Reaction of vinyl triflates of α-keto esters and imides with secondary amines: synthesis of α,β-diamino carboxylic acid derivatives through aziridinium ions

Article abstract of DOI:10.1016/j.tet.2006.07.085

Reaction between secondary amines and vinyl triflates of α-keto esters and imides under solvent-free condition provides a ready access to α,β-diamino carboxylates.

Full text of DOI:10.1016/j.tet.2006.07.085

Tetrahedron 62 (2006) 10255–10270
Reaction of vinyl triflates of a-keto esters and imides with
secondary amines: synthesis of a,b-diamino carboxylic acid
derivatives through aziridinium ions
*
ꢀ
Marie-Jose Tranchant and Vincent Dalla
´
´
Laboratoire de Chimie, Faculte des Sciences et Techniques de l’Universite du Havre, URCOM, BP 540,
25 rue Philippe Lebon, 76058 Le Havre Cedex, France
Received 18 May 2006; revised 11 July 2006; accepted 25 July 2006
Available online 1 September 2006
Abstract—Reaction between secondary amines and vinyl triflates of a-keto esters and imides under solvent-free condition provides a ready
access to a,b-diamino carboxylates.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
amines which, through sequential conjugate addition–
intramolecular nucleophilic substitution, should provide an
unprecedented route towards aziridinium ions (type II,
Scheme 1).7 The latter, which are recognized as very reactive
transient electrophilic intermediates,8 are expected to be ring
opened during their formation by a second equivalent of
amine to provide a,b-diamino carboxylic acid derivatives
(Scheme 1).9
Tandem (also described as domino or cascade) reactions,
which permit complex molecules to be constructed in a
one-pot assembly, are an important topic in organic synthe-
sis.1 Vinyl triflates of a-keto acid derivatives, which contain
three contiguous electrophilic centres, are therefore very
promising substrates in this field. However, it is rather sur-
prising to note that this readily available class of compounds
remains unexplored.2 We have recently started investigating
their potential in a series of tandem reactions and showed
their effectiveness in this area.3,4 We notably demonstrated
that such molecules are highly reactive with primary amines
to provide a reliable access to aziridine carboxylates4,5
through an overall aza-MIRC (Michael intramolecular ring
closure) process.6 The logical progression in terms of substi-
tution pattern now called for the addition of secondary
Herein are reported preliminary results establishing that this
path can be accomplished offering a new route to a,b-di-
amino carboxylic esters through an unusual aziridinium
ion formation mode.
2. Results and discussion
2.1. Reaction of the vinyl triflates with 2 equiv of a single
secondary amine
CO2Me
NR1R2
R4R3N
R
CO2Me
OTf
In a first series of experiments, the cinnamate derivative 1
(R¼Ph in Scheme 1) was reacted with various secondary
amines in neat conditions. These solvent-free conditions
were selected to overcome the intrinsic low reactivity of cin-
namate acceptors towards aza-nucleophiles.4 Amines were
used in excess to ensure homogeneous reaction conditions
with this crystalline substrate (Table 1). Once formed, the in-
termediate I (Scheme 1) was expected to evolve spontane-
ously into an aziridinium ion II owing to the very high
electrophilic character of the Ca atom bearing the triflate
and ester functionalities. Accordingly, the reactions were car-
ried out at room temperature unless otherwise indicated.
Since a,b-primary diamino carboxylic acids would be partic-
ularly useful final products, both diallylamine and dibenzyl-
amine were examined as synthetic ammonia equivalents.
R
R1R2NH
R3R4NH
(or R1R2NH)
R2R1N
R
CO2Me
OTf
R
CO2Me
-
NR1R2
TfO
+
II
I
Scheme 1.
* Corresponding author. Tel.: +332 32 74 44 01; fax: +332 32 74 43 91;
e-mail: vincent.dalla@univ-lehavre.fr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.085

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
Table 1. Reaction of vinyl triflate 1 with secondary amines
2.3:1 to 2.8:1. The successful set of results depicted in
runs 1, 2 and 6–8 compares favourably with similar reactions
carried out on methyl cinnamate itself, and is testament of
the powerful role served by the triflate group to accelerate
the ordinarily slow uncatalyzed 1,4-additions of the weak
Michael donor secondary amines.
CO2Me
N(R)2
(R)2N
Ph
CO2Me
OTf
(R)2NH
Ph
Runsa Amine
1
2t-c
Time
Products t–c (yields %)b Yields (%)b
1
2
(Me)2NH10 24 h
2at (38)c
2ac (51)
2at (50)
2bc (20)c
(Me)2NHd 30 min 2at (39)c
Overall, the low reactivity of the acyclic hindered amines
towards the cinnamate derivative 1 provides a severe limit
for the reaction. In terms of reactivity, conjugate acceptors
substituted by an alkyl group at the b-position ordinarily out-
perform their b-aryl analogues in the 1,4-addition reactions
of amines. Therefore, we next evaluated the b-ethyl vinyl
triflate 4 as a prototypic more electrophilic candidate for
this aza-MIRC process (Scheme 2).
3e
4f
5f
6
(Et)2NH
(Allyl)2NH 7 d
(Bn)2NH 7 d
4 d
2bt (33)
53c
2ct/2cc 2:1 59(73)g,h
No reaction
Morpholine 1 h
Pyrrolidine 1 h
Piperidine 1 h
2et (61)
2ft (51)
2gt (70)
2ec (23)i
84
7
8
2fc (18)c
2gc (30)i
100
a
Unless otherwise indicated, the reactions were conducted at room temper-
ature.
Isolated yields.
The stereochemistry of 2at, 2bt and 2ft was determined by spectroscopic
correlation (see Section 2.3).
An aqueous solution (50%) was used.
Enamine 3b was isolated in 11% yield.
The reaction was stirred at 40 ꢀC for 7 days.
b
c
Me
CO2Me
Nu
Et
CO2Me
CO2Me
Nu
i
d
e
f
OTf
Et
or i'
N
4
g
h
i
Yield in brackets based on recovered starting triflate.
Enamine 3c was isolated in 14% yield.
The stereochemistry of 2et and 2gt was determined by chemical correla-
O
N
5at (43%)
5bt (9%)
5ac (36%)
5bc (11%)
Nu=
tion using the Sharpless method8c,d (see Section 2.3).
N
6 (65%)
Nu=
Of the acyclic amines tested (runs 1–5), only dimethylamine,
rapidly and cleanly provided the expected diamino adducts
2at–c in a 1:1.3 ratio (run 1).10 More interestingly, even
aqueous (Me)2NH could be used, affording a prompt reac-
tion with an identical stereochemical profile (run 2).11
Scheme 2. (i) Morpholine (3.5 equiv), rt, 5 min; (i0) Diallylamine
(3.5 equiv), rt, 8 h (not optimized).
Since compound 4 is an oil, a minimum amount of the
amines (3.5 equiv) was used. Substrate 4 actually turned
out to be exceedingly responsive towards both cyclic and
acyclic amines, as proven first by its reaction with morpho-
line, which readily gave the separable desired dimorpholino
esters 5at–c in 80% yield and almost no diastereoselectivity.
The vinyl triflate 4 also disappeared rapidly upon reaction
with diallylamine, to afford separable adducts 5bt and 5bc
in only 20% yield (Scheme 2). In this case, the major product
was the allylic a-amino ester 6, obtained as a sole geometri-
cal isomer Z or E, the stereochemistry of which could not be
The lack of stereoselectivity obtained in this reaction was
similar to that previously observed in cases of aziridine syn-
theses, and suggests a non stereoselective protonation of the
enolate formed after the conjugate addition of the amine.4
The reaction of diethylamine (run 3) was slow and provided
the expected diamino esters 2bt–c (1.4:1 ratio) in moderate
yield, contaminated by side-products (TLC monitoring)
among them the enamine 3b (stereochemistry not deter-
mined) (Fig. 1). Type 3 enamines are common impurities
in this type of chemistry.12 An even slower but more selec-
tive reaction took place with diallylamine, affording, after
1 week the stereomeric mixture of inseparable diamino
esters 2ct–c (2.3:1 ratio) in correct yield along with the
enamine 3c as a unique impurity (run 4).
1
determined due to interference in the H NMR spectrum
between the vinylic protons at C3 and C4 and the vinylic
hydrogen atoms of the diallylamine moiety. Carrying out
the reaction at 60 ꢀC did not change the reaction profile,
with similar yields of 5bt–c and 6 being obtained. This dis-
appointing result markedly contrasts with a set of examples
recently published by Zhu and co-workers13 describing the
highly a-selective and generally efficient-opening of an
N,N-dibenzyl aziridinium salt derived from serine methyl
ester by a range of nucleophiles, including the sterically
demanding and poorly nucleophilic N,N-dibenzyl amine.14
In line with Zhu’s results, it should be postulated that the
diamines 5at–c and 5bt–c obtained herein originate from
an a-regioselective aziridinium opening, which is the in-
verse to the b-selectivity expected for the reactions involving
the cinnamate derivative 1.15 Overall, this result supports the
occurrence of an aziridinium pathway (Scheme 1), the open-
ing of which, either in the cis or trans form, is retarded at the
expense of a less sterically demanding elimination process
leading to compound 6 (Scheme 3).
On the other hand, no trace of addition product of dibenzyl-
amine could be detected even after prolonged heating. This
first set of experiments clearly shows that the reaction
strongly depends on steric effects.
As expected, the less sterically demanding and more nucleo-
philic cyclic amines reacted equally well as dimethylamine,
giving a stereomeric mixture of all separable diamines
2et–gt of anti stereochemistry11 and 2ec–gc of syn stereo-
chemistry11 (runs 6–8) with a anti/syn ratio ranging from
R2, R1 = Et
3b
CO2Me
R2R1N
Ph
R2, R1 = Allyl 3c
The result of the reaction between 4 and diallylamine clearly
reveals that a more generally acceptable solution must be
Figure 1. Structure of the enamines 3b and c obtained as side-products
through this work.

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10257
NR2
are the active intermediates in the chemistry exposed herein.
Moreover, the replacement of the methoxy carbonyl group in
the cinnamate derivative 1 by the more activating imide
function in compound 10 questions about the influence of
such an imide group on the regioselectivity of the aziridi-
nium opening process (a- vs b-), which is known to be
highly b-selective in the ester series.15
(R)2NH
SN2
CO2Me
NR2
R
R
CO2Me
OTf
(R)2NH
-
(20%)
5bt + 5bc
OTf
N
+
CO2Me
4
2.2. Reaction of the vinyl triflates 1 and 10 with two
amines of different nucleophilicities
(R)2NH
CO2Me
(R =
)
Elimination
Major pathway
NR2
In order to expand the scope of the present methodology, we
sought to develop conditions by which the aziridinium II
(Scheme 1) could be continuously trapped by a second
nucleophile (Nu2) weaker than the first reactive amine (Nu1).
(65%)
6
Scheme 3.
found for an efficient aza-MIRC reaction of acyclic second-
ary amines towards vinyl triflates derived from a-keto acids.
This prompted us to examine the use of unsaturated imides
as more electrophilic substrates.16 Hence, imides 7 and 10
were prepared in three steps (a. LiOH, b. (COCl)2/cat
DMF then c. N-lithium salt of oxazolidin-2-one) from the
methyl esters 1 and 4 and their reaction with diallylamine
was evaluated (Scheme 4). Conjugate addition to imide 7
was immediately rewarded by yield enhancement (68%
yield for 8bt–c as an inseparable mixture vs 20% yield for
5bt–c). Hence, the formation of the allylic a-amino acid de-
rivative 9 (one geometrical isomer, analogous to the product
6) was reduced from 65% (Scheme 2) to 19%. Reaction of
the cinnamoyl derivative 10 with diallylamine provided
additional insight into the beneficial impact of an imide
acceptor. In this case, the reaction rate was enhanced by at
least a seven-fold factor (in comparison with the reaction
of 1), affording an inseparable mixture of diamino imides
11bt–c in high yield and with an increased diastereomeric
ratio of 88:12 (see for comparison Table 1, run 3).
A model reaction was investigated by which morpholine
(3 equiv) was added to a solution of substrate 1 in aniline
(30 equiv). A very slow reaction took place at room temper-
ature18 to afford the easily separable diastereomers 12at (less
polar, syn)11 and 12ac (more polar, anti)11 in 64% yield,
along with the dianilino adduct (not shown) in 8% yield
(Scheme 5). Although the formation of this dianilino adduct
is, in the present case, anecdotic, it reveals that the aniline de-
rivatives behave as secondary amines rather than as primary
ones, an interesting feature that could potentially be ex-
ploited to expand the scope of the chemistry practiced herein.
NH
NH
CO2Me
OTf
CO2Me
CO2Me
i
N
O
N
O
Ph
+
1
12ac
12at
(36%)
(28%)
Scheme 5. (i) Aniline (30 equiv), morpholine (3 equiv), rt, 168 h.
O
O
N
Me
O
The structure of 12at–c could be tentatively assigned by
O
O
N
O
OTf
1
means of H and 13C NMR spectroscopies, which shows
N
R
N
O
O
N
N
O
i
that one molecule each of morpholine and aniline has been
incorporated in both cases. Regiochemistry was confirmed
by GC/MS analysis as the fragment ion [C6H5CHNHC6H5]+
was clearly observed for both diastereomers. These results
strongly support an aziridinium mechanism since direct
intermolecular displacement of the triflate group by aniline
in type I intermediate (Scheme 1) should have led to the for-
mation of the opposite regioisomer. Moreover, this result
corroborates with recent literature precedents, which have
revealed high levels of regiocontrol in openings of unsym-
metrical benzyl aziridinium ions.15
R
R=C2H5
7
8bt-c (68%)
9 (19%)
ratio not determined
R=C6H5
10
11bt-c (91%)
ratio: 88 : 12
Scheme 4. (i) Diallylamine (3.5 equiv), rt, 1 h for 7, 24 h (unoptimized)
for 10.
The diamino compounds so obtained could, in principle,
have been obtained by direct intermolecular SN2 substitution
of the triflate group in the b-amino a-triflyloxy carbonyl
intermediate I (Scheme 1) without the need to invoke an
aziridinium ion. Owing to the above-mentioned very high
electrophilic character expected for the a-carbon in type I
intermediate, in conjunction with the comments relative
to Scheme 3 and with several recent publications in the
area of diamine synthesis from vicinal N,N-dialkylamino
alcohols, wherein the contribution of aziridinium forms
was clearly demonstrated,13,17 it is likely that aziridiniums
These solvent-free conditions were effective across a series
of combination of good and weak amine donors (R1R2NH
and Nu2, respectively) to give the crossed diamines in the
31–65% range of yields (Table 2). Combined with aniline,
piperidine and pyrrolidine displayed quite higher reactivity
than morpholine (2 h vs 7 days), and the outcome of their
reactions was improved at 40 ꢀC (runs 2 and 3). Generally,
a virtually perfect regiocontrol did occur, favouring products
of types 12 and 14 resulting from an opening of the aziridi-
nium at the benzylic position (runs 1–4 and 6).15 Use of
diallylamine as the weak nucleophile in combination with

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
Table 2. Reactions of vinyl triflates 1 and 10 with two amines of different nucleophilicities
O
O
O
O
= R1R2N = Nu1
= Nu2
O
N
Nu2
Ph
X
R2
N
X
R1R2NH (= Nu1)
Nu2
X
N
R1
Ph
OTf
Ph
N
N
1
or
10
12atc-12etc ( X = OMe)
13b (X = OMe, 6%)
15b (X = Oxazolidinone, 11%)g
14atc-14btc ( X = Oxazolidinone)
Runs
X
R1R2NH (equiv)
Nu2 (equiv)
Conditions
Products (yields %)a
anti/syn
1b
2c
3c
4c
5c
6c
7c
OMe
OMe
OMe
OMe
OMe
Morpholine (3)
Piperidine (2)
Aniline (30)
Aniline (30)
168 h, 20 ꢀC
2 h, 40 ꢀC
12at (28)
12ac (36)
12bc (32)
12cc (19)
56/44h
54/46h
30/70i
12bt (27)d
12ct (46)
Pyrrolidine (2)
Morpholine (1.5)
Morpholine (1.5)
Morpholine (2)
Morpholine (2)
Aniline (30)
2 h, 40 ꢀC
tBuNH2 (30)
Diallylamine (30)
Aniline (10)
30 min, 20 ꢀC
24 h, 40 ꢀC
1 h, 20 ꢀC
12dt/12dc 1:2 (31)e
66/33h
12et/12ec 1:1 (41)f
j
Oxazolidinone
Oxazolidinone
14at (43)
14bt (28)
14ac (8)
14bc (10)g
16/84k
j
Diallylamine (10)
1 h, 20 ꢀC
a
Isolated yields.
When the reaction was carried out at 40 ꢀC, no acceleration was observed and 12at and 12ac were isolated in 12 and 22% yields, respectively.
Time not optimized.
A pure sample of the less polar adduct 12bt could not be secured due to contamination by the anti dipiperidino ester 2gt. A similar reaction profile was
observed carrying out the reaction at rt.
b
c
d
e
The adducts were not separable. Moreover, stereomeric aziridine carboxylates and dimorpholino esters 2et–c were also isolated in 25 and 28% yields,
respectively.
f
The regioisomer 13b (one stereomer, stereochemistry not determined) was isolated in 6% yield.
The regioisomers 15bt and 15bc (stereochemistry not determined) were isolated in 8 and 3% yields, respectively.
Stereochemistry determined by chemical correlation using the Sharpless method8c,d (see Table 3 and comments thereof).
Stereochemistry determined by spectroscopic correlation (see Table 3 and comments thereof).
Stereochemistry not determined.
g
h
i
j
Stereochemistry determined by chemical correlation using the Sharpless method8c,d after methanolysis (see Scheme 8 and comments thereof).
k
morpholine made exception to this rule, with the expected
adducts 12et–c and 14bt–c being accompanied by low
amounts of regioisomers 13 and 15 (runs 5 and 7). This
observation compares with the previous Chuang–Sharpless
reports and supports the evidence that the nature of the
nucleophile is a key parameter in the regiochemical outcome
of type II aziridinium (Scheme 1) opening.8c,d When the
imide 10 (X¼oxazolidinone) was processed, yields similar
to those exhibited in the ester series were observed whereas
stereoselectivity was improved (as also previously observed
in the case of using only one amine: Scheme 4) and, perhaps
more interestingly, its sense reversed (runs 6 and 7 vs runs 1
and 2). The presence of intense peaks for the fragments ions
[C6H5CHNHC6H5]+ and [C6H5CHN(C3H5)2]+ in the GC/
MS spectra of the major isomers 14at–c and 14bt–c accounts
for a usual b-selective aziridinium opening pathway, and fur-
thermore proves that the functional group interconversions
at the carbonyl moiety is less influential than the amine
structure with respect to the regiochemical outcome of
aziridinium opening.
obtained in a stereochemically pure form throughout this
study. Several attempts to obtain crystals suitable for X-ray
crystallography from diamines 2et–gt, 12at–ct failed. There-
fore, we elected to use a sequence recently implemented by
Sharpless and Chuang to synthesize anti 2,3-diamino ethyl
esters from ethyl glycidate.8c,d Methyl glycidic ester 16
was synthesized in 48% yield (not optimized) by a Darzens’
reaction between a-chloro methyl acetate and benzaldehyde
promoted by NaH (Scheme 6). In agreement with the
Chuang and Sharpless results, compound 16 was efficiently
transformed in two steps into the aziridinium reservoirs
18a (N(R)2¼morpholine) and 18b (N(R)2¼piperidine) as
depicted in Scheme 6. The use of pyrrolidine as the amine
component was less satisfactory, affording in the oxirane
ring opening step the desired amino alcohol 17c in a disap-
pointing 26% yield after flash-chromatography on silica
O
i
ii
CO2Me
(R)2N
Ph
PhCHO
Ph
OMe
O
OH
Even if closer inspection of the reaction conditions is further
needed to maximize the yield of the desired products in these
crossed reactions, we have shown for the first time that addi-
tion of two different amines to the double bond of activated
vinyl triflates is possible through an original pathway includ-
ing aziridinium ion formation followed by in situ opening by
a second amine.
16
17a-c
O
Cl
Ph
O
iii
OMe
N(R)2
O
N
Ph
18a-b
19
Scheme 6. (i) a-Chloro methyl acetate (1 equiv), NaH (1 equiv), THF, 0 ꢀC,
1 h, 48% yield; (ii) (R)2NH (1 equiv), MeOH, reflux, 12 h, (R)2¼
(CH2CH2)2O 17a (74%), (R)2¼(CH2)5 17b (78%), (R)2¼(CH2)4 17c
(26%); (iii) MsCl (1.05 equiv), NEt3 (1.05 equiv), CH2Cl2, 0 ꢀC to rt, 3 h,
(R)2¼(CH2CH2)2O 18a (94%), (R)2¼(CH2)5 18b (96%), (R)2¼N(CH2)4
19 (90%).
2.3. Stereochemical determination
The last part of this work was aimed at determining the
stereochemistry of the diamino carboxylic acid derivatives

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10259
1
gel. An even worse result was obtained during the mesylation
protocol aimed at producing the required 3-chloro-2-pyrroli-
dino methyl ester 18c. The latter was indeed not formed and
the oxiranyl N-pyrrolidino carboxamide 19 was isolated
instead in 90% yield.
respects (Rf, mp, H and 13C NMR) with the syn adduct
12at previously characterized. No trace of the diastereoiso-
mer 12ac could be detected. Provided that no epimerization
has taken place at the enolizable position, this experiment
demonstrates that the stereochemistry of the crossed imide
adducts correlates well with that of the corresponding
methyl esters, that is, the less polar adduct 14at is the syn
isomer and the more polar one 14ac is the anti isomer.
With the stereochemically pure (anti) aziridinium ion reser-
voirs 18a and 18b in hand, the stage was now set for the
stereochemical establishments. In line with the Chuang–
Sharpless results, subjection of 18a and 18b to the appropri-
ate amines under optimal conditions (1 equiv each of the
amine and K2CO3 in refluxing acetonitrile) gave in all cases
examined a single product in nearly quantitative yields
(Scheme 7). The comparison of the physical and analytical
0.1 equiv M(OTf)n
no reaction
MeOH/Toluene, reflux
overnight
O
O
NH
1
data of the diamino esters so obtained (Rf, mp, H NMR
N
O
spectra) with those obtained through our aza-MIRC
approach (Table 3, lines 1 and 2 and 6–8) led to the following
conclusions.
N
14at
O
1 equiv K2CO3
O
NH
NR1R2
=
=
=
99%
R2
MeOH, heating, 30 min
yield 6%
2et
N
O
OMe
O
N
R1
N
i
N
18a
NH
OMe
12at
NR
1R2
O
93%
94%
12ac
12dc
Ph
Scheme 8.
O
NH
NR1R2
3. Conclusion
R2
O
N
R1
99%
94%
N
NR1R2
NR1R2
=
=
N
To summarize, we have shown that vinyl triflates of a-keto
esters and imides react with secondary amines in solvent-
free conditions to provide a,b-diamino carboxylates in good
yields, yet modest stereoselectivity through the probable
occurrence of an aziridinium ion. This reaction involves an
unprecedented aza-MIRC process leading to an aziridinium
ion, which is opened in situ by a second equivalent of amine.
We have also demonstrated that introduction of two amines
of markedly different nucleophilicities may be possible.
i
2gt
OMe
18b
Ph
NH
12bc
Scheme 7. (i) K2CO3 (1 equiv), R1R2NH (1.1 equiv), CH3CN, reflux, 3 h.
When the cinnamate triflate 1 is processed by 2 equiv of the
same amine, the diamino ester with the anti stereochemistry
is produced as the less polar isomer and, correspondingly, the
diamino ester with the syn stereochemistry is formed as the
more polar isomer. In stark contrast, in the cases of using
two different amines, the diamine with the anti stereo-
chemistry is formed as the more polar isomer. Key data
ascertaining these stereochemical establishments, including
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded, respectively, at 200
and 50 MHz. The infrared spectra were recorded on a
Perkin–Elmer FT-IR paragon 1000 spectrometer. Thin-layer
chromatographies (TLC) were performed with aluminium
plates (0.20 mm) precoated with fluorescent silica gel, using
EtOAc/hexanes as eluent. Reaction components were then
visualized under UV light and dipped in a Dragendorff
solution. Silica gel (230–400 mesh) was used for flash-
chromatography separations. Gas chromatography/mass
spectrometry (GC/MS) was performed with a GC apparatus
equipped with ꢁa112 m capillary column, at 90 ꢀC for 2 min,
then 10 ꢀC min up to 290 ꢀC. The elemental analyses were
carried out by the microanalysis laboratory of INSA,
F-76130 Mt St Aignan, France.
1
Rf values, melting points and chemical shifts in H NMR
spectroscopy for the MeO group in the case of adducts bear-
ing two identical amino groups (lines 1–5),19 are provided in
Table 3.
To complete this study on the stereochemical outcome of the
crossed reactions, we verified whether the rationale applied
to the methyl ester series would be also effective in the imide
series. To this end, attempts to transform 14at–c into their
methyl ester analogues using a recent Cu(OTf)2-catalyzed
methanolysis procedure20 left the substrates untouched
(Scheme 8). Processing other metal triflate catalysts (Yb,
Sn, Sc) also failed to give the expected esters 12a. After
a considerable number of trials, we found that, when treated
with K2CO3 (1 equiv) in refluxing dry methanol the less po-
lar (major) oxazolidinone adduct 14at was totally consumed
within 30 min to give several products among them the less
polar methyl ester 12at was isolated in a disappointingly low
6% yield (Scheme 8) and proved to be identical in all
4.2. Formation of the vinyl triflates 1, 4, 7 and 10
The preparation and analytical data of the methoxy car-
bonyls vinyl triflates 1 and 4 were reported recently.4

10260
M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
Table 3. Stereochemical establishments for the diamines originating from the methyl cinnamate-derived vinyl triflate 1
Structure
Stereochemistry
Rf
Mp (ꢀC)
d MeOa
O
0.60b
0.60
0.41
162
160–165
100
3.76
3.76
3.38
N
Chuang–Sharpless
Aza-MIRC t anti
Aza-MIRC c
CO2Me
N
O
2e
N
Chuang–Sharpless
Aza-MIRC t anti
Aza-MIRC c
0.55c
0.55
0.38
102
101–103
123–125
3.84
3.84
3.36
CO2Me
CO2Me
N
2g
N
Aza-MIRC t anti
Aza-MIRC c
0.68d
0.37
3.69
3.29
N
2f
NMe2
Aza-MIRC t anti
Aza-MIRC c
0.44e
0.12
3.75
3.38
CO2Me
NMe2
2a
NEt2
0.65c
0.34
3.65
3.43
CO2Me
Aza-MIRC t anti
Aza-MIRC c
NEt2
2b
NH
Chuang–Sharpless
Aza-MIRC t
Aza-MIRC c anti
0.22c
0.33
0.22
117
135–136
116–118
3.41
3.52
3.41
CO2Me
N
12a
O
NH
Chuang–Sharpless
Aza-MIRC t
Aza-MIRC c anti
0.43c
0.58
0.43
183
3.40
3.49
3.40
f
CO2Me
CO2Me
183–184
N
12b
t
NH
Bu
Chuang–Sharpless
Aza-MIRC tg
Aza-MIRC c anti
0.30c
0.32
0.30
3.70
3.63
3.70
N
O
12d
Aza-MIRC t
Aza-MIRC c anti
0.60c
0.42
NH
CO2Me
N
12c
Values in parts per million corresponding to the chemical shift in 1H NMR spectroscopy.
Eluent: cyclohexane/EtOAc 4:6.
Eluent: cyclohexane/EtOAc 8:2.
a
b
c
d
e
f
Eluent: cyclohexane/EtOAc 6:4.
Eluent: cyclohexane/EtOAc 5:5.
No melting point is given due to contamination of the less polar stereomer 12bt by the dipiperidino adduct 2gt.
The two stereomers 12dt–c were not separated. However, their ratio could be evaluated by 1H NMR spectroscopy (12dc/12dt¼2:1).
g

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10261
4.2.1. General procedures for the preparation of the
imides triflates 7 and 10.
4.2.1.2.1. (Z)-3-Phenyl-2-trifluoromethanesulfonyloxy
propenoic N-oxazolidin-2-one carboxamide (7).
4.2.1.1. Saponification. A solution of anhydrous LiOH
(3 equiv) in water (15 ml) was added dropwise over 30 min
at 0 ꢀC to a solution of the methyl ester 1 or 4 (1 g) in THF
(15 ml). At the end of the addition, the reaction was stirred
for an additional period of 15 min at 0 ꢀC. The cryogenic
bath was removed and the stirring was pursued for 10 min.
An aqueous solution of sodium hydrogen carbonate (10%)
was added, the two phases were decanted and the aqueous
layer was extracted rapidly three times with ether. The aque-
ous phase was carefully acidified using 6 M hydrochloric
acid, saturated with sodium chloride and extracted three
times with dichloromethane. After two washings with brine,
drying over magnesium sulfate and evaporation of the
solvent, the crystals were dried under high vacuum and
used directly without purification.
O
O
N
O
OTf
7
Yield 50%. White solid, mp 112 ꢀC; IR (n, cmꢁ1, CHCl3)
1794.2, 1587.3; 1H NMR (200 MHz, CDCl3) d 4.09 (t,
J¼7.8 Hz, 2H), 4.52 (t, J¼7.8 Hz, 2H), 7.09 (s, 1H), 7.4–
7.48 (m, 3H), 7.6–7.7 (m, 2H); 13C NMR (62.5 MHz,
CDCl3) d 43.3, 62.9, 108.7 (CF3), 115.1 (CF3), 121.5 (CF3),
127.9 (CF3), 128.9, 129.6, 130.7, 131.2, 136.4, 152.1,
162.3; LRMS m/z 365 (M+, 5), 232 (45), 204 (64), 105 (45),
89 (Base). Anal. Calcd for C13H10NO6F3S (365.28): C,
42.74; H, 2.76; N, 3.83. Found: C, 42.57; H, 2.98; N, 3.70.
4.2.1.2.2. (Z)-2-Trifluoromethylsulfonyloxy pentenoic
N-oxazolidin-2-one carboxamide (10).
4.2.1.1.1. (Z)-3-Phenyl-2-trifluoromethylsulfonyloxy
propenoic acid.
O
O
O
N
OTf
10
O
OH
OTf
Yield 45%. White solid, mp 43 ꢀC; IR (n, cmꢁ1, CHCl3)
1797.0, 1698.2; 1H NMR (200 MHz, CDCl3) d 1.11 (t,
J¼7.8 Hz, 3H), 2.39 (quint, J¼7.8 Hz, 2H), 4.03 (t,
J¼7.8 Hz, 2H), 4.46 (t, J¼7.8 Hz, 2H), 6.39 (t, J¼7.8 Hz,
1H); 13C NMR (62.5 MHz, CDCl3) d 12.2, 19.9, 43.3,
62.7, 112.1 (CF3), 116.3 (CF3), 120.6 (CF3), 124.8 (CF3),
137.2, 137.6, 149.0, 161.6; LRMS m/z 231 (M+ꢁ96, 2),
184 (32), 114 (29), 88 (67), 69 (Base). Anal. Calcd for
C9H10NO6F3S (317.24): C, 34.07; H, 3.17; N, 4.41. Found:
C, 34.27; H, 3.09; N, 4.26.
Yield 60–70%. Pale green solid, mp 104 ꢀC (decomposi-
tion); IR (n, cmꢁ1, CHCl3) 1712; 1H NMR (200 MHz,
CDCl3) d 7.45–7.55 (m, 3H), 7.65–7.75 (m, 3H), 12
(COOH, 1H); 13C NMR (62.5 MHz, CDCl3) d 108.7
(CF3), 115.1 (CF3), 121.5 (CF3), 127.9 (CF3), 129, 129.4,
130.9, 131.8, 133.7, 133.8, 134.2, 138.2, 166.5.
4.2.1.1.2. (Z)-2-Trifluoromethylsulfonyloxy pentenoic
acid.
O
4.3. General procedure for the reaction of amines with
the alkoxymethyl vinyl triflates 1 and 4
OH
OTf
Yield 81%. White solid; 1H NMR (200 MHz, CDCl3) d 1.15
(t, J¼7.8 Hz, 3H), 2.41 (quint, J¼7.8 Hz, 2H), 6.91 (t,
J¼7.8 Hz, 1H).
To 100 mg of the triflate was added in one portion 1 ml of the
amine. The mixture was magnetically stirred for 1 h, the ex-
cess of solvent was removed under vacuum and the residue
was purified by flash-column chromatography, eluting with
cyclohexane/EtOAc.
4.2.1.2. Imide formation. To a solution of the above
carboxylic acids (1 equiv) in dry dichloromethane
(2 ml mmolꢁ1) were added dropwise under an argon atmo-
sphere oxalyl chloride (2 equiv) and DMF (one drop). After
stirring for 1 h, the volatiles were carefully evaporated and
dry tetrahydrofuran (5 mP) was added under argon to the
acid chloride. This solution was kept at ꢁ80 ꢀC. In the same
time, to a solution of 2-oxazolidinone (1.05 equiv) in dry
THF (2 ml mmolꢁ1) was added under an argon atmosphere
at ꢁ80 ꢀC a commercially available solution of n-butyl-
lithium 1.6 M in hexane (1.05 equiv per substrate equiv).
After stirring for 30 min, this solution was added dropwise
at ꢁ80 ꢀC to the solution of the acid chloride. After stirring
for 1 h, water and ethyl ether (5 ml mmolꢁ1) and solid NaCl
were added until saturation of the aqueous phase. After
decantation, the aqueous layer was extracted three times
with ethyl ether (5 ml mmolꢁ1). The organic layer was dried
over magnesium sulfate and concentrated to afford a crude
product, which was purified by flash-chromatography.
4.3.1. Methyl 2,3-bis-dimethylamino-3-phenyl propa-
noate (2a). The reaction gave two diastereomers but only
the less polar diamino adduct 2at could be recovered. Eluent
used for the flash-column chromatography: cyclohexane/
EtOAc 60:40 to EtOAc.
NMe2
CO2Me
NMe2
2at
Less polar isomer 2at, Rf¼0.44 (cyclohexane/EtOAc 50:50).
White solid; yield 31 mg, 38%; mp 101–103 ꢀC; IR (n,
1
cmꢁ1, CHCl3) 1725.7; H NMR (200 MHz, CDCl3, 25 ꢀC)
d 2.05 (s, 6H), 2.20 (s, 6H), 3.75 (s, 3H), 3.85 (d,
J¼11.7 Hz, 1H), 3.99 (d, J¼11.7 Hz, 1H), 7.06–7.19 (m,
2H), 7.21–7.41 (m, 3H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 41.2, 41.3, 50.8, 67.5, 67.7, 127.3, 127.6, 129.5,

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
171.5; LRMS m/z 205 (M+ꢁ45, <1), 191 (9), 134 (Base).
Anal. Calcd for C14H22O2N2 (250.34): C, 67.17; H, 8.86;
N, 11.19. Found: C, 67.27; H, 8.93; N, 11.06.
Rf¼0.36. Yellow oil (contaminated by 2bc); yield 12 mg,
11% (estimated by 1H NMR spectroscopy); 1H NMR
(200 MHz, CDCl3) d 1.03 or 1.09 (t, J¼7.0 Hz, 6H), 3.05–
3.20 (m, 2H), 3.34 (s, 3H), 4.80 (s, 1H), 7.10–7.20 (m,
3H), 7.35–7.45 (m, 2H).
NMe2
CO2Me
NMe2
4.3.4. Methyl 2,3-bis-diallylamino-3-phenyl propanoate
(2c). Eluent used for the flash-column chromatography: cy-
clohexane/EtOAc 80:20. Stereomeric adducts 2ct and 2cc
were obtained as an inseparable mixture in an approximative
2.3:1 ratio. Rf¼0.57.
2ac
More polar isomer 2ac, Rf¼0.12 (cyclohexane/EtOAc
50:50). White solid; yield 41 mg, 51%; mp 57 ꢀC; IR (n,
cmꢁ1, CHCl3) 1725.7; H NMR (200 MHz, CDCl3, 25 ꢀC)
1
d 2.19 (s, 6H), 2.46 (s, 6H), 3.38 (s, 3H), 3.92 (d,
J¼11.7 Hz, 1H), 4.03 (d, J¼11.7 Hz, 1H), 7.12–7.18 (m,
2H), 7.25–7.39 (m, 3H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 40.7, 41.4, 50.5, 66.0, 67.3, 127.6, 127.7, 129.5,
132.7, 169.6; LRMS m/z 206 (M+ꢁ44, 1), 191 (6), 134
(Base). Anal. Calcd for C14H22O2N2 (250.34): C, 67.17;
H, 8.86; N, 11.19. Found: C, 67.09; H, 8.95; N, 11.13.
NAll2
NAll2
CO2Me
CO2Me
NAll2
2cc
+
NAll2
2ct
Colourless oil; yield 69 mg, 59%; IR (n, cmꢁ1, CHCl3)
1
1728.4; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.40–2.56
(2dd, J¼8.6 Hz, 14.1 Hz, 2H, diast. 1+diast. 2), 2.75–2.95
(2dd, J¼8.6 Hz, 14.1 Hz, 2H, diast. 1+diast. 2), 3.2–3.4
(m, 6H, diast. 1+diast. 2), 3.35 (s, 3H, diast. 1), 3.49–3.59
(m, 6H, diast. 1+diast. 2), 3.73 (s, 3H, diast. 2), 4.10 (d,
J¼11.7 Hz, 1H, diast. 1), 4.14 (d, J¼11.7 Hz, 1H, diast.
2), 4.28 (d, J¼11.7 Hz, 1H, diast. 1), 4.33 (d, J¼11.7 Hz,
1H, diast. 2), 4.9–5.3 (m, 8H, diast. 1+diast. 2), 5.2–5.5
(m, 1H, diast. 1+diast. 2), 5.6–6.0 (m, 3H, diast. 1+diast.
2), 7.05–7.19 (m, 2H, diast. 1+diast. 2), 7.22–7.36 (m, 3H,
4.3.2. Methyl 2,3-bis-diethylamino-3-phenyl propanoate
(2b). Eluent used for the flash-column chromatography:
cyclohexane/EtOAc 80:20.
NEt2
CO2Me
NEt2
2bt
13
diast. 1+diast. 2); C NMR (50 MHz, CDCl3, 25 ꢀC)
Less polar diastereomer 2bt, Rf¼0.65. Colourless oil; yield
33 mg, 33%; IR (n, cmꢁ1, CHCl3) 1725.7; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 0.75 (t, J¼7.0 Hz, 6H), 0.96
(t, J¼7.0 Hz, 6H), 1.90–2.12 (m, 2H), 2.20–2.40 (m, 2H),
2.49–2.79 (m, 4H), 3.69 (s, 3H), 4.02 (d, J¼11.7 Hz, 1H),
4.24 (d, J¼11.7 Hz, 1H), 7.08–7.35 (m, 5H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 13.6, 14.0, 44.1, 44.2, 50.5,
63.1, 64.2, 126.7, 127.3, 129.7, 135.5, 173.2; LRMS m/z
247 (M+ꢁ59, 2), 175 (2), 162 (80), 91 (Base). Anal. Calcd
for C18H30O2N2 (306.45): C, 70.54; H, 9.86; N, 9.14. Found:
C, 70.30; H, 9.99; N, 9.26.
d 50.6, 52.5, 53, 53.3, 53.3, 60.6, 61.8, 62.4, 62.8, 116.8,
116.9, 117, 117.3, 127, 127.4, 127.5, 127.9, 129.3, 129.8,
134.1, 135.4, 136.2, 136.8, 137.3, 137.4, 171.4, 172.6.
4.3.5. Methyl 3-diallylamino-3-phenyl propenoate (3c).
NAll2
CO2Me
H
3c
Rf¼0.26. Yellow oil; yield 10 mg, 14%; IR (n, cmꢁ1, CHCl3)
1725.4; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 3.43 (s, 3H),
3.7–3.8 (m, 4H), 4.89 (s, 1H), 5.10–5.30 (m, 4H), 5.60–
5.85 (m, 2H), 7.15–7.25 (m, 2H), 7.35–7.45 (m, 3H);
LRMS m/z 258 (M++1, 3), 257 (M+, 27), 226 (22), 216
(33), 186 (Base).
NEt2
CO2Me
NEt2
2bc
More polar diastereomer 2bc, Rf¼0.34. Colourless oil; yield
20 mg, 20%; IR (n, cmꢁ1, CHCl3) 1725.7; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 1.03 or 1.09 (t, J¼7.0 Hz,
12H), 2.03–2.19 (m, 2H), 2.29–2.46 (m, 2H), 2.58–2.76
(m, 2H), 2.80–2.99 (m, 2H), 3.43 (s, 3H), 4.02 (d,
J¼10.9 Hz, 1H), 4.25 (d, J¼10.9 Hz, 1H), 7.12–7.35 (m,
4.3.6. Methyl 2,3-dimorpholino-3-phenyl propanoate
(2e). Eluent used for the flash-column chromatography:
cyclohexane/EtOAc 40:60.
O
13
5H); C NMR (50 MHz, CDCl3, 25 ꢀC) d 13.9, 13.9,
43.2, 44.0, 50.5, 61.5, 64.0, 127.1, 127.8, 128.3, 129.1,
137.2, 172.0; LRMS m/z 247 (M+ꢁ59, 2), 175 (2), 162
(80), 91 (Base). Anal. Calcd for C18H30O2N2 (306.45): C,
70.54; H, 9.86; N, 9.14. Found: C, 70.71; H, 9.97; N, 9.41.
N
CO2Me
N
2et
O
4.3.3. Methyl 3-diethylamino-3-phenyl propenoate (3b).
Less polar diastereomer 2et, Rf¼0.60. White solid; yield
33 mg, 61%; mp 160–63 ꢀC; IR (n, cmꢁ1, CHCl3) 1728.4;
1H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.10–2.26 (m, 2H),
2.39–2.65 (m, 6H), 3.19–3.36 (m, 2H), 3.36–3.48 (m, 2H),
3.51–3.59 (m, 4H), 3.76 (s, 3H), 3.85 (d, J¼11.7 Hz, 1H),
NEt2
CO2Me
H
3b

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10263
4.02 (d, J¼11.7 Hz, 1H), 7.05–7.12 (m, 2H), 7.25–7.36 (m,
3H); 13C NMR (50 MHz, CDCl3, 25 ꢀC) d 49.6, 49.9, 50.9,
67.1, 67.4, 67.7, 67.8, 127.4, 127.6, 129.2, 133.1, 171.5;
LRMS m/z 275 (M+ꢁ59, 5), 176 (Base). Anal. Calcd for
C18H26O4N2 (334.42): C, 64.65; H, 8.08; N, 8.37. Found:
C, 64.89; H, 8.29; N, 8.26.
4.3.8. Methyl 2,3-dipiperidino-3-phenyl propanoate (2g).
Eluent used for the flash-column chromatography: cyclo-
hexane/EtOAc 80:20.
N
CO2Me
O
N
2gt
N
CO2Me
Less polar diastereomer 2gt, Rf¼0.55. White solid; yield
40 mg, 70%; mp 101–103 ꢀC; IR (n, cmꢁ1, CHCl3)
N
1
1726.9; H NMR (200 MHz, CDCl3, 25 ꢀC) d 0.97–1.54
2ec
O
(m, 12H, piperidine), 1.97–2.18 (m, 2H), 2.31–2.58 (m,
6H), 3.72 (s, 3H), 3.84 (d, J¼11.7 Hz, 1H), 4.02 (d,
J¼11.7 Hz, 1H), 7.02–7.17 (m, 2H), 7.18–7.35 (m, 3H);
13C NMR (50 MHz, CDCl3, 25 ꢀC) d 24.5, 26.3, 26.8,
50.5, 50.6, 51.0, 68.4, 68.6, 126.7, 127.2, 129.4, 134.4,
172.3; LRMS m/z 243 (M+ꢁ31, 4), 174 (Base). Anal. Calcd
for C20H30O2N2 (330.47): C, 72.69; H, 8.15; N, 8.47. Found:
C, 72.53; H, 8.06; N, 8.44.
More polar diastereomer 2ec, Rf¼0.41. Yellow solid;
yield 12 mg, 23%; mp 100 ꢀC; IR (n, cmꢁ1, CHCl3)
1731.1 cmꢁ1; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.34–
1
2.60 (m, 4H), 2.68–2.90 (m, 4H), 3.38 (s, 3H), 3.60–3.75
(m, 8H), 3.87 (d, J¼11.7 Hz, 1H), 4.05 (d, J¼11.7 Hz,
1H), 7.07–7.17 (m, 2H), 7.23–7.35 (m, 3H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 49.2, 49.7, 51.0, 66.0, 67.2,
67.5, 67.7, 127.9, 128.0, 129.1, 134.2, 170.0; LRMS m/z
275 (M+ꢁ59, 5), 176 (Base). Anal. Calcd for C18H26O4N2
(334.42): C, 64.65; H, 8.08; N, 8.37. Found: C, 64.71; H,
8.16; N, 8.31.
N
CO2Me
N
2gc
4.3.7. Methyl 2,3-dipyrrolidino-3-phenyl propanoate
(2f). Eluent used for the flash-column chromatography:
cyclohexane/EtOAc 60:40.
More polar diastereomer 2gc, Rf¼0.38. White solid; yield
18 mg, 30%; mp 123–125 ꢀC; IR (n, cmꢁ1, CHCl3)
1731.9; H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.20–1.62
1
N
(m, 12H), 2.20–2.52 (m, 4H), 2.60–2.80 (m, 4H), 3.36 (s,
3H), 3.84 (d, J¼11.7 Hz, 1H), 4.03 (d, J¼11.7 Hz, 1H),
7.08–7.15 (m, 2H), 7.19–7.31 (m, 3H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 24.7, 24.9, 26.7, 26.9, 50.1,
50.5, 50.6, 66.7, 67.9, 127.2, 127.7, 129.1, 135.5, 171.0;
LRMS m/z 243 (M+ꢁ31, 4), 174 (Base). Anal. Calcd for
C20H30O2N2 (330.47): C, 72.69; H, 8.15; N, 8.47. Found:
C, 72.93; H, 8.38; N, 8.57.
CO2Me
N
2ft
Less polar diastereomer 2ft, Rf¼0.68. Yellow solid; yield
25 mg, 51%; mp 99–102 ꢀC; IR (n, cmꢁ1, CHCl3) 1725.7;
1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.35–1.62 (m, 8H),
2.19–2.56 (m, 6H), 2.57–2.74 (m, 2H), 3.69 (s, 3H), 4.06
(d, J¼11.7 Hz, 1H), 4.24 (d, J¼11.7 Hz, 1H), 7.09–7.20
(m, 2H), 7.21–7.36 (m, 3H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 22.7, 23.4, 47.9, 49.1, 50.9, 65.1, 66.5, 127.0,
127.4, 129.6, 134.2, 172.8; 243 (M+ꢁ59, 3), 160 (Base).
Anal. Calcd for C18H26O2N2 (302.42): C, 71.49; H, 8.66;
N, 9.26. Found: C, 71.62; H, 8.81; N, 9.13.
4.3.9. Methyl 2,3-dimorpholino pentanoate (5a). Only the
less polar diastereoisomer could be isolated in pure form.
Eluent used for the flash-column chromatography: cyclo-
hexane/EtOAc 60:40.
O
N
N
CO2Me
CO2Me
N
5at
N
O
2fc
More polar diastereomer 2fc, Rf¼0.37. White solid; yield
9 mg, 18%; mp 78–81 ꢀC; IR (n, cmꢁ1, CHCl3) 1725.4; 1H
NMR (200 MHz, CDCl3, 25 ꢀC) d 1.52–1.80 (m, 8H),
2.33–245 (m, 2H), 2.55–2.92 (m, 6H), 3.29 (s, 3H), 3.88
(d, J¼9.4 Hz, 1H), 3.98 (d, J¼9.4 Hz, 1H), 7.10–7.32 (m,
Less polar diastereomer 5at, Rf¼0.40. White solid; yield
1
44 mg, 43%; mp 109 ꢀC; IR (n, cmꢁ1, CHCl3) 1691.1; H
NMR (200 MHz, CDCl3, 25 ꢀC) d 1.0 (t, J¼7.8 Hz, 3H),
1.30–1.80 (m, 2H), 2.42–2.60 (m, 6H), 2.64–2.89 (m, 3H),
3.09 (d, J¼10.9 Hz, 1H), 3.42–3.70 (m, 8H), 3.67 (s, 3H);
13C NMR (50 MHz, CDCl3, 25 ꢀC) d 13.2, 20.6, 49.8,
50.2, 50.6, 63.8, 67.4, 67.9, 71.2, 171.5; LRMS m/z 227
(M+ꢁ59, 20), 128 (Base). Anal. Calcd for C14H26O4N2
(286.37): C, 58.72; H, 9.15; N, 9.78. Found: C, 58.83; H,
9.07; N, 9.54.
13
5H); C NMR (50 MHz, CDCl3, 25 ꢀC) d 22.9, 23.5,
49.7, 50.6, 51.1, 67.4, 68.4, 127.4, 127.7, 129.2, 170.6;
LRMS m/z 243 (M+ꢁ59, 3), 160 (Base). Anal. Calcd for
C18H26O2N2 (302.42): C, 71.49; H, 8.66; N, 9.26. Found:
C, 71.73; H, 8.52; N, 9.11.

10264
M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
O
N
4.4. General procedure for the reaction of diallylamine
with the oxazolidinone vinyl triflates 7 and 10
CO2Me
To 100 mg of the triflate was added in one portion 4 equiv of
diallylamine (0.15 ml for the reaction with triflate 7, 0.13 ml
for the reaction with triflate 10). The mixture was mag-
netically stirred for 5 h (case of triflate 7) or for 20 h (case
of triflate 10) and directly purified by flash-column chroma-
tography, eluting with cyclohexane/EtOAc 60:40.
N
O
5ac
More polar diastereomer 5ac, Rf¼0.34 (contaminated by the
first diastereomer). Orange solid; yield 21 mg, 36%; mp 69–
70 ꢀC; IR (n, cmꢁ1, CHCl3) 1725.7; H NMR (200 MHz,
1
4.4.1. 2,3-Bis-diallylamino pentanoic N-oxazolidin-2-one
carboxamide (8b). Eluent used for the flash-column
chromatography: cyclohexane/EtOAc 60:40. Stereomeric
adducts 8bt and 8bc were obtained as an inseparable mixture
in a nearly 1.5:1 ratio. Rf¼0.53.
CDCl3, 25 ꢀC) d 0.91 (t, J¼7.8 Hz, 3H), 1.30–1.80 (m,
2H), 2.47–2.60 (m, 6H), 2.7–2.96 (m, 3H), 3.18 (d,
J¼9.4 Hz, 1H), 3.42–3.70 (m, 8H), 3.67 (s, 3H).
4.3.10. Methyl 2,3-bis-diallylamino pentanoate (5b). Elu-
ent used for the flash-column chromatography: cyclohexane/
EtOAc 95:05.
O
O
O
NAll2
O
NAll2
O
N
N
O
+
NAll2
NAll2
8bc
NAll2
8bt
CO2Me
Colourless oil; yield 63 mg, 68%; IR (n, cmꢁ1, CHCl3)
5bt
NAll2
1
1690.0, 1775.0 cmꢁ1; H NMR (200 MHz, CDCl3, 25 ꢀC)
d 0.87 (t, J¼7.04 Hz, 3H, diast. 1), 0.99 (t, J¼7.04 Hz,
3H, diast. 2), 0.9–1.1 (m, 1H, diast. 2), 1.35–1.50 (m, 1H,
diast. 2), 1.50–1.75 (m, 2H, diast. 1), 2.89–3.57 (m, 10H,
diast. 1+diast. 2), 3.97 (t, J¼8.6 Hz, 2H, diast. 1+diast. 2),
4.32 (t, J¼8.6 Hz, 2H, diast. 1), 4.34 (t, J¼8.6 Hz, 2H, diast.
2), 4.95–5.3 (m, 8H, diast. 1+diast. 2), 5.51–5.96 (m, 4H,
Less polar diastereomer 5bt, Rf¼0.40. Yellow oil; yield
10 mg, 9%; IR (n, cmꢁ1, CHCl3) 1725.7; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 0.95 (t, J¼7.04 Hz, 3H),
1.32–1.76 (m, 2H), 2.70–3.50 (m, 10H), 3.64 (s, 3H),
4.98–5.22 (m, 8H), 5.53–5.83 (m, 4H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 13.1, 21.1, 50.4, 53.6, 54.0,
59.6, 66.2, 116.0, 117.0, 136.4, 137.8, 172.5; LRMS m/z
247 (Mꢁ59, 6), 138 (Base). Anal. Calcd for C18H30O2N2
(306.45): C, 70.54; H, 9.86; N, 8.47. Found: C, 70.83; H,
10.13; N, 8.24.
13
diast. 1+diast. 2); C NMR (50 MHz, CDCl3, 25 ꢀC)
d 12.1, 13.4, 20.9, 22.2, 42.3 (2), 52.9, 53.2, 53.5, 53.9,
58.6, 60.3, 61.5, 61.7, 61.8, 62.6, 115.6 (2), 116.4, 116.9,
136.1, 136.2, 137.2, 138.5, 153.3, 153.5, 173.2, 173.8.
NAll2
4.4.2. (Z or E)-2-Diallylamino pent-3-enoic N-oxazolidin-
2-one carboxamide (9).
CO2Me
5bc
NAll2
O
O
More polar diastereomer 5bc, Rf¼0.28. Yellow oil; yield
12 mg, 11%; IR (n, cmꢁ1, CHCl3) 1722.9; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 0.88 (t, J¼7.04 Hz, 3H),
0.92–1.80 (m, 2H), 2.70–3.55 (m, 10H), 3.64 (s, 3H),
4.94–5.30 (m, 8H), 5.54–5.91 (m, 4H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 12.1, 23.0, 50.7, 52.9, 53.8,
58.0, 64.8, 115.7, 117.5, 136.4, 138.5, 172.0; LRMS m/z
247 (Mꢁ59, 6), 138 (Base). Anal. Calcd for C18H30O2N2
(306.45): C, 70.54; H, 9.86; N, 8.47. Found: C, 70.64; H,
10.00; N, 8.39.
N
O
NAll2
9
Rf¼0.34. Yellow oil; yield 13 mg, 23%; IR (n, cmꢁ1, CHCl3)
1698.2, 1780.5; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.72
(d, J¼6.3 Hz, 3H), 2.89–3.40 (m, 4H), 3.98 (t, J¼7.8 Hz,
2H), 4.37 (t, J¼7.8 Hz, 2H), 5.05–5.25 (m, 4H), 5.31 (d,
J¼7.8 Hz, 1H), 5.46–5.95 (m, 4H); 13C NMR (50 MHz,
CDCl3, 25 ꢀC) d 18.2, 42.6, 53.9, 62.0, 62.8, 117.5, 124.8,
135.7, 152.7, 174.9; LRMS m/z 264 (M+, <1), 223 (6),
150 (Base). Anal. Calcd for C14H20O3N2 (264.32): C,
63.61; H, 7.62; N, 10.60. Found: C, 63.68; H, 7.70; N, 10.43.
4.3.11. Methyl 2-diallylamino pent-3-enoate (6).
CO2Me
4.4.3. 2,3-Bis-diallylamino-3-phenyl propanoic N-oxazo-
lidin-2-one carboxamide (11b). Stereomeric adducts 11bt
and 11bc were obtained as an inseparable mixture in a nearly
7:1 ratio. Eluent used for the flash-column chromatography:
cyclohexane/EtOAc 70:30. Rf¼0.5.
6
NAll2
Rf¼0.14. Yellow oil; yield 46 mg, 65%; IR (n, cmꢁ1, CHCl3)
1
1731.1; H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.71 (d,
J¼6.3 Hz, 3H), 3.08–3.3 (d, J¼6.3 Hz, 4H), 3.68 (s, 3H),
3.91 (d, J¼7.8 Hz, 1H), 5.05–5.22 (m, 4H), 5.42–5.90 (m,
13
4H); C NMR (50 MHz, CDCl3, 25 ꢀC) d 18.0, 51.6,
O
O
O
NAll2
O
NAll2
53.5, 65.7, 117.7, 125.6, 131.2, 135.6, 172.9; LRMS m/z
209 (M+, 1), 182 (6), 150 (Base). Anal. Calcd for
C12H19O2N (209.29): C, 68.86; H, 9.15; N, 6.69. Found:
C, 68.77; H, 9.19; N, 6.81.
O
O
N
N
+
NAll2
NAll2
11bt
11bc

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10265
1
Colourless oil; yield 91 mg, 91%; IR (n, cmꢁ1, CHCl3)
1736.9; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.42–2.68
(m, 4H), 3.31 (d, J¼6.3 Hz, 1H), 3.41 (s, 3H), 3.61–3.72
(t, J¼4.7 Hz, 4H), 4.72 (d, J¼6.3 Hz, 1H), 6.51 (d,
J¼8.6 Hz, 2H), 6.63 (t, J¼7.0 Hz, 1H), 7.07 (dd,
J¼7.0 Hz, 8.6 Hz, 2H), 7.20–7.35 (m, 5H); 13C NMR
(50 MHz, CDCl3, 25 ꢀC) d 51.1, 51.4, 56.4, 66.8, 74.0,
113.3, 117.5, 126.6, 127.6, 128.5, 129.1, 139.5, 146.9,
170.8; LRMS m/z 340 (M+, 10), 281 (35); 180 (Base).
Anal. Calcd for C20H24O3N2 (340.42): C, 70.56; H, 7.10;
N, 8.23. Found: C, 70.71; H, 7.28; N, 8.11.
1
1692.7, 1775.0; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.4
(dd, J¼7.8 Hz, 14.8 Hz, 2H, diast. 2), 2.62 (dd, J¼8.6 Hz,
14.1 Hz, 2H, diast. 1), 3.30–3.8 (m, 8H, diast. 1+diast. 2),
3.91–4.25 (m, 1H, diast. 1+diast. 2), 4.3–4.5 (m, 1H, diast.
1+diast. 2), 4.4 (d, J¼10.9 Hz, 1H, diast. 1+diast. 2),
5.05–5.25 (m, 8H, diast. 1+diast. 2), 5.7 (d, J¼10.9 Hz,
1H, diast. 1+diast. 2), 5.8–6 (m, 4H, diast. 1+diast. 2); 13C
NMR (50 MHz, CDCl3, 25 ꢀC) d 42.3, 52.9, 53.2, 59.7,
61.5, 62.0, 116.1, 116.2 (diast. min.), 116.3 (diast. min.),
117.0, 127.4, 127.5 (diast. min.), 127.8, 129.6, 130.0 (diast.
min.), 135.1, 136.0 (diast. min.), 136.9 (diast. min.), 137.2,
152.8, 172.8.
4.5.1.2. Methyl 3-anilino-2-piperidino-3-phenyl pro-
panoate (12b). Eluent used for the flash-column chromato-
graphy: cyclohexane/EtOAc 80:20.
4.5. Crossed reactions of two different amines with vinyl
triflate 1
NH
CO2Me
4.5.1. General procedure. To 100 mg of the triflate 1 were
successively added in one portion 30 equiv of the less
nucleophilic amine (0.88 ml aniline or 1 ml tert-butylamine
or 1.19 ml diallylamine) and the more nucleophilic amine:
morpholine (3 equiv, 89 ml), piperidine (2 equiv, 73 ml),
pyrrolidine (2 equiv, 53 ml) (cases of aniline and tert-butyl-
amine), or morpholine (1.5 equiv, 44 ml) (case of diallyl-
amine). The mixture was stirred at the temperature
indicated in Table 2 until total disappearance of the starting
material (TLC monitoring). The excess of the less nucleo-
philic amine was removed under vacuum and the crude mix-
ture was directly purified by flash-column chromatography,
eluting with cyclohexane/EtOAc.
N
12bt
Less polar diastereomer 12bt (contaminated by the dipiper-
idino compound 2gt; 12bt/2gt¼1:0.66 deduced from the 1H
NMR spectrum), Rf¼0.58. Yellow solid; yield 48 mg (29 mg
12bt, 19 mg 2gt), 27%; 1H NMR (200 MHz, CDCl3, 25 ꢀC)
d 1.35–1.78 (m, 6H), 2.38–2.57 (m, 4H), 3.26 (d, J¼10.2 Hz,
1H), 3.49 (s, 3H), 4.45 (d, J¼10.2 Hz, 1H), 5.5 (s, 1H, NH),
6.49 (d, J¼7.8 Hz, 2H), 6.62 (t, J¼7.0 Hz, 1H), 7.0–7.15 (m,
2H), 7.20–7.35 (m, 3H), 7.41 (d, J¼7.0 Hz, 2H).
NH
4.5.1.1. Methyl 3-anilino-2-morpholino-3-phenyl pro-
panoate (12a). Eluent used for the flash-column chromato-
graphy: cyclohexane/EtOAc 80:20.
CO2Me
N
12bc
NH
More polar diastereomer 12bc, Rf¼0.43. White solid; yield
35 mg, 32%; mp 183–184 ꢀC; IR (n, cmꢁ1, CHCl3)
CO2Me
1
1731.1; H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.35–1.78
N
(m, 6H), 2.38–2.57 (m, 4H), 3.26 (d, J¼6.2 Hz, 1H), 3.40
(s, 3H), 4.70 (d, J¼6.2 Hz, 1H), 5.2 (s, 1H, NH), 6.51 (d,
J¼7.0 Hz, 2H), 6.66 (t, J¼7.0 Hz, 1H), 7.05 (t, J¼7.0 Hz,
2H), 7.20–7.35 (m, 5H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 24.3, 25.9, 51.2, 51.9, 56.6, 74.6, 113.4, 117.3,
126.8, 127.4, 128.4, 129.0, 140.0, 146.2, 171.4; LRMS
m/z 194 (M+ꢁ156, 1); 182 (Base). Anal. Calcd for
C21H26O2N2 (338.46): C, 74.52; H, 7.74; N, 8.27. Found:
C, 74.41; H, 7.88; N, 8.11.
12at
O
Less polar diastereomer 12at, Rf¼0.33. Yellow solid; yield
28 mg, 28%; mp 135–136 ꢀC; IR (n, cmꢁ1, CHCl3)
1
1731.3; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.50–2.75
(m, 4H), 3.32 (d, J¼10.9 Hz, 1H), 3.52 (s, 3H), 3.59–3.82
(m, 4H), 4.49 (d, J¼10.9 Hz, 1H), 5.34 (s, 1H, NH), 6.51
(d, J¼8.6 Hz, 2H), 6.66 (t, J¼7.04 Hz, 1H), 7.05 (t,
J¼8.6 Hz, 2H), 7.20–7.35 (m, 3H), 7.40–7.48 (m, 2H); 13C
NMR (50 MHz, CDCl3, 25 ꢀC) d 49.5, 51.1, 56.0, 67.4,
73.6, 113.9, 118.0, 127.4, 127.8, 128.7, 129.1, 140.7,
147.8, 169.0; LRMS m/z 340 (M+, 10), 281 (35), 180
(Base). Anal. Calcd for C20H24O3N2 (340.42): C, 70.56;
H, 7.10; N, 8.23. Found: C, 70.64; H, 7.25; N, 8.15.
4.5.1.3. Methyl 3-anilino-2-pyrrolidino-3-phenyl
propanoate (12c). Eluent used for the flash-column chroma-
tography: cyclohexane/EtOAc 80:20.
NH
CO2Me
NH
CO2Me
N
12ct
N
Less polar diastereomer 12ct, Rf¼0.60. White solid; yield
48 mg, 46%; mp 134–135 ꢀC; IR (n, cmꢁ1, CHCl3) 1725.7;
1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.72–1.85 (m, 4H),
2.60–2.75 (m, 2H), 2.80–2.97 (m, 2H), 3.48 (s, 3H), 3.65
12ac
O
More polar diastereomer 12ac, Rf¼0.22. White solid; yield
35 mg, 35%; mp 116–118 ꢀC; IR (n, cmꢁ1, CHCl3)

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
(d, J¼10.2 Hz, 1H), 4.49 (d, J¼10.2 Hz, 1H), 5.0 (s, 1H,
NH), 6.54 (d, J¼8.6 Hz, 2H), 6.66 (t, J¼7.0 Hz, 1H), 7.06
(dd, J¼7.0 Hz, 8.6 Hz, 2H), 7.18–7.38 (m, 3H), 7.46 (d,
J¼7.0 Hz, 2H); 13C NMR (50 MHz, CDCl3, 25 ꢀC) d 23.5,
48.2, 50.9, 58.1, 69.5, 114.0, 117.7, 127.3, 127.6, 128.5,
128.9, 141.1, 148.1, 170.1; LRMS m/z 194 (M+ꢁ130, 1),
182 (Base). Anal. Calcd for C20H24O2N2 (324.42): C,
74.04; H, 7.45; N, 8.63. Found: C, 73.94; H, 7.52; N, 8.55.
Rf¼0.40. White solid; yield 44 mg, 41%; mp 108 ꢀC; IR (n,
1
cmꢁ1, CHCl3) 1728.4; H NMR (200 MHz, CDCl3, 25 ꢀC)
d 2.40–2.92 (m, 6H, diast. 1+diast. 2), 3.22–3.5 (m, 4H,
diast. 1+diast. 2), 3.42 (s, 3H, diast. 1), 3.71–3.78 (m, 2H,
diast. 1+diast. 2), 3.78 (s, 3H, diast. 2), 3.89 (d, J¼
11.7 Hz, 1H, diast. 1), 3.93 (d, J¼11.7 Hz, 1H, diast. 2),
4.31 (d, J¼11.7 Hz, 1H, diast. 1), 4.36 (d, J¼11.7 Hz, 1H,
diast. 2), 5.10–5.25 (m, 4H), 5.62–5.95 (m, 2H), 7.15–
7.25 (m, 2H), 7.30–7.42 (m, 3H); 13C NMR (50 MHz,
CDCl3, 25 ꢀC) d 49.7 (CH2), 50.8 (CH3), 52.7 (CH2), 53.4
(CH2), 60.3 (CH), 60.6 (CH), 67.2 (CH2), 67.6 (CH2),
116.9 (CH2), 127.1 (CH), 127.5 (CH), 127.6 (CH), 128.0
(CH), 129.2 (CH), 129.4 (CH), 137.1 (CH), 137.4 (CH),
170.0 (C]O), 171.3 (C]O); LRMS m/z 285 (M+ꢁ59,
8), 186 (92). Anal. Calcd for C20H28O3N2 (344.46): C,
69.74; H, 8.19; N, 8.13. Found: C, 69.69; H, 8.25; N, 8.21.
NH
CO2Me
N
12cc
More polar diastereomer 12cc, Rf¼0.42. Pale yellow oil;
1
yield 18 mg, 17%; IR (n, cmꢁ1, CHCl3) 1736.9; H NMR
(200 MHz, CDCl3, 25 ꢀC) d 1.75–1.90 (m, 4H), 2.55–2.72
(m, 4H), 3.28 (d, J¼4.7 Hz, 1H), 3.42 (s, 3H), 4.65 (d,
J¼4.7 Hz, 1H), 5.45 (br, 1H, NH), 6.53 (d, J¼7.8 Hz, 2H),
6.65 (t, J¼7.8 Hz, 1H), 7.08 (t, J¼7.0 Hz, 2H), 7.23–7.40
4.5.1.6. Methyl 2-diallylamino-3-morpholino-3-phenyl
propanoate (13b). This product was obtained as a single
stereomer.
O
13
(m, 5H); C NMR (50 MHz, CDCl3, 25 ꢀC) d 23.2, 51.4,
51.8, 58.8, 73.6, 113.2, 117.1, 126.5, 127.5, 128.5, 129.0,
139.8, 147.4, 171.4; LRMS m/z 194 (M+ꢁ130, 1), 182
(Base). Anal. Calcd for C20H24O2N2 (324.42): C, 74.04;
H, 7.45; N, 8.63. Found: C, 74.09; H, 7.48; N, 8.39.
N
CO2Me
NAll2
13b
Rf¼0.45. Colourless oil; yield 6 mg, 6%; IR (n, cmꢁ1
,
4.5.1.4. Methyl 3-tert-butylamino-2-morpholino-3-
phenyl propanoate (12d). The stereomeric adducts 12dt
and 12dc were obtained as an inseparable mixture in an
approximative 1:2 ratio. Eluent used for the flash-column
chromatography: cyclohexane/EtOAc 80:20.
CHCl3) 1695.5, 1777.8; 1H NMR (200 MHz, CDCl3,
25 ꢀC) d 2.28–2.52 (m, 4H), 2.93 (dd, J¼7.05 Hz, 14.1 Hz,
2H), 3.37 (s, 3H), 3.45–3.75 (m, 6H), 4.01 (d, J¼11.7 Hz,
1H), 4.10 (d, J¼11.7 Hz, 1H), 5.05–5.3 (m, 4H), 5.75–
5.95 (m, 2H), 7.08–7.19 (m, 2H), 7.23–7.38 (m, 3H); 13C
NMR (50 MHz, CDCl3, 25 ꢀC) d 49.4, 50.8, 53.3, 62.0,
67.2, 67.4, 117.1, 127.7, 127.9, 129.2, 136.8, 171.3;
LRMS m/z 285 (10, M+ꢁ59, 2), 176 (Base). Anal. Calcd
for C20H28O3N2 (344.46): C, 69.74; H, 8.19; N, 8.13. Found:
C, 69.86; H, 8.33; N, 7.96.
t
t
BuNH
BuNH
CO2Me
CO2Me
+
N
N
12dc
12dt
O
O
Rf¼0.32. White solid; yield 33 mg, 31%; IR (n, cmꢁ1
,
4.6. Crossed reactions of two different amines with vinyl
triflate 10
CHCl3) 1728.4; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 0.81
(s, 9H, diast. min.), 0.85 (s, 9H, diast. maj.), 2.05–2.5 (m,
4H, diast. min.+diast. maj.), 3.11 (d, J¼10.9 Hz, 1H, diast.
min.), 3.25–3.35 (m, 4H, diast. min.), 3.40–3.50 (m, 4H,
diast. maj.), 3.55 (d, J¼10.9 Hz, 1H, diast. maj.), 3.63 (s,
3H, diast. min.), 3.70 (s, 3H, diast. maj.), 3.98 (d,
J¼10.9 Hz, 1H, diast. maj.), 4.04 (d, J¼10.9 Hz, 1H, diast.
min.), 7.20–7.35 (m, 5H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 29.1 and 30.3, 49.9 and 50.3, 50.8 and 51.7, 55.9
and 57.3, 67.4 and 67.5, 73.0 and 75.3, 126.7, 127.1,
127.7, 127.9, 128.0, 128.6, 129.4, 133.0, 171.0 and 177.0;
LRMS m/z 248 (M+ꢁ72, 1), 106 (Base).
4.6.1. General procedure. To a mixture of 10 equiv of the
less nucleophilic amine (0.25 ml aniline or 0.33 ml diallyl-
amine) and 2 equiv of the more nucleophilic amine (48 ml
morpholine) was added 100 mg of the triflate in one portion.
The mixture was stirred for 3 h, the residual less nucleophilic
amine was removed under vacuum and the crude mixture
directly purified by flash-column chromatography, eluting
with cyclohexane/EtOAc.
4.6.1.1. 3-Anilino-2-morpholino-3-phenyl pentanoic
N-oxazolidin-2-one carboxamide (14a). Eluent used for the
flash-column chromatography: cyclohexane/EtOAc 40:60.
4.5.1.5. Methyl 3-diallylamino-2-morpholino-3-phenyl
propanoate (12e). Eluent used for the flash-column chroma-
tography: cyclohexane/EtOAc 80:20. Stereomeric adducts
12et and 12ec were obtained as an inseparable mixture of
diastereomers in a nearly 1:1 ratio.
O
O
NH
N
O
N
NAll2
NAll2
CO2Me
CO2Me
14at
O
+
N
O
N
O
Less polar diastereomer 14at, Rf¼0.36. White solid; yield
46 mg, 43%; mp 170–173 ꢀC; IR (n, cmꢁ1, CHCl3)
12ec
12et

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10267
1783.3; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.57–2.88 (m,
4H), 3.43–4.27 (m, 6H), 4.38–4.59 (d+t, Jd¼10.2 Hz,
Jt¼7.4 Hz, 3H), 5.22 (d, J¼10.2 Hz, 1H), 5.22 (s, 1H,
NH), 6.52 (d, J¼8.6 Hz, 2H), 6.60–6.8 (m, 1H), 7.05 (t,
J¼8.6 Hz, 2H), 7.20–7.35 (m, 3H), 7.40–7.48 (m, 2H); 13C
NMR (50 MHz, CDCl3, 25 ꢀC) d 42.2, 47.8, 49.3, 57.0,
61.7, 62.8, 67.5, 67.6, 113.1, 113.9, 118.0, 118.1, 127.8,
127.9, 128.5, 129.0, 129.3, 140.0, 147.9, 152.7, 170.3;
LRMS m/z 213 (M+ꢁ182, 3), 182 (Base). Anal. Calcd for
C22H25O4N3 (395.46): C, 66.82; H, 6.37; N, 10.62. Found:
C, 66.89; H, 6.43; N, 10.38.
J¼11.7 Hz, 1H), 5.05–5.3 (m, 4H), 5.65 (d, J¼11.7 Hz,
1H), 5.7–5.95 (m, 2H), 7.15–7.45 (m, 5H); LRMS m/z 287
(M++2ꢁ114, 2), 186 (Base).
4.6.1.3. 2-Diallylamino-3-morpholino-3-phenyl penta-
noic N-oxazolidin-2-one carboxamide (15).
O
O
O
N
O
N
NAll2
15bt
O
O
NH
Less polar diastereomer 15bt, Rf¼0.51. Colourless oil; yield
8 mg, 8%; IR (n, cmꢁ1, CHCl3) 1725.7; 1H NMR (200 MHz,
CDCl3, 25 ꢀC) d 2.28–2.42 (m, 2H), 2.5–2.65 (m, 2H), 3.30–
3.80 (m, 10H), 3.9–4.4 (m, 2H), 4.2 (d, J¼11.7 Hz, 1H), 5.1–
5.3 (m, 4H), 5.67 (d, J¼11.7 Hz, 1H), 5.75–5.98 (m, 2H),
O
N
N
14ac
O
13
7.1–7.3 (m, 5H); C NMR (50 MHz, CDCl3, 25 ꢀC)
More polar diastereomer 14ac, Rf¼0.31.Yellow solid; yield
d 42.4, 49.7, 53.6, 61.7, 67.2, 68.0, 77.2, 116.3, 127.8,
128.0, 128.6, 129.3, 137.2, 153.0, 170.2; LRMS m/z 223
(M+ꢁ176, 1), 176 (Base).
8 mg, 8%; mp 170 ꢀC; IR (n, cmꢁ1, CHCl3) 1777.8; H
1
NMR (200 MHz, CDCl3, 25 ꢀC) d 2.51–2.78 (m, 4H),
3.37–3.74 (m, 5H), 3.74–4.0 (m, 2H), 4.12–4.33 (m, 1H),
4.83 (d, J¼7.8 Hz, 1H), 5.16 (d, J¼7.8 Hz, 1H), 6.54 (d,
J¼7.8 Hz, 2H), 6.64 (t, J¼7.8 Hz, 1H), 7.07 (t, J¼7.8 Hz,
2H), 7.16–7.42 (m, 5H); 13C NMR (50 MHz, CDCl3,
25 ꢀC) d 42.5, 50.6, 57.0, 61.9, 67.0, 67.8, 113.8, 117.8,
126.9, 127.6, 128.5, 129.1, 139.7, 146.7, 173.3, 181.5;
LRMS m/z 213 (M+ꢁ182, 3), 182 (Base).
O
O
O
N
O
N
NAll2
15bc
More polar diastereomer 15bc, Rf¼0.34. Colourless oil; yield
3 mg, 3%; IR (n, cmꢁ1, CHCl3) 1775.04, 1695.48; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 2.35–2.52 (m, 4H), 2.55–2.7
(m, 2H), 3.12–3.35 (m, 6H), 4.0–4.1 (m, 2H), 4.3–4.42
(m, 2H), 4.35 (d, J¼12.5 Hz, 1H), 5.0–5.15 (m, 4H), 5.5–
5.7 (m, 2H), 5.67 (d, J¼12.5 Hz, 1H), 7.12–7.35 (m, 5H);
13C NMR (50 MHz, CDCl3, 25 ꢀC) d 42.4, 49.5, 53.4, 61.3,
61.8, 62.2, 67.3, 116.3, 127.2, 127.6, 129.7, 134.0, 136.8,
153.0, 171.7; LRMS m/z 223 (M+ꢁ176, 10), 176 (Base).
4.6.1.2. 3-Diallylamino-2-morpholino-3-phenyl penta-
noic N-oxazolidin-2-one carboxamide (14b). Eluent used
for the flash-column chromatography: cyclohexane/EtOAc
50:50.
O
O
NAll2
O
N
N
O
14bt
4.7. Stereochemical determinations
Less polar diastereomer 14bt, Rf¼0.30. Colourless oil; yield
30 mg, 28%; IR (n, cmꢁ1, CHCl3) 1775.0, 1695.5; 1H NMR
(200 MHz, CDCl3, 25 ꢀC) d 2.65 (dd, J¼8.6 Hz, 13.3 Hz,
2H), 2.85–3.0 (m, 3.5H), 3.4–3.65 (m, 3.5H), 3.65–3.80
(m, 3.5H), 3.80–3.95 (m, 1H), 4.02–4.35 (m, 2.5H), 4.44
(d, J¼11.7 Hz, 1H), 5.1–5.3 (m, 4H), 5.69 (d, J¼11.7 Hz,
1H), 5.80–6.05 (m, 2H), 7.15–7.45 (m, 5H); 13C NMR
(50 MHz, CDCl3) d 42.1, 49.5, 52.9, 60.6, 61.6, 61.9, 67.8,
117.2, 127.4, 128, 129.3, 129.7, 135.0, 137.0, 153.3,
170.1; LRMS m/z 287 (M++2ꢁ114, 2), 186 (Base). Anal.
Calcd for C22H29O4N3 (399.49): C, 66.14; H, 7.31; N,
10.52. Found: C, 66.28; H, 7.49; N, 10.28.
4.7.1. Stereochemical determination of diamine carbox-
ylates.
4.7.1.1. Methyl 3-phenyl glycidate (16). To a solution of
benzaldehyde (10.6 g, 100 mmol) and methyl chloro acetate
(10.86 g, 100 mmol) in dry tetrahydrofuran (200 ml) was
added NaH (4 g, 100 mmol, 60% in suspension in oil) by
small portions at 0 ꢀC. After stirring for 1 h, the solution
was quenched with an aqueous solution of 0.5 M HCl
(100 ml). Ether (100 ml) was added, the aqueous layer was
extracted three times with ether (30 ml) and the combined
organic layers were dried over MgSO4. After concentration
under vacuum, the crude mixture was purified by flash-
column chromatography, eluting with cyclohexane/EtOAc
80:20 (Rf¼0.18), to afford the title compound as a colourless
oil (8.1 g, 48% yield).
O
O
NAll2
O
N
N
O
14bc
CO2Me
O
16
More polar diastereomer 14bc, Rf¼0.14. Yellow oil; yield
1
11 mg, 10%; H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.6
1H NMR (200 MHz, CDCl3, 25 ꢀC) d 3.51 (d, J¼1.6 Hz,
1H), 3.82 (s, 3H), 4.08 (d, J¼1.6 Hz, 1H), 7.20–7.40
(m, 5H).
(dd, J¼8.6 Hz, 14.1 Hz, 2H), 2.85–2.95 (m, 3H), 3.4–3.9
(m, 7H), 4.03–4.15 (m, 1H), 4.19–4.32 (m, 1H), 4.4 (d,

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
4.7.1.2. Methyl 2-hydroxy-3-morpholino-3-phenylpro-
Mp 84 ꢀC; Rf¼0.16 (cyclohexane/EtOAc 2:8); IR (n, cmꢁ1
,
panoate (17a). The title compound was synthesized using
the Sharpless protocol8c,d (epoxy ester 16 4.6 g,
25.84 mmol, morpholine 2.26 ml, 25.84 mmol, methanol
25 ml). Recrystallization of the crude product from ether
gave the pure regioisomer 17a (5 g, 74%) as a colourless
crystalline solid.
CHCl3) 1646.1; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.75–
1.85 (br s, 1H+m, 4H), 2.45–2.6 (m, 2H), 2.62–2.76 (m, 2H),
3.56 (d, J¼3.1 Hz, 1H), 3.58 (s, 3H), 4.72 (d, J¼3.1 Hz, 1H),
7.24–7.39 (m, 5H); 13C NMR (50 MHz, CDCl3) d 23.4,
52.1, 52.8, 72.3, 72.4, 128.0, 128.1, 128.6, 137.4, 172.5;
LRMS m/z 218 (M+ꢁ31, 2), 82 (Base). Anal. Calcd for
C14H19O3N (249.31): C, 67.44; H, 7.68; N, 5.62. Found:
C, 67.72; H, 7.79; N, 5.57.
O
N
4.7.1.5. Methyl 3-chloro-2-morpholino-3-phenylpro-
panoate (18a). The title compound was synthesized using
the Sharpless protocol8c,d (amino alcohol 17a 4.24 g,
16 mmol, triethylamine 2.45 ml, 17.6 mmol, methanesul-
fonyl chloride 1.36 ml, 17.6 mmol, dichloromethane 16 ml).
After stirring for 3 h, the ammonium mesylate was removed
by treating the solution on a plug of silica gel, eluting with
ether. Concentration under vacuum afforded 18a (4.41 g,
97%, colourless crystalline solid) as a regioisomeric 3:1
mixture.
CO2Me
OH
17a
Mp 96 ꢀC; Rf¼0.18 (cyclohexane/EtOAc 6:4); IR (n, cmꢁ1
,
CHCl3) 1739.4; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 2.38–
2.65 (m, 4H+OH), 3.57 (d, J¼3.9 Hz, 1H), 3.62 (s, 3H), 3.73
(t, J¼4.7 Hz, 4H), 4.79 (d, J¼3.9 Hz, 1H), 7.30–7.35 (m,
5H); 13C NMR (50 MHz, CDCl3) d 51.5, 52.2, 67.0, 70.1,
72.3, 128.2, 128.3, 129.0, 135.5, 173.1; LRMS m/z 206
(M+ꢁ59, 2), 176 (Base). Anal. Calcd for C14H19O4N
(265.31): C, 63.38; H, 7.21; N, 5.28. Found: C, 63.33; H,
7.34; N, 5.24.
Cl
CO2Me
N
4.7.1.3. Methyl 2-hydroxy-3-piperidino-3-phenylpro-
panoate (17b). The title compound was synthesized using
the Sharpless protocol8c,d (epoxy ester 16 3 g, 16.85 mmol,
piperidine 1.75 ml, 17.69 mmol, methanol 19 ml). Purifica-
tion of the crude product by flash-column chromatography,
eluting with cyclohexane/EtOAc 5:5 gave the pure
regioisomer 17b as the major compound (3.5 g, 78%) as a
colourless crystalline solid (the other regioisomer was also
isolated (188 mg, 4%).
18a
O
Mp 112–113 ꢀC; Rf¼0.57 (cyclohexane/EtOAc 6:4); IR (n,
1
cmꢁ1, CHCl3) 1733.9; H NMR (200 MHz, CDCl3, 25 ꢀC)
d 2.25–2.72 (m, 4H, two regioisomers), 3.28–3.45 (m, 4H,
major regioisomer), 3.28–3.45 (m, 4H, major regioisomer),
3.55–3.62 (m, 4H, minor regioisomer), 3.74 (d, J¼10.9 Hz,
1H, major regioisomer), 3.84 (s, 3H, two regioisomers),
4.08 (d, J¼10.9 Hz, 1H, minor regioisomer), 4.78 (d,
J¼10.9 Hz, 1H, minor regioisomer), 5.16 (d, J¼10.9 Hz,
1H, major regioisomer), 7.30–7.45 (m, 5H); 13C NMR
(50 MHz, CDCl3) d 50.1, 51.6, 52.7 (minor), 55.3 (minor),
59.1, 61.9 (minor), 67.0, 67.2 (minor), 72.2 (minor), 73.6,
127.8, 128.2 (minor), 128.3 (minor), 128.4, 128.6, 128.9 (mi-
nor), 138.4, 169.2; LRMS m/z 224 (M+ꢁ59, 16), 158 (Base).
Anal. Calcd for C14H18O3NCl (283.75): C, 59.26; H, 6.39; N,
4.94. Found: C, 59.33; H, 6.41; N, 5.01.
N
CO2Me
OH
17b
Mp 88 ꢀC; Rf¼0.32 (cyclohexane/EtOAc 5:5); IR (n, cmꢁ1
,
CHCl3) 1739.4; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.32–
1.70 (m, 6H), 1.6 (br s, 1H), 2.35–2.5 (m, 4H), 3.58 (s, 3H),
3.59 (d, J¼5.5 Hz, 1H), 4.81 (d, J¼5.5 Hz, 1H), 7.29–7.34
(m, 5H); 13C NMR (50 MHz, CDCl3) d 24.3, 26.1, 51.9,
52.0, 70.7, 72.5, 127.9, 128.1, 129.0, 136.1, 173.3; LRMS
m/z 204 (M+ꢁ59, 5), 174 (Base). Anal. Calcd for
C15H21O3N (263.34): C, 68.41; H, 8.03; N, 5.32. Found:
C, 68.48; H, 7.99; N, 5.35.
4.7.1.6. Methyl 3-chloro-2-piperidino-3-phenylpropa-
noate (18b). The title compound was synthesized using
the Sharpless protocol8c,d (amino alcohol 17b 2.48 g,
9.43 mmol, triethylamine 1.44 ml, 10.37 mmol, methane-
sulfonyl chloride 802 ml, 10.37 mmol, dichloromethane
10 ml). After stirring for 3 h, the ammonium mesylate was
removed by treating the solution on a plug of silica gel, elut-
ing with ether. Concentration under vacuum afforded the
pure regioisomer 18b (2.53 g, 96%) as a colourless crystal-
line solid. In contrast to its morpholino analogue 18a, com-
pound 18b decomposes on standing at room temperature and
therefore must be stored in the freezer at ꢁ20 ꢀC. At this
temperature, 18b is indefinitely quite stable.
4.7.1.4. Methyl 2-hydroxy-3-pyrrolidino-3-phenyl-
propanoate (17c). The title compound was synthesized
using the Sharpless protocol8c,d (epoxy ester 16 3.5 g,
19.74 mmol, pyrrolidine 1.73 ml, 20.73 mmol, methanol
20 ml). Purification of the crude product by flash-column
chromatography, eluting with cyclohexane/EtOAc 3:7 to
0:10 gave the epoxide amide 19 (600 mg, 13%) and the
desired pure regioisomer 17c (1.3 g, 26%) as colourless
crystalline solids.
Cl
CO2Me
N
18b
N
CO2Me
Mp 88 ꢀC; Rf¼0.69 (cyclohexane/EtOAc 8:2); IR (n,
OH
1
cmꢁ1, CHCl3) 1731.1; H NMR (200 MHz, CDCl3, 25 ꢀC)
17c

M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
10269
d 1.1–1.3 (br s, 1H+m, 6H), 2.20–2.35 (m, 2H), 2.50–2.65
(m, 2H), 3.71 (d, J¼11 Hz, 1H), 3.83 (s, 3H), 5.17 (d,
J¼11 Hz, 1H), 7.30–7.40 (m, 5H); 13C NMR (50 MHz,
CDCl3) d 24.2, 26.2, 51.1, 51.3, 59.6, 74.2, 127.9, 128.2,
128.3, 138.9, 169.7; LRMS m/z 246 (M+ꢁ35, 2), 156
(Base). Anal. Calcd for C15H20O2NCl (281.78): C, 63.94;
H, 7.15; N, 4.97. Found: C, 63.90; H, 7.21; N, 4.91.
gave analytical data identical in all respects with those de-
scribed for the more polar product 12ac obtained by our
aza-MIRC methodology.
4.7.1.10. Methyl 2,3-dipiperidino-3-phenyl propa-
noate (2gt).
N
4.7.1.7. trans-2,3-Epoxy-3-phenyl-propenoic N,N-pyr-
rolidinylcarboxamide (19). The title compound was
obtained instead of the expected chloro amine 18c using
the Sharpless protocol8c,d (amino alcohol 17c 1.3 g,
5.22 mmol, triethylamine 800 ml, 5.74 mmol, methanesul-
fonyl chloride 444 ml, 5.74 mmol, dichloromethane 5 ml).
After stirring for 3 h, the ammonium mesylate was removed
by filtering the solution on a plug of silica gel, eluting with
ether. Concentration under vacuum afforded the pure com-
pound 19 (1.02 g, 90%) as a colourless crystalline solid.
CO2Me
N
2gt
The title compound was synthesized using the Sharpless
protocol8c,d (amino chloride 18b 282 mg, 1 mmol, K2CO3
138 mg, 1 mmol, morpholine 109 ml, 1.1 mmol, acetonitrile
2 ml). The pure compound 2g so obtained (327 mg, 99%)
gave analytical data identical in all respects with those
described for the less polar product 2gt obtained by our
aza-MIRC methodology.
O
N
O
19
4.7.1.11. Methyl 3-anilino-2-piperidino-3-phenyl
propanoate (12bc).
Mp 56 ꢀC; Rf¼0.25 (cyclohexane/EtOAc 3:7); IR (n, cmꢁ1
,
CHCl3) 1739.4; 1H NMR (200 MHz, CDCl3, 25 ꢀC) d 1.85–
2.15 (m, 4H), 2.52–3.75 (m, 4H), 3.57 (d, J¼1.6 Hz, 1H),
4.15 (d, J¼1.6 Hz, 1H), 7.32–7.42 (m, 5H); 13C NMR
(50 MHz, CDCl3) d 23.3, 51.9, 52.6, 72.2, 125.6, 127.5,
127.9, 135.7, 172.4; LRMS m/z 217 (M+, 7), 82 (Base).
Anal. Calcd for C13H15O2N (217.76): C, 71.86; H, 6.96;
N, 6.44. Found: C, 72.0; H, 6.91; N, 6.31.
NH
CO2Me
N
12bc
The title compound was synthesized using the Sharpless
protocol8c,d (amino chloride 18b 282 mg, 1 mmol, K2CO3
138 mg, 1 mmol, aniline 100 ml, 1.1 mmol, acetonitrile
2 ml). The pure compound 12b so obtained (317 mg, 94%)
gave analytical data identical in all respects with those
described for the more polar product 12bc obtained by our
aza-MIRC methodology.
4.7.1.8. Methyl 2,3-dimorpholino-3-phenyl propanoate
(2et).
O
N
CO2Me
4.7.1.12. Methyl 3-tert-butylamino-2-morpholino-3-
phenyl propanoate (12dc).
N
2et
O
t
Bu
NH
The title compound was synthesized using the Sharpless pro-
tocol8c,d (amino chloride 18a 284 mg, 1 mmol, K2CO3
138 mg, 1 mmol, morpholine 96 ml, 1.1 mmol, acetonitrile
2 ml). The pure compound 2e so obtained (331 mg, 99%)
gave analytical data identical in all respects with those
described for the less polar product 2et obtained by our
aza-MIRC methodology.
CO2Me
N
O
12dc
The title compound was synthesized using the Sharpless
protocol8c,d (amino chloride 18a 284 mg, 1 mmol, K2CO3
138 mg, 1 mmol, tert-butylamine 114 ml, 1.1 mmol, aceto-
nitrile 2 ml). The 1H NMR spectrum of the pure compound
12d so obtained (300 mg, 94%, mp 90 ꢀC) exhibited signals
identical to those of the major stereomer in the adduct 12dt–
c obtained by our aza-MIRC methodology. 13C NMR
(50 MHz, CDCl3) d 30.4, 50.3, 50.8, 51.3, 55.9, 67.2, 75.4,
126.7, 127.1, 128.0, 133.0, 171.0. Anal. Calcd for
C18H28O3N2 (320.43): C, 67.47; H, 8.82; N, 8.74. Found:
C, 67.64; H, 8.95; N, 8.85.
4.7.1.9. Methyl 3-anilino-2-morpholino-3-phenyl pro-
panoate (12ac).
NH
CO2Me
N
12ac
O
The title compound was synthesized using the Sharpless
protocol8c,d (amino chloride 18a 284 mg, 1 mmol, K2CO3
138 mg, 1 mmol, aniline 100 ml, 1.1 mmol, acetonitrile
2 ml). The pure compound 12a so obtained (316 mg, 93%)
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.07.085.

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M.-J. Tranchant, V. Dalla / Tetrahedron 62 (2006) 10255–10270
Fernandez de le Pradilla, R.; Garcia, A.; Flores, A. Chem.
Rev. 2005, 105, 3167.
References and notes
10. In the course of related work aimed at developing these reac-
tions in solution, we discovered that dissolving compound 1
in freshly distilled DMF which had been refluxed overnight
on potassium hydroxide produced a smooth reaction leading
to the a,b-diamino adducts 2at–c. Applying this procedure to
an m-nitro aryl analogue of 1 as the vinyl triflate component
even gave a spontaneous and exothermic reaction furnishing
the stereomeric diamino adducts within few minutes. This tech-
nique may be considered as a valuable water-free source of
dimethylamine.
11. Letters t and c referred to the less and more polar diastereo-
mers, respectively. The stereochemical attribution of these
adducts has been made by chemical correlation using the
Sharpless methodology8c,d (details are included in Section
2.3 at the end of the manuscript).
1. For recent reviews on tandem reactions, see: (a) Bunce, R. A.
Tetrahedron 1995, 51, 13103; (b) Tietze, L. F. Chem. Rev.
1996, 96, 115; (c) Simon, C.; Constantieux, T.; Rodriguez, J.
Eur. J. Org. Chem. 2004, 4957; (d) Ramon, D. J.; Yus, M.
Angew. Chem., Int. Ed. 2005, 44, 1602; (e) Guo, H.; Ma, J.
Angew. Chem., Int. Ed. 2006, 45, 354; (f) Pellissier, H.
Tetrahedron 2006, 62, 1619; (g) Pellissier, H. Tetrahedron
2006, 62, 2143.
2. To the best of our knowledge, only a few examples of use of this
class of compounds, each dealing with Pd-catalyzed coupling
reactions, have been reported. See: (a) Beccalli, E. M.;
Gelmi, M. L.; Marchesini, A. Tetrahedron 1998, 54, 6909;
(b) Beccalli, E. M.; Clerici, F. L.; Marchesini, A. Tetrahedron
2000, 56, 2699; (c) Ceccarelli, S.; Piarulli, U.; Gennari, C.
€
J. Org. Chem. 2000, 65, 3105; (d) Siegel, K.; Bruckner, R.
12. The formation of type 3 enamines was a major problem
encountered during the development of similar reactions in
solution. After screening various solvents, it was found that
reaction could be conducted efficiently in DME, enamine
formation being reduced to a great extent. Dalla, V.;
Tranchant, M. J., unpublished results.
13. Couturier, C.; Blanchet, J.; Schlama, T.; Zhu, J. Org. Lett. 2006,
8, 2183.
14. Diallylamine is expected to be a higher nucleophile than
dibenzylamine. This seems to be confirmed by the results in
Table 1, runs 4 and 5.
15. For previous studies documenting the highly regioselective
opening of benzylic aziridinium salts, see: (a) Refs. 8a–d and
8h of the present article; (b) Dieter, K. R.; Deo, N.; Lagu, B.;
Dieter, L. W. J. Org. Chem. 1992, 57, 1663; (c) Freedman, J.;
Vaal, M. J.; Huber, E. W. J. Org. Chem. 1991, 56, 670; (d)
Okuda, M.; Tomioka, K. Tetrahedron Lett. 1994, 35, 4585;
(e) Rossiter, B. E.; Miao, G. J. Org. Chem. 1995, 60, 8424;
(f) Saravanan, P.; Bisai, A.; Baktharanan, S.; Chandrasekhar,
M.; Singh, V. K. Tetrahedron 2002, 58, 4693; (g) Andrews,
D. R.; Dahanukar, V. H.; Eckert, J. M.; Gala, D.; Lucas,
B. S.; Schumacher, D. P.; Zavialov, I. A. Tetrahedron Lett.
2002, 43, 6121.
Chem.—Eur. J. 1998, 4, 1116; (e) Kalwinsh, I.; Metten, K.;
Br€uckner, R. Heterocycles 1995, 40, 939.
3. Dalla, V.; Decroix, B. Tetrahedron Lett. 2002, 43, 1657.
4. Tranchant, M. J.; Dalla, V.; Jabin, I.; Decroix, B. Tetrahedron
2002, 58, 8425.
5. See also: (a) de Saint-Fuscien, C.; Tarrade, A.; Dauban, P.;
Dodd, R. H. Tetrahedron Lett. 2000, 41, 6393; (b) Tarrade,
A.; Dauban, P.; Dodd, R. H. J. Org. Chem. 2003, 68, 9521.
6. For some recent developments in the aza-MIRC chemistry:
(a) For the use of a,b-unsaturated carbonyl derivatives
a-substituted by a leaving group. See Ref. 5 and references
therein; (b) For the use of N-alkoxy amines, see: Cardillo, G.;
Gentilucci, L.; De Matteis, V. J. Org. Chem. 2002, 67, 5957
and Ref. 8 cited therein; (c) For the use of nosyloxycarbamates,
see: Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A.
Tetrahedron 1998, 54, 6169; Fioravanti, S.; Pellacani, L.;
Morreale, S.; Tardella, P. A. Synthesis 2001, 1975;
Fioravanti, S.; Pellacani, L.; Morreale, S.; Tardella, P. A.
J. Org. Chem. 2002, 67, 4972.
7. Recently, a comparable but inverse approach for accessing
transient aziridinium ions, based on sequential alkylation
followed by aza-Michael addition of N–H aziridine to elec-
tron-deficient 6-iodo alkynes, has been published. Zhu, W.;
Cai, G.; Ma, D. Org. Lett. 2005, 7, 5545.
16. See Ref. 6b.
17. For representative example, see Refs. 8a–d (especially Ref. 8b)
of the present manuscript and references cited therein.
18. No substantial enhancement of the reaction rate was observed
at 40 ꢀC, these conditions actually compromising the reaction
profile, with notable formation of increased quantities of
dimorpholino adducts 2et–c.
19. Unfortunately, no NMR correlations were found for the crossed
diamino esters and therefore no conclusive evidence could be
drawn for the overall series (Table 3, case of 12c, last line).
Also, the NMR correlation did not match the diamines
5a–bt–c derived from the b-ethyl vinyl triflate 4 (see Scheme
2), the stereochemistry of which, therefore, could not be deter-
mined.
8. For some recent leading references in the chemistry of aziridi-
nium ions, see: (a) de Sousa, S. E.; O’Brien, P.; Ploumellec, P.
J. Chem. Soc., Perkin Trans. 1 1998, 1483; (b) O’Brien, P.;
Towers, T. D. J. Org. Chem. 2002, 67, 304; (c) Chuang,
T. H.; Sharpless, K. B. Org. Lett. 1999, 1, 1435; (d) Chuang,
T. H.; Sharpless, K. B. Org. Lett. 2000, 2, 3555; (e) Liu, K.;
Marchington, A. P.; Boden, N.; Rayner, C. M. J. Chem. Soc.,
Perkin Trans. 1 1997, 511; (f) Rayner, C. M. Synlett 1997,
11; (g) Graham, M. A.; Wadsworth, A. H.; Zahid, A.;
Rayner, C. M. Org. Biomol. Chem. 2003, 1, 834; (h) Couty,
F.; Evano, G.; Prim, D. Tetrahedron Lett. 2005, 46, 2253.
9. For the utility of a,b-diamino acids and esters, see the follow-
ing reviews: (a) Lucet, D.; Le Gall, T. L.; Mioskowski, C.
Angew. Chem., Int. Ed. 1998, 37, 2580; (b) Viso, A.;
20. Orita, A.; Nagano, Y.; Hirano, J.; Otera, J. Synlett 2001, 637.