Highly diastereoselective [3+2] cycloadditions between nonracemic p-tolylsulfinimines and iminoesters: An efficient entry to enantiopure imidazolidines and vicinal diaminoalcohols

Article abstract of DOI:10.1002/chem.200204674

A new procedure for the asymmetric synthesis of imidazolidines and vicinal diamines is reported. The 1,3-dipolar cycloaddition between nonracemic p-tolylsulfinimines and azomethine ylides generated in situ from aiminoesters and LDA produces N-sulfinylimid

Full text of DOI:10.1002/chem.200204674

FULL PAPER
Highly Diastereoselective [3‡2] Cycloadditions between Nonracemic
p-Tolylsulfinimines and Iminoesters:An Efficient Entry to Enantiopure
Imidazolidines and Vicinal Diaminoalcohols
Alma Viso,*[a] Roberto Ferna¬ndez de la Pradilla,*[a] Ana GarcÌa,[a] Carlos Guerrero-
Strachan,[a] Marta Alonso,[a] Mariola Tortosa,[a] Aida Flores,[a] MartÌn MartÌnez-Ripoll,[b]
Isabel Fonseca,[b] Isabelle Andre¬,[b] and Ana RodrÌguez[c]
Abstract: A new procedure for the
asymmetric synthesis of imidazolidines
and vicinal diamines is reported. The
1,3-dipolar cycloaddition between non-
racemic p-tolylsulfinimines and azome-
thine ylides generated in situ from a-
iminoesters and LDA produces N-sulfi-
nylimidazolidines with a high degree of
stereocontrol. In contrast, the presence
of Lewis acids promotes formation of
the cycloadducts through a highly dia-
stereoselective process with opposite
stereochemistry. Subsequent transfor-
mations of the imidazolidines including
oxidative, reductive, and hydrolytic
processes that provide easy access to
vicinal diaminoalcohols have been ex-
plored. Among these, reductive cleav-
age of the aminal with LiAlH4 is an
extremely efficient and general reaction
for the synthesis of enantiopure N-
sulfinyl-N'-benzyldiaminoalcohols.
Keywords:
heterocycles
cycloadditions
¥ imidazolidines
¥
¥
sulfinimines ¥ ylides
a
Introduction
R3
a
b
R5
R5HN
b
NHR4
N
N
The 1,3-dipolar cycloaddition between alkenes and dipoles is
one of the most powerful tools for the synthesis of 5-mem-
bered heterocycles.[1] In particular, azomethine ylides which
are commonly generated in situ, have proved to be versatile
intermediates for the reaction with alkenes to produce
pyrrolidines[2] with high stereocontrol, and this well-estab-
lished methodology allows the use of a variety of chiral
auxiliaries or chiral catalysts in the synthesis of nonracemic
pyrrolidines.[1d, e, 3] In contrast, the majority of the routes
towards enantiopure 1,3-imidazolidines A utilize the conden-
sation of aldehydes B and chiral 1,2-diamines C and are often
limited to the use of C2-symmetric diamines to reduce the
number of possible final diastereomers (Scheme 1,
R4
Imine
Ylide
R1
R3CHO
R1
R2
R2
R3
C
A
B
O
S
1,2-diamine
1,3-imidazolidine
M
N
pTol
N
O
R1
OMe
E
D
Scheme 1. Strategies for the synthesis of enantiopure 1,3-imidazolidines.
route a). Consequently, the success of this approach relies on
an efficient access to optically pure vicinal diamines.[4]
Notwithstanding the well-established synthetic usefulness of
enantiopure imidazolidines,[5] reports on dipolar cycloaddi-
tions between azomethine ylides and imines are scarce
(Scheme 1, route b)[6] and the asymmetric variant of this
process had not been documented.[7]
Chiral sulfinimines are readily available in both enantio-
meric forms and have proved to be valuable intermediates for
the synthesis of different nitrogen-containing targets.[8] These
compounds display excellent facial selectivity towards nucleo-
philes, and removal of the chiral sulfinyl auxiliary is easy.[9]
The above facts along with our interest in the development of
sulfur-directed methodology prompted us to consider sulfini-
mines as precursors to enantiopure 1,3-imidazolidines by 1,3-
dipolar cycloadditions with azomethine ylides. Thus, here we
disclose a full description of the first examples of the
asymmetric 1,3-dipolar cycloaddition of azomethine ylides D
¬
[a] A. Viso, R. Fernandez de la Pradilla, A. GarcÌa,
C. Guerrero-Strachan, M. Alonso, M. Tortosa, A. Flores
¬
Instituto de QuÌmica Organica, CSIC
Juan de la Cierva, 3, 28006 Madrid (Spain)
Fax : (‡34)91-564-4853
E-mail: iqov379@iqog.csic.es
¬
[b] M. MartÌnez-Ripoll, I. Fonseca, I. Andre
Departamento de CristalografÌa
Instituto de QuÌmica-FÌsica Rocasolano
CSIC, Serrano 119, 28006 Madrid (Spain)
[c] A. RodrÌguez
¬
Departamento de QuÌmica Inorganica
Universidad de Castilla-La Mancha
13071 Ciudad Real (Spain)
Supporting information for this article is available on the WWW under
http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2003, 9, 2867 2876
DOI:10.1002/chem.200204674
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2867

¬
A. Viso, R. Fernandez de la Pradilla et al.
FULL PAPER
with enantiopure sulfinimines E to produce enantiopure
imidazolidines A.[10] In this account we will also report in full
the Lewis acid mediated stepwise condensation between
enolates derived from a-iminoesters and sulfinimines[10b] as
well as expedient and novel transformations of the resulting
N-sulfinylimidazolidines A into enantiopure nonsymmetrical
vicinal diamines C (Scheme 1).
the sulfinimine and allowing the reaction to warm up to
approximately 48C produced just two of the eight possible 1,3-
imidazolidines, 3a and 4a, as a 95:5 mixture along with small
amounts of starting material (ca. 15%). The major isomer 3a
was isolated in 50% yield from this mixture by crystalliza-
tion.[12] Comparable behavior was found when the a-imi-
noester derived from alanine methyl ester was employed.
Thus, 1,3-imidazolidines 3b and 4b were obtained in a 95:5
ratio and the major isomer was isolated in 47% yield. By
placing a nitro group at the para position of the aromatic ring
attached to the sulfinimine (R1 ˆ p-NO2C6H4, 1b), a more
reactive dipolarophile was obtained which underwent com-
plete conversion to cycloadducts 3c and 4c with a slight
improvement in the facial selectivity (97:3). Similar behavior
was observed when the dipole was generated with LDA and
the a-iminoester derived from leucine methyl ester and
benzaldehyde (3d:4d 98:2). We also obtained excellent
diastereocontrol with the sulfinimines 1c (R1 ˆ 3-pyr) and
1d (R1 ˆ 2-furyl) under the reaction conditions, and 1,3-
imidazolidines 3e and 3 f were obtained as practically single
isomers; however, again the more electron-deficient sulfini-
mine (1c) provided a better yield of the cycloadducts.
The structural determination of the cycloadducts was based
on their spectral features. Thus, for N-sulfinylimidazolidines
3a f, the unusually upfield signals attributed to protons of
the carbomethoxy groups at C4 (s, 2.97 3.27 ppm) indicated a
cis relative arrangement to the phenyl group at C5. Further
proof of the relative stereochemistry of the new chiral centers
was found by D-NOE (3a: H2 H5 ˆ 1.3 %, CH2Ph H2 ˆ
4.3%). However, the definitive proof of the facial outcome of
the process was established by an X-ray diffraction analysis of
3a.[13] Furthermore, to confirm that 3a and 4a were facial
isomers regarding the sulfinyl group, they were independently
oxidized to N-sulfonylimidazolidines 5a and ent-5a respec-
tively with identical optical rotation but opposite sign
(Scheme 3).
Results and Discussion
1,3-Dipolar cycloadditions: To begin our study we selected
sulfinimine 1a (R1 ˆ Ph, Scheme 2) and iminoester 2a,
derived from benzaldehyde and phenylalanine methyl ester.
To our dismay many of the common conditions used to
generate the dipole did not lead to the desired cycloaddition
(LiBr/Et3N/CH3CN, NaHMDS/THF, etc.). Instead starting
material was recovered from the reaction mixtures. After
considerable experimentation we found that generation of the
dipole with LDA (nBuLi, iPr2NH),[11] followed by addition of
Ph
O
Li
N
THF, 20 h
S
R2
OMe
pTol
N
+
−78 to 4 °C
O
R1
1a: R1 = Ph
1b: R1 = p-NO2C6H4
1c: R1 = 3-pyr
2a: R2 = CH2Ph
2b: R2 = Me
2c: R2 = iBu
1d: R1 = 2-fur
O
O
Ph
Ph
S
S
pTol
pTol
N
N
N
H
N
H
+
R1
R1
R2
R2
CO2Me
MeO2C
55%[a] (95:5)[b]
53% (95:5)
80% (97:3)
70% (98:2)
80% (99:1)
37% (98:2)
R
R
R
R
R
R
1 = Ph, R2 = CH2Ph
1 = Ph, R2 = Me
1 = p-NO2C6H4, R2 = CH2P
1 = p-NO2C6H4, R2 = iBu
1 = 3-pyr, R2 = CH2Ph
1 = 2-fur, R2 = CH2Ph
3a:
3b:
3c:
3d:
3e:
3f:
4a:
4b:
4c:
4d:
4e:
4f:
Ph
pTolSO2
mCPBA
N
3a
4a
N
H
CH2Cl2
65%
Ph
MeO2C
5a
Scheme 2. 1,3-Dipolar cycloaddition between azomethine ylides and
enantiopure sulfinimines. [a] Except for 3e and 3 f, combined yields are
given. [b] Ratios measured by integration of the crude 1H NMR spectra.
Ph
mCPBA
ent-5a
CH2Cl2
67%
Scheme 3. Oxidation of N-sulfinylimidazolidines 3a and 4a with mCPBA.
Abstract in Spanish: En este trabajo se describe un nuevo
procedimiento de sÌntesis de imidazolidinas y diaminas
vecinales que implica la cicloadicion 1,3-dipolar entre p-
The remarkably high stereoselectivity and the absence of
any detectable open-chain intermediates in the reaction made
us consider a 1,3-dipolar pathway for the process with an endo
approach, which allows an overlap between the ester (ylide)
and the aromatic group R1
¬
tolilsulfiniminas no racemicas e iluros de azometino, generados
¬
in situ a partir de a-iminoesteres y LDA, y que transcurre con
alto grado de estereocontrol. Por otra parte, la presencia de
¬
¬
acidos de Lewis promueve la formacion de las imidazolidinas
R2
(sulfinimine), to the less hindered
con estereoquÌmica opuesta. Se han estudiado procesos de
Ph
N
Li
b face of sulfinimines 1[14a] on the
side of the sulfur lone pair, as
shown in Figure 1, to provide
3a f as the predominant cyclo-
adducts. It should be pointed out
that our process displayed a re-
OMe
¬
¬
¬
oxidacion, reduccion e hidrolisis de las imidazolidinas que en
algunos casos permiten el acceso a diaminoalcoholes vecinales.
En este contexto, la apertura reductora del aminal con LiAlH4,
O
O
S
N
pTol
R1
¬
es una reaccion eficiente y general que da lugar a N-sulfinil-N'-
Figure 1. Stereochemical out-
come of the 1,3-dipolar cyclo-
addition process.
bencildiaminoalcoholes enantiopuros.
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www.chemeurj.org
Chem. Eur. J. 2003, 9, 2867 2876

Diastereoselective [3‡2] Cycloadditions
2867 2876
Table 1. Lewis acid mediated cyclizations between glycine iminoesters and
p-tolylsulfinimines.
markable facial selectivity opposite to that observed for most
f]
other additions of enolates to sulfinimines.[14b
Ar
O
1) LDA (2.1 equiv)
O
Ar
2) Lewis acid
S
N
Lewis acid mediated cyclizations: At this stage we focused our
efforts on the extension of the scope of our methodology to
other substrates and a variety of conditions were tested with
benzylidene glycinate (2d) (R2 ˆ H) as the azomethine ylide
precursor and p-tolylsulfinimines derived from aliphatic and
aromatic aldehydes as dipolarophiles. Unfortunately, most
experiments did not give the desired imidazolidines[15] and
therefore we examined the effect of Lewis acids as potential
promoters of the cycloadditions.[16] Initially, we selected BF3 ¥
OEt2, and after considerable experimentation[17] we found
that the reaction of 1a and 2d indeed provided a satisfactory
isolated yield (85%) of an 83:17 mixture of diastereomeric
imidazolidines 7a and 8a along with a small amount (5%) of
the corresponding N-sulfinyldiaminoester (Table 1, entry 1).
In contrast to the cycloadditions previously studied, we
observed a rapid disappearance of the starting material
S
+
NH
pTol
3.25 equiv
pTol
N
N
−78 to −20 ˚C
R1
O
R1
OMe
CO2Me
2 (2 equiv)
6
1
O
O
N
Ar
Ar
N
3) 0.1 M CHCl3
RT
S
S
pTol
pTol
N
N
H
H
+
4) PhCHO
R1
[a]
R1
MgSO4
CO2Me
CO2Me
7
8
Entry 1 (R1)
2 (Ar)
Lewis acid Ratio 7:8[b]
Yield
[%][c]
1
2
3
4
5
1a (Ph)
1a (Ph)
1a (Ph)
1a (Ph)
1a (Ph)
2d (Ph)
2d (Ph)
2d (Ph)
2d (Ph)
BF3 ¥ Et2O 7a (83):8a (17) 85
Et2AlCl 7a (83):8a (17) 43
Ti(OiPr)3Cl 7a (60):8a (40) 40
SnCl4 7a (70):8a (30) 55
2e (p-MeOC6H4) BF3 ¥ Et2O 7b (87):8b (13) 53
BF3 ¥ Et2O 7c (76):8c (24) 67
1
(10 min, at À788C), but when the H NMR spectrum of the
6
1e (p-MeOC6H4) 2d (Ph)
crude reaction mixture was recorded immediately after
workup, the desired cycloadducts could barely be detected.
7
8
9
1f (p-ClC6H4)
1g (p-FC6H4)
1c (3-pyr)
2d (Ph)
2d (Ph)
2d (Ph)
BF3 ¥ Et2O 7d (90):8d (10) 61
BF3 ¥ Et2O 7e (83):8e (17) 66
BF3 ¥ Et2O
7 f (90):8f (10) 60
1
However, when we recorded subsequent H NMR spectra of
10
11
12
13
14
1h (1-naphthyl) 2d (Ph)
BF3 ¥ Et2O 7g (83):8g (17) 72
BF3 ¥ Et2O 7h (98):8h (2) 83
the same sample, increasing amounts of cycloadducts 7a and
8a and the disappearance of a number of other signals,
tentatively attributed to iminoesters 6, were observed. These
observations prompted us to allow the crude mixtures to stand
in 0.1m CHCl3 solution and monitor the progress of the
1i (-(CH2)2Ph)
1j (Et)
2d (Ph)
2d (Ph)
2d (Ph)
2d (Ph)
BF3 ¥ Et2O
BF3 ¥ Et2O
7i (95):8i (5)
7j (95):8j (5) 93
64
1k (iPr)
1l (Me)
BF3 ¥ Et2O 7k (92):8k (8) 64
[a] Optionally, step 4 can accelerate (1 2 h) the cyclization with comparable ratios
and yields. [b] Measured by integration of the 1H NMR spectra of the crude.
[c] Combined yields of pure imidazolidines 7 and 8.
1
cyclization by H NMR spectroscopy at intervals of about
24 h. In most cases, after 2 4 d we could not detect significant
changes in the composition of the mixture. These results may
be rationalized in terms of a stepwise process initiated by
addition of an iminoester derived enolate to the sulfinimine
followed by cyclization of the open-chain intermediate 6,
presumably promoted by the presence of trace amounts of
acidic species in solution.[18] Additionally, the isolation of
variable amounts of N-sulfinyldiaminoesters derived from 6
also supports a stepwise mechanism under these conditions.[19]
A number of different Lewis acids were then tested leading
to comparable diastereoselectivities. The generality of the
reaction was then explored by using BF3 ¥ OEt2 as an acidic
promoter, and the results are gathered in Table 1. The
increase in facial selectivity found for glycine derivative 2e,
which has a more electron-rich imine moiety (Arˆ p-
CH3OC6H4), is noteworthy. On the other hand, a decrease
of facial selectivity was observed when sulfinimine 1e was
treated with iminoester 2d (R1 ˆ p-CH3OC6H4). A significant
improvement in facial selectivity was accomplished when
electron-poor sulfinimines (1 f, R1 ˆ p-ClC6H4 and 1c, R1 ˆ 3-
pyr) were tested, while other aromatic groups (1g, R1 ˆ p-
FC6H4, 1h, R1 ˆ 1-naphthyl) behaved as 1a (R1 ˆ Ph) in terms
of facial selectivity. In addition, these reaction conditions led
to excellent yields and selectivities when sulfinimines 1i l,
which have aliphatic groups (R1 ˆ CH2CH2Ph, Et, iPr, Me),
were used as starting materials. Finally, despite the consid-
erable generality of our methodology for the preparation of
N-sulfinylimidazolidines, some substrates failed to give the
expected products; p-tolylsulfinimines derived from furfural,
cinnamaldehyde, and pivalaldehyde provided complex reac-
tion mixtures under the above conditions.[20] Additionally, the
tert-butylsulfinimine analog of 1a (R1 ˆ Ph) again produced a
complex reaction mixture.
The gross structure of these adducts (7a k), including the
relative stereochemistry around the ring, was established by
detailed inspection of their spectroscopic features. The trans
relative stereochemistry (C4 C5) was secured by the cou-
pling constant (J4,5 ˆ 4 6 Hz) along with the 1H NMR
chemical shifts observed for the carbomethoxy group (s,
3.75 3.82 ppm). However, these studies did not allow a
conclusive stereochemical assignment relative to the chiral
sulfur atom. This crucial matter was subsequently solved by an
X-ray analysis of 18a[13] (see below), a derivative of 7a, which
established the predominant facial outcome of our enolate
addition/cyclization protocol. This may be accounted for in
terms of addition of the chelated iminoester enolate to the less
hindered b face of sulfinimines 1, anti to the p-tolyl group,
upon activation by the Lewis acid (Figure 2). On the other
hand, the trans stereochemistry around the C4 C5 bond may
be accounted for by an open
Li
O
Ar
pTol
O
transition state with
a less
N
S
N
crowded arrangement of the
substituents, although at this
point we cannot rule out coor-
dination of the sulfinyl oxygen
atom with the lithium atom of
the enolate.
OMe
R1
H
F3B
Figure 2. Stereochemical out-
come of the Lewis acid medi-
ated condensation of sulfini-
mines
1
and glycine-derived
enolates.
Chem. Eur. J. 2003, 9, 2867 2876
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2869

¬
A. Viso, R. Fernandez de la Pradilla et al.
FULL PAPER
Ph
The effect of Lewis acid catalysis on the cycloaddition
between sulfinimines and a-substituted iminoesters 2a and 2b
(R2 ˆ Bn and CH3) paralleled the previous observations for
glycinate derivatives (R2 ˆ H) although with diminished syn/
anti selectivity at C4 and C5. Thus, the treatment of 1a with 2a
in the presence of BF3 ¥ OEt2 or Cp2TiCl2 resulted in a mixture
of cycloadducts in which 9a was the major product (Table 2).
In addition, the use of TiCl4 provided a remarkably high
diastereo and facial selectivity even though deoxygenation to
sulfenamide 10a[13] was simultaneously observed (entry 3,
(9a‡10a):11a, 92:4). p-Tolylsulfinimines 1 f (R1 ˆ p-ClC6H4)
and 1k (R1 ˆ iPr) showed similar behavior upon reaction with
iminoester 2b to give 9b and 9c as major products,
respectively. Interestingly, these highly substituted N-sulfinyl-
imidazolidines displayed lower rates of epimerization (see
footnote [b] in Table 2) at the aminal upon standing in
solution or purification by chromatography (silica gel).
The general structure of adducts 9a c was readily derived
from their spectral features.[21] However, a definitive proof of
the relative configuration of the ring and the sulfur atoms for
the mayor product was obtained by an X-ray analysis of
15a',[13] a derivative of 9a (see below), thereby establishing
the main facial sense of the process. Furthermore, an X-ray
analysis of N-sulfenylimidazolidine 10a[13] was also carried out
to establish its structure and absolute configuration.
Given the above results, we decided to explore the
reactivity of p-tolylsulfonimines with a-iminoesters under
both uncatalyzed and catalyzed conditions. Thus, the treat-
ment of 1m with 2a in the presence of LDA resulted in an
89:11 mixture of racemic N-sulfonylimidazolidines 5a and
12a; this suggests that both concerted and stepwise mecha-
nisms are operative to some extent. In addition, in the
presence of BF3 ¥ OEt2 this substrate provided an even lower
selectivity (5a:12a 67:33). In contrast, the reaction between
sulfonimine 1m and the glycine-derived iminoester 2d gave
just monotosyldiaminoesters 13 and with a fairly low syn:anti
selectivity (syn:anti 30:70) (Scheme 4).
Ph
pTolSO2
pTolSO2
N
N
SO2pTol
N
H
N
N
H
+
+
2a
Ph
Ph
Ph
Ph
Ph
CO2Me
MeO2C
5a
(LDA, THF)
(LDA, THF, BF3·Et2O)
1m
12a
89 : 11
67 : 33
pTolSO2NH
O
LDA, THF, BF3·Et2O
1m
+
2d
Ph
OMe
NH2
13
syn : anti
30 : 70
Scheme 4. Condensation of sulfonimine 1m with iminoesters.
definitive structural proof and a complementary route to 5a
and 12a.
Synthesis of 1,2-diamines: The N-sulfinylimidazolidines pro-
duced by our methodology are nicely functionalized for
subsequent manipulations. Indeed, both nitrogen atoms are
already differentiated and both aryl rings can be readily
varied. Furthermore, the ester group should be an additional
™handle∫ for synthetic applications. Our studies on the
reactivity of these imidazolidines will be discussed next.
Initially, acidic hydrolysis of N-sulfinylimidazolidine 3a with
TFA in methanol[22] led to desulfinylation and fragmentation
of the molecule to phenylalanine methyl ester. This observa-
tion prompted us to explore the reduction of the ester to the
primary alcohol with the expectation that this adjustment of
functionality would avoid the undesired fragmentation.
After a number of failed experiments with different
reducing agents,[23] we found that the treatment of cycloadduct
3a with a large excess of LiAlH4 (9 equiv, 18 h) in Et2O
resulted in concurrent deoxygenation at sulfur and ester
reduction to afford sulfenamide 14a (65%, n ˆ 0, Scheme 5).
Shorter reaction times provided a substantial amount of
starting material (3a), and forcing reaction conditions allowed
the isolation of variable amounts of N-sulfinyldiaminoalcohol
17a derived from the simultaneous reduction of the ester and
reductive opening of the aminal. A more erratic behavior was
observed for N-sulfinylimidazolidine 3e and N-sulfonylimi-
The structural assignment of N-sulfonylimidazolidines 5a
and 12a was mainly based on their spectral data. Further-
more, chemical correlations with the corresponding N-sulfi-
nylimidazolidines 3a and 9a by oxidation at sulfur (mCPBA)
provided 5a and 12a as enantiopure materials; this provided a
Table 2. Lewis acid mediated cyclizations of alanine and phenylalanine iminoesters and p-tolylsulfinimines.
O
(
)
O n
Ph
N
Ph
N
S
S
pTol
pTol
N
1) LDA
N
H
H
2) Lewis acid
3) 0.1 M CHCl3, RT
+
R1
+
+
4
+
2
3
R1
1
R2
CO2Me
MeO2C
R2
9: n = 1
11
10: n = 0
Entry
1 (R1)
2 (R2)
Lewis acid
syn 3 ‡ 4 [%][a]
anti 9 [%][a,b]
anti 10 [%][a]
10a (62)
anti 11 [%][a]
Yield [%][c]
1
2
3
4
5
1a (Ph)
1a (Ph)
1a (Ph)
1 f (p-ClC6H4)
1k (iPr)
2a (CH2Ph)
2a (CH2Ph)
2a (CH2Ph)
2b (Me)
BF3 ¥ OEt2
Cp2TiCl2
TiCl4
BF3 ¥ OEt2
BF3 ¥ OEt2
3a ‡ 4a (24)
9a (64)
9a (60)
9a (30)
9b (63)
9c (84)
11a (12)
11a (10)
11a (4)
87
88
54
80
80
4a (30)
4a (4)
3g (22)
3h (16)
11b (15)
2b (Me)
[a] Stereochemistry referred to the relative positions of R1 and CO2CH3 groups at the imidazolidine ring. Ratio of isomers measured by integration of the
1H NMR spectra of the crude; except for entries 1 3, the structural assignments are tentative. [b] Minor amounts (5 20%) of the epimer at the aminal (C2)
are included; for 9c this epimer at C2 can reach 40% of the total product. [c] Combined yield.
2870
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www.chemeurj.org
Chem. Eur. J. 2003, 9, 2867 2876

Diastereoselective [3‡2] Cycloadditions
2867 2876
selectively gave hydroxymethylimidazolidine 15b[24] (entries 3
and 4). A definitive structural proof for this family of
imidazolidines was provided by an X-ray analysis of para-
nitrobenzoate 15a', which was derived from 15a by selective
esterification.
(
)
n
O
(
)
n
(
)
O
O n
Ph
NH
Ph
NH
S
S
pTol
S
pTol
pTol
NH
N
N
LiAlH4, Et2O
NH
+
Ph
R1
R1
R1
MeO2C
Ph
Ph
Ph
OH
OH
14a: n = 0, R1 = Ph
17a
3a: n = 1, R1 = Ph
3e: n = 1, R1 = 3-pyr
Given our previous results, we anticipated a more straight-
forward behavior in the reduction of N-sulfinylimidazolidines
7, derived from iminoglycine 2d, due to the ester moiety being
less hindered in these compounds. Indeed, imidazolidine 7a
reacted smoothly to produce N-benzyl-N-sulfinyldiaminoal-
cohol 17 f. In some experiments, particularly with short
reaction times, small amounts of 15c were obtained. Similarly,
other related N-sulfinylimidazolidines gave N-sulfinyldiami-
noalcohols 17g k in good yields. The scope of this procedure
is broad with regard to the nature of R1 (aromatic for 7a, 7e,
and 7 f or aliphatic for 7h j). This process may be understood
in terms of initial reduction of the ester functionality followed
by aminal cleavage via an N-metalated intermediate and
subsequent reduction of the transient imino group thus
generated. To further probe this hypothesis we surveyed a
number of reducing agents in pursuit of the selective
reduction of the ester while preserving the heterocyclic
moiety. Thus, the use of NaBH4/LiIgave good yields of
imidazolidines 15c e.[25] Subsequent treatment of 15c with
LiAlH4 in Et2O afforded diaminoalcohol 17 f. As mentioned
14b: n = 0, R1 = 3-pyr 17b
14c: n = 1, R1 = 3-pyr
14d: n = 2, R1 = Ph
17c
5a: n = 2, R1 = Ph
Scheme 5. Reductive transformations of 4-benzyl-N-sulfinyl- and 4-ben-
zyl-N-sulfonylimidazolidines.
dazolidine 5a which yielded mixtures of unreacted starting
materials, hydroxymethylimidazolidines 14b d, and N-tosyl-
or N-sulfinyl-N-benzyldiaminoalcohols 17b, c. We found
these reductions to be very sluggish presumably due to the
carboxylate being very hindered.
In contrast, substrate 9a, in which the relative arrangement
of R1 and the ester is trans, displayed a more reproducible
behavior and gave a good yield of hydroxymethylimidazoli-
dine 15a (Table 3). Subsequently, we found that 9c (R1 ˆ iPr,
R2 ˆ Me) reacts with LiAlH4 in Et2O to give a 63% yield of
17e; although shorter reaction times may produce the
hydroxymethylimidazolidine, we cannot rule out that the
bulky aliphatic isopropyl group accelerates the reductive
cleavage. Finally, N-tosylimidazolidine 12a provided a good
yield of 17d (63%, 08C to RT, 2 h); however, after a short
time and at low temperature (À208C to 08C, 10 min), 12a
before, the structural assignments of imidazolidines 7a
k
produced under Lewis acid catalysis were established by an
X-ray analysis of sulfinamide 17 f.[26]
Finally, once the ester group was removed, N-sulfenyl and
N-sulfinyl hydroxymethylimidazolidines (14a, 15a) under-
went smooth aminal methanolysis along with sulfur nitrogen
bond cleavage under acidic conditions to produce diastereo-
meric diamines 18a and 18b, respectively. In contrast, N-
sulfonylimidazolidines 15b and 15 f (obtained by selective
esterification of 15b) underwent aminal cleavage with the p-
toluenesulfonamide group remaining unaltered (Scheme 6). It
Table 3. Reductive transformations of N-sulfinyl- and N-sulfonylimidazoli-
dines.
(
)
O n
Ph
NH
S
pTol
N
reducing agent
A or B
R1
CO2Me
R2
7,9,12
(
)
n
O
(
)
O n
Ph
H
S
pTolSO2NH
Ph
pTol
Ph
S
N
pTol
NH
S
pTol
N
NHBn
OH
NH2
N
Ph
+
NH
+
R1
N
H
NH2
Ph
O
TFA, MeOH
95%
R1
Bn
R2
Ph
Ph
OH
R2
15
OH
17
16
OH
Ph
14a
18a
Entry Substrate
Method[a] 15 [%][b] 17 [%][b]
(
)
n
O
Ph
N
S
9a (n ˆ 1, R1 ˆ Ph, R2 ˆ Bn)
9c (n ˆ 1, R1 ˆ iPr, R2 ˆ Me)
12a (n ˆ 2, R1 ˆ Ph, R2 ˆ Bn)
12a (n ˆ 2, R1 ˆ Ph, R2 ˆ Bn)
7a (n ˆ 1 R1 ˆ Ph, R2 ˆ H)
7a
A
15a (75)
NHP2
R2
pTol
1
2
3
4
N
NHP3
OP1
A[c]
A[d]
A
17e (63)
H
TFA, MeOH
75-95%
R1
Ph
15b (82) 17d (17)
17d (63)
OP1
Ph
5
A
17f (83)
18b: P1 = P2 = P3 = H
1 = Ph, R2 = Bn
18c: P1 = P3 = H, P2= pTolSO2
R1 = Ph, R2 = H
15a: P1 = H, n = 1
15b: P1 = H, n = 2
15f: P1 = p-NO2Bz,
n = 2
6[e]
7[e]
8[e]
9
B
15c (78)
R
7e (n ˆ 1, R1 ˆ p-FC6H4, R2 ˆ H)
7e
A
17g (72)
p-NO2BzCl,
Et3N, 68%
B
A
15d (71)
17h (71)
7f (n ˆ 1, R1 ˆ 3-pyr, R2 ˆ H)
7h (n ˆ 1, R1 ˆ (CH2)2Ph, R2 ˆ H)
7h
18d: P1 = p-NO2Bz
O
10
A
17i (68)
P
2 = pTolSO2, P3 = H
1 = Ph, R2 = H
18e: P1 = P2 = H, P3 = Bn
1 = iPr, R2 = Me
18f: P1 = P2 = H, P3 = Bn
1 = Ph, R2 = H
S
11
12
13
B
15e (79)
pTol
NH
R
7i (n ˆ 1, R1 ˆ Et, R2 ˆ H)
A
17j (79)
NHBn
OH
TFA, MeOH
75-80%
R1
7j (n ˆ 1, R1 ˆ iPr, R2 ˆ H)
A
17k (75)
R
R2
[a] Method A: LiAlH4, Et2O, 0 8C to RT, 2 7 h; method B: NaBH4, LiI, THF,
RT. [b] Yield of pure isolated compounds. [c] 15 h. [d] THF, À20 to 08C,
10 min; reversible isomerization of 15b to oxazolidine 16 was observed.[24] [e] In
these cases combined yields are given, since reductions were performed with
mixtures 7/8.
17e: R1 = iPr, R2 = Me
17f: R1 = Ph, R2 = H
R
Scheme 6. Synthesis of highly substituted vicinal diaminoalcohols under
acidic conditions.
Chem. Eur. J. 2003, 9, 2867 2876
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2871

¬
A. Viso, R. Fernandez de la Pradilla et al.
FULL PAPER
General procedure for the 1,3-dipolar cycloaddition of sulfinimines with
azomethine ylides: A 100-mL round-bottomed flask fitted with a stirrer bar
and a rubber septum was charged with anhydrous THF (5 mLmmolÀ1) and
iPr2NH (2.1 equiv) under an atmosphere of argon. The mixture was cooled
to 08C and nBuLi (2.1 equiv) was added dropwise. The reaction mixture
was stirred at 08C for 10 min and then cooled to À788C and stirred for an
additional 10 min. A solution of the N-(benzylidene)aminoester (2.0 equiv)
in THF (5 mLmmolÀ1), previously dried over 4 ä sieves, was added
dropwise. The reaction mixture was stirred at À788C for 25 min and then a
solution of the corresponding sulfinimine (1 equiv) in THF (5 mLmmolÀ1),
previously dried over 4 ä sieves, was added dropwise. The reaction vessel
was sealed under argon and placed in a refrigerator (ca. 48C). After 20 h,
should be pointed out that, to the best of our knowledge, the
substitution pattern of diamines 18a d is unprecedented in
the literature. Additionally, treatment of N-sulfinyldiaminoal-
cohols 17e and 17 f with TFA/MeOH resulted in smooth
desulfinylation to give 18e and 18 f in good yields.
Conclusions
In summary, we have developed two new highly diastereose-
lective methods for the synthesis of enantiopure N-sulfinyli-
midazolidines from p-tolylsulfinimines. The first method
relies on a diastereoselective 1,3-dipolar cycloaddition of
azomethine ylides generated from a-iminoesters and enan-
tiopure sulfinimines, and the latter involves a highly stereo-
controlled stepwise condensation of iminoester-derived eno-
lates and sulfinimines in the presence of BF3 ¥ OEt2. I n
addition, we have explored the reactivity of related N-
sulfonylimines under both conditions. Subsequently, we have
successfully undertaken the study of the transformation of the
resulting N-sulfonyl- and N-sulfinylimidazolidines into a
variety of differentially protected vicinal diamines by using
reductive and/or hydrolytic protocols. Within this context, the
concurrent reduction of the ester and cleavage of the aminal
to produce N-sulfinyl-N'-benzyldiaminoalcohols is particular-
ly noteworthy.
the reaction was quenched with
a saturated solution of NH4Cl
(4 mLmmolÀ1), diluted with EtOAc (8 mLmmolÀ1), and the layers were
separated. The aqueous layer was extracted with EtOAc, and the combined
organic extracts were washed with
a saturated solution of NaCl
(4 mLmmolÀ1), dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure to give a crude product, which was purified by
column chromatography on silica gel using the appropriate mixture of
solvents.
(À)-Methyl [(2S,4R,5R,SS)-4-benzyl-5-p-nitrophenyl-2-phenyl-1-(p-tolyl-
sulfinyl)-1,3-imidazolidin-4-yl]carboxylate (3c) and methyl [(2R,4S,5S,SS)-
4-benzyl-5-p-nitrophenyl-2-phenyl-1-(p-tolylsulfinyl)-1,3-imidazolidin-4-
yl]carboxylate (4c): Prepared from a solution of LDA [iPr2NH (27 mL,
21 mg, 0.21 mmol) and nBuLi (1.27m, 0.16 mL, 0.21 mmol)] with a solution
of methyl 2-benzyl-2-(benzylideneamino)acetate (2a, 53 mg, 0.20 mmol)
and a solution of (S)-(‡)-N-p-nitrobenzylidene-p-toluenesulfinamide (1b,
30 mg, 0.10 mmol) according to the general procedure (formation of
cycloadduct was observed at À788C) (20 h) to give a 97:3 mixture of
cycloadducts 3c and 4c (80%) and traces of sulfinimine 1b after
purification by chromatography (5 30% EtOAc/hexane). From this
mixture of 3c and 4c, pure 3c (36 mg, 65%) was obtained by recrystalliza-
tion (30% Et2O/hexane) as a pale yellow solid. Rf ˆ 0.14 (20% EtOAc/
1
hexane); m.p. 155 1598C; [a]D20 ˆ À145.6 (c ˆ 1.03); H NMR (300 MHz,
CDCl3): d ˆ 7.80 (dm, J ˆ 9.0 Hz, 2H; Ar-H), 7.77 (dm, J ˆ 8.9 Hz, 2H; Ar-
H), 7.57 7.47 (m, 3H; Ar-H), 7.25 7.16 (m, 5H; Ar-H), 7.19 (d, J ˆ 8.2 Hz,
2H; Ar-H), 7.04 (d, J ˆ 8.1 Hz, 2H; Ar-H), 6.85 (d, J ˆ 8.1 Hz, 2H; Ar-H),
5.93 (d, J ˆ 10.6 Hz, 1H; H-2), 4.88 (s, 1H; H-5), 3.44 (d, J ˆ 14.2 Hz, 1H;
CH2Ph), 3.37 (d, J ˆ 14.2 Hz, 1H; CH2Ph), 3.35 (d, J ˆ 10.7 Hz, 1H; NH-3),
3.03 (s, 3H; CO2Me), 2.16 ppm (s, 3H; Me-Tol); 13C NMR (50 MHz,
CDCl3): d ˆ 170.2, 147.9, 146.5, 141.8, 138.7, 137.7, 135.7, 130.1 (2C), 129.5,
129.2 (2C), 128.7 (2C), 128.6 (2C), 128.2 (2C), 127.0, 125.2 (2C), 122.3
(2C), 77.2, 75.8, 64.5, 51.8, 41.0, 21.1 ppm; IR (CHCl3): nÄ ˆ 3450, 3030, 2930,
Experimental Section
General: Reagents and solvents were handled by using standard syringe
techniques. Hexane, toluene, and CH2Cl2 were distilled from CaH2, and
Et2O and THF from sodium. Et3N and iPr2NH were distilled from CaH2.
BF3 ¥ OEt2 was distilled from CaH2 just prior to use; it was collected over
granular CaH2 and argon was bubbled through for 5 min. Crude products
were purified by flash chromatography on Merck 230 400 mesh silica gel
(previously treated with Et3N, 25 mLgÀ1 silica gel) with distilled solvents
(when a mixture of solvents is used, the percentage refers to the first
component given). Analytical TLC was carried out on Merck (Kieselgel
60F-254) silica gel-coated plates with detection by UV light and develop-
ment with iodine, acidic vanillin solution, 10% phosphomolybdic acid
solution in ethanol, or 15% KMnO4 in water containing 5% NaOH and
10% K2CO3. All reagents were commercial products purchased from
Aldrich, Acros, Fluka, or Merck. Organolithium reagents were titrated
prior to use.[27] Most starting materials were obtained by known proce-
dures: 1a n,[28] 1m,[29] and 2[30]. Throughout this section, the volume of
solvents is reported in mLmmolÀ1 of starting material. Infrared spectra
(IR) were obtained on a Perkin Elmer 681 and on a Perkin Elmer
Spectrum One. 1H and 13C NMR spectra were recorded on a Bruker AM-
200 (200 MHz), Varian Gemini-200 (200 MHz), Varian INOVA-300
(300 MHz), and Varian INOVA-400 (400 MHz) with CDCl3 as solvent
and with the residual solvent signal as internal reference (CDCl3, 7.24 and
77.0 ppm). The following abbreviations are used to describe peak patterns
when appropriate: s (singlet), d (doublet), t (triplet), q (quartet), quint
(quintuplet), m (multiplet), br (broad), ap (apparent). Melting points were
determined on a Reichert Kofler microscope and are uncorrected. Optical
rotations were measured in CHCl3 solution on a Perkin Elmer 241
polarimeter at 208C using a sodium lamp. Low-resolution mass spectra
were recorded by direct injection onto a Hewlett Packard 5973 MSD
instrument using the electronic impact technique with an ionization energy
of 70 eV (EI) or on a Hewlett Packard 1100 MSD instrument using the
atmospheric pressure chemical ionization (APCI) or electrospray (ES)
chemical ionization techniques in positive or negative modes. Elemental
analyses were carried out on a Perkin Elmer 240 C and on a Heraus CHN-
1740, 1600, 1520, 1450, 1350, 1260, 1210, 1090, 1070, 860, 810, 750, 700 cmÀ1
;
MS (EI): m/z (%): 356 (5), 324 (9), 292 (26), 246 (12), 208 (20), 176 (93), 139
(84), 117 (49), 91 (100), 90 (63), 65 (45); elemental analysis calcd (%)
C31H29N3O5S (555.65): C 67.01, H 5.26, N 7.56, S 5.77; found: C 66.99, H 5.24,
N 7.55, S 5.48.
Compound 4c (partial data): 1H NMR (300 MHz, CDCl3): d ˆ 5.80 (d, J ˆ
10.7 Hz, 1H; H-2), 5.08 (s, 1H; H-5), 3.14 (s, 3H; CO2Me), 2.20 ppm (s, 3H;
Me-Tol).
(À)-Methyl [(2S,4R,5R,SS)-4-benzyl-2-phenyl-5-(3-pyridyl)-1-(p-tolylsul-
finyl)-1,3-imidazolidin-4-yl]carboxylate (3e): Prepared from a solution of
LDA [iPr2NH (100 mL, 79 mg, 0.78 mmol) and nBuLi (1.6m, 0.45 mL,
0.72 mmol)] with a solution of methyl 2-benzyl-2-(benzylideneamino)ace-
tate (2a, 160 mg, 0.60 mmol) and a solution of (S)-(‡)-N-(2-pyridylmethy-
lidene)-p-toluenesulfinamide (1c, 73 mg, 0.30 mmol) according to the
general procedure (10 h). After purification by chromatography (5 65%
EtOAc/CH2Cl2) this gave pure cycloadduct 3e (122 mg, 80%) as a white
solid, which was recrystallized from 25% CH2Cl2/hexane. Rf ˆ 0.39 (20%
EtOAc/CH2Cl2); m.p. 158 1608C; [a]2D0 ˆ À51.1 (c ˆ 1.30); 1H NMR
(300 MHz, CDCl3): d ˆ 8.23 (dd, J ˆ 4.9, 1.7 Hz, 1H; Ar-H), 8.12 (d, J ˆ
1.8 Hz, 1H; Ar-H), 7.80 (dm, J ˆ 8.5 Hz, 2H; Ar-H), 7.57 7.47 (m, 3H; Ar-
H), 7.26 7.19 (m, 8H; Ar-H), 6.91 6.86 (m, 3H; Ar-H), 5.94 (d, J ˆ
11.1 Hz, 1H; H-2), 4.83 (s, 1H; H-5), 3.43 (AB system, 2H; CH2Ph), 3.37
(d, J ˆ 10.7 Hz, 1H; NH-3), 3.05 (s, 3H; CO2Me), 2.19 ppm (s, 3H; Me-
Tol); 13C NMR (50 MHz, CDCl3): d ˆ 170.0, 148.8, 147.6, 141.2, 138.2, 137.7,
135.7 (2C), 134.4, 129.9 (2C), 129.1, 128.8 (2C), 128.7 (2C), 127.8 (2C),
127.3 (2C), 126.6, 124.8 (2C), 121.8, 77.4, 75.5, 62.8, 51.4, 40.4, 20.8 ppm; IR
ˆ
(CHCl3): nÄ ˆ 2930, 2860, 1730 (C O), 1640, 1600, 1530, 1490, 1450, 1340,
¬
O-Rapid instruments at Instituto de QuÌmica Organica, CSIC (Madrid).
1270, 1160, 1100, 1010, 1000, 720, 700, 660 cmÀ1; elemental analysis calcd
2872
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 2867 2876

Diastereoselective [3‡2] Cycloadditions
2867 2876
(%) C30H29N3O3S (511.63): C 70.43, H 5.71, N 8.21, S 6.27; found: C 70.06, H
5.54, N 8.43, S 6.38.
CH2Cl2); [a]2D0 ˆ ‡78.5 (c ˆ 1.10); 1H NMR (300 MHz, CDCl3): d ˆ 7.64
7.57 (m, 4H; Ar-H), 7.40 7.23 (m, 5H; Ar-H), 5.95 (s, 1H; H-2), 3.95
(apquint, J ˆ 5.9 Hz, 1H; H-5), 3.77 (s, 3H; CO2Me), 3.44 (m, 1H; H-4),
2.39 (s, 3H; Me-Tol), 0.67 ppm (d, J ˆ 6.6 Hz, 3H; Me); DNOE between
H-2/Ar-H (7.64): 0.5%, H-4/Me: 1.9%, H-5/Me: 0.9%, H-5/Ar-H (7.61):
0.3%, Me/H-4: 0.5%, Me/H-5: 0.8%, Me/Ar-H (7.64): 0.1%; 13C NMR
(50 MHz, CDCl3): d ˆ 171.5, 141.5, 140.8, 140.6, 129.5 (2C), 128.4 (2C),
128.2, 127.0 (2C), 125.6 (2C), 81.4, 67.1, 53.2, 52.5, 21.9, 21.4 ppm; IR
(CHCl3): nÄ ˆ 3306, 3030, 2952, 1745, 1644, 1596, 1492, 1448, 1376, 1351,
1276, 1206, 1130, 1089, 1068, 935, 813, 758, 737, 699 cmÀ1; MS(ES): m/z (%):
General procedure for the Lewis acid catalyzed condensation between
iminoester enolates and p-tolylsulfinimines: A 100-mL round-bottomed
flask fitted with a stirrer bar and a rubber septum was charged with
anhydrous THF (5 mLmmolÀ1 of sulfinimine) and iPr2NH (2.6 equiv)
under an atmosphere of argon. The mixture was cooled to 08C and nBuLi
(2.1 equiv) was added dropwise. The reaction mixture was stirred at 08C for
10 min and then cooled to À788C and stirred for an additional 10 min. A
solution of the N-(benzylidene)aminoester (2.0 equiv) in THF
(5 mLmmolÀ1 of sulfinimine), previously dried over 4 ä sieves, was added
dropwise. The reaction mixture was stirred at À788C for 25 30 min and
‡
‡
739 [2M‡Na] (15), 359 [M‡H] (100); elemental analysis calcd (%)
C19H22N2O3S (358.45): C 63.66, H 6.19, N 7.82, S 8.95; found: C 63.47, H
6.12, N 8.01, S 8.68.
then
a solution of the corresponding sulfinimine (1 equiv) in THF
(5 mLmmolÀ1), previously dried over 4 ä sieves, was added dropwise
followed by freshly distilled BF3 ¥ OEt2 (3.25 equiv). Upon addition of the
Lewis acid, the orange reaction mixture turned pale yellow and the mixture
was allowed to warm up slowly to approximately À208C until the starting
material (15 min 3 h) disappeared. The reaction was then quenched with a
5% solution of NaHCO3 (6 mLmmolÀ1). When the mixture had reached
about 08C, the layers were separated and the organic phase was washed
with a saturated solution of NaCl (4 mLmmolÀ1). The aqueous layer was
extracted twice with CH2Cl2, and the combined organic extracts were dried
over anhydrous Na2SO4, filtered, and concentrated under reduced pressure
to give a yellow oil. This crude product mixture was dissolved in CHCl3
(0.1m) and the ensuing cyclization was monitored by 1H NMR spectro-
scopy. After 2 4 d, the mixture was purified by column chromatography on
silica gel with the appropriate mixture of solvents as eluent. In an
alternative procedure, 0.5 equiv of PhCHO and MgSO4 (1.3gmmolÀ1) was
added to the CHCl3 solution to accelerate the cyclization. In all experi-
ments, variable amounts of a related imidazolidine formed by dimerization
of the iminoester were also obtained.
Compound 8k (partial data from a 92:8 mixture): Rf ˆ 0.36 (30% Et2O/
1
CH2Cl2); H NMR (200 MHz, CDCl3): d ˆ 5.74 (s, 1H; H-2), 1.30 ppm (d,
J ˆ 6.6 Hz, 3H; Me).
General procedure for oxidation of sulfinamides to sulfonamides with
mCPBA: mCPBA (1.5 3.0 equiv, 70%) was added at 08C to a solution of
the sulfinamide in CH2Cl2 (10 mLmmolÀ1) under an argon atmosphere.
The reaction mixture was allowed to warm up slowly to room temperature
and was monitored by TLC. The reaction was quenched with 1m aqueous
Na2S2O4 (5 mLmmolÀ1), a saturated solution of NaHCO3 (3 mLmmolÀ1),
and H2O (4 mLmmolÀ1), diluted with EtOAc (8 mLmmolÀ1); the layers
were separated, and the aqueous layer was extracted with EtOAc (3 Â ,
5 mLmmolÀ1). The organic layer was washed with a saturated solution of
NaCl (4 mLmmolÀ1), dried over MgSO4, filtered, and concentrated under
reduced pressure to give a crude product that was purified by column
chromatography.
(À)-Methyl [(2S,4R,5R)-4-benzyl-2,5-diphenyl-1-(p-tolylsulfonyl)-1,3-imi-
dazolidin-4-yl]carboxylate (5a): Prepared from sulfinamide 3a (11 mg,
0.02 mmol) and mCPBA (8 mg, 0.046 mmol) according to the general
procedure (12 h) to give sulfonamide 5a (7 mg, 65%) after chromatog-
raphy (50 100% CH2Cl2/hexane) as a white solid that was recrystallized
from Et2O. Similarly, oxidation of 4a gave ent-5a (62%) with comparable
optical rotation of opposite sign {[a]2D0 ˆ ‡31.8 (c ˆ 0.49) for ent-5a}.
Compound 5a: Rf ˆ 0.37 (CH2Cl2); m.p. 115 1198C; [a]2D0 ˆ À31.2 (c ˆ
0.46); 1H NMR (300 MHz, CDCl3): d ˆ 7.60 7.56 (m, 2H; Ar-H), 7.39 7.13
(m, 15H; Ar-H), 7.06 (d, J ˆ 8.2 Hz, 2H; Ar-H), 5.77 (d, J ˆ 11.6 Hz, 1H;
H-2), 4.96 (s, 1H; H-5), 3.30 (d, J ˆ 11.8 Hz, 1H; NH-3), 3.20 (d, J ˆ
14.0 Hz, 1H; CH2Ph), 3.05 (s, 3H; CO2Me), 2.82 (d, J ˆ 13.9 Hz, 1H;
CH2Ph), 2.31 ppm (s, 3H; Me-Tol); 13C NMR (50 MHz, CDCl3): d ˆ 169.9,
143.6, 139.0, 137.7, 135.9, 130.1 (2C), 129.2 (2C), 128.9, 128.5 (2C), 128.0
(4C), 127.8 (2C), 127.7 (2C), 127.6 (2C), 126.9, 78.7, 75.4, 72.2, 51.7, 41.0,
21.5 ppm; IR (KBr): nÄ ˆ 3450, 3040, 2960, 1740, 1600, 1260, 1090, 1020, 800,
700, 660 cmÀ1; MS (EI): m/z (%): 467 (3), 283 (2), 266 (32), 260 (9), 206 (21),
176 (18), 155 (36), 117 (14), 92 (18), 91 (100), 90 (42), 77 (36); elemental
analysis calcd (%) C31H30N2O4S (562.57): C 70.70, H 5.74, N 5.32, S 6.09;
found: C 70.39, H 5.89, N 5.40, S 5.86.
(À)-Methyl [(2S,4S,5R,SS)-2-phenyl-5-(3-pyridyl)-1-(p-tolylsulfinyl)-1,3-
imidazolidin-4-yl)]carboxylate (7 f) and methyl [(2R,4R,5S,SS)-2-phenyl-
5-(3-pyridyl)-1-(p-tolylsulfinyl)-1,3-imidazolidin-4-yl)]carboxylate
Prepared from a solution of LDA [iPr2NH (0.18 mL, 131 mg, 1.30 mmol)
and nBuLi (1.42m, 0.74 mL, 1.05 mmol)] with solution of methyl
(8 f):
a
2-(benzylideneamino)acetate (2d, 177 mg, 1.00 mmol) and a solution of
(S)-(‡)-N-(3-pyridinemethylidene)-p-toluenesulfinamide (1c, 122 mg,
0.5 mmol) by adding BF3 ¥ OEt2 (231 mg, 0.20 mL, 1.625 mmol) according
to the general procedure (3 h 30 min) to give
a 90:10 mixture of
cycloadducts 7 f and 8 f (126 mg, 60%) after purification by chromatog-
raphy (80% CHCl3/hexane, then 0 100% Et2O/CHCl3 and then 5%
MeOH/Et2O). Pure 7 f (90 mg, 40%) was obtained as a white solid from
this mixture by recrystallization (Et2O). Rf ˆ 0.23 (20% EtOH/hexane);
m.p. 155 1588C; [a]2D0 ˆ À48.3 (c ˆ 0.46); 1H NMR (300 MHz, CDCl3):
d ˆ 8.19 (dd, 1H, J ˆ 4.8, 1.7 Hz; Ar-H), 7.88 (d, 1H, J ˆ 2.0 Hz; Ar-H), 7.73
(d, 2H, J ˆ 7.5 Hz; Ar-H), 7.50 7.40 (m, 3H; Ar-H), 7.28 (d, 2H, J ˆ 8.2 Hz;
Ar-H), 6.91 (d, 3H, J ˆ 8.0 Hz; Ar-H), 6.80 (dd, 2H, J ˆ 7.9, 4.8 Hz; Ar-H),
6.05 (d, 1H, J ˆ 5.6 Hz, H-2), 4.87 (d, 1H, J ˆ 6.2 Hz; H-5), 3.80 (m, 1H;
H-4), 3.76 (s, 3H; CO2Me), 3.27 (brt, 1H, J ˆ 7.7 Hz; NH-3), 2.19 ppm (s,
3H; Me-Tol); 13C NMR (300 MHz, CDCl3): d ˆ 170.8, 148.8, 147.8, 141.6,
139.8, 138.9, 136.8, 134.3, 128.8 (2C), 127.2 (2C), 125.4 (2C), 122.5, 80.6,
68.5, 57.9, 52.6, 21.1 ppm; IR (CHCl3): nÄ ˆ 3400, 3300, 1725, 1550, 1430,
General procedure for the reaction between sulfinylimidazolidines and
LiAlH4: A round-bottomed flask was charged with anhydrous Et2O or
THF (6 mLmmolÀ1 of imidazolidine) and LiAlH4 (3 9 equiv). After
10 min, the resulting suspension was cooled to 08C and a solution of the
‡
1180, 1110, 1070,1040, 740, 670 cmÀ1; MS (APCI): m/z (%): 422 [M‡H]
corresponding imidazolidine in anhydrous Et2O or THF (4 mLmmolÀ1
)
(100), 282 (77); elemental analysis calcd (%) C23H23N3O3S (421.56): C
65.54, H 5.50, N 9.97, S 7.61; found: C 65.40, H 5.66, N 9.78, S 7.94.
was added dropwise and the reaction mixture was stirred at room
temperature and monitored by TLC. When the reaction had reached
completion (2 18 h), the mixture was quenched with a saturated NaHCO3
solution (4 mLmmolÀ1), H2O (4 mLmmolÀ1), and diluted with CH2Cl2
(8 mLmmolÀ1). The resulting suspension was filtered through Celite, the
residue was thoroughly washed with CH2Cl2, and the layers were
separated. The aqueous layer was extracted with CH2Cl2 (3 times,
Compound 8 f (partial data): Rf ˆ 0.23 (20% EtOH/hexane); 1H NMR
(300 MHz, CDCl3): d ˆ 5.94 (s, 1H; H-2), 5.09 (d, 1H, J ˆ 7.4 Hz; H-5), 3.79
(s, 3H; CO2Me), 2.32 ppm (s, 3H; Me-Tol).
(‡)-Methyl [(2S,4S,5R,SS)-5-methyl-2-phenyl-1-(p-tolylsulfinyl)-1,3-imi-
dazolidin-4-yl]carboxylate (7k) and methyl [(2R,4R,5S,SS)-5-methyl-2-
phenyl-1-(p-tolylsulfinyl)-1,3-imidazolidin-4-yl]carboxylate (8k): Prepared
from a solution of LDA [iPr2NH (0.64 mL, 461 mg, 4.56 mmol) and nBuLi
(1.6m, 2.6 mL, 4.18 mmol)] with a solution of methyl 2-(benzylideneami-
no)acetate (2d, 673 mg, 3.80 mmol) and a solution of (S)-(‡)-N-ethyl-
idene-p-toluenesulfinamide (1l, 344 mg, 1.90 mmol) by adding BF3 ¥ OEt2
(863 mg, 0.77 mL, 6.08 mmol) according to the general procedure (10 min)
to give a 92:8 mixture of cycloadducts 7k and 8k (441 mg, 64%) as a
yellowish oil after purification by chromatography (5 25% Et2O/CH2Cl2).
A second careful purification by chromatography (5 20% Et2O/CH2Cl2)
afforded pure imidazolidine 7k (309 mg, 45%). Rf ˆ 0.37 (30% Et2O/
8 mLmmolÀ1). The combined organic extracts were washed with
a
saturated NaCl solution (4 mLmmolÀ1), dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure to give a crude product,
which was purified by column chromatography on silica gel.
(À)-[(2S,4S,5R,SS)-4-Benzyl-2,5-diphenyl-1-(p-tolylsulfinyl)-1,3-imidazoli-
din-4-yl]methanol (15a): Prepared from a suspension of LiAlH4 (3 equiv,
12 mg, 0.31 mmol) in Et2O and sulfinamide 9a (53 mg, 0.10 mmol) with
further additions of LiAlH4 (3 equiv) after 3 h and (3 equiv) after 12 h at
room temperature according to the general procedure (16 h) to give
hydroxymethylsulfinamide 15a (37.5 mg, 75%) as a colorless oil after
Chem. Eur. J. 2003, 9, 2867 2876
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2873

¬
A. Viso, R. Fernandez de la Pradilla et al.
FULL PAPER
chromatography (15 100% EtOAc/hexane). Rf ˆ 0.31 (50% EtOAc/
hexane); [a]2D0 ˆ À95.4 (c ˆ 1.42); 1H NMR (300 MHz, CDCl3): d ˆ 7.78
(d, J ˆ 6.9 Hz, 2H; Ar-H), 7.54 7.45 (m, 3H; Ar-H), 7.24 7.20 (m, 2H; Ar-
H), 7.13 7.10 (m, 4H; Ar-H), 7.09 6.99 (brs, 3H; Ar-H), 6.93 6.90 (m,
3H; Ar-H), 6.82 (d, J ˆ 8.1 Hz, 2H; Ar-H), 5.80 (s, 1H; H-2), 4.78 (s, 1H;
H-5), 3.75 (d, J ˆ 11.1 Hz, 1H; CH2OH), 3.60 (d, J ˆ 11.1 Hz, 1H; CH2OH),
2.44 (d, J ˆ 13.9 Hz, 1H; CH2Ph), 2.17 (s, 3H; Me-Tol), 2.06 (d, J ˆ 13.9 Hz,
1H; CH2-Ph), 1.70 1.50 ppm (br, 2H; NH, OH); 13C NMR (50 MHz,
CDCl3): d ˆ 140.9, 140.8, 139.7, 138.8, 136.8, 130.1 (2C), 128.9 (4C), 128.6
(2C), 128.3, 128.0 (2C), 127.4 (4C), 126.4 (2C), 125.4 (2C), 77.2, 68.6, 62.8,
62.1, 40.1, 21.1 ppm; IR (CCl4): nÄ ˆ 3400, 3060, 3030, 2930, 1490, 1450, 1090,
1050, 700, 605 cmÀ1; MS (EI): m/z (%): 352 (2), 311 (7), 260 (6), 223 (9), 194
(9), 168 (16), 141 (17), 139 (26), 115 (27), 91 (100), 77 (35), 65 (17), 6 (14);
elemental analysis calcd (%) C30H20N2O2S (482.64): C 74.66, H 6.27, N 5.80,
S 6.64; found: C 74.95, H 6.54, N 5.55, S 6.48.
temperature and monitored by TLC (this often required spotting from
aliquots worked up with saturated aqueous K2CO3). Upon completion (5
24 h), the solvent was removed in vacuo, the residue was diluted with
CH2Cl2 (10 mLmmolÀ1), and extracted with 15% aqueous HCl (2 Â
10 mLmmolÀ1); the combined aqueous layer was cooled to 58C, and
CH2Cl2 (10 mLmmolÀ1) was added. The resulting biphasic solution was
carefully neutralized with solid NaHCO3 (to pH 7.5 9), the organic layer
was separated, and the aqueous layer was extracted with CH2Cl2 (2 Â
5 mLmmolÀ1). The combined organic extracts were washed with water
(4 mLmmolÀ1) and brine (6 mLmmolÀ1), dried (Na2SO4), concentrated,
and purified by column chromatography on silica gel. Alternatively, upon
completion of the reaction, solid NaOH (ca. 7.5 mmolmmolÀ1) was added
and the mixture was stirred at room temperature (ca. 10 h), the solvent was
removed under reduced pressure, and the residue was taken up in CH2Cl2
and then 10 20% EtOH/CH2Cl2 and filtered through a short plug of silica
gel.
(À)-(2S,3R,SS)-2-(Benzylamino)-5-phenyl-3-(p-tolylsulfinylamino)pentan-
1-ol (17i): Prepared from a suspension of LiAlH4 (149 mg, 3.66 mmol) in
Et2O and 7h (1327 mg, 3.16 mmol) according to the general procedure (4 h
30 min). Purification by chromatography (0 5% MeOH/CH2Cl2) afforded
diaminoalcohol 17i (274 mg, 0.62 mmol, 68%) as a colorless oil. Rf ˆ 0.30
(5% MeOH/CH2Cl2); [a]2D0 ˆ À117.5 (c ˆ 1.60); 1H NMR (300 MHz,
CDCl3): d ˆ 7.54 (d, J ˆ 8.2 Hz, 2H; Ar-H), 7.34 7.22 (m, 7H; Ar-H),
7.21 7.08 (m, 3H; Ar-H), 6.78 (d, J ˆ 8.2 Hz, 2H; Ar-H), 5.03 (d, J ˆ
8.3 Hz, 1H; S-NH), 3.85 (d, J ˆ 13.1 Hz, 1H; N-CH2Ph), 3.70 (d, J ˆ
13.1 Hz, 1H; N-CH2Ph), 3.64 (dd, J ˆ 11.6, 4.4 Hz, 1H; H-1), 3.56 (dd,
J ˆ 11.6, 7.3 Hz, 1H; H-1), 3.30 (m, 1H; H-3), 2.72 (ddd, J ˆ 7.1, 4.4, 2.6 Hz,
1H; H-2), 2.41 (s, 3H; Me-Tol), 2.18 2.01 (m, 2H; CH2-5), 1.72 1.59 (m,
1H; H-4), 1.44 1.34 ppm (m, 1H; H-4); 13C NMR (50 MHz, CDCl3): d ˆ
141.5, 141.3, 140.2, 140.1, 129.5 (2C), 128.5 (2C), 128.3 (2C), 128.2 (2C),
128.0 (2C), 127.3, 125.9 (2C), 125.7, 61.6, 58.9, 52.9, 51.3, 35.8, 32.0,
21.3 ppm; IR (film): nÄ ˆ 3317, 3060, 3026, 2925, 1601, 1494, 1453, 1086, 1046,
(‡)-(2R,3R)-2-Benzyl-2,3-diamino-3-phenyl-propan-1-ol (18a): Prepared
from sulfenamide 14a (10 mg, 0.021 mmol), with TFA (5 equiv, 8 mL,
11.8 mg, 0.103 mmol) in MeOH according to the general procedure (5 h).
Chromatography (0 65% MeOH/Et2O) gave diamine 18a (5.2 mg, 95%)
as a colorless oil. Rf ˆ 0.18 (30% MeOH/Et2O); [a]2D0 ˆ ‡11.0 (c ˆ 0.55);
1H NMR (300 MHz, CDCl3): d ˆ 7.42 7.10 (m, 10H; Ar-H), 4.12 (s, 1H;
H-3), 3.60 (d, J ˆ 11.5 Hz, 1H; CH2OH), 3.25 (d, J ˆ 11.2 Hz, 1H; CH2OH),
2.68 (d, J ˆ 13.4 Hz, 1H; CH2Ph), 2.56 (d, J ˆ 13.4 Hz, 1H; CH2Ph), 2.40
2.10 ppm (brs, 5H; 2NH2, OH); 13C NMR (50 MHz, CDCl3): d ˆ 141.2,
136.3, 130.7 (2C), 128.5 (2C), 128.3 (2C), 128.1 (2C), 128.0, 126.7, 67.6, 65.0,
57.0, 40.6 ppm; IR (CCl4): nÄ ˆ 3350, 3060, 3030, 2930, 1725, 1600, 1590,
1500 cmÀ1; MS (ES): m/z (%): 225 (2), 208 (3), 195 (5), 177 (3), 165 (14), 150
(100), 133 (22), 106 (34), 91 (87), 77 (23), 69 (23), 57 (37); elemental analysis
calcd (%) C16H20N2O (256.34): C 74.97, H 7.86, N 10.93; found: C 74.73, H
7.65, N 10.82.
‡
812, 747, 699 cmÀ1; MS (ES): m/z (%): 423 [M‡H] (100); elemental
(À)-(2S,3R)-3-Amino-2-benzylamino-3-phenylpropan-1-ol (18 f): Pre-
pared from sulfinyldiaminoalcohol 17 f (17 mg, 0.04 mmol) with TFA
(5 equiv, 16 mL, 23 mg, 0.20 mmol) in MeOH according to the general
procedure (24 h). Chromatography (CH2Cl2 to 50% EtOH/CH2Cl2) gave
diaminoalcohol 18 f (7.0 mg, 75%) as a white solid that was recrystallized
from Et2O. Similarly, from a 50:50 mixture of 17 f and 17 f' racemic 18 f was
obtained. Compound 18 f: Rf ˆ 0.20 (25% EtOH/CH2Cl2); m.p. 176
1778C; [a]2D0 ˆ À46.3 (c ˆ 0.80); 1H NMR (300 MHz, CDCl3): d ˆ 7.35
7.23 (m, 10H; Ar-H), 4.06 (d, J ˆ 6.7 Hz, 1H; H-3), 3.87 (d, J ˆ 13.2 Hz,
1H; CH2Ph), 3.70 (d, J ˆ 13.2 Hz, 1H; CH2Ph), 3.65 (dd, J ˆ 11.5, 4.0 Hz,
1H; CH2OH), 3.45 (dd, J ˆ 11.4, 3.2 Hz, 1H; CH2OH), 2.81 ppm (m, 5H;
H-2, NH2, NH, OH); 1H NMR (300 MHz, 408C, CDCl3): d ˆ 7.35 7.23 (m,
10H; Ar-H), 4.06 (d, J ˆ 6.6 Hz, 1H; H-3), 3.87 (d, J ˆ 13.2 Hz, 1H;
CH2Ph), 3.71 (d, J ˆ 13.2 Hz, 1H; CH2Ph), 3.65 (dd, J ˆ 11.4, 4.1 Hz, 1H;
CH2OH), 3.45 (dd, J ˆ 11.4, 3.4 Hz, 1H; CH2OH), 2.81 (ddd, J ˆ 6.7, 3.5 Hz,
1H; H-2), 2.75 ppm (brs, 4H; NH2, NH, OH); 13C NMR (50 MHz, CDCl3):
d ˆ 143.2, 138.9, 128.7 (2C), 128.5 (2C), 128.3 (2C), 127.6, 127.4, 126.6 (2C),
62.7, 61.1, 57.3, 51.7 ppm; IR (KBr): nÄ ˆ 3320, 2930, 2860, 1735, 1650, 1540,
1455, 1375, 1360, 1335, 1290, 1125, 1065, 1040, 1010, 740, 695 cmÀ1; MS
analysis calcd (%) C25H30N2O2S (422.585): C 71.06, H 7.16, N 6.63, S 7.59;
found: C 70.89, H 7.34, N 6.46, S 7.33.
General procedure for the reaction between sulfinylimidazolidines and
NaBH4/LiI: A round-bottomed flask was charged with anhydrous THF
(2 mLmmolÀ1 of imidazolidine) and LiI(2 3 equiv) was added, followed
by NaBH4 (2 3 equiv). The resulting suspension was cooled to 08C and a
solution of the corresponding imidazolidine in anhydrous THF
(6 mLmmolÀ1) was added dropwise, and the reaction mixture was stirred
at 08C (30 min) and then at room temperature and monitored by TLC.
When the reaction had reached completion (2 3 h), the mixture was
quenched with a 5% NaHCO3 solution (2 mLmmolÀ1) and diluted with
CH2Cl2 (8 mLmmolÀ1) and the layers were separated. The aqueous layer
was extracted with CH2Cl2 (3 times, 8 mLmmolÀ1). The combined organic
extracts were washed with a saturated NaCl solution (4 mLmmolÀ1), dried
over anhydrous Na2SO4, filtered, and concentrated under reduced pressure
to give a crude product, which was purified by column chromatography on
silica gel.
(Æ)-[(2S,4S,5R,SS)-2-Phenyl-5-(2-phenylethyl)-1-(p-tolylsulfinyl)-1,3-imi-
dazolidin-4-yl]methanol (15e): Prepared from LiI(120 mg, 0.90 mmol) in
THF, with NaBH4 (35 mg, 0.90 mmol) and 7h (135 mg, 0.30 mmol)
according to the general procedure (3 h). Alcohol 15e (100 mg, 79%)
was obtained after chromatography (Et2O/EtOH 40:1) as a white solid that
was recrystallized from Et2O/CH2Cl2. Rf ˆ 0.24 (40:1 CH2Cl2/EtOH); m.p.
136 1398C; 1H NMR (300 MHz, CDCl3): d ˆ 7.57 7.54 (m, 2H; Ar-H),
7.50 (d, J ˆ 8.3 Hz, 2H; Ar-H), 7.43 7.34 (m, 3H; Ar-H), 7.27 (d, J ˆ 8.3 Hz,
2H; Ar-H), 7.16 7.12 (m, 2H; Ar-H), 6.71 (dd, J ˆ 7.8, 1.7 Hz, 2H; Ar-H),
5.75 (s, 1H; H-2), 3.79 3.64 (m, 3H; H-4, CH2OH), 3.25 (td, J ˆ 7.1, 2.3 Hz,
1H; H-5), 2.78 (brs, 1H; NH-3), 2.42 (s, 3H; Me-Tol), 2.27 2.06 (m, 2H;
CH2-2'), 1.38 (m, 1H; H-1'), 1.00 ppm (m, 1H; H-1'); 13C NMR (50 MHz,
CDCl3): d ˆ 141.5, 140.8, 140.3, 140.1, 129.5 (2C), 128.7 (2C), 128.6, 128.2
(2C), 128.0 (2C), 127.0 (2C), 125.8, 125.1, 80.4, 64.8, 62.4, 54.8, 37.8, 32.7,
21.4 ppm; IR (KBr): nÄ ˆ 3435, 2933, 1656, 1500, 1454, 1058, 960, 811, 753,
‡
(APCI): m/z (%): 257 [M‡H] (100); elemental analysis calcd (%)
C16H20N2O (256.34): C 74.97, H 7.86, N 10.93; found: C 75.13, H 7.35, N
10.72.
Acknowledgements
This research was supported by DGIMCYT (Grants PPQ2000 1330 and
BQU2001 0582) and CAM (08.5/0079/2000). We thank MEC and CAM
for doctoral fellowships to M.T. and A.F.
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697 cmÀ1; MS (ES): m/z (%): 863 [2M‡Na] (33), 443 [M‡Na] (41), 421
‡
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71.38, H 6.72, N 6.66, S 7.62; found: C 71.19, H 7.02, N 6.75, S 7.54.
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CH2Cl2 was employed) and the reaction mixture was stirred at room
2874
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 2867 2876

Diastereoselective [3‡2] Cycloadditions
2867 2876
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and forming lithium butoxide. However no change was observed in
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[13] CCDC 188087, -188088, REBHAH, CEZSUV contains the supple-
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Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
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Chem. Eur. J. 2003, 9, 2867 2876
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2875

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A. Viso, R. Fernandez de la Pradilla et al.
FULL PAPER
[18] iPr2NHBF3 was detected in the CDCl3 solution of the reaction crude
by 1H NMR spectroscopy. This species is likely to be formed in the
reaction mixture from iPr2NH and BF3 upon raising the temperature
from À788C to À208C and persisted after aqueous workup.
[26] The structure of the minor cycloadduct 8a was confirmed by chemical
means. Thus, the treatment of an equimolecular mixture of 7a and 8a
with LiAlH4 in Et2O gave a 50:50 mixture of 17 f and a diastereomer
(structure not shown, 17 f'). Desulfinylation of this mixture afforded
exclusively racemic diaminoalcohol 18 f. In some cases, to avoid
tedious separations, mixtures of 7a/8a and 7b/8b were reduced
(NaBH4/LiIor LiAlH 4) to produce diastereomeric mixtures of 17g/
17g', 15c/c', 15d/d' that were separated easily and this allowed partial
characterization of the minor compounds. See experimental proce-
dures for details.
[19] Variable amounts of N-sulfinyldiaminoesters derived from 6 were
frequently isolated (5 20%). Their quantitative conversion to the
corresponding imidazolidines 7 and 8 upon treatment with PhCHO
and MgSO4 provided a definitive structural proof for these side
products along with an increase of the global yield of 7 and 8.
[20] Decomposition of the starting materials upon prolonged reaction
times has been tentatively proposed. For cinnamaldehyde-derived
[27] Titration of nBuLi: S. C. Watson, J. E. Easthman, J. Organomet.
Chem. 1967, 9, 165 168.
ˆ
ˆ
sulfinimine we cannot rule out a competition between C N and C C
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a
slow isomerization (3 6 h) to just one diastereomer of the
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P. G. Hultin, Synlett 1997, 171 172.
Received: December 18, 2002 [F4674]
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 2867 2876