Screening of chiral phosphines as catalysts for the enantioselective [3+2] annulations of N-tosylimines with allenic esters

Article abstract of DOI:10.1016/j.tet.2007.09.022

The use of chiral, binaphthyl-based phosphepines as catalysts improves previous results for the enantioselective [3+2] cyclisation reactions between allenic esters and N-tosylimines, both in terms of conversion rate and enantioselectivity. Pyrrolines bear

Full text of DOI:10.1016/j.tet.2007.09.022

Tetrahedron 63 (2007) 11920–11927
Screening of chiral phosphines as catalysts for the
enantioselective [3D2] annulations of N-tosylimines with
allenic esters
*
ꢀ
Nicolas Fleury-Bregeot, Ludovic Jean, Pascal Retailleau and Angela Marinetti
Institut de Chimie des Substances Naturelles, CNRS UPR 2301 1, avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
Received 15 June 2007; revised 10 September 2007; accepted 11 September 2007
Available online 15 September 2007
Abstract—The use of chiral, binaphthyl-based phosphepines as catalysts improves previous results for the enantioselective [3+2] cyclisation
reactions between allenic esters and N-tosylimines, both in terms of conversion rate and enantioselectivity. Pyrrolines bearing 1-naphthyl,
phenyl, o-tolyl and p-MeO-phenyl substituents on the stereogenic alpha-carbon have been obtained with enantiomeric excesses up to 64–80%.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
groups),1b to g-substituted allenoates2b,3 as well as to alkynoa-
tes.1b,4 Recently the use of an allenic ketone has also been re-
ported.2b,5 Triphenylphosphine was routinely used as an
efficient and highly chemoselective catalyst in the reaction
of2,3-butadienoateswithimines, whileitsratherweaknucleo-
philicity prevented its use for the activation of 2-butynoates.
Tributylphosphine proved to be a more suitable catalyst for re-
actions involving both acetylenic substrates1b,4 and sterically
hindered g-substituted allenic esters.3 As a general trend,
increasedefficiencyisobservedwhenmorenucleophilicphos-
phines were used, however, fine matching of the substrate–
Lewis base promoter pairs may be necessary to attain high
catalytic activity.2b
The [3+2] annulation between imines and a three-carbon
synthon generated from electron poor alkynes or allenes
has been introduced in 1997 by Lu1 as an original method
for the synthesis of pyrroline rings (Scheme 1). In principle,
any Lewis bases are potential catalysts for this reaction,
however, only phosphines have been found to date as suit-
able promoters, while the nitrogen nucleophiles tested so
far led to different products, i.e., either azetidine or dihydro-
pyridine derivatives.2 Both allenic esters and 2-butynoates
have been used as starting materials and are supposed to
enter the same catalytic cycle leading to 3-pyrrolines.
The synthetic potential of the cycloaddition reaction in
Scheme 1 has been substantiated, among others, by its
use as a key step in the large scale synthesis of new fam-
ilies of NK1 antagonists based on pyrrolidine moieties
(Scheme 2).6 The synthetic procedure for the preparation
of these compounds involves HPLC separation of enan-
tiomers of a pyrroline obtained in the phosphine-
catalysed cycloaddition step. This example adequately
highlights the usefulness of the method as well as the
relevance of a possible enantioselective version of these
reactions.
Z
SO2Ar
•
SO2Ar
N
R
R'
R3P cat.
R
R
N
+
or
R'
Z
Z
Scheme 1. Phosphine-promoted [3+2] annulation of activated allenes or
alcynes with imines.
Initial studies involved methyl 2,3-butadienoate and aromatic
N-tosylimines (R¼Ph, o- and p-MeO-Ph, 1-naphthyl, 2-furyl,
etc.) or cinnamaldimine as reaction partners. Later on, the
scopeofthereactionwasextendedtoiminesactivatedbyalter-
native electron-withdrawing groups (diphenylphosphinyl,
p-nitrobenzenesulfonyl and b-trimethylsilylethanesulfonyl
Thus, with the aim of setting an enantioselective [3+2] annu-
lation procedure, we have started a systematic screening of
various non-racemic phosphine promoters. Preliminary
results have been reported in a previous communication.7
Herein we wish to report details of these studies, as well
as more recent results showing that the efficiency of the
annulation reactions can be improved by means of the
binaphthyl phosphepine catalysts A1 and A2.8
Keywords: [3+2] Cyclisations; Asymmetric organocatalysis; Nitrogen het-
erocycles; Chiral phosphines; Phosphepines.
* Corresponding author. Tel.: +33 1 69 82 30 36; fax: +33 1 69 07 72 47;
e-mail: angela.marinetti@icsn.cnrs-gif.fr
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.022

´
N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11921
activity, which might be ascribed to the weak nucleophilic
character and steric hindrance of these triarylphosphines.
For comparison, it is noteworthy that the same cyclisation re-
action is efficiently promoted by PPh3 (80% isolated yield).
PhanePHOS (G) also displayed a quite low catalytic activity
while affording the highest ee of this preliminary screening
(64% ee). Higher conversion rates were observed with the
atropisomeric triaryl-monophosphines MOP (D) and Quinap
(E), which bear heteroatom donor groups on the aryl moiety,
as well as with the Trost ligand (F). The possible role of the
additional heteroatom is unclear. In the case of Quinap, in-
volvement of nitrogen as the nucleophilic promoter instead
of phosphorus could be envisioned, however, it can be rea-
sonably ruled out as isoquinoline itself does not display
any catalytic activity under the same reaction conditions.
P
R
(S)-A1 R = Ph
(S)-A2 R = t-Bu
2. Results and discussion
The development of enantioselective organocatalysis with
phosphorus nucleophiles is at a very early stage9 and little
is known about the structural requirements for efficient cat-
alysts. This is why our studies towards the setting of an
asymmetric version of the [3+2] cyclisation reactions above
started with the systematic screening of commercially avail-
able chiral phosphines. In addition, several monodentate and
bidentate chiral phosphetanes from our previous studies (L
and M)10 have also been included in the screening tests.
The annulation of ethyl 2,3-butadienoate with N-tosyl-
1-naphthaldimine (Eq. 1) was selected as a model reaction.
Results obtained with representative phosphines11 are
summarized in Scheme 2.
As expected, a satisfying catalytic activity was observed
with the electron-rich di- and trialkyl heterocyclic phos-
phines bearing phospholane (H), phosphetane (L and M)
and phosphepine (A) moieties as shown in Scheme 2.
The phospholane-based Me-BPE (H) affords a racemic pyr-
roline product. Together with literature data, this result high-
lights the rather unpredictable behaviour of BPE in
nucleophilic cyclisation reactions. Indeed, if the catalytic ac-
tivity is generally satisfying, high enantiomeric excesses, up
to 72% ee, have been obtained only in the [4+2] annulations
of imines with allenes,9d while almost racemic products are
formed in the [3+2] annulations between allenes and either
enones9g or imines (this work).
Ts
N
Ts
CO2Et
PR3 (10%)
ð1Þ
+
N
•
CH2Cl2, r.t., 24h
1-Naph
CO2Et
1a
2a
3a
In the ferrocene-derived phosphetanes, L10b,12 and M,10a
tuning of the R-substituents allows to optimize, to some
extent, the conversion rates and/or enantioselectivity, with
ees up to 48%. In addition to these ferrocene-derived
Atropisomeric diphosphines such as Binap (B) and MeO-
Biphep (C) afforded enantiomeric excesses of about 50%,
however, their use is hampered by the rather low catalytic
N
O
O
PPh2
PPh2
OMe
PPh2
MeO
MeO
PPh2
PPh2
NH
HN
PPh2
PPh2Ph2P
Trost ligand (F)
(S)-BINAP (B)
13% yield, 45% ee
(R)-MeO-Biphep (C)
(R)-MOP (D)
(R)-QUINAP (E)
22% yield, 53% ee
45% yield, 11% ee
61% yield 28% ee
60% yield, 19% ee
R
P
R
P
PPh2
P
P
R
Fe
R
P
R
P
Fe
R
PPh2
R
Phosphetane (L)
(R,R)-Me-BPE (H)
(S)-PHANEPHOS (G)
32% yield, 64% ee
Phosphepine (A)
FerroTANE (M)
(S,S)-L1 R = i-Pr
50% yield, 44% ee
(S,S)-L2 R = Cy
55% yield, 48% ee
(R,R)-M1 R = Me
72% yield, 3% ee
(R,R)-M2 R = Et
50% yield, 22% ee
(S,S)-M3 R = i-Pr
70% yield, 37% ee
(S)-A1 R = Ph
70% yield, 0% ee
75% yield, 40% ee
(S)-A2 R = t-Bu
70% yield, 54% ee
Scheme 2.

´
N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11922
phosphetanes, a few other chiral phosphetanes have been
tested so far in the same cyclisation reaction, including
main results (conversion rates and enantiomeric excesses)
obtained with phosphepines A1 and A2 are reported in Table
1, in comparison with those obtained with Et-FerroTANE
and Phanephos. The few literature data available so far on
the same reactions are also recalled in the table. These
data concern the use of the Gladysz organometallic phos-
phine having metal-centred chirality, Cp(NO)(P-
(R,R)-2,4-dimethyl-1-phenylphosphetane,
(R,R)-2,4-di-
methyl-1-mesitylphosphetane13 and bis((S,S)-2,4-dicyclo-
hexylphosphetano)ethane.14 They afford, however,
enantiomeric excesses lower than 10%. Thus it seems that
the somewhat higher enantioselectivity observed with phos-
phetanes L or M cannot be ascribed to the phosphetane
structure itself, it might rather result from specifically com-
bining ferrocene and phosphetane units.
15
Ph3)ReCH2PPh2 ; reaction conditions (8 days at ꢀ20 ꢁC
with a substrate/catalyst ratio of 20 mol %) are significantly
different from those used in our experiments.
From the work of Fu,9d,g the tert-butyl-phosphepine A2 is
known to promote the asymmetric [3+2] cycloadditions of
allenes with enones and the [4+2] annulations of allenes
with imines in very high enantiomeric excesses up to 90%
and 98% ee, respectively. Such high enantioselectivity levels
have not been observed in the [3+2] cycloadditions of
Scheme 2, as a maximum ee of 54% has been obtained.
The catalytic activity of A proved, however, satisfying
when compared to most of the chiral phosphines
evaluated so far, with a conversion rate of about
75–80% after 24 h at room temperature. Thus, phosphepines
A have been selected for more extended screenings where
the encouraging preliminary results above have been sub-
stantiated by additional tests on different substrates, by vary-
ing both the imine substituent and the allene ester group. The
All reactions in Table 1 were performed under argon, with
equimolar amounts of reactants, 10 mol % catalyst, in
dichloromethane at room temperature for 24 h. At first,
N-tosylimines bearing various aryl groups16 on the a-carbon
have been reacted with ethyl 2,3-butadienoate 1a to afford
pyrrolines 3b–e. Conversion rates up to 85% have been mea-
sured by NMR, the starting imine and small amounts of the
corresponding aldehyde being also observed in the final mix-
tures. With respect to enantioselectivity, the use of the tert-
butyl-substituted phosphepine A2 as the catalyst afforded
the best results, with enantiomeric excesses up to 79%.
The highest ee was obtained in the cyclisation between ethyl
2,3-butadienoate and the electron-rich p-anisyl substituted
imine 2d, which gave, however, a rather low conversion
rate at room temperature (63%). In the same reaction,
Table 1. Survey of different imines in combination with allenes 1a and 1b
Ts
N
Ts
PR3* (10%)
CO2 R
Ar
+
N
•
CH2Cl2, r.t., 24h
Ar
CO2 R
1a, R = Et
1b, R = Cy
2a-g
3b-e
4a-g
Ar = 1-naphthyl (2a), p-NO2-Ph (2b),
Ph (2c), p-MeO-Ph (2d), o-Me-Ph (2e),
benzo[1,3]dioxol-5-yl (2f), 2-furyl (2g)
Product
Ar
Phosphepine (S)-A1
ee%a
Phosphepine (S)-A2
Et-Ferrotane (R,R)-M2
PhanePHOS (S)-G
Ref. 15b
R
Conv
Conv
ee%
Conv
ee%
Conv
ee%
Yield
ee%
3b
3c
3d
3e
4a
4b
4c
4d
4e
Et
Et
Et
Et
Cy
Cy
Cy
Cy
Cy
p-NO2-Ph
Ph
70
76
52
43
>95
78
>95
69
18
45
21
25
64c
38
42
53
60
85d
72e
43
71
80
88
23
28
—
21
31
38
37
6
26
—
54
90
92
93
51
60
54
p-MeO-Ph
o-Me-Ph
1-Naphthyl
p-NO2-Ph
Ph
63f
79 (86)m
66
41
80g
66
>95
18
90h
86i
43
62
80
52
>95j
84k
p-MeO-Ph
o-Me-Ph
>95
>95l
O
4f
Cy
Cy
55
78
26
91
80
62
O
4g
2-Furyl
48
46
a
Enantiomeric excesses have been measured by chiral HPLC.
Conditions: 20 mol % catalyst, chlorobenzene, ꢀ20 ꢁC, 8 days.
racemate crystallizes preferentially from the mixture.7
Isolated yields: 80%.
Isolated yields: 64%.
Isolated yields: 60%.
Isolated yields: 72%.
Isolated yields: 88%.
Isolated yields: 81%.
Isolated yields: 86%.
Isolated yields: 60%.
Isolated yields: 87%.
ee for reaction performed in acetone.
b
c
Isolated yield: 91%. As mentioned in our previous communication, the enantiomeric excess of this pyrroline can be increased by crystallisation, given that the
d
e
f
g
h
i
j
k
l
m

´
N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11923
heating at 50 ꢁC allows conversion to be improved from 63
Ts
N
Ts
to 75%, with only a small decrease in enantioselectivity
(ee¼75%). When acetone was used instead of dichlorome-
thane as the solvent, at room temperature, the ee increased
up to 86%.
A1 or A2 (10%)
Ar
N
CO2R
+
CH2Cl2, 24h
Ar
CO2R
2a
2d
5a R = Me
5b R = Cy
6a, R = Me, Ar = 1-naphthyl
4d, R = Cy, Ar = p-MeO-Ph
In a second series of experiments, the nature of the allenic
ester group has been considered for its possible effects on
the reaction rates and enantioselectivity. The preliminary
tests already mentioned in our previous communication7
showed that in the reaction between N-tosyl-naphth-
aldimine 2a and various allenic esters 1, promoted by
Et-FerroTANE (M2), increased enantioselectivities were
obtained for bulkier alkyls as the ester substituents: pyrro-
lines17 having ees of 22%, 2% and 52% were obtained for
Phosphepine A2
Phosphepine A1
Product
6a
T
conv
Ee%
conv
Ee%
61
r.t.
45°C
r.t.
75a
51
25
-
-
74b
56c
53
79
4d
-
-
a
b
c
Isolated yields: 68%; 65%; 48%
Scheme 3.
i
R¼Et, Ph and Pr, respectively. However, the practical use
Both phosphepines A1 and A2 are suitable catalysts for
these reactions. With phosphepine A2 the reaction between
methyl 2-butynoate and 5a displayed a low conversion rate
at room temperature (25% and 61% ee), which could nev-
ertheless be increased to 74% when the reaction was per-
formed at 45 ꢁC. A small decrease in enantioselectivity
was observed then. Starting from cyclohexyl 2-butynoate
5b (Scheme 3), pyrroline 4d has been obtained with lower
conversion rates and comparable enantiomeric excesses
with respect to those obtained from the corresponding
allene 1b (Table 1), under as far as possible identical exper-
imental conditions.
of bulky allenic esters is often hampered by their low con-
version rates. Unlike this, when cyclohexyl 2,3-butadi-
enoate 1b was used as the substrate, a high conversion
rate, an especially clean reaction and a slightly increased
enantiomeric excess, compared to the ethyl ester (31% vs
22%), were observed. Cyclohexyl 2,3-butadienoate 1b was
thus envisioned as a suitable substrate for further evalua-
tion of phosphepines A.
Cyclohexyl 2,3-butadienoate is available from the corre-
sponding phosphorane Ph3P¼CHCO2Cy, by Wittig reaction
with ketene generated in situ from acetyl chloride and tri-
ethylamine,18 as described in Section 3. In the [3+2] cyclisa-
tion reactions with N-tosylimines, under the usual conditions
above, cyclohexyl butadienoate afforded higher conversion
rates than the corresponding ethyl ester. Most substrates,
including the o-tolyl- and 1-naphthyl-substituted imines 2e
and 2a, could be converted quantitatively into the corre-
sponding pyrrolines, 4. In the reaction of 1b with N-to-
sylbenzaldimine 2c, promoted by phosphepine A1, the
catalyst amount could be reduced to 5%, which led to 4c
with an 83% conversion rate, in otherwise identical condi-
tions.
The absolute configurations of the final pyrrolines 3, 4 and 6
are unknown so far. However, the sense of chiral induction
from tert-butyl-phosphepine (S)-A1 has been inferred from
the X-ray crystal structure of pyrroline 7a obtained from
D-menthyl 2-butynoate (Scheme 4). The stereochemical out-
come of these reactions is primarily controlled by the chiral
phosphine and the menthyl group having only minor effects
on chiral induction.19
Ts
Ts
N
(S)-A2 (10%)
Ph
N
CO2Men
+
Conversion rates were improved to about 85% also for the
less reactive electron-rich imine 2d, and the resulting pyrro-
line 4d displayed an 80% enantiomeric excess when the tert-
butyl-phosphepine A2 was used as the catalyst.
CH2Cl2, 24h, 52%
Ph
CO2Men
5c, Men = d-menthyl
2c
(S)-7a (+ 7b)
(78:22 ratio)
Scheme 4.
These results support our previous remark on the particular
suitability of the cyclohexyl ester 1b as the allenic substrate
in these cyclisation reactions, as far as conversion rates are
considered. Concerning the enantioselectivity levels, the re-
action found to be highly substrate dependant and no regular
trend is observed when the size of the ester substituent is
increased.
The major epimer, 7a, displays an S-configuration at the pyr-
roline carbon atom (Fig. 1).20
Finally, in order to potentially expand the scope and syn-
thetic utility of these [3+2] cyclisation reactions, we consid-
ered using acetylenic ester as starting materials, given that
butynoates are more easily available substrates, compared
to allenic esters. They usually display, however, lower reac-
tivity.
Methyl and cyclohexyl 2-butynoate (5a,b) were reacted with
the N-tosylimines 2a and 2d to afford the expected pyrro-
lines 6a and 4d, as shown in Scheme 3.
Figure 1. ORTEP drawing for pyrroline 7a.

´
N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11924
On the whole, the use of the phosphepine catalysts A im-
proves previous results for the enantioselective [3+2] cycli-
sation reactions between allenic esters and N-tosylimines,
both in terms of conversion rate and enantioselectivity. An
appropriate choice of the allenic ester, 1a or 1b, combined
with the suitable phosphepine catalyst, A1 or A2, allows
enantiomeric excesses up to 64–86% to be obtained for
pyrrolines bearing 1-naphthyl, phenyl, o-tolyl and p-MeO-
phenyl substituents on the stereogenic alpha-carbons. Albeit
lower conversion rates are observed, 2-butynoates also rep-
resent suitable substrates for these cyclisation reactions.
]CH2), 5.61 (t, 4J¼6.6 Hz, 1H, ]CH); 13C NMR
(CDCl3) d 23.6 (CH2), 25.5 (CH2), 31.6 (CH2), 73.1
(OCH), 79.1 (]CH2), 88.4 (]CH), 165.1 (CO2–), 215.6
(C) ppm.
3.3. Cyclohexyl 2-butynoate 5b
This compound was prepared in analogy to the procedure of
Moyano and co-workers.25 To a stirred ice-cooled solution
containing 2-butynoic acid (1.0 g, 1.19 mmol) and cyclo-
hexanol (1.4 mL, 1.33 mmol) in dichloromethane
(12 mL), a solution of dicyclohexylcarbodiimide (2.45 g,
1.19 mmol)
and
4-dimethylaminopyridine
(0.15 g,
3. Experimental
3.1. General
1.19 mmol) in CH2Cl2 (12 mL) was added dropwise. The
mixture was stirred at 0 ꢁC for 3 h, then warmed up to
room temperature. The resulting precipitate was filtered
out and washed with dichloromethane. After evaporation
of the solvent, Kugelrohr distillation of the crude product
NMR spectra have been recorded on Bruker Avance 300 or
Avance 500 spectrometers. All reactions have been per-
formed under inert atmosphere (argon). N-Tosyl-arylimines
2 were prepared via the BF3$Et2O catalysed condensation of
tosylamine with aldehydes, in a Dean–Stark apparatus,
according to the literature method.21,6a N-Tosyl 1-naphthal-
dimine, N-tosylbenzaldimine, N-tosyl p-NO2-benzaldimine,
N-tosyl p-MeO-benzaldimine,21 N-tosyl o-Me-benzaldi-
mine22 N-tosyl-2-(2-furyl)imine23 and N-tosyl-2-(ben-
zo[1,3]dioxol-5-yl)imine23b are known compounds.
1
(120 ꢁC, 10 mbar) afforded 5b in 86% yield (1.7 g). H
NMR (CDCl3) d 1.2–1.6 (6H), 1.75 (2H), 1.9 (2H), 2.00
(s, 3H, Me), 4.84 (1H, OCH); 13C NMR (CDCl3) d 3.8
(Me), 23.8 (CH2), 25.2 (CH2), 31.4 (CH2), 72.9 (C), 74.6
(OCH), 84.8 (C), 153.3 (CO2CH) ppm.
3.4. General procedure for the phosphine-promoted
cyclisation reactions
N-Tosylimine 2 (0.3 mmol) and the allenic ester 1 (or alkyne
5) (0.33 mmol) were dissolved in CH2Cl2 (1 mL) under
argon. The chiral phosphine (3ꢂ10ꢀ2 mmol) was added
and the mixture was stirred at room temperature for about
24 h. After evaporation of the solvent, the residue was chro-
matographed on silica gel with heptane/ethyl acetate mix-
tures. Given the small scale of these catalytic tests, the
reported yields might not be totally accurate, they are never-
3.2. Cyclohexyl 2,3-butadienoate 1b
A stirred solution of cyclohexyl bromoacetate24 (7.4 g,
33.6 mmol) and triphenylphosphine (9.7 g, 37.0 mmol) in
toluene (100 mL) was heated at 100 ꢁC for 12 h. Filtration
of the solution gave the corresponding phosphonium salt
1
(13.3 g, 27.5 mmol, 83% yield). H NMR (CDCl3) d 1.0–
1.6 (10H), 4.60 (1H, OCH), 5.45 (d, JH–P¼14.1 Hz, 2H,
2
1
theless consistent with the conversion rates based on H
PCH2), 7.6–8.0 (15H, Ph); 31P NMR (CDCl3) d 21 ppm.
NMR analysis of the crude mixtures. Except for the imine
derived aldehyde, no other definite side products have
been observed in detectable amount. Enantiomeric excesses
for pyrrolines 3, 4 and 6 have been measured by chiral
HPLC. Reference sample of racemic pyrrolines have been
obtained with either PBu3 or PPh3 as the catalyst. The signs
of optical rotation for the final 3-pyrrolines have been deter-
mined in CHCl3 for enantiomerically enriched samples. The
absolute stereochemistry of the cycloadducts was not deter-
mined.
A two-layer system of the phosphonium bromide in 70 mL
dichloromethane and a 1.2 M solution of NaOH in water
(45 mL) were vigorously shaken in a separation funnel, after
which the layers were separated. The water layer was
washed with dichloromethane. The organic layers were
dried over MgSO4 and the solvent was evaporated to yield
10.9 g (27.1 mmol, 98% yield) of cyclohexyl (triphenyl-
phosphoranilydene)acetate. 1H NMR (CDCl3) d 0.6–2.0
(10H), 2.8 (br d, J¼23 Hz, 1H, P]CH), 4.56 (1H, OCH),
7.4–7.7 (15H, Ph); 31P NMR (CDCl3) d 16 and 18 ppm.
3.4.1. Ethyl 2,5-dihydro-2-(1-naphthyl)-1-tosylpyrrole-3-
carboxylate 3a. Pale yellow oil; 1H NMR (CDCl3) d 0.74 (t,
J¼7.2 Hz, 3H, Me), 2.16 (s, 3H, Me), 3.75 (m, 2H, CH2CH3),
A solution of ylide (10.9 g, 27.1 mmol) and triethylamine
(3.9 mL, 27.8 mmol) in dichloromethane (90 mL) was
stirred at room temperature while a solution of acetyl chlo-
ride (2.0 mL, 27.1 mmol) in dichloromethane (10 mL) was
added dropwise. The mixture was stirred for 12 h. Dichloro-
methane was removed under reduced pressure. Pentane was
added to the residue and the solid triphenylphosphine oxide
was removed by filtration. After evaporation of the solvent,
rapid distillation of the residue on a Kugelrohr apparatus
(100 ꢁC, 1 mbar) afforded 1.6 g (9.6 mmol, 36%) of the al-
lene. Alternatively, the final product can be purified by col-
umn chromatography on silica gel with pentane/ether 90:10
2
4.45 (ddd, JAB¼17.1 Hz, 3J¼6.0 Hz, 4J¼1.8 Hz, 1H,
2
NCH2), 4.64 (dt, JAB¼17.1 Hz, J¼2.5 Hz, 1H, NCH2),
6.45 (br, 1H, NCH), 6.8 (3H), 7.1–7.2 (4H), 7.3–7.4 (2H),
7.6–7.7 (2H), 8.11 (d, J¼8.4 Hz, 1H); 13C NMR (CDCl3)
d 13.6 (Me), 21.4 (Me), 53.5 (NCH2), 55.1 (OCH2), 64.8
(NCH), 123.3, 125.0, 125.4, 126.1, 126.8, 126.9, 128.5,
128.6, 129.0, 131.4 (C), 133.6 (C), 135.1 (NCH2CH]),
135.2 (C), 135.5 (C), 136.8 (C), 143.0 (C-Me), 161.8
(CO2Et) ppm. HRMS calcd for C24H23NO4S$Na:
444.1245, found: 444.1230. HPLC: Chiracel AD, hexane/
isopropanol 80:20, 1 mL/min, 12.0 min [(+)-enantiomer]
and 13.6 min. The (S)-configurated phosphepines A afford
the (+)-enantiomer as the major enantiomer.
1
as the eluent (Rf¼0.4). H NMR (CDCl3) d 1.3–1.6 (6H),
4
1.7–1.9 (4H), 4.81 (m, 1H, OCH), 5.19 (d, J¼6.6 Hz, 2H,

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N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11925
3.4.2. Ethyl 2,5-dihydro-2-(4-nitrophenyl)-1-tosylpyr-
role-3-carboxylate 3b. Pale yellow oil; NMR spectra for
compound 3c in C6D6 have been reported in Ref. 15.
1H NMR (CDCl3) d 1.13 (t, J¼7.0 Hz, 3H, Me), 2.40
(s, 3H, Me), 4.0 (m, 2H, CH2CH3), 4.50 (dd, J¼4.0,
2.5 Hz, 2H, NCH2), 5.75 (td, J¼3.5, 2.5 Hz, 1H, NCH),
6.83 (m, 1H, NCH2CH]), 7.23 (d, J¼8.0 Hz, 2H), 7.46 (d,
J¼8.5 Hz, 2H), 7.54 (d, J¼8.0 Hz, 2H), 8.11 (d, J¼8.5 Hz,
2H); 13C NMR (CDCl3) d 14.1 (Me), 21.5 (Me), 55.4
(NCH2), 61.1 (OCH2), 68.2 (NCH), 123.5, 127.2, 128.8,
129.8, 134.8 (C), 135.0 (C), 136.6 (NCH2CH]), 144.1
(C), 147.2 (C), 147.5 (C), 161.3 (CO2Et) ppm. HRMS calcd
for C20H20N2O6S$Na: 439.0940, found: 439.0954. HPLC:
Chiracel OJ, hexane/isopropanol 70:30, 1 mL/min, 27 min
[(+)-enantiomer] and 38 min.
(d, J¼8.5 Hz, 2H); 13C NMR (CDCl3) d 21.4 (Me), 23.3
(CH2), 23.4 (CH2), 25.0 (CH2), 31.1 (CH2), 31.3 (CH2),
55.3 (NCH2), 68.2 (NCH), 73.8 (OCH), 123.4, 127.1,
128.8, 129.8, 134.8 (C), 135.3 (C), 136.6 (NCH2CH]),
144.1 (C), 147.2 (C), 147.5 (C), 160.8 (CO2Cy) ppm.
HRMS calcd for C24H26N2O6S$Na: 493.1409, found:
493.1427. HPLC: AD column, hexane/isopropanol 80:20,
1 mL/min, 18.2 and 28.5 min.
3.4.8. Cyclohexyl 2,5-dihydro-2-phenyl-1-tosylpyrrole-3-
carboxylate 4c. Colourless oil; 1H NMR (CDCl3) d 1.1–1.8
2
(10H), 2.38 (s, 3H, Me), 4.38 (ddd, JAB¼17.0 Hz,
3J¼6.0 Hz, 4J¼2.0 Hz, 1H, NCH2), 4.53 (dt, 2JAB¼17.0 Hz,
J¼2.5 Hz, 1H, NCH2), 4.66 (1H, OCH), 5.77 (1H, NCH),
6.82 (1H, NCH2CH]), 7.14 (d, J¼8.5 Hz, 2H, Ts), 7.23
(5H, Ph), 7.40 (d, J¼8.5 Hz, 2H, Ts); 13C NMR (CDCl3)
d 21.4 (Me), 23.1 (CH2), 23.3 (CH2), 25.2 (CH2), 30.9
(CH2), 31.3 (CH2), 54.8 (NCH2), 69.0 (NCH), 73.2
(OCH), 127.0, 127.9, 128.2, 129.4, 135.5 (NCH2CH]),
135.7 (C), 136.4 (C), 139.4 (C), 143.2 (C-Me), 161.3
(CO2Cy) ppm. MS (ESI) m/z 448 (M+Na). HRMS calcd
for C24H27NO4S$Na: 448.1559, found: 448.1536. HPLC:
Chiracel AD, hexane/isopropanol 80:20, 1 mL/min,
6.5 min [(+)-enantiomer] and 7.1 min.
3.4.3. Ethyl 2,5-dihydro-2-phenyl-1-tosylpyrrole-3-carb-
oxylate 3c. White solid, mp 115 ꢁC. NMR data for com-
pound 3c have been reported in Refs. 1b and 15. HRMS
calcd for C20H21NO4S$Na: 394.1089, found: 394.1104.
HPLC: Chiracel OD, hexane/isopropanol 80:20, 1 mL/min,
9.6 min [(ꢀ)-enantiomer] and 12.0 min.
3.4.4. Ethyl 2,5-dihydro-2-(4-methoxyphenyl)-1-tosyl-
pyrrole-3-carboxylate 3d. Pale yellow solid, mp 72 ꢁC;
NMR data for 3d have been reported in Refs. 1b and 15.
13C NMR (CDCl3) d 13.9 (Me), 21.5 (Me), 54.7 (NCH2),
55.2 (OMe), 60.8 (OCH2), 68.5 (NCH), 113.6 (CHo-MeO),
127.1, 128.9, 129.4, 131.7 (C), 135.1 (NCH2CH]), 135.7,
136.0, 143.1 (C-Me), 159.3 (C-OMe), 161.9 (CO2Et) ppm.
HRMS calcd for C21H23NO5S$Na: 424.1195, found:
424.1199. HPLC: Chiracel AD, hexane/isopropanol 80:20,
1 mL/min, 8.5 and 11.7 min.
3.4.9. Cyclohexyl 2,5-dihydro-2-(4-methoxyphenyl)-1-to-
1
sylpyrrole-3-carboxylate 4d. White solid, mp 151 ꢁC; H
NMR (CDCl3) d 1.1–1.8 (10H), 2.39 (3H, Me), 3.80 (3H,
2
OMe), 4.35 (ddd, JAB¼17.0 Hz, J¼6.0, 2.0 Hz, 1H,
2
NCH2), 4.50 (dt, JAB¼17.0 Hz, J¼2.3 Hz, 1H, NCH2),
4.67 (1H, OCH), 5.73 (NCH), 6.76 (d, J¼9.0 Hz, 2H),
6.78 (1H, NCH2CH]), 7.14 (4H), 7.42 (d, J¼8.0 Hz, 2H,
Ts); 13C NMR (CDCl3) d 21.4 (Me), 23.1 (CH2), 23.3
(CH2), 25.2 (CH2), 31.0 (CH2), 31.3 (CH2), 54.6 (NCH2),
55.3 (OMe), 68.5 (NCH), 73.1 (OCH), 113.6 (CHo-MeO),
127.0, 129.0, 129.4, 131.7 (C), 135.1 (NCH2CH]), 135.9
(C), 136.4 (C), 143.1 (C-Me), 159.4 (C-OMe), 161.4
(CO2Cy) ppm. HRMS calcd for C25H29NO5S$Na:
478.1664, found: 478.1672. HPLC: Chiracel AD, hexane/
isopropanol 80:20, 1 mL/min, 10.5 and 15.8 min.
3.4.5. Ethyl 2,5-dihydro-2-(o-tolyl)-1-tosylpyrrole-3-carb-
oxylate 3e. White solid, mp 110–115 ꢁC; 1H NMR
(CDCl3) d 1.10 (t, J¼7.2 Hz, 3H, Me), 2.36 (s, 3H, Me),
2.57 (s, 3H, Me), 4.0 (m, 2H, CH2CH3), 4.39 (dd,
2JAB¼17.1 Hz, 3J¼6.0 Hz, 4J¼2.1 Hz, 1H, NCH2), 4.58
2
(dt, JAB¼17.1 Hz, J¼2.1 Hz, 1H, NCH2), 6.08 (1H,
NCH), 6.81–6.83 (2H), 6.9 (m, 1H), 7.09–7.13 (4H), 7.34
(d, J¼8.1 Hz, 2H, Ts); 13C NMR (CDCl3) d 13.8 (Me),
19.1 (Me), 21.4 (Me), 54.9 (NCH2), 60.8 (OCH2), 64.8
(NCH), 126.0, 127.5, 127.7, 128.0, 129.8, 130.4, 135.1
(NCH2CH]), 135.9 (C), 136.5 (C), 136.6 (C), 137.5 (C),
143.0 (C-Me), 161.8 (CO2Et) ppm. HRMS calcd for
C21H23NO4S$Na: 408.1245, found: 408.1274. HPLC: Chir-
acel OD, hexane/isopropanol 80:20, 1 mL/min, 9.0 and
11.5 min [(+)-enantiomer].
3.4.10. Cyclohexyl 2,5-dihydro-2-(o-tolyl)-1-tosylpyr-
role-3-carboxylate 4e. Pale yellow oil; H NMR (CDCl3)
d 1.0–1.8 (10H), 2.37 (s, 3H, Me), 2.57 (s, 3H, Me), 4.38
1
2
(ddd, JAB¼17.0 Hz, J¼6.5, 2.0 Hz, 1H, NCH2), 4.58 (dt,
2JAB¼17.0 Hz, J¼2.5 Hz, 1H, NCH2), 4.62 (1H, OCH),
6.07 (1H, NCH), 6.82 (2H), 6.92 (1H), 7.1 (4H), 7.33 (d,
J¼8.0 Hz, 2H, Ts); 13C NMR (CDCl3) d 19.2 (Me), 21.4
(Me), 23.5 (CH2), 23.7 (CH2), 25.1 (CH2), 31.0 (CH2),
31.5 (CH2), 54.8 (NCH2), 64.8 (NCH), 73.5 (OCH), 125.9,
126.9, 127.5, 127.6, 129.3, 130.4, 135.1 (NCH2CH]),
136.6 (C), 136.8 (C), 137.5 (C), 143.0 (C-Me), 161.3
(CO2Cy) ppm. HRMS calcd for C21H23NO4S$Na:
408.1245, found: 408.1268. HPLC: Chiracel AD, hexane/
isopropanol 80:20, 1 mL/min, 4.7 min [(+)-enantiomer]
and 5.5 min.
3.4.6. Cyclohexyl 2,5-dihydro-2-(1-naphthyl)-1-tosylpyr-
role-3-carboxylate 4a. White solid, mp 83 ꢁC, NMR data
and chiral HPLC analysis for 4a have been reported in
Ref. 7. HRMS calcd for C28H29NO4S$Na: 498.1715, found:
498.1725.
3.4.7. Cyclohexyl 2,5-dihydro-2-(4-nitrophenyl)-1-tosyl-
pyrrole-3-carboxylate 4b. Pale yellow solid, mp 137 ꢁC;
1H NMR (CDCl3) d 1.0–1.8 (10H), 2.41 (s, 3H, Me), 4.50
(ddd, JAB¼17.0 Hz, J¼6.0 Hz, J¼2.0 Hz, 1H, NCH2),
4.54 (dt, J¼17.0, 2.5 Hz, 1H, NCH2), 4.6 (1H, OCH), 5.79
(1H, NCH), 6.86 (1H, NCH2CH]), 7.22 (d, J¼8.0 Hz,
2H), 7.45 (d, J¼8.5 Hz, 2H), 7.52 (d, J¼8.0 Hz, 2H), 8.13
3.4.11. Cyclohexyl 2,5-dihydro-2-(benzo[1,3]dioxol-5-yl)-
1-tosylpyrrole-3-carboxylate 4f. Pale yellow solid, mp
2
3
4
1
118 ꢁC; H NMR (CDCl3) d 1.2–1.8 (10H), 2.40 (s, 3H,
Me), 4.36 (ddd, 2JAB¼17.0 Hz, J¼6.0, 2.0 Hz, 1H, NCH2),
2
4.50 (dt, JAB¼17.0 Hz, J¼2.5 Hz, 1H, NCH2), 4.69 (1H,
OCH), 5.67 (1H, NCH), 5.90 (d, J¼1.5 Hz, 1H, OCH2O),

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N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11926
5.93 (d, J¼1.5 Hz, 1H, OCH2O), 6.58 (1H), 6.70 (d,
J¼7.5 Hz, 1H), 6.78 (2H), 7.18 (d, J¼8.0 Hz, 2H, Ts),
7.47 (d, J¼8.0 Hz, 2H, Ts); 13C NMR (CDCl3) d 20.1
(Me), 23.1 (CH2), 23.3 (CH2), 25.2 (CH2), 31.0 (CH2),
31.3 (CH2), 54.7 (NCH2), 68.7 (NCH), 73.2 (OCH), 101.1
(OCH2O), 107.8 (CHAr), 107.9 (CHAr), 121.9 (CHAr),
127.1, 129.4, 133.4 (C), 135.2 (NCH2CH]), 135.8 (C),
136.3 (C), 143.2 (C-Me), 147.3 (CAr), 147.5 (CAr), 161.3
(CO2Cy) ppm. HRMS calcd for C25H27NO6S$Na:
492.1457, found: 492.1467. HPLC: Chiracel OD, hexane/
isopropanol 93:7, 1 mL/min, 21.5 and 24.7 min.
125.4, 126.0, 126.6 (C), 127.0, 128.4, 129.0, 131.5 (C),
133.6 (C), 134.8 (NCH2CH]), 135.6 (C),137.3 (C), 142.9
(C-Me), 161.3 (CO2 Pr) ppm. HRMS calcd for
C25H25NO4S$Na: 458.1402, found: 458.1418. MS (ESI)
m/z 458 (M+Na). HPLC: WHELK column, hexane/isopropa-
nol 90:10, 1 mL/min, 25 min [(+)-enantiomer] and 28 min.
i
3.4.16. D-Menthyl 2,5-dihydro-2-(1-phenyl)-1-tosylpyr-
role-3-carboxylate 7. The procedure above afforded
a 78:22 mixture of 7a+7b. From this mixture, the major epi-
mer has been obtained in pure form by crystallisation from
heptanes/ethyl acetate. Compound 7a: colourless solid; mp
165 ꢁC; 1H NMR (CDCl3) d 0.43 (d, 3J¼7.0 Hz, 3H,
CHMe2), 0.56 (d, 3J¼6.8 Hz, 3H, CHMe2), 0.88 (d,
3J¼6.5 Hz, 3H, CHMe), 0.7–1.0 (4H), 1.09 (m, 1H), 1.4
(m, 1H), 1.55 (1H), 1.64 (d, J¼12.5 Hz, 1H, CH2), 1.87
(d, J¼11.5 Hz, 1H, CH2), 2.38 (s, 3H, Me), 4.33 (ddd,
2JAB¼17.0 Hz, 3J¼6.0 Hz, 4J¼1.5 Hz, 1H, NCH2), 4.53
3.4.12. Cyclohexyl 2,5-dihydro-2-(furan-2-yl)-1-tosylpyr-
role-3-carboxylate 4g. Pale yellow oil; H NMR (CDCl3)
1
d 1.2–1.8 (10H), 2.40 (s, 3H, Me), 4.30 (ddd, 2JAB¼17.0 Hz,
2
J¼6.0, 2.0 Hz, 1H, NCH2), 4.48 (dt, JAB¼17.0 Hz,
J¼2.3 Hz, 1H, NCH2), 4.75 (1H, OCH), 5.90 (1H, NCH),
6.30 (1H), 6.36 (1H), 6.85 (NCH2CH]), 7.17 (1H), 7.20
(d, J¼8.0 Hz, 2H, Ts), 7.48 (d, J¼8.0 Hz, 2H, Ts); 13C
NMR (CDCl3) d 21.5 (Me), 23.1 (CH2), 23.3 (CH2), 25.2
(CH2), 31.0 (CH2), 31.3 (CH2), 54.2 (NCH2), 61.8 (NCH),
73.2 (OCH), 109.1 (CHfuryl), 110.4 (CHfuryl), 127.0, 129.5,
133.5 (C), 135.7 (C), 136.8 (NCH2CH]), 142.0 (CHfuryl),
143.2 (C), 151.4 (Cfuryl), 161.1 (CO2Cy) ppm. HRMS calcd
for C22H25NO5S$Na: 438.1351, found: 438.1370. HPLC:
Chiracel OD, hexane/isopropanol 90:10, 1 mL/min, 10.9
and 12.4 min.
2
(d, JAB¼17.0 Hz, 1H, NCH2), 4.59 (m, 1H, OCH), 5.77
(1H, NCH), 6.89 (1H, NCH2CH]), 7.12 (d, J¼8.0 Hz,
2H, Ts), 7.2–7.33 (5H, Ph), 7.436 (d, J¼8.0 Hz, 2H, Ts);
13C NMR (CDCl3) d 15.4 (Me), 20.9 (Me), 21.4 (Me),
21.9 (Me), 22.7 (CH2), 25.0 (CHMe2), 31.3 (CHMe), 34.0
(CH2), 40.8 (CH2), 46.8 (CH), 54.5 (NCH2), 68.8 (NCH),
74.8 (OCH), 127.0, 128.0, 128.2, 129.3, 135.9 (C), 136.1
(NCH2CH]), 136.2 (C), 139.2 (C), 143.1 (C-Me), 161.6
(CO2Men) ppm. MS (ESI) m/z 504 (M+Na). HRMS calcd
for C28H35NO4S$Na: 504.2185, found: 504.2166. Crystals
suitable for X-ray diffraction have been obtained by slow
crystallisation from an heptane/ethyl acetate mixture.
3.4.13. Methyl 2,5-dihydro-2-(1-naphthyl)-1-tosylpyr-
1
role-3-carboxylate 6a. Pale yellow oil; H NMR data for
compound 3m have been reported previously.1b 13C NMR
(CDCl3) d 21.4 (Me), 51.7 (OMe), 55.1 (NCH2), 65.1
(NCH), 123.2, 125.0, 125.4, 126.1, 126.8, 126.9, 128.5,
128.7, 129.0, 131.3 (C), 133.7 (C), 134.9 (C), 135.4
(NCH2CH]), 135.4 (C), 136.4 (C), 143.0 (C-Me), 162.2
(CO2Me) ppm. HRMS calcd for C23H21NO4S$Na:
430.1089, found: 430.1069. HPLC: Chiracel AD, hexane/
isopropanol 80:20, 1 mL/min, 13.4 min [(+)-enantiomer]
and 16.6 min.
Acknowledgements
We thank Dr. Thomas Riermeier (Degussa AG, Hanau, Ger-
many) for a generous gift of the chiral phosphines A1 (catA-
SiumÒKPh) and A2 (catASiumÒKtB).
References and notes
3.4.14. Phenyl 2,5-dihydro-2-(1-naphthyl)-1-tosylpyr-
role-3-carboxylate 3f. Pale yellow oil; H NMR (CDCl3)
1
1. (a) Xu, Z.; Lu, X. Tetrahedron Lett. 1997, 38, 3461–3464; (b)
Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031–5041.
2. (a) Zhao, G.-L.; Huang, J.-W.; Shi, M. Org. Lett. 2003, 5, 4737–
4739; (b) Zhao, G.-L.; Shi, M. J. Org. Chem. 2005, 70, 9975–
9984.
3. Zhu, X.-F.; Henry, C. E.; Kwon, O. Tetrahedron 2005, 61,
6276–6282.
4. Xu, Z.; Lu, X. Tetrahedron Lett. 1999, 40, 549–552.
5. Wallace, D. J.; Sida, R. L.; Reamer, R. A. J. Org. Chem. 2007,
72, 1051–1054.
6. (a) Wager, T. T.; Welch, W.; O’Neill, B. T. WO Patent 2004/
110996, Pfizer, 2004; (b) Segelstein, B. E.; Wager, T. T. U.S.
Patent 2005/0,272,800, Pfizer, 2005; (c) Humphrey, J. M.;
Chappie, T. A. WO Patent 2005/115976, Pfizer, 2005.
7. Jean, L.; Marinetti, A. Tetrahedron Lett. 2006, 47, 2141–2145.
8. These phosphines are available under the trade name
catASiumÒKPh and catASiumÒKtB. (a) Gladiali, S.; Dore,
A.; Fabbri, D.; De Lucchi, O.; Manassero, M. Tetrahedron:
Asymmetry 1994, 5, 511–514; (b) Chi, Y.; Zhang, X.
Tetrahedron Lett. 2002, 43, 4849–4852; (c) Junge, K.;
Oehme, G.; Monsees, A.; Riermeier, T.; Dingerdissen, U.;
Beller, M. Tetrahedron Lett. 2002, 43, 4977–4980.
d 2.28 (s, 3H, Me), 4.65 (ddd, JAB¼17.4 Hz, J¼6.0,
1.5 Hz, 1H, NCH2), 4.86 (dt, JAB¼17.3 Hz, J¼2.7 Hz, 1H,
NCH2), 6.6–6.7 (3H), 6.93 (d, J¼8.4 Hz, 2H), 7.1–7.4
(7H), 7.4–7.5 (2H), 7.7–7.8 (2H), 8.23 (d, J¼7.8 Hz, 1H);
13C NMR (CDCl3) d 14.1 (Me), 55.2 (NCH2), 65.0
(NCH), 121.0, 123.2, 125.0, 125.5, 125.9, 126.3, 127.0,
128.6, 128.9, 129.0, 129.2, 131.4 (C), 133.7 (C), 134.8
(C), 135.5 (C), 136.2 (C), 137.2 (NCH2CH]), 143.1
(C-Me), 149.8 (CPh), 160.0 (CO2Ph) ppm. MS (ESI) m/z
492 (M+Na). HPLC: AD column, hexane/isopropanol
80:20, 1 mL/min, 15.0 and 16.5 min.
3.4.15. Isopropyl 2,5-dihydro-2-(1-naphthyl)-1-tosylpyr-
role-3-carboxylate 3g. Pale yellow oil; H NMR (CDCl3)
1
d 0.47 (d, J¼6.0 Hz, 3H, Me), 0.89 (d, J¼6.3 Hz, 3H, Me),
2.17 (s, 3H, Me), 4.50 (ddd, JAB¼16.8 Hz, J¼6.0, 2.1 Hz,
1H, NCH2), 4.56–4.70 (2H, NCH2+OCHMe2), 6.48 (m,
1H, NCH), 6.8 (3H), 7.1–7.2 (4H), 7.4 (2H), 7.61 (d,
J¼7.8 Hz, 1H), 7.70 (d, J¼7.8 Hz, 1H), 8.13 (d, J¼8.4 Hz,
1H); 13C NMR (CDCl3) d 20.9 (Me), 21.3 (Me), 21.4 (Me),
55.0 (NCH2), 64.5 (NCH), 68.3 (OCH), 123.4, 124.9,

´
N. Fleury-Bregeot et al. / Tetrahedron 63 (2007) 11920–11927
11927
9. For representative reports see: (a) Zhu, G.; Chen, Z.; Jiang, Q.;
Xiao, D.; Cao, P.; Zhang, X. J. Am. Chem. Soc. 1997, 119,
3836–3837; (b) Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao,
P.; Zhang, X. J. Org. Chem. 1998, 63, 5631–5635; (c) Zhu,
X.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716–4717; (d)
Wurz, R. P.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 12234–
12235; (e) Pereira, S. I.; Adrio, J.; Silva, A. M. S.; Carretero,
J. C. J. Org. Chem. 2005, 70, 10175–10177; (f) Shi, M.;
Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc. 2005, 127, 3790–
3800; (g) Wilson, J. E.; Fu, G. C. Angew. Chem., Int. Ed.
2006, 45, 1426–1429; (h) MacKay, J. A.; Vedejs, E. J. Org.
Chem. 2006, 71, 498–503; (i) See Ref. 5.
16. Aliphatic imines have not been considered in this first screen-
ing. Compared to arylimines, they are known to give sluggish
reactions with allenic esters or 2-butynoates: see Ref. 1.
17. Characterisations for the new pyrroline derivatives of this
series are reported in Section 3.
18. For analogous reactions see: (a) Lang, R. W.; Hansen, H.-J.
Org. Synth. 1984, 62, 202–209; (b) Pinho e Melo, T. M.;
Cardoso, A. L.; Rocha Gonsalves, A. M.; Pessoa, J. C.;
~
Paixao, J. A.; Beja, A. M. Eur. J. Org. Chem. 2004, 4830–4839.
19. Further details and additional experiments will be reported
later.
20. Crystallographic data for compound 7a have been deposited
with the Cambridge Crystallographic Data Centre as supple-
mentary publication nos. CCDC6. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: +44 (0) 1223 336033
or e-mail: deposit@ccdc.cam.ac.uk).
21. McKay, W. R.; Proctor, G. R. J. Chem. Soc., Perkin Trans. 1
1981, 2435–2442.
22. Davis, F. A.; Lamendola, J.; Nadir, U.; Kluger, E. W.;
Sedergran, T. C.; Panunto, T. W.; Billmers, R.; Jenkins, R.;
Turchi, I. J.; Watson, W. H.; Chen, J. S.; Kimura, M. J. Am.
Chem. Soc. 1980, 102, 2000–2005.
23. (a) Harris, J. M.; Padwa, A. J. Org. Chem. 2003, 68, 4371–
4381; (b) Trost, B. M.; Marrs, C. J. Org. Chem. 1991, 56,
6468–6470.
24. Obtained from bromoacetyl bromide and cyclohexanol in the
presence of Et3N/DMAP. (a) Gryszkiewicz-Trochimowski,
^
10. (a) Marinetti, A.; Labrue, F.; Genet, J.-P. Synlett 1999, 1975–
1977; (b) Marinetti, A.; Jus, S.; Labrue, F.; Lemarchand, A.;
^
Genet, J.-P.; Ricard, L. Synthesis 2001, 2095–2104; (c)
Marinetti, A.; Carmichael, D. Chem. Rev. 2002, 102, 201–230.
11. Other well known chiral phosphines including MonoPhos,
MandyPhos, Josiphos and PHOX have been evaluated. All
afforded very low conversion rates and enantioselectivities.
12. Phosphetane (S,S)-L2 (R¼Cy) is a new compound. It has been
prepared according to the procedure reported in Ref. 10b. 31
P
1
NMR (CDCl3) d 22 ppm; H NMR (CDCl3) d 0.5–2 (24H),
2.57 (m, 1H), 2.74 (m, 1H), 2.90 (dd, AB, JAB¼14 Hz,
J¼3.0 Hz, 1H, PCH2), 2.98 (dd, AB, JAB¼14 Hz, J¼4.5 Hz,
1H, PCH2), 4.06 (2H, CHFc), 4.14 (7H, CHFc+Cp) ppm.
HRMS calcd for C26H37FeP: 436.1982, found: 436.2025.
13. Marinetti, A.; Kruger, V.; Buzin, F.-X. Tetrahedron Lett. 1997,
38, 2947–2950.
^
ꢀ
14. Marinetti, A.; Jus, S.; Genet, J.-P.; Ricard, L. J. Organomet.
Chem. 2001, 624, 162–166.
E.; Gryszkiewicz-Trichimowski, O.; Levy, R. Bull. Soc.
Chim. Fr. 1953, 462–465; (b) M€uller, P.; Fernandez, D.;
Nury, P.; Rossier, J.-C. Helv. Chim. Acta 1999, 82, 935–946.
ꢁ
25. Fonquerna, S.; Moyano, A.; Pericas, M. A.; Riera, A.
Tetrahedron 1995, 51, 4239–4254.
15. Scherer, A.; Gladysz, J. A. Tetrahedron Lett. 2006, 47, 6335–
6337; For other catalytic applications of the same phosphine,
see: Seidel, F.; Gladysz, J. A. Synlett 2007, 986–988.