-dione 17 (88%), 4-azido-3-bromopyrrol-2-one 18 (84%),
and 4-benzotriazol-1-ylpyrrol-2-one 19 (92%).
INTRODUCTION
The discovery of the occurrence of the tetramic acid ring system, a tautomer of pyrrolidin-2,4-dione, in a
number of natural products and pigments coincided with the discovery of their diverse biological
activities.1 Reported syntheses of tetramic acids (Scheme 1) are by the intramolecular formation of bond
a(i–vi), b(vii–ix) or c(x, xi). Bond a is made by cyclization of (i) γ-amino-β-keto esters;2 (ii)

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HETEROCYCLES, Vol. 76, No. 2, 2008
γ-bromoesters;3
(iii)
γ-amino
cyclic-enol
esters;4
(iv)
5-(2-amino-1-hydroxyethyliden)-
2,2-dimethyl-1,3-dioxan-4,6-diones (Meldrum’s acid esters);5 (v) aminomethyl pyrone esters;6 or (vi)
aminomethyl isoxazole carboxylic acids.7 Bond b is formed by (vii) Wittig olefination,8 of
α-triphenylphosphoranylidene amides with immobilized ylides;9 (viii) Dieckmann type cyclization of
succinimides10 and (ix) other Dieckmann cyclizations.11 Bond c is closed by (x) alcoholysis of
spiro-β-lactams;12 and (xi) nucleophilic cyclizations of γ-bromo β-keto carboxamides.13
R2'
R2' = COR4, CO2R, Ar
PS = polystyrene
PPh3(PS)
R2'
O
Y = CO2R, CN
O
O
O
N
R1
O
Me
N
N
Y
R1
base
O
R4O2C
N
R3
R1
R2
O
(viii)
(ix)
R3
N
R1
(vii)
Me
(x)
MeOH
O
CO2H
O
R2
R3
b
coupling
agents
O
O
N
(vi)
(v)
CH2Br
NHBzl
(xi)
(i)
base
NHR1
OMe
a
HO
N
c
R1
1
O
base
R2
R3
(iv)
O
CO2R
(ii)
R1NH2
CO2R
O
(iii)
O
NHR1
N R1(Bzl or PG)
H
R3
Me
Me
R1 = Ts
O
O
CO2R
Br
R4O
O
O
O
Me
Me
R = alkyl
PG = protecting group
R3
HO
O
NHR1
R1 = PG
NHR1
R3
R3
Scheme 1. General Tetramic Acid Syntheses by the Formation of Bonds a, b, or c
Natural tetramic acids, exist as enolized lactams 1 of pyrrolidin-2,4-diones 2.1 Earlier reports of
compounds containing the DOT(dioxotriphenylphosphoranylidene)-moiety as part of the
DOT-pyrrolidine substructure 3 include a byproduct during the preparation of showdomycin,14 a flash
vacuum pyrolysis method (FVP, 600–900 °C, 102 Torr)15 accompanied by thermal extrusion of
triphenylphosphine oxide to form an alkyne and anomalous “spontaneous”16 cyclizations at rt,17 and a
byproduct without logical explanation of its formation.18 The DOT-piperidine substructure was
previously synthesized but no further reactions were attempted.16a,19 We previously reported

HETEROCYCLES, Vol. 76, No. 2, 2008
1403
stereospecific C-acylations of (carboxymethylene)triphenylphosphorane with N-protected peptidic
(α-aminoacyl)benzotriazoles to give peptidic α-triphenylphosphoranylidene esters.20
Attempted
hydrogenolysis of N-Cbz-γ-amino-β-oxo-α-triphenylphosphoranylidene ester 7b gave DOT-pyrrolidine
9b (45%) by cyclization of the expected linear free amine. Crystalline DOT-pyrrolidines are stable to
aldehydes,21 strong bases,22 and high temperatures,15 and we now show DOT-pyrrolidines form versatile
intermediates. We now report the first convenient synthesis of DOT-pyrrolidines 9a–c,
DOT-tetrahydropyrrolizine
9d,
DOT-piperidine
30,
5-amino-4-triphenylphosphonio-2,4-
dihydropyrrol-3-one bromides 15a–c, and 3-ammonio-2-triphenylphosphoniotetrahydropyrrolizin-1-one
dibromide 15d.
R3
R3
PPh3
NH
O
O
HO
O
DOT moiety
O
O
NH
NH
R5
R5
3
1
2
DOT-pyrrolidine
RESULTS AND DISCUSSION
N-Cbz-amino acids 4a–e were converted by known methodology into N-Cbz-aminoacylbenzotriazoles
5a–e (Scheme 2). N-Acylbenzotriazoles have been reported by the Katritzky group as efficient neutral
coupling reagents for chiral N-acylation, regioselective C-acylation, and O-acylation of aldehydes. They
are sufficiently reactive to form amide bonds at ambient temperature, but stable enough to resist side
reactions.23 N-Protected (α-aminoacyl)benzotriazoles are efficient reagents for acylation of amino
amides, amino sulfonamides, amino thiol esters, small peptides with alkyl side chains, small peptides with
multi-functional groups , and amino ketones.23,24
In the present work, N-Cbz-(aminoacyl)benzotriazoles 5a–e C-acylated (ethoxycarboylmethylene)
triphenylphosphorane (6) under microwave irradiation (Table 1) to give N-Cbz-γ-amino-β-oxo-
α-triphenylphosphoranylidene esters 7a–c (83–91%) (Scheme 3), 7d (66%) (Scheme 4), and
N-Cbz-δ-amino-β-oxo-α-triphenylphosphoranylidene ester 7e (77%) (Scheme 4), following our recently
developed procedure.20 We supported the structures of 7a–c in that communication. We confirmed by
1H-NMR, 13C-NMR, and elemental analysis structure 7d suggested by Aitken.25 The structure of novel

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HETEROCYCLES, Vol. 76, No. 2, 2008
1
7e was supported by H-NMR, 13C-NMR, and elemental analysis. A single cavity microwave
synthesizer provides an effective reproducible and safe technique for promoting a variety of reactions and
shortening reaction times while reducing pollution by using less solvent.26 The 13C-NMR chemical
shifts and JPC coupling values of the γ-C, β-keto, α-C=P, and ester/amide carbon signals (Table 2) show
the P-(ipso)Ph, P-(ortho)Ph, P-(meta)Ph, and P-(para)Ph carbon signals remain essentially invariant and
13
the C-NMR chemical shifts and JPC values, to be insensitive to changes in solvent and temp,27 but
reflecting local electron densities.28
OH
Bt
Bt
Bt
SOCl2, BtH
DCM, 1h
O
Cbz
NH
O
Cbz
NH
O
Cbz
NH
O
Cbz
NH
R1
Me
5b
Ph
4a-c
5a
5c
OH
Bt
O
Cbz
SOCl2, BtH
DCM, 1h
O
Cbz
N
N
N
N
Bt =
N
4a-d
5d
OH
Bt
SOCl2, BtH
DCM, 1h
O
HN Cbz
O
HN Cbz
4e
5e
Scheme 2
Hydrobromic acid N-deprotected 7a–e to give γ-amino-β-oxo-α-triphenylphosphoranylidene ester salts
8a–c (21–99%), 8d (90%), and δ-amino-β-oxo-α-triphenylphosphoranylidene ester salt 8e (92%) for
Method I.29 A broad signal around 9 ppm in the 1H-NMR spectra supported P-salt formation. The salt
mixtures were isolated by column chromatography (SiO2). Extension of the stirring time in the 33%
hydrobromic acid solution for up to 5h resulted in formation of dibromide salts, which were easily
isolated as white powders by filtration from diethyl ether in most cases. In one case the highly
hygroscopic dibromide salt resulted in a low yield of achiral monobromide ammonium salt 8a (21%) due
to loss during isolation. Melting points were generally not sharp with initial conversion to amorphous
semi-solids typically in the range between 100–200 °C, followed by a session of bubbling and
recrystallization, which then melted again above 200 °C probably due to the thermal cyclization involving
the loss of ethanol. The structures of novel 8a–e were supported by 1H-NMR, 13C-NMR, and elemental
analysis.

HETEROCYCLES, Vol. 76, No. 2, 2008
1405
Table 1. Isolated Yields for α-Amino Acid Intermediates and Cyclized Products
Entry
R1
R2
N-Cbz Amino Acid 4
7
8
9
9′c
60
45
45
45b
14
85
79
79
64
15
71
70
72
66b
a
b
c
H
H
Cbz-Glycine
91
86
83
66
21a
99
91
90
20(97)
98(99)
90(99)
79(88b)
Me
CH2Ph
H
H
Cbz-(L)Alanine
Cbz-(L)Phenylalanine
Cbz-(L)Proline
d
R1–(CH2)3–R2
9 yield from Method I-(ii + iii), with the yield for step (iii) given in parenthesis. 9′ yield from Method II-(iv). aHygroscopic.
bTetrahydropyrrolizine. cYield from Recrystallization
Ph3P+
O
Ph3P+
O
Ph3P
O
Ph3P
O
CO2Et
Cbz
NH
CO2Et
PPh3
CO2Et
CO2Et
+NH3
CO2Et
(ii)
5a-c
R
+N
R
+NH3
Br-
21 - 99%
(i)
R1
6
83 - 91%
Me
2 Br-
2 Br-
R
Ph
8c R = H
10
7a-c
8a
8b
See Table 1
(v)
95%
(vi)
R = Me
99%
(iii)
99%
(iii)
(iii)
Ph3P
(i) µ-Wave, MeCN
60 °C, 10 min
Method I-(ii + iii)
(ii) 33% HBr in AcOH
rt, 5h
97%
99%
CO2Et
O
Ph3P
O
NH2
Ph3P
O
O
Ph3P
O
O
(iv)
12
(iii) Aq Base, EtOH
rt, 5h
N
Ph
NH
O
R
NH
45 - 60%
Method II-(iv)
(iv) 5%Pd(C), H2
EtOH, rt, 48h
(v) MeI, NaH,
DCM:THF, 16 h
(vi) NEt3
Me
9b
Ph
9a
9c
R = H
(v)
11 R = Me
92%
DCM, rt, 1h
Scheme 3
The DOT-pyrrolidines 9a–c and DOT-pyrrolizines 9d were prepared by Method I (20–98%) and by
Method II (45–60%) and DOT-piperidine 9e was prepared by Method I (60%). The starting salts 8a–d
were dissolved in ethanol and then aq base was added, which resulted in precipitation of a white solid.
Extraction with dichloromethane gave DOT-pyrrolidines 9a–c (97–99%) and DOT-pyrrolizines 9d (88%)
to complete Method I. N-Methylation of 8c with methyl iodide and sodium hydride gave linear
N-trimethylated DOT-salt 10 (95%). N-Methylation of 9c afforded DOT-pyrrolidine 11 (92%).
Treatment of 8c with triethylamine in dichloromethane cleanly gave the linear free amine 12.
Hydrogenolysis of 7a–d with palladium on charcoal in ethanol required 48 h and crystallization gave
9b–d (45%) for Method II. To furnish achiral 9a (60%), with Method II conditions, heating under reflux

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HETEROCYCLES, Vol. 76, No. 2, 2008
in ethanol was required. Achiral 8e was heated under reflux in aq base to afford 9e (65%). We provide
supporting characterization for the structures of compounds 9a,b,d,e which were previously reported
1
13
without characterization. The structure of novel 9c was supported by H-NMR, C-NMR (Table 2),
elemental analysis, and X-ray crystallography.
Table 2. The 13C-NMR Chemical Shifts, δ in ppm (JPC in Hz) 7–9a–e, 10–12
Entry
7ab
7bb
7cb
7dc
7dd
7e
γ-C
β-Keto
α-C=P
Ester/Amide
167.3 (14.3)
166.7 (14.3)
166.9 (14.3)
167.3 (15.5)
167.1 (14.3)
167.5 (14.3)
166.7 (13.2)
166.2 (12.6)
166.4 (12.0)
166.2 (12.6)
166.8 (13.2)
177.4 (17.4)
176.2 (16.6)
175.9 (16.0)
179.7 (16.0)
171.1 (10.9)
166.8 (10.9)
173.8 (16.6)
167.2 (14.3)
P-(ipso)Ph
P-(ortho)Ph
133.1 (9.7)
133.0 (9.7)
133.1 (9.7)
132.6 (9.7)
133.0 (9.7)
132.6 (9.7)
132.9 (10.3)
132.8 (9.7)
133.0 (9.7)
133.0 (9.7)
132.8 (9.7)
134.0 (10.9)
133.9 (10.9)
133.9 (10.9)
133.8 (10.9)
133.3 (10.3)
132.2 (10.3)
133.8 (10.9)
132.9 (9.7)
P-(meta)Ph
128.6 (12.6)
128.5 (12.6)
128.5 (12.6)
128.1 (12.6)
128.2 (12.0)
128.2 (12.6)
128.6 (12.6)
129.0 (12.6)
129.0 (12.6)
128.9 (12.6)
128.9 (12.6)
128.7 (12.6)
128.7 (12.6)
128.7 (13.2)
128.7 (13.2)
128.2 (12.6)
128.2 (13.2)
128.6 (12.6)
128.5 (12.6)
P-(para)Ph
131.9 (2.9)
131.8 (2.9)
131.7 (2.9)
131.2 (2.9)
131.3 (2.3)
131.3 (2.3)
132.1 (2.3)
132.3 (2.9)
132.3 (<4.0)a
132.5 (2.9)
132.1 (<4.0)a
132.9 (2.9)
132.8 (2.3)
132.8 (2.9)
132.8 (2.9)
131.7 (2.9)
131.9 (2.9)
132.6 (2.9)
131.6 (2.9)
49.3 (8.6)
52.4 (8.6)
56.8 (8.6)
62.2 (7.4)
62.7 (6.3)
39.6 (6.9)
45.4 (8.0)
51.1 (8.6)
55.9 (8.6)
63.6 (9.7)
37.1 (7.4)
190.3 (<4.0)a
194.7 (<4.0)a
193.5 (<4.0)a
194.8 (2.9)
195.3 (2.9)
195.5 (3.4)
185.3 (5.7)
190.5 (4.6)
189.0 (4.6)
187.7 (5.2)
192.4 (4.0)
68.9 (112.8)
68.8 (111.1)
70.1 (108.8)
68.6 (109.9)
69.0 (111.1)
71.2 (110.5)
69.5 (111.1)
68.1 (109.4)
69.1 (108.2)
69.6 (109.9)
69.7 (109.4)
64.2 (122.6)
62.8 (122.5)
64.0 (122.0)
65.2 (117.4)
70.0 (115.1)
75.9 (104.2)
64.1 (123.1)
69.3 (108.2)
125.7 (93.3)
126.0 (93.3)
125.9 (93.9)
125.9 (93.9)
126.1 (93.3)
125.9 (93.3)
124.1 (93.3)
124.9 (92.8)
124.8 (92.8)
124.2 (93.9)
125.7 (92.8)
122.8 (93.3)
122.9 (92.8)
122.7 (93.3)
122.6 (92.8)
125.0 (92.8)
123.1 (93.3)
122.7 (92.8)
126.4 (93.3)
8af
8beh
8ceh
8dg
8eeh
9aj
52.4 (13.2) 194.8 (8.6)
58.0 (13.7) 197.7 (7.4)
63.5 (13.2) 195.5 (7.4)
69.1 (13.2) 197.6 (8.0)
9bj
9c
9dj
9ej
37.1 (9.2)
71.0 (8.6)
191.9 (4.6)
184.4 (6.3)
10k
11
67.6 (13.2) 193.9 (6.9)
12
57.2 (7.4)
198.0 (2.9)
aSmall couplings not clearly resolved were estimated as less than 4.0 Hz. blit.20 cRotamer I. dRotamer II. e(+NH3)/(+PPh3) Dibromide.
f(+NH3) Monobromide. g(+PPh3) monobromide. hNMR in DMSO-d6. jpreviously reported without characterization.lit.15 k(+NMe3)/(+PPh3)
Dibromide

HETEROCYCLES, Vol. 76, No. 2, 2008
1407
Ph3P+
O
Ph3P
O
Ph3P
O
O
PPh3
CO2Et
Br-
5d
(i)
(iii)
(ii)
CO2Et
Cbz
N
CO2Et
rt, 5h
88%
N
66%
90%
6
NH
7d
8d
9d
(iv)
45%
2 Br-
Ph3P
O
Ph3P+
Ph3P
O
O
PPh3
5e
(i)
CO2Et
HN Cbz
(iii)
(ii)
CO2Et
NH3
+
CO2Et
NH
O
77%
92%
reflux, 15h
65%
6
8e
7e
9e
(i) µ-Wave, MeCN
60 °C, 10 min
Method I-(ii + iii)
(ii) 33% HBr in AcOH
rt, 5h
(iii) Aq Base, EtOH
Method II-(iv)
1) Pd(C), H2
2) FVP, 600 oC
CO2Et
9e
+
NH2
34%
16%
(iv) 5% Pd(C), H2
EtOH, rt, 48h
lit.15
Scheme 4
Transformations
similar
to
those
reported
above
for
5a–e
with
6
converted
(triphenylphosphoranylidene)acetonitrile (13) into N-Cbz-γ-amino-β-oxo-α-triphenylphosphoranylidene
nitriles 14a–c (79–85%) (Scheme 5), 14d (64%) (Scheme 6), and N-Cbz-δ-amino-β-oxo-
α-triphenylphosphoranylidene nitrile 14e (63%) (Scheme 6). Compounds 14b,c have been reported by
Harvey et al.,29 by Paris et al.,30a and by Wasserman et al.30b without elemental analysis for the
preparation
of
peptidyl
α-ketoesters
and
α-ketoamides.29,30
The
N-Cbz-δ-amino-β-oxo-α-triphenylphosphoranylidene nitrile 14e has been reported, without
characterization,31 as an interesting precursor to β-amino-α-keto esters,32 or for the synthesis of
enantioselective 3-hydroxypyrrolidin-2-ones. We now report 1H-NMR, 13C-NMR, and elemental analysis
to support the structures of 14b,c,e. The structures of novel 14a,d were supported by 1H-NMR, 13C-NMR
(Table 3), and elemental analysis.
Comparable treatment of nitriles 14a–d with hydrobromic acid caused simultaneous N-deprotection and
cyclization to afford 5-amino-4-triphenylphosphonio-2,4-dihydropyrrol-3-one bromides 15a–c (70–72%),
and 3-ammonio-2-triphenylphosphoniotetrahydropyrrolizin-1-one dibromide 15d (66%). The same
method applied to 14e gave linear 15e (35%), possibly due to the extra degrees of freedom associated
1
with this salt. The structures of novel 15a–e were supported by H-NMR, 13C-NMR (Table 3), and
elemental analysis.

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HETEROCYCLES, Vol. 76, No. 2, 2008
Br-
Ph3P+
NH2
NH2
(ii)
15a
15b
O
71%
N
Br-
Ph3P+
Ph3P
O
5a-c
(i)
PPh3
CN
Cbz
N
R2
(ii)
CN
O
79 - 85%
N
70%
13
R1
Me
Br-
14a-c
See Table 1
Ph3P+
(ii)
NH2
(i) µ-Wave, MeCN
60 °C, 10 min
(ii) 33% HBr, AcOH
rt, 5h
72%
O
15c
N
Ph
NH
NH
Ph3P
Ph3P
Ph3P
Ph3P
O
Pd(C), H2
EtOAc
CN
CN
H
CN
O
O
O
H
N Cbz
N Cbz
NH2
Et
Et
Et
Et
lit. 30b,c
isolated ratio 1:1:2
Scheme 5
Table 3. The 13C-NMR Chemical Shifts, δ in ppm (JPC in Hz) 14–15a–e
Entry
14a
γ-C
β-Keto
α-C=P
Imino/Nitrile
120.6 (14.9)
120.7 (14.9)
121.0 (16.0)
121.5 (15.4)
121.3 (14.7)
121.8 (16.6)
170.3 (17.2)
168.8 (17.2)
169.3 (16.6)
170.9 (15.5)
120.8 (16.0)
P-(Ipso)Ph
P-(Ortho)Ph
133.5 (10.3)
133.2 (10.3)
133.5 (10.3)
133.2 (10.5)
133.4 (10.5)
133.3 (10.3)
133.6 (10.9)
133.6 (10.9)
133.7 (10.9)
133.5 (10.9)
133.4 (10.3)
P-(Meta)Ph
129.2 (13.2)
129.0 (12.6)
129.1 (12.6)
128.8 (12.6)
128.9 (12.6)
129.0 (13.2)
130.1 (13.2)
130.1 (13.1)
130.0 (12.6)
130.0 (13.1)
129.3 (13.2)
P-(Para)Ph
133.3 (3.4)
131.7 (4.0)
133.2 (3.4)
132.9 (2.8)
132.8 (2.8)
133.1 (2.9)
134.6 (2.9)
134.6 (2.9)
134.5 (2.9)
134.6 (2.9)
133.5 (2.3)
47.5 (10.9) 189.9 (<4.0)a 46.4 (127.7)
122.3 (93.3)
122.3 (93.3)
122.4 (93.9)
122.6 (93.4)
122.9 (93.4)
122.6 (93.9)
119.7 (93.3)
120.1 (93.3)
119.7 (92.8)
119.4 (92.8)
121.8 (93.3)
14bb
14cc
14dd
14de
14ef
15a
52.2 (9.0)
57.2 (9.0)
61.8 (9.1)
62.4 (9.1)
38.6 (9.2)
194.3 (3.6)
46.5 (127.5)
192.9 (<4.0)a 47.9 (126.0)
194.7 (3.5)
194.9 (3.5)
46.2 (126.3)
46.3 (127.0)
194.9 (<4.0)a 49.0 (126.0)
52.2 (10.3) 194.5 (6.3)
58.5 (10.3) 197.7 (5.7)
63.3 (10.3) 195.3 (6.3)
70.0 (10.3) 196.2 (5.7)
64.8 (125.4)h
63.1 (124.3)h
64.0 (127.8)h
65.9 (119.1)h
50.4 (124.3)
15b
15c
15dg
15e
33.4 (8.0)
195.0 (4.0)
aSmall couplings not clearly resolved were estimated as less than 4.0 Hz. blit.34 clit.25 dRotamer I. eRotamer II. flit.26
gIsolated as +NH3/+PPh3 dibromide, double bond at C4–C5. hα-C–P+.

HETEROCYCLES, Vol. 76, No. 2, 2008
1409
2 Br-
Ph3P
Ph3P+
CN
Cbz
N
+NH3
PPh3
CN
(i)
(ii)
5d
O
O
66%
64%
N
13
14d
15d
Ph3P
Ph3P
PPh3
5e
(i)
CN
NH3
CN
(ii)
+
Br-
O
CN
O
HN Cbz
63%
35%
13
14e
15e
(i) µ-Wave, MeCN
60 °C, 10 min
(ii) 33% HBr in AcOH
rt, 5h
Scheme 6
Figure 1. X-Ray Crystal Structure of 9c (Left), and Preliminary X-ray Crystal Structure of 15c Showing
with Two H2O Molecules and Br– Anion (Right)
The structure of 9c was unambiguously confirmed by X-ray crystallography which showed the
O–C–C–(P)–C–O atoms to lie in approximately the same plane, to within 0.003(3) Å (Figure 1). The P=C
bond length of 1.732(2) Å and the attached C-C bond lengths (1.422(3) and 1.450(2) Å) and the C=O
bond lengths (1.230(2) and 1.253(2) Å) are all very similar to those in the only two other
DOT-pyrrolidines to have been crystallographically characterized.14,18 As is common with amides, the
molecules pack in pairs about a crystallographic center of inversion with N-H…O=C hydrogen bonds. In
addition a preliminary X-ray crystallographic study on a highly twinned crystal confirmed the structure of
(2RS)-5-amino-2-benzyl-4-triphenylphosphonio-2,4-dihydropyrrol-3-one bromide hydrate (15c). Both
9c and 15c are racemic suggesting racemization was caused by the HBr treatment.
Bromination of 11 in the presence of acid gave 3,3-dibromopyrrolidin-2,4-dione 16 (79%) (Scheme 7).

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HETEROCYCLES, Vol. 76, No. 2, 2008
Treatment of 11 with ethoxytrimethylsilane (TMSOEt) and NBS gave 16 (44%) and
3,3-dibromo-5-hydroxypyrrolidin-2,4-dione 17 (44%), the structure of which was confirmed by X-ray
crystallography (Figure 2). In 17 the molecules pack in chains with the hydroxy hydrogen atom H-bonded
to the carbonyl of an adjacent molecule. Treatment of 11 with azidotrimethylsilane (TMSN3) and NBS
gave 4-azido-3-bromopyrrol-2-one 18 (84%). 1-Chlorobenzotriazole (BtCl) transformed 11 into
4-benzotriazolpyrrol-2-one 19 (92%).
Br
Br
O
NBS (2.0 eq)
16
17
RCO2H (1.4 eq)
O
N
Me
THF, 5 min
79%
Ph
Br
Br
NBS (2.0 eq)
O
TMSOEt (1.4 eq)
O
+
16
N
DCM, 5 min
88%
Me
Ph3P
Ph
O
OH
O
Br
N
Me
NBS (1.4 eq)
O
TMSN3 (1.4 eq)
Ph
N3
Ph
18
N
Me
11
DCM, 5 min
84%
H
O
BtCl (1.1 eq)
Bt
19
DCM, 5 min
92%
N
Me
Ph
Scheme 7
Figure 2. X-Ray Crystal Structure of 17 (Left), and Intermolecular Hydrogen Bonding (Right)

HETEROCYCLES, Vol. 76, No. 2, 2008
1411
CONCLUSIONS
We now report the first convenient method to 2,4-dioxo-3-triphenylphosphoranylidene pyrrolidines,
1,3-dioxo-2-triphenylphosphoranylidene tetrahydropyrrolizine, 2,4-dioxo-3-triphenylphosphoranylidene
piperidine, 5-amino-4-triphenylphosphonio-2,4-dihydropyrrol-3-one bromides, and 3-ammonio-2-
triphenylphosphoniotetrahydropyrrolizin-1-one dibromide. In particular, our Method I is versatile,
inexpensive, reproducible, and high yielding. Racemization was caused by HBr, however the novel
13
linear salts could be cleanly N-methylated, neutralized without cyclization, or cyclized. The C-NMR
chemical shifts and JPC values provide information for the analysis of distabilized
triphenylphosphoranylidene systems, JPC couplings increased with less partial positive character and
decreased with more partial positive character on the respective carbons.
We have also developed four novel applications for DOT-pyrrolidines. The first highly versatile33
3,3-dibromopyrrolidine-2,4-dione34 with a racemic stereocenter, was obtained without Lewis acid.35 The
first 3,3-dibromo-5-hydroxypyrrolidine-2,4-dione was obtained and unambiguously identified by X-ray
crystallography. 4-Azido-3-bromopyrrol-2-one was obtained, where previously reported in the literature
chloro derivatives were used to make β-lactams,36 and bromo derivatives were trapped with
triphenylphosphine to make a Staudinger reagent.37 The first 4-benzotriazolpyrrol-2-one was obtained.
In conclusion the versatile and stable 2,4-dioxo-3-triphenylphosphoranylidene can be easily added
synthetically to rings and then easily transformed to provide novel structures.
EXPERIMENTAL
Melting points were determined on a capillary point apparatus equipped with a digital thermometer. NMR
1
13
spectra were recorded in CDCl3 or DMSO-d6 with TMS for H (300 MHz) and C (75 MHz) as the
internal reference. The N-Cbz-amino acids were purchased from Fluka and were used without further
purification. Acetonitrile was freshly distilled from calcium hydride. Microwave heating was carried
out with a single mode cavity Discover® Microwave Synthesizer (CEM Corporation, NC), producing
continuous irradiation at 2455 MHz.
PREPARATION OF N-ACYLBENZOTRIAZOLES 5a–e
The 5a–e were prepared from the corresponding N-protected amino acids (25 mmol) and excess BtH in
the presence of thionyl chloride, following recently developed procedures.23 We confirmed the structure
of 5d, previously reported by the Katritzky group, here with improved resolution of rotamer signals.
The structure of novel 5e was supported by 1H-NMR, 13C-NMR and elemental analysis.
(2S)-1-Benzyloxycarbonyl(benzotriazol-1-carbonyl)pyrrolidine (5d). (Two rotameric forms) (6.3 g,
72%) Clear oil. [α]23 D –139.6 (c 1.83, DMF).24e 1H NMR (CDCl3) δ 1.99–2.14 (m, 2H), 2.15–2.26 (m,

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HETEROCYCLES, Vol. 76, No. 2, 2008
1H), 2.54–2.68 (m, 1H), 3.64–3.88 (m, 2H), 4.95–5.11 (m, 1H), 5.12–5.24 (m, 1H), 5.83–5.88 (m, 1H),
6.97–7.06 (m, 2H), 7.30–7.42 (m, 3H), 7.50–7.56 (m, 1H), 7.65–7.70 (m, 1H), 8.11–8.16 (m, 1H),
8.19–8.31 (m, 1H). 13C NMR (CDCl3) δ 23.7, 24.5, 30.7, 31.6, 46.9, 47.3, 59.2, 60.0, 67.3, 114.3, 114.5,
120.2, 126.4, 127.5, 127.9, 128.1, 128.5, 130.5, 130.6, 145.9, 154.0, 154.9, 171.1, 171.6. Anal. Calcd.
for C19H18N4O3: C, 65.13; H, 5.18; N, 15.99. Found: C, 64.98; H, 5.24; N, 15.77.
3-(Benzotriazol-1-yl)-1-(benzyloxy)carbonylaminopropan-3-one (5e). (7.3 g, 90%) White needles
(from Et2O) mp 111–112 °C. 1H NMR (CDCl3) δ 3.66–3.69 (m, 2H), 3.74–3.80 (m, 2H), 5.09 (s, 2H),
5.47 (br s, 1H), 7.28–7.36 (m, 5H), 7.48–7.53 (m, 1H), 7.62–7.67 (m, 1H), 8.11 (d, J = 8.2 Hz, 1H), 8.23
(d, J = 8.2 Hz, 1H). 13C NMR (CDCl3) δ 35.9, 36.1, 66.8, 114.2, 120.2, 126.3, 128.1, 128.5, 130.5,
130.8, 136.2, 146.1, 156.2, 171.2. Anal. Calcd for C17H16N4O3: C, 62.95; H, 4.97; N, 17.27. Found: C,
63.19; H, 4.86; N, 17.41.
PREPARATION OF α-TRIPHENYLPHOSPHORANYLIDENE ESTERS 7a–e
Compounds 7a–e were prepared from the corresponding 5a–e (1.1 mmol) and 7 (1.0 mmol) in MeCN (1
mL) in a dry 50 mL round bottom flask equipped with a magnetic stir bar and a condenser. The flask
containing the reaction mixture was exposed to microwave irradiation (120 W) for 10 min at a temp of
60 °C, and cooled with high-pressure air through an inbuilt system in the instrument until temp fell below
30 °C. The reaction mixture was diluted with ethyl acetate and washed with a saturated aq sodium
carbonate. The organic layer was collected, dried over anhydrous magnesium sulfate, filtered, and
concentrated in vacuo to give the crude product, which was purified by column chromatography (SiO2,
hexane:EtOAc = 3:1).
(2S)-1-Benzyloxycarbonyl-2-(ethoxycarbonyltriphenylphosphoranylidenacetyl)pyrrolidine
(7d).
(Two rotameric forms) (0.38 g, 66%) (49%)25 White microcrystals (from CHCl3 / hexane) mp
129–130 °C. [α]23 D –36.4 (c 1.50, CH2Cl2) ([α]20 D –45.0 (c 1.03, CH2Cl2)).lit.25 1H NMR (CDCl3) δ
0.66 (t, J = 7.1 Hz, 3H), 1.75 (br s, 2H), 1.98–2.16 (m, 1H), 2.30–2.50 (m, 1H), 3.35–3.56 (m, 2H),
3.62–3.84 (m, 2H) 4.89–5.27 (m, 2H), 5.64–5.76 (m, 1H), 7.20–7.74 (m, 20H). 13C NMR (CDCl3) δ
13.4, 22.7, 23.5, 30.5, 31.5, 46.6, 47.1, 58.0, 58.1, 62.2 (JCP = 7.4 Hz), 62.7 (JCP = 6.3), 65.7, 65.9, 68.7
(JCP = 109.9 Hz), 69.0 (JCP = 111.1 Hz), 125.9 (JCP = 93.9 Hz), 126.1 (JCP = 93.3 Hz), 126.3, 126.9, 127.2,
127.3, 127.9, 128.1 (JCP = 12.6 Hz), 128.2 (JCP = 12.0 Hz), 131.2 (JCP = 2.9 Hz), 131.3 (JCP = 2.3 Hz),
131.6, 131.8, 132.6 (JCP = 9.7 Hz), 133.0 (JCP = 9.7 Hz), 137.1, 137.2, 154.2 (JCP = 4.0 Hz), 167.1 (JCP =
15.5 Hz), 167.3 (JCP = 14.3 Hz), 194.9 (JCP = 2.9 Hz), 195.4 (JCP = 2.9 Hz). Anal. Calcd for
C35H34NO5P: C, 72.53; H, 5.91; N, 2.42. Found: C, 72.19; H, 5.90; N, 2.76.
5-(Benzyloxy)carbonylamino-1-ethoxy-2-triphenylphosphoranylidenpentan-1,3-dione (5e). (0.43 g,
77%) Yellowish needles (from Et2O) mp 88–92 °C. 1H NMR (CDCl3) δ 0.64 (t, J = 7.0 Hz, 3H), 3.15 (t, J

HETEROCYCLES, Vol. 76, No. 2, 2008
1413
= 5.5 Hz, 2H), 3.40–3.50 (m, 2H), 3.71 (q, J = 7.0 Hz, 2H), 5.06 (s, 2H), 5.57 (t, J = 5.1Hz, 1H),
13
7.23–7.52 (m, 15H), 7.59–7.70 (m, 5H). C NMR (CDCl3) δ 13.3, 37.2, 39.6 (JCP =6.3 Hz), 58.1, 65.7,
71.2 (JCP =110.5 Hz), 125.9 (JCP = 93.3 Hz), 127.5, 128.0, 128.2 (JCP = 12.6 Hz), 131.3 (JCP = 2.3 Hz),
131.7, 132.6 (JCP = 9.7 Hz), 136.6, 155.9, 167.5 (JCP = 14.3 Hz) 195.5 (JCP = 3.4 Hz). Anal. Calcd for
C33H32NO5P: C, 71.60; H, 5.83; N, 2.53. Found: C, 71.57; H, 5.97; N, 2.45.
PREPARATION OF DOT-SALTS 8a–e
Bromide salts 8a–e were prepared from the corresponding 7a–e. Compounds 7a–e (2.0 mmol) were
stirred for 5 h in 33% HBr in acetic acid (10 mL). The reaction mixture was diluted with Et2O (150 mL)
and stirred for 12 h. The white precipitated salt 8c was filtered from the solution and used without
further purification.
4-Ammonio-1-ethoxy-2-triphenylphosphoranylidenbutan-1,3-dione Bromide (8a).
Hygroscopic
(0.20 g, 21%) White plates (from CH2Cl2 / EtOAc) mp 101–103 °C. 1H NMR (CDCl3) δ 0.67 (t, J = 7.0
Hz, 3H), 3.72 (q, J = 7.0 Hz, 2H), 4.18 (br s, 2H), 6.83 (br s, 3H), 7.47–7.69 (m, 15H). 13C NMR
(CDCl3) δ 13.4, 45.4 (JCP = 8.0 Hz), 49.8, 58.7, 69.5 (JCP = 111.1 Hz), 124.1 (JCP = 93.3 Hz), 128.6 (JCP =
12.6 Hz), 132.1 (JCP = 2.3 Hz), 132.9 (JCP = 10.3 Hz), 166.7 (JCP = 13.2 Hz), 185.3 (JCP = 5.7 Hz). Anal.
Calcd for C24H25BrNO3P: C, 59.27; H, 5.18; N, 2.88. Found: C, 58.64; H, 5.29; N, 2.52
(4RS)-4-Ammonio-1-ethoxy-2-triphenylphosphoniopentan-1,3-dione Dibromide (8b).
(1.15 g,
99%) White microcrystals (from CH2Cl2 / EtOAc) mp 147–150 °C. 1H NMR (DMSO-d6) δ 0.48 (t, J =
7.0 Hz, 3H), 1.45 (d, J = 6.3 Hz, 3H), 3.50–3.64 (m, 2H), 4.80–4.97 (m, 1H), 7.59–7.69 (m, 15H), 7.80
(br s, 3H), 8.51 (br s, 1H). 13C NMR (DMSO-d6) δ 13.3, 17.4, 51.1 (JCP = 8.6 Hz), 58.2, 68.1 (JCP
=
109.4 Hz), 124.9 (JCP = 92.8 Hz), 129.0 (JCP = 12.6 Hz), 132.3 (JCP = 2.9 Hz), 132.8 (JCP = 9.7 Hz), 166.2
(JCP = 12.6 Hz), 190.5 (JCP = 4.6 Hz). Anal. Calcd for C25H28Br2NO3P: C, 51.66; H, 4.86; N, 2.41.
Found: C, 51.32; H, 4.88; N, 2.35.
(4RS)-4-Ammonio-1-ethoxy-5-phenyl-2-triphenylphosphoniopentan-1,3-dione Dibromide (8c).
(1.20 g, 91%) White microcrystals (from CH2Cl2 / EtOAc) mp 145–147 °C. 1H NMR (DMSO-d6) δ
0.46 (t, J = 7.1 Hz, 3H), 2.80 (dd, J = 14.0, 9.2 Hz, 1H), 3.38 (dd, J = 14.0, 4.3 Hz, 1H), 3.50–3.66 (m,
2H), 5.18 (br s, 1H), 5.68 (br s, 4H), 7.25–7.45 (m, 5H), 7.56–7.77 (m, 15H). 13C NMR (DMSO-d6) δ
13.3, 37.4, 55.9 (JCP = 8.6 Hz), 58.3, 69.1 (JCP = 108.2 Hz), 124.8 (JCP = 92.8 Hz), 126.9, 128.5, 129.0
(JCP = 12.6 Hz), 129.6, 132.3, 133.0 (JCP = 9.7 Hz), 136.0, 166.4 (JCP = 12.0 Hz), 188.9 (JCP = 4.6 Hz).
Anal. Calcd for C31H32Br2NO3P: C, 56.64; H, 4.91; N, 2.13. Found: C, 57.09; H, 4.93; N, 2.22.
(2RS)-2-(Ethoxycarbonyltriphenylphosphonioacetyl)pyrrolidine Bromide (8d).
(0.95 g, 90%)
White microcrystals (from CH2Cl2 / EtOAc) mp 81–83 °C. 1H NMR (CDCl3) δ 0.69 (t, J = 7.3 Hz, 3H),
1.61–1.80 (m, 1H), 2.02–2.20 (m, 2H), 2.65–2.84 (m, 1H), 3.16 (br s, 1H), 3.40–3.60 (m, 1H), 3.73–3.85

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HETEROCYCLES, Vol. 76, No. 2, 2008
(m, 3H), 5.38 (br s, 1H), 7.42–7.71 (m, 15H), 10.70 (br s, 1H). 13C NMR (CDCl3) δ 13.6, 24.5, 31.8,
46.5, 59.2, 63.6 (JCP = 9.7 Hz), 69.6 (JCP = 109.9 Hz), 124.2 (JCP = 93.9 Hz), 128.9 (JCP = 12.6 Hz), 132.5
(JCP = 2.9 Hz), 133.0 (JCP = 9.7 Hz), 166.2 (JCP = 12.6 Hz), 187.7 (JCP = 5.2 Hz). Anal. Calcd for
C27H29BrNO3P: C, 61.61; H,5.55; N, 2.66. Found: C, 61.28; H, 5.45; N, 3.34.
(5-Ammonio-1-ethoxy-2-triphenylphosphoniopentan-1,3-dione) Dibromide (8e). (1.08 g, 92%)
White plates (from CH2Cl2 / Et2O) mp 126–128 °C. 1H NMR (DMSO-d6) δ 0.50 (t, J = 7.0 Hz, 3H),
2.80–2.95 (m, 2H), 3.22 (t, J = 6.3 Hz, 2H), 3.56 (q, J = 7.0 Hz, 2H), 7.55–7.80 (m, 18H), 9.50 (br s, 1H).
13C NMR (DMSO-d6) δ 13.4, 35.3, 37.1 (JCP = 7.4 Hz), 55.1, 57.9, 69.7 (JCP = 109.4 Hz), 125.7 (JCP
=
92.8 Hz), 128.9 (JCP = 12.6 Hz), 132.1, 132.8 (JCP = 9.7 Hz), 166.8 (JCP = 13.2 Hz), 192.4 (JCP = 4.0 Hz).
Anal. Calcd for C25H28Br2NO3P: C, 51.66; H, 4.86; N, 2.41. Found: C, 51.35; H, 4.88; N, 2.14.
PREPARATION OF DOT-PYRROLIDINES 9a–c, DOT-PYRROLIZINE 9d, AND
DOT-PIPERIDINE 9e
Method I: Compounds 9a–e were prepared from the corresponding 8a–e. Salts 8a–d (1.0 mmol) were
dissolved in EtOH (1.0 mL) and added to aq sodium hydroxide (10.0 mL, 7.5 M), which precipitated a
white solid almost immediately. Extraction with dichloromethane was performed after 5 h. Compound
9e was prepared from 8e, following the same procedure with reflux in aq sodium hydroxide (7.5 M) for
15 h.
Method II: Compounds 9a–d were prepared from the corresponding 7a–d. A round bottom flask
charged with ester 7a–d (2.0 mmol) and 5% palladium charcoal (2 eq) were stirred vigorously in EtOH,
under a hydrogen atmosphere for 48 h. The reaction mixture was filtered through celite and diluted with
EtOAc to crystallize 9a–d.
3-Triphenylphosphoranylidenpyrrolidin-2,4-dione (9a). (0.35 g, 97%) (Method I 20%) (Method II
0.43 g, 60%) (21%)15 White needles (from CH2Cl2 / EtOAc) mp 222–224 °C. 1H NMR (CDCl3) δ 3.79
(s, 2H), 5.40 (br s, 1H), 7.47–7.56 (m, 6H), 7.58–7.74 (m, 9H). 13C NMR (CDCl3) δ 52.4 (JCP = 13.2
Hz), 64.2 (JCP = 122.6 Hz), 122.8 (JCP = 93.3 Hz), 128.7 (JCP = 12.6), 132.9 (JCP = 2.9 Hz), 134.0 (JCP =
10.9 Hz), 177.4 (JCP = 17.4 Hz), 194.8 (JCP = 8.6 Hz). Anal. Calcd for C22H18NO2P: C, 73.53; H, 5.05;
N, 3.90. Found: C, 73.28; H, 4.98; N, 3.88.
(5RS)-5-Methyl-3-triphenylphosphoranylidenpyrrolidin-2,4-dione (9b). (0.37 g, 99%) (Method I
98%) (Method II 0.34 g, 45%) (58%)15 White needles (from CH2Cl2 / EtOAc) mp 210–211 °C. 1H
NMR (CDCl3) δ 1.34 (d, J = 6.7 Hz, 3H), 3.87 (q, J = 6.7 Hz, 1H), 5.30 (s, 1H), 7.40–7.80 (m, 15H).
13C NMR (CDCl3) δ 18.5, 58.0 (JCP = 13.7 Hz), 62.8 (JCP = 122.5 Hz), 122.9 (JCP = 92.8 Hz), 128.7 (JCP =
12.6 Hz), 132.8 (JCP = 2.3 Hz), 133.9 (JCP = 10.9 Hz), 176.2 (JCP = 16.6 Hz), 197.7 (JCP = 7.4 Hz). Anal.
Calcd for C23H20NO2P: C, 73.98; H, 5.40; N, 3.75. Found: C, 73.72; H, 5.38; N, 3.46. HRMS m/z Calcd

HETEROCYCLES, Vol. 76, No. 2, 2008
1415
for C23H20NO2P 373.1226 [M+H]+, Found 373.1215.
(5RS)-5-Benzyl-3-triphenylphosphoranylidenpyrrolidin-2,4-dione (9c). (0.45 g, 99%) (Method I
89%) (Method II 0.40 g, 45%) White plates (from CH2Cl2 / EtOAc) mp 238–242 °C. 1H NMR (CDCl3)
δ 2.82 (dd, J = 13.7, 8.1 Hz, 1H), 3.18 (dd, J = 13.2, 3.4 Hz, 1H), 4.05–4.08 (m, 1H), 5.17 (s, 1H),
7.20–7.30 (m, 5H), 7.44–7.63 (m, 15H). 13C NMR (CDCl3) δ 38.7, 63.5 (JCP = 13.2 Hz), 64.0 (JCP
=
122.0 Hz), 122.7 (JCP = 93.3 Hz), 126.3, 128.2, 128.7 (JCP = 13.2 Hz), 129.6, 132.8 (JCP = 2.9 Hz), 133.9
(JCP = 10.9 Hz), 137.8, 175.9 (JCP = 16.0 Hz), 195.5 (JCP = 7.4 Hz). Anal. Calcd for C29H24NO2P: C,
77.49; H, 5.38; N, 3.12. Found: C, 77.22; H, 5.45; N, 2.76. HRMS m/z Calcd for C29H24NO2P 450.1617
[M+H]+, Found 450.1628.
(2RS)-2-(Triphenylphosphoranyliden)tetrahydropyrrolizin-1,3-dione (9d). (0.35 g, 88%) (Method I
79%) (Method II 0.36 g, 45%) (60%)15 White needles (from CH2Cl2 / EtOAc) mp 211–213 °C. 1H
NMR (CDCl3) δ 1.60–1.73 (m, 1H), 1.88–2.18 (m, 3H), 3.04–3.12 (m, 1H), 3.70 (dt, J = 11.2, 7.5 Hz,
1H) 3.99 (app t, J = 7.7 Hz, 1H), 7.4–7.7 (m, 15H). 13C NMR (CDCl3) δ 27.0, 28.2, 44.6, 65.2 (JCP
=
117.4 Hz), 69.1 (JCP = 13.2 Hz), 122.6 (JCP = 92.8 Hz), 128.7 (JCP = 13.2 Hz), 132.8 (JCP = 2.9 Hz), 133.8
(JCP = 10.9 Hz), 179.7 (JCP = 16.0 Hz), 197.6 (JCP = 8.0 Hz). Anal. Calcd for C25H22NO2P: C, 75.18; H,
5.55; N, 3.51. Found: C, 74.96; H, 5.62; N, 3.47.
3-Triphenylphosphoranylidenpiperidin-2,4-dione (9e). (0.29 g, 65%) (Method I 60%) (34%)15 White
microcrystals (from CH2Cl2 / EtOAc) mp 241–243 °C. 1H NMR (CDCl3) δ 2.42 (t, J = 6.3 Hz, 2H),
3.37 (dt, J = 6.3, 2.8 Hz, 2H), 5.65 (br s, 1H), 7.39–7.53 (m, 9H), 7.64–7.71 (m, 6H). 13C NMR (CDCl3)
δ 37.1 (JCP = 9.2 Hz), 37.9, 70.0 (JCP = 115.1 Hz), 125.0 (JCP = 92.8 Hz), 128.2 (JCP = 12.6 Hz), 131.7
(JCP = 2.9 Hz), 133.3 (JCP = 10.3 Hz), 171.1 (JCP = 10.9 Hz), 191.9 (JCP = 4.6 Hz). Anal. Calcd for
C23H20NO2P: C, 73.98; H, 5.40; N, 3.75. Found: C, 74.03; H, 5.55; N, 3.59.
PREPARATION OF DIBROMIDE SALT 10
To a solution of 8c (1.0 g, 1.52 mmol) dissolved in a solvent mixture (THF:CH2Cl2 = v:v = 1:1, 40 mL),
sodium hydride 60% on mineral oil (0.610 g, 15.2 mmol) was added and stirred for 1 h. Methyl iodide
(1.0 mL, 15.2 mmol) was added dropwise to the reaction mixture with stirring at rt. The reaction
mixture was stirred for a further 16 h. The solvent mixture was evacuated and the residue was extracted
with CH2Cl2. The crude product was filtered and subjected to column chromatography (SiO2,
CH2Cl2:MeOH = 98:2).
(4RS)-4-Trimethylammonio-1-ethoxy-5-phenyl-2-triphenylphosphoniopentan-1,3-dione Dibromide
(10). (1.01 g, 95%) White needles (CH2Cl2 / Et2O) mp 189–191 °C. 1H NMR (CDCl3) δ 0.38 (t, J =
7.0 Hz, 3H), 2.43 (s, 1H), 3.04 (t, J = 11.9 Hz, 1H), 3.23–3.51 (m, 11H), 6.02 (dd, J = 11.2, 3.5 Hz, 1H),
7.08–7.11 (m, 2H), 7.25–7.32 (m, 9H), 7.36–7.52 (m, 7H), 7.48–7.54 (m, 3H). 13C NMR (CDCl3) δ 12.6,

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32.6, 52.2, 58.8, 71.0 (JCP = 8.6 Hz), 75.9 (JCP = 104.2 Hz), 123.1 (JCP = 93.3 Hz), 126.7, 128.1, 128.2
(JCP = 13.2 Hz), 128.8, 131.9 (JCP = 2.9 Hz), 132.2 (JCP = 10.3 Hz), 133.3, 166.8 (JCP = 10.9 Hz), 184.4
(JCP = 6.3 Hz). Anal. Calcd for C34H38Br2NO3P: C, 58.38; H, 5.48; N, 2.00. Found: C, 58.22; H, 5.78; N,
1.98.
PREPARATION OF N-METHYLATED DOT-PYRROLIDINE 11
To a solution of 9c (1.0 g, 2.2 mmol) dissolved in a solvent mixture (THF:CH2Cl2 = v:v = 1:1, 40 mL),
sodium hydride 60% on mineral oil (0.890 g, 22.2 mmol) was added. Methyl iodide (1.4 mL, 22.2
mmol) was added dropwise to the reaction mixture and stirred at rt for 16 h. The solvent mixture was
evacuated and the residue was extracted with CH2Cl2. The crude product was filtered and subjected to
column chromatography (SiO2, CH2Cl2:MeOH = 98:2).
(5RS)-5-Benzyl-1-methyl-3-triphenylphosphoranylidenpyrrolidin-2,4-dione (11). (0.95 g, 92%)
White plates (EtOAc) mp 180–182 °C. 1H NMR (CDCl3) δ 2.94 (s, 3H), 3.13 (d, J = 4.1 Hz, 2H), 3.93
(t, J = 4.2 Hz, 1H), 7.17–7.25 (m, 5H), 7.36–7.46 (m, 12H), 7.54–7.60 (m, 3H). 13C NMR (CDCl3) δ
27.7, 35.0, 64.1 (JCP = 123.1 Hz), 67.6 (JCP = 13.2 Hz), 122.7 (JCP = 92.8 Hz), 126.0, 127.8, 128.6 (JCP =
12.6 Hz), 130.1, 132.6 (JCP = 2.9 Hz), 133.8 (JCP = 10.9 Hz), 136.7, 173.8 (JCP = 16.6 Hz), 193.9 (JCP
=
6.9 Hz). Anal. Calcd for C30H26NO2P: C, 77.74; H, 5.65; N, 2.95. Found: C, 77.45; H, 5.70; N, 2.96.
PREPARATION OF LINEAR FREE AMINE 12
To a solution of 8c (0.66 g, 1.0 mmol) dissolved in CH2Cl2 (10 mL), triethylamine (3.0 eq) was added and
stirred for 1 h. The solvent mixture was washed with saturated aq sodium chloride. The organic layer
was dried with anhydrous magnesium sulfate, filtered, and removed under vacuum to give 12.
(4RS)-4-amino-1-ethoxy-5-phenyl-2-(triphenylphosphoranyliden)pentan-1,3-dione (12). (0.45 g,
quantitative) Clear oil, 1H NMR (CDCl3) δ 0.63 (t, J = 7.0 Hz, 3H) 1.53 (br s, 2H), 2.50 (dd, J = 12.6, 9.1
Hz, 1H), 3.31 (dd, J = 12.6, 4.9 Hz, 1H), 3.62–3.78 (m, 2H), 4.92 (dd, J = 9.1, 4.9 Hz, 1H), 7.14–7.31 (m,
5H), 7.40–7.65 (m, 15H). 13C NMR (CDCl3) δ 13.6, 42.4, 57.2 (JCP = 7.4 Hz), 58.4, 69.3 (JCP = 108.2
Hz), 125.8, 126.4 (JCP = 93.3 Hz), 128.1, 128.5 (JCP = 12.6 Hz), 129.6, 131.6 (JCP = 2.9 Hz), 132.9 (JCP =
9.7 Hz), 139.8, 167.2 (JCP = 14.3 Hz), 198.0 (JCP = 2.9 Hz). Anal. Calcd for C30H26NO2P: C, 75.14; H,
6.10; N, 2.83. Found: C, 74.37; H, 6.06; N, 2.97.
PREPARATION OF α-TRIPHENYLPHOSPHORANYLIDENE NITRILES 14a–e
Compounds 14a–e were prepared from the corresponding 5a–e (1.1 mmol) and 13 (1.0 mmol), following
the procedure developed for 7a–e.
4-Benzyloxycarbonylamino-3-oxo-2-triphenylphosphoranylidenbutane nitrile (14a). (0.42 g, 85%)
White microcrystals (from Et2O / hexanes) mp 171–173 °C. 1H NMR (CDCl3) δ 4.41 (d, J = 4.3 Hz,

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1417
2H), 5.09 (s, 2H), 5.59 (br s, 1H), 7.26–7.40 (m, 5H), 7.42–7.72 (m, 15H). 13C NMR (CDCl3) δ 46.4
(JCP = 127.7 Hz), 47.5 (JCP = 10.9 Hz), 66.4, 120.6 (JCP = 14.9 Hz), 122.3 (JCP = 93.3 Hz), 127.8, 128.3,
129.2 (JCP = 13.2 Hz), 133.3 (JCP = 3.4 Hz), 133.5 (JCP = 10.3 Hz), 136.6, 156.0, 189.9. Anal. Calcd for
C30H25N2O3P: C, 73.16; H, 5.12; N, 5.69. Found: C, 72.80; H, 5.08; N, 5.59.
(4S)-Benzyloxycarbonylamino-3-oxo-2-triphenylphosphoranylidenpentane nitrile (14b). (0.40 g,
79%) (76%)30a (85%)30b White microcrystals (from Et2O / hexanes) mp 73–75 °C. [α]23 D +21.5 (c 1.00,
CH2Cl2) ([α]20 D +18.96 (c 1.00, CHCl3))30b. 1H NMR (CDCl3) δ 1.53 (d, J = 6.7 Hz, 3H), 4.92–5.02 (m,
1H), 5.08 (s, 2H), 5.75 (d, J = 6.9 Hz, 1H), 7.22–7.36 (m, 5H), 7.40–7.72 (m, 15H). 13C NMR (CDCl3)
δ 19.4, 46.5 (JCP = 127.5 Hz), 52.2, 66.0, 120.7 (JCP = 14.9 Hz), 122.3 (JCP = 93.3 Hz), 127.6, 128.2,
129.0 (JCP = 12.6 Hz), 131.7 (JCP = 4.0 Hz), 131.8, 133.2 (JCP = 10.3 Hz), 136.5, 155.2, 194.3. Anal.
Calcd for C31H27N2O3P: C, 73.51; H, 5.37; N, 5.53. Found: C, 73.13; H, 5.38; N, 5.36.
(4S)-Benzyloxycarbonylamino-3-oxo-5-phenyl-2-triphenylphosphoranylidenpentane nitrile (14c).
(0.44 g, 79%) (78%)29 (77%)30a White microcrystals (from CH2Cl2 / Et2O) mp 101–103 °C. [α]23 D +7.6
(c 1.10, CH2Cl2). 1H NMR (CDCl3) δ 3.06 (dd, J = 13.9, 7.0 Hz, 1H), 3.34 (dd, J = 13.9, 4.9 Hz 1H),
5.03 (s, 2H), 5.16 (q, J = 7.0 Hz, 1H), 5.49 (d, J = 7.0 Hz, 1H), 7.17–7.30 (m, 10H), 7.40–7.67 (m, 15H).
13C NMR (CDCl3) δ 38.7, 47.9 (JCP = 126.0 Hz), 57.2 (JCP = 9.0 Hz), 66.3, 121.0 (JCP = 16.0 Hz), 122.4
(JCP = 93.9 Hz), 126.4, 127.8. 128.1, 128.3, 129.1 (JCP = 12.6 Hz), 129.7, 133.2 (JCP = 3.4 Hz), 133.5 (JCP
= 10.3 Hz), 136.8, 155.5, 192.9. Anal. Calcd for C37H31N2O3P: C, 76.27; H, 5.36; N, 4.81. Found: C,
76.52; H, 5.38; N, 2.94.
(2S)-1-Benzyloxycarbonyl-(cyanotriphenylphosphoranylidenacetyl)pyrrolidine (14d).
(Two
rotameric forms) (0.34 g, 64%) White microcrystals (from CH2Cl2 / Et2O) mp 141–143 °C. [α]23 D –12.7
(c 1.20, CH2Cl2). 1H NMR (CDCl3) δ 1.79–2.12 (m, 3H), 2.29–2.47 (m, 1H), 3.44–3.58 (m, 2H),
4.99–5.27 (m, 3H), 7.21–7.70 (m, 20H). 13C NMR (CDCl3) δ 23.6, 24.4, 30.4, 31.6, 46.2 (JCP = 126.3
Hz), 46.3 (JCP = 127.0 Hz), 46.8, 47.4, 61.8 (JCP = 9.1 Hz), 62.4 (JCP = 9.1 Hz), 66.4, 121.3 (JCP = 14.7
Hz), 121.5 (JCP = 15.4 Hz), 122.6 (JCP = 93.4 Hz), 122.9 (JCP = 93.4 Hz), 126.9, 127.2, 127.4, 127.4,
128.1, 128.2, 128.4, 128.8 (JCP = 12.6 Hz), 128.9 (JCP = 12.6 Hz), 131.8, 131.9, 132.8 (JCP = 2.8 Hz).
132.9 (JCP = 2.8 Hz), 133.2 (JCP = 10.5 Hz), 133.4 (JCP = 10.5 Hz), 136.9, 137.0, 154.2, 154.4, 194.7 (JCP
= 3.5 Hz), 194.9 (JCP = 3.5 Hz). HRMS m/z Calcd for C33H29N2O3P 533.1989 [M+H]+, Found
533.1995.
5-Benzyloxycarbonylamino-3-oxo-2-triphenylphosphoranylidenpentane nitrile (14e).
(0.32 g,
63%) White microcrystals (from Et2O/hexanes) mp 156–158 °C. 1H NMR (CDCl3) δ 2.95 (t, J = 5.9 Hz,
2H), 3.45–3.50 (m, 2H), 5.08 (s, 2H), 5.41 (br s, 1H), 7.24–7.38 (m, 5H), 7.44–7.64 (m, 15H). 13C NMR
(CDCl3) δ 36.9, 38.6 (JCP = 9.2 Hz), 49.0 (JCP = 126.0 Hz), 66.1, 121.8 (JCP = 16.6 Hz), 122.6 (JCP = 93.9
Hz), 127.7, 127.8, 128.2, 129.0 (JCP = 13.2 Hz), 133.1 (JCP = 2.9 Hz), 133.3 (JCP = 10.3 Hz), 136.6, 156.0,

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195.0. Anal. Calcd for C31H27N2O3P: C, 73.51; H, 5.37; N, 5.53. Found: C, 73.50; H, 5.37; N, 5.50.
PREPARATION OF 2,4-DIHYDROPYRROL-3-ONE SALTS 15a–c, PYRROLIZIN-1-ONE SALT
15d, AND NITRILE SALT 15e
Compounds 15a–e were prepared from the corresponding 14a–e (1.0 mmol) following the procedure
developed for salts 8a–e.
5-Amino-4-triphenylphosphonio-2,4-dihydropyrrol-3-one Bromide (15a). (0.31 g, 71%) White
plates (from CH2Cl2 / Et2O) mp 255–258 °C. 1H NMR (CDCl3) δ 3.99 (s, 2H), 7.64–7.71 (m, 12H),
7.74–7.81 (m, 3H), 8.72 (br s, 1H). 13C NMR (CDCl3) δ 52.2 (JCP = 10.3 Hz), 64.8 (JCP = 125.4 Hz),
119.7 (JCP = 93.3 Hz), 130.1 (JCP = 13.2 Hz), 133.6 (JCP = 10.9 Hz), 134.6 (JCP = 2.9 Hz), 170.3 (JCP
=
17.2 Hz), 194.5 (JCP = 6.3 Hz). Anal. Calcd for C22H20BrN2OP: C, 60.15; H, 4.59; N, 6.38; Found: C,
60.11; H, 4.94; N, 5.59.
(2RS)-5-Amino-2-methyl-4-triphenylphosphonio-2,4-dihydropyrrol-3-one Bromide (15b). (0.26 g,
70%) White plates (from CH2Cl2 / Et2O) mp 260–262 °C. 1H NMR (CDCl3) δ 1.45 (d, J = 7.0 Hz, 3H),
1.72 (br s, 2H), 4.03 (q, J = 7.0 Hz, 1H), 7.63–7.69 (m, 12H), 7.75–7.81 (m, 3H), 8.76 (br s, 1H). 13C
NMR (CDCl3) δ 17.3, 58.5 (JCP = 10.3 Hz), 63.1 (JCP = 124.3 Hz), 120.1 (JCP = 93.3 Hz), 130.1 (JCP
=
13.1 Hz), 133.6 (JCP = 10.9 Hz), 134.6 (JCP = 2.9 Hz), 168.8 (JCP = 17.2 Hz), 197.7 (JCP = 5.7 Hz). Anal.
Calcd for C23H22BrN2OP: C, 60.94; H, 4.89; N, 6.18. Found: C, 60.58; H, 4.78; N, 5.96.
(2RS)-5-Amino-2-benzyl-4-triphenylphosphonio-2,4-dihydropyrrol-3-one Bromide (15c). (0.38 g,
72%) White plates (from CH2Cl2 / Et2O) mp 253–255 °C. 1H NMR (CDCl3) δ 1.69 (s, 2H), 3.11 (dd, J
= 14.0, 4.9 Hz, 1H), 3,21 (dd, J = 14.0, 3.5 Hz, 1H), 4.28 (t, J = 4.2 Hz, 1H), 7.32–7.42 (m, 11H),
7.54–7.59 (m, 6H), 7.71–7.76 (m, 3H), 9.06 (br d, JHP = 2.1 Hz, 1H). 13C NMR (CDCl3) δ 36.6, 63.3
(JCP = 10.3 Hz), 64.0 (JCP = 127.8 Hz), 119.7 (JCP = 92.8 Hz), 126.8, 128.4, 130.0 (JCP = 12.6 Hz), 130.6,
133.7 (JCP = 10.9 Hz), 134.5 (JCP = 2.9 Hz), 134.9, 169.3 (JCP = 16.6 Hz), 195.3 (JCP = 6.3 Hz). Anal
Calcd for C29H26BrN2OP + H2O: C, 63.63; H, 5.16; N, 5.12. Found: C, 63.21; H, 4.77; N, 4.94.
(4RS)-3-Ammonio-2-triphenylphosphonio-tetrahydropyrrolizin-1-one Dibromide (15d). (0.37 g,
66%) White plates (from CH2Cl2 / Et2O) mp 238–240 °C. 1H NMR (CDCl3) δ 1.48–1.59 (m, 1H),
1.93–2.25 (m, 3H), 3.57–3.70 (m, 1H), 3.81–3.88 (m, 1H), 4.02–4.08 (m, 1H), 7.54–7.64 (m, 11H),
7.69–7.79 (m, 4H). 13C NMR (CDCl3) δ 26.7, 27.8, 49.1, 65.9 (JCP = 119.1 Hz), 70.0 (JCP = 10.3 Hz),
119.4 (JCP = 92.8 Hz), 130.0 (JCP = 13.1 Hz), 133.5 (JCP = 10.9 Hz), 134.6 (JCP = 2.9Hz), 170.9 (JCP
=
15.5 Hz), 196.2 (JCP = 5.7 Hz). Anal. Calcd for C25H25Br2N2OP: C, 53.59; H, 4.50; N, 5.00. Found: C,
53.99; H, 4.39; N, 4.52.
1-Ammonio-3-oxo-4-triphenylphosphoranylidenpentan-5-nitrile Bromide (15e). (0.16 g, 35%)
White microcrystals (from Et2O / hexanes) mp 238–244 °C. 1H NMR (CDCl3) δ 3.17–3.24 (m, 4H),

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1419
7.42 (br s, 3H), 7.51–7.68 (m, 15H). 13C NMR (CDCl3) δ 33.4 (JCP = 8.0 Hz), 37.0, 50.4 (JCP = 124.3
Hz), 120.8 (JCP = 16.0 Hz), 121.8 (JCP = 93.3 Hz), 129.3 (JCP = 13.2 Hz), 133.4 (JCP = 10.3 Hz), 133.5
(JCP = 2.3 Hz), 195.0 (JCP = 4.0 Hz). Anal. Calcd for C23H24BrN2O2P: C, 58.61; H, 5.13; N, 5.94.
Found: C, 58.63; H, 5.15; N, 5.39.
PREPARATION OF 3,3-DIBROMOPYRROLIDIN-2,4-DIONE 16
4-Chlorobenzoic acid (0.05 g, 0.32 mmol) and 14 (0.13 g, 0.28 mmol) were refluxed in THF (25 mL) for
1 h, no reaction was detected by TLC. Upon the addition of NBS (0.17 g, 0.56 mmol) the reaction was
completed after 5 min of stirring at rt. The organic phase was washed with saturated aq sodium chloride.
The crude product was subjected to column chromatography (SiO2, hexane:EtOAc = 4:1).
(5RS)-5-Benzyl-3,3-dibromo-1-methylpyrrolidin-2,4-dione (16). (0.08 g, 79%) Yellowish oil. 1H NMR
(CDCl3) δ 3.06 (s, 3H), 3.23 (d, J = 4.9 Hz, 2H), 4.51 (t, J = 4.9 Hz, 1H), 7.07–7.11 (m, 2H), 7.22–7.33
(m, 3H). 13C NMR (CDCl3) δ 29.4, 35.5, 44.7, 66.6, 127.8, 128.9, 129.6, 133.7, 164.8, 194.4. Anal.
Calcd for C12H11Br2NO2: C, 39.92; H, 3.07; N, 3.88. Found: C, 40.45; H, 3.22; N, 3.40.
PREPARATION OF 3,3-DIBROMO-5-HYDROXY-PYRROLIDIN-2,4-DIONE 17
Ethoxytrimethylsilane (0.057 g, 0.5 mmol) and NBS (0.115 g, 0.65 mmol) were combined in CH2Cl2 (1
mL) for 2 min and added to 14 (0.15 g, 0.3 mmol) separately dissolved in CH2Cl2 (1 mL). The reaction
was complete after 5 min stirring at rt. The crude product was subjected to column chromatography
(SiO2, hexane:EtOAc = 4:1) and allowed a mixture (1:1) of 16 (0.05 g, 44%) and 17 (0.05 g, 44%) to be
obtained in 88% yield, without workup.
(5RS)-5-Benzyl-3,3-dibromo-5-hydroxy-1-methylpyrrolidin-2,4-dione (17). (0.05 g, 44%) White
sheets (CHCl3) mp 134–136 °C. 1H NMR (CDCl3) δ 3.13 (s, 3H), 3.21 (d, J = 14.0 Hz, 1H), 3.38 (d, J =
14.0 Hz, 1H), 4.66 (br s, 1H), 7.05–7.09 (m, 2H), 7.24–7.28 (m, 3H). 13C NMR (CDCl3) δ 25.9, 41.1, 42.6,
90.8, 128.1, 129.0, 130.4, 131.8, 165.1, 194.3. Anal. Calcd for C12H11Br2NO3 C, 38.23; H, 2.94; N, 3.72.
Found: C, 37.48; H, 2.82; N, 3.50.
PREPARATION OF 4-AZIDO-3-BROMOPYRROL-2-ONE 18
N-Bromosuccinimide (0.135 g, 0.76 mmol) and TMS-azide (0.1 mL, 0.76 mmol) were combined in
CH2Cl2 (5 mL) and added to 14 (0.25 g, 0.54 mmol) dissolved in CH2Cl2 (1 mL). The reaction was
stirred at rt for 5 min. The crude product was subjected to column chromatography (SiO2,
hexane:EtOAc = 4:1), without workup.
1
(5RS)-4-Azido-5-benzyl-3-bromo-1-methylpyrrol-2-one (18). (0.14 g, 84%) Clear oil. H NMR
(CDCl3) δ 2.93 (dd, J = 14.7, 4.9 Hz, 1H), 2.95 (s, 3H), 3.16 (dd, J = 14.7, 4.2 Hz, 1H), 4.08 (t, J = 4.9 Hz,
1H), 7.07–7.11 (m, 2H), 7.23–7.31 (m, 3H). 13C NMR (CDCl3) δ 28.7, 35.8, 63.3, 103.1, 127.4, 128.7,

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129.0, 134.0, 149.3, 165.8. C12H11BrN4O HRMS m/z Calcd 307.0194, 309.0174 [M+H]+, Found
307.0190, 309.0119.
PREPARATION OF 4-BENZOTRIAZOLPYRROL-2-ONE 19
1-Chlorobenzotriazole (0.7 g, 0.48 mmol) and 14 (0.2 g, 0.43 mmol) were dissolved together in CH2Cl2 (1
mL). The reaction was stirred at rt for 5 min. The crude product was subjected directly to column
chromatography (SiO2, hexane:EtOAc = 9:1) without workup.
(5RS)-4-(Benzotriazol-1-yl)-5-benzyl-1-methylpyrrol-2-one (19). (0.12 g, 92%) Yellow microcrystals
1
(Et2O) mp 124–126 °C. H NMR (CDCl3) δ (Bt1:Bt2 = 1:1) 2.90 (dd, J = 14.0, 4.9 Hz, 1H), 3.13–3.30
(m, 7H), 3.37–3.50 (m, 2H), 5.21 (t, J = 4.2 Hz, 1H), 5.34 (t, J = 4.2 Hz, 1H), 6.47 (s, 1H), 6.49 (s, 1H),
6.65–6.68 (m, 2H), 6.99 (t, J = 7.7 Hz, 2H), 7.11–7.14 (m, 4H), 7.31 (d, J = 8.4 Hz, 1H), 7.40–7.60 (m,
5H), 7.87–7.98 (m, 3H), 8.16 (d, J = 7.7 Hz, 1H). 13C NMR (CDCl3) δ 28.8, 29.0, 35.1, 35.8, 62.0, 62.7,
112.5, 115.0, 116.4, 117.6, 118.6, 120.5, 125.3, 125.7, 127.4, 127.4, 128.5, 128.5, 128.8, 128.8, 128.8,
131.6, 133.0, 133.5, 143.8, 144.7, 145.2, 145.9, 164.6, 164.7. Anal. Calcd for C18H16N4O: C, 71.01; H,
5.30; N, 18.41. Found: C, 68.94; H, 4.96; N, 18.81. Reduced product C18H14N4O HRMS m/z Calcd
303.0120, 325.1060 [M+H]+, [M+Na]+ Found 303.1233, 325.1054, observed ions consistent with M =
C18H16N4O.
X-Ray Crystallography
Intensity data were collected with an APEX II CCD area detector using monochromatized Mo Kα (λ =
0.71073 Å) radiation. The intensities were corrected for Lorentz and polarization effects and for
absorption. The structures were solved by direct methods and refined on F2 by full-matrix least-squares
procedures. All non-hydrogen atoms were refined with anisotropic displacement coefficients. The
positions of hydrogen atoms were refined with isotropic displacement coefficients equal to 1.2 times the
isotropic equivalent of their carrier atoms. Crystallographic data have been deposited with the Cambridge
Crystallographic Data Centre (CCDC Nos 668264 and 668265). Copies of the data can be obtained free
of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: +44 1223 336033;
E-mail: deposit@ccdc.cam.ac.uk.
Crystal data for (9c): C29H24NO2P, MW 449.460, monoclinic, space group P21/n, a = 10.7276(2), b =
o
14.2746(3), c = 14.8455(4) Å, β = 90.353(1) o, V = 2273.28(9) Å3, F(000) = 944, Z = 4, T = -180 C,
colorless block, 0.44 x 0.22 x 0.12 mm, µ (MoKα) = 0.148 mm-1, Dcalcd = 1.313 g.cm-3, 2θmax 50o,
wR(F2) = 0.0997 (all 4022 data), R = 0.0402 (3788 data with I > 2σI).
Crystal data for (17): C12H11Br2NO3, MW 377.04, monoclinic, space group P21/n, a = 6.8928(5), b =
o
28.975(2), c = 7.0527(5) Å, β = 110.311(2) o, V = 1320.99(16) Å3, F(000) = 736, Z = 4, T = -170 C,
colorless plate, 0.53 x 0.26 x 0.14 mm, µ (MoKα) = 6.135 mm-1, Dcalcd = 1.896 g.cm-3, 2θmax 53o,

HETEROCYCLES, Vol. 76, No. 2, 2008
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wR(F2) = 0.0754 (all 2540 data), R = 0.0268 (2274 data with I > 2σI).
REFERENCES
1. a) H.–G. Henning and A. Gelbin, Adv. Heterocycl. Chem., 1993, 57, 139. b) S. J. Shimshock and P.
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