Enantiomerically pure α-alkylidene β-amino esters from asymmetric addition of metal dienolates to N-sulfinylimines

Article abstract of DOI:10.1021/jo972303q

Lithium dienolate of 3-butenoic methyl ester was reacted with enantiomerically pure N-arylsulfinyl phenylimines (1 and 2) under different conditions. The reactions were completely regioselective -the C-C coupling occurs at the 2-position of dienolate - and highly stereoselective at the iminic carbon. In the presence of different Lewis acids (ZnCl₂, ZnBr₂, and ScTf₃) mixtures of two α-vinyl, β-arylsulfmylamino esters (epimers at C-α) were obtained, being the stereoselectivity depending on the nature of the aryl sulfinyl moiety and the Lewis acid used. Desulfinylation of these mixtures followed by isomerization of the double bond with Na₂CO₃ allowed the synthesis of the optically pure CE)-α-ethylidene-β-amino ester 10 in quite high overall yield. The addition of the lithium dienolate to sulfinylimines in the absence of the Lewis catalysts yielded mixtures containing important amounts of the optically pure N-arylsulfinyl α-ethylidene-β-amino esters, which became the exclusive product of the reaction when N-2-methoxynaphthylsulfinyl phenylimine 2 was used as starting product.

Full text of DOI:10.1021/jo972303q

J . Org. Chem. 1998, 63, 7157-7161
7157
En a n tiom er ica lly P u r e r-Alk ylid en e â-Am in o Ester s fr om
Asym m etr ic Ad d ition of Meta l Dien ola tes to N-Su lfin ylim in es
J . L. Garc´ıa Ruano,*,† I. Ferna´ndez,*,‡ M. del Prado Catalina,† J . A. Hermoso,§
J . Sanz-Aparicio,§ and M. Mart´ınez-Ripoll§
Departamento de Quı´mica Orga´nica, Universidad Auto´noma, Cantoblanco, 28049 Madrid, Spain,
Departamento de Quı´mica Orga´nica y Farmace´utica, Facultad de Farmacia, Universidad de Sevilla,
41017 Sevilla, Spain, and Departamento de Cristalografı´a, Instituto de Qu´ımica-Fı´sica Rocasolano,
CSIC, 28006 Madrid, Spain
Received December 22, 1997
Lithium dienolate of 3-butenoic methyl ester was reacted with enantiomerically pure N-arylsulfinyl
phenylimines (1 and 2) under different conditions. The reactions were completely regioselectives
the C-C coupling occurs at the 2-position of dienolatesand highly stereoselective at the iminic
carbon. In the presence of different Lewis acids (ZnCl2, ZnBr2, and ScTf3) mixtures of two R-vinyl,
â-arylsulfinylamino esters (epimers at C-R) were obtained, being the stereoselectivity depending
on the nature of the aryl sulfinyl moiety and the Lewis acid used. Desulfinylation of these mixtures
followed by isomerization of the double bond with Na2CO3 allowed the synthesis of the optically
pure (E)-R-ethylidene-â-amino ester 10 in quite high overall yield. The addition of the lithium
dienolate to sulfinylimines in the absence of the Lewis catalysts yielded mixtures containing
important amounts of the optically pure N-arylsulfinyl R-ethylidene-â-amino esters, which became
the exclusive product of the reaction when N-2-methoxynaphthylsulfinyl phenylimine 2 was used
as starting product.
In tr od u ction
are susceptible to transformation to compounds lacking
the C-R chiral center.6
Enantiopure sulfinimines (thiooxime S-oxides) are
interesting building blocks in asymmetric synthesis, as
they lead to important molecules bearing a chiral amino
group. Although there are several groups actively work-
ing in this field,1-3 the most significant contributions in
both, preparation and synthetic applications of these
substrates have been reported by Davis and co-workers.3
One of the most interesting reactions of these substrates
is that which takes place with ester enolates, affording
compounds easily transformed into â-amino acids.4 Nev-
ertheless, to our knowledge, only alkyl acetates have been
used as a source of enolates. This lack of diversity is due
to the fact that esters other than acetates lead to
R-substituted â-amino acids having two chiral centers
(C-R and C-â), with the subsequent loss of diastereo-
selectivity.5 A solution to this problem is the use of
dienolates as nucleophiles, because the resulting products
The addition of dienolates to electrophiles is a useful
and attractive process for C-C bond formation. As the
dienolate possesses two nucleophilic sites, the coupling
can occur either at the 2- or at the 4-position, depending
on the metal counterion, the solvent, the temperature,
and the structure of the starting material. A survey of
the literature has shown that while the addition of
dienolates to carbonyl compounds is a well-documented
process,7 examples of addition to imines are scarce.8,9 The
later condensation yields â- or δ-amino esters with at
least one chiral center, important synthons, especially
in optically pure form, as they constitute the framework
of a large number of biologically active molecules. In the
chiral version of this addition, the reactions of (-)-
menthyl 3-butenoate with several achiral imines were
studied with discouraging results, because neither the
diastereoselectivity nor the asymmetric induction were
satisfactory.9 The long distance between the reaction site
and the chiral centers is probably responsible for the low
efficiency in the chiral induction. Chiral imines derived
† Universidad Auto´noma.
‡ Universidad de Sevilla
§ CSIC.
(1) (a) Hua, D. H.; Lagneau, N.; Wang, H.; Chen, J . S. Tetrahedron:
Asymmetry 1995, 6, 394 (and references therein). (b) Oppolzer, W.;
Froelich, O.; Wiaux-Zamar, C.; Bernardinelli, G. Tetrahedron Lett.
1997, 38, 2825. (c) Viso, A.; Ferna´ndez de la Pradilla, R.; Guerrero-
Strachan, C.; Alonso, M.; Mart´ınez-Ripoll, M.; Andre´, I. J . Org. Chem.
1997, 62, 2316. (d) Balasubramanian, T.; Hassner, A. Tetrahedron Lett.
1996, 37, 5755.
(2) (a) Garc´ıa-Ruano, J . L.; Ferna´ndez, I.; del Prado-Catalina, M.;
Alcudia-Cruz, A. Tetrahedron: Asymmetry 1996, 7, 3407. (b) Garc´ıa-
Ruano, J . L.; Ferna´ndez, I.; Hamdouchi, C. Tetrahedron Lett. 1995,
36, 295.
(3) Davis, F. A.; Reddy, R. E.; Szewczyk, J . M.; Reddy, G. V.;
Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, R. T.; Zhou, P.; Carroll,
P. J . J . Org. Chem. 1997, 62, 2555 (and references therein).
(4) (a) Davis, F. A.; Reddy, R. T.; Reddy, R. E. J . Org. Chem. 1992,
57, 6387. (b) Davis, F. A.; Reddy, R. E.; Szewczyk, J . M. J . Org. Chem.
1995, 60, 7037. (c) Davis, F. A.; Szewczyk, J . M.; Reddy, R. E. J . Org.
Chem. 1996, 61, 2222. (d) Fujisawa, T.; Kooriyama, Y.; Shimizu, M.
Tetrahedron Lett. 1996, 37, 3881.
(5) In this sense, we studied the reaction of the lithium enolate of
ethyl butyrate with compound 1 at -78 °C. The formation of a mixture
containing significant amounts of four different diastereomers was
established from the proton NMR spectra of the reaction crude. Only
one of them could be easily separated by flash chromatography, but
its configurational assignment was not made.
(6) The double dond can be isomerized under basic conditions by
treatment with Na2CO3.
(7) For leading references on the addition of dienolates to carbonyl
compounds see, for example: (a) Bellassoued, M.; Habbachi, F.;
Gaudemar, M. Tetrahedron 1987, 43, 1785. (b) Bellassoued, M.;
Habbachi, F.; Gaudemar, M. Tetrahedron 1985, 41, 1299. (c) J ohnson,
P. R.; White, J . D. J . Org. Chem. 1984, 49, 4424. (d) Dugger, R. W.;
Heatchcock, C. H. J . Org. Chem. 1980, 45, 1181.
(8) El Borgi, A.; Bellassoued, M.; Moreau, J . L. C. R. Acad. Sci. II
1988, 307, 1805.
(9) van Maanen, H. L.; Kleijn, H.; J astrzebski, J . T. B. H.; Lakin,
M. T.; Spek, A. L.; van Koten, G. J . Org. Chem. 1994, 59, 7839.
S0022-3263(97)02303-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/29/1998

7158 J . Org. Chem., Vol. 63, No. 21, 1998
Garc´ıa Ruano et al.
Sch em e 1
Ta ble 1. Rea ction of N-Su lfin ylim in es 1 a n d 2 w ith
from optically pure (R)-1-phenylethylamine afforded
some good results.9 For a most effective control of the
stereoselectivity, the use of a sulfinyl sulfur as the chiral
controller at the R position to the nitrogen atom of the
imine (i.e. N-sulfinylimines) seemed very appealing.
Moreover, the ability of the sulfinyl oxygen to be associ-
ated with the counterion metal of the dienolate could be
an interesting factor to control the regioselectivity by
favoring the coupling at the 2-position of the dienolate.
In the present paper, we report our ongoing studies
directed toward the evaluation of the ability of the
sulfinyl group as a chiral controller in the addition of
dienolates to optically pure N-arylsulfinylimines. From
the obtained results we have evidenced that the sulfinyl
group completely controls the regioselection of the reac-
tion (only products from the coupling at the 2-position
are formed), in the opposite sense to that observed for
the imines previously mentioned (only products from the
coupling at the 4-position were formed).9 Otherwise, the
influence of the metal counterion of the dienolate and
the arylsulfinyl moiety on the composition of the reaction
mixtures has also been evaluated. The conditions allow-
ing the obtained mixtures to evolve into optically pure
R-alkylidene-â-amino esters, interesting building blocks
in asymmetric synthesis, are also reported. From this
study it has been shown that the sulfinyl group acts not
only as a good chiral controller but also as a useful
protective group for the amine, which can be easily
removed.
Meta l Dien ola tes of Meth yl 3-Bu ten oa te
LAa
(MXn)
yield
(%)
anti/ syn ratiob
4:5 (or 6:7)
entry
N-sulfinylimine
1
2
3
4
5
6
1
1
1
2
2
2
ZnCl2
ZnBr2
ScTf3
ZnCl2
ZnBr2
ScTf3
70
82
34
82
90
89
78:22
65:35
87:13
(30:70)
(37:64)
(63:38)
a
The dienolates were generated by deprotonation of the ester
with 1 equiv of LDA, followed by transmetalation with Lewis acid
b
(MXn). The ratios of isomers were determined on the crude by
integration of characteristic 1H-NMR signals.
Moreover, only two of the four possible diastereoisomers
were detected in the mixtures, which suggested that the
control of the stereoselectivity of the addition had been
complete just in one of the two prochiral centers. The
configurational assignment of the obtained compounds
was carried out as follows. Diastereomers 6 and 7,
resulting from the addition of the zinc dienolate of methyl
3-butenoate to compound 2, were separated by column
chromatography. The major one, 7, was purified by
crystallization from hexane, and these crystals were
suitable for X-ray analysis. The molecular structure of
7 allowed us to know its relative configuration, which
evidenced the syn relative stereochemistry of their chiral
carbons. As the configuration at the sulfinyl sulfur was
known to be SS, the absolute configuration of 7 could be
assigned as (SS,R2,R3).
Resu lts a n d Discu ssion
The configurational assignment of the other diastere-
omer 6, as well as those of the p-tolyl derivatives 4 and
5, could be ascertained according to the transformations
indicated in Scheme 2. Desulfinylation of 7 (SS,R2,R3)
by treatment with TFA at 0 °C yielded the syn â-amino
ester 8 with (R2,R3) configuration. The same treatment
converted compound 6 into 9, which is a diastereoisomer
of 8, and therefore indicated that 8 and 9 must exhibit
the opposite relative configuration, thus allowing us to
assign the anti stereochemistry to compound 9. The
reaction of 8, 9, or their mixture with a saturated Na2-
CO3 aqueous solution yielded optically pure, isomerized
compound 10 with [R]D ) -40 (c 0.1, CHCl3). These
results indicated that both trifluoroacetates, 8 and 9, had
the same configuration at C-3, but the opposite one at
C-2, which allowed us to conclude that the configuration
of 9 must be (S2,R3) and therefore that (SS,S2,R3) must
be assigned to its precursor 6, as indicated in Scheme 1.
Desulfinylation of compound 4 (which was diastereo-
merically pure isolated from the 4 + 5 mixture) yielded
compound 9, which indicated that configuration (SS,S2,R3)
must be assigned to 4. Analogously, the mixture 4 + 5
The reactions of the lithium dienolate of (E)-methyl
2-butenoate with optically pure (+)-(S)-(E)-N-(benzylidene)-
p-toluenesulfinamide 1,10 (+)-(S)-(E)-N-(benzylidene)-2-
methoxy-1-naphthylsulfinamide 2,10 and (+)-(S)-(E)-N-
(benzylidene)-tert-butylsulfinamide 32a under different
conditions have been studied (Scheme 1). The results
obtained for compounds 1 and 2 in the presence of Lewis
acids as catalysts are summarized in Table 1. The
reactions were conducted at -78 °C in THF as solvent.
In other solvents, such as toluene or ether, the coupling
did not occur. Warming the reaction mixture to -20 °C
before quenching resulted in polymerization of dienolate
and unaltered starting N-sulfinylimine was recovered.
No reaction was observed in the case of the N-sulfinyl-
imine 3, which could be a consequence of the hindered
tert-butylsulfinyl group.
The reactions of substrates 1 and 2 were completely
regioselective affording exclusively the â-amino esters
resulting from the coupling at the 2-position of dienolate.
(10) Davis, F. A.; Zhou, P.; Liang, C.-H.; Reddy, R. E. Tetrahedron:
Asymmetry 1995, 6, 1511.

Enantiomerically Pure R-Alkylidene â-Amino Esters
J . Org. Chem., Vol. 63, No. 21, 1998 7159
Sch em e 2
Sch em e 3
Ta ble 2. Rea ction of N-Su lfin ylim in es 1 a n d 2 w ith
Lith iu m , Sod iu m , or P ota siu m Dien ola tes of Meth yl
3-Bu ten oa te
was transformed into the mixture 8 + 9 with TFA, which
evidenced identical absolute configuration for compounds
5 and 7.
product ratiob
The results obtained in the above-mentioned chemical
correlation prompted us to evaluate the synthetic scope
of the sequence to obtain optically pure R-ethylidene
â-amino acids from sulfinylimines. Thus, by treating the
mixture 4 + 5, obtained in conditions of the entry 2 (Table
1), with TFA (0 °C) for 5 h, followed by reaction of the
resulting crude with saturated solution of Na2CO3 (3 h),
afforded optically pure compound 10 in 65% overall yield
starting from the sulfinylimine 1. This yield was even
higher (75%) when the same sequence was reproduced
from the mixture 6 + 7 obtained from 2 in conditions of
the entry 5 (Table 1). The (E)-configuration of the double
bond of compound 10 was established by NOE experi-
ments (Scheme 2).
N-
reaction yield
time (h) (%)
4:5:11
(or 6:7:12)
entry sulfinylimine
basea
LDA
1
2
3
4
5
6
7
1
1
1
1
1
2
2
2c
2d
3c
3c
8c
8c
8d
85
75
65
70
-
18:0:82
31:9:60
46:0:54
30:0:70
-
LDA
LHMDS
NaHMDS
KHMDS
LDA
82
75
(0:0:100)
(9:37:54)
LDA
a
The dienolates were generated by deprotonation of the ester
b
with different bases. The ratios of isomers were determined on
the crude by integration of characteristic 1H-NMR signals. c Pro-
d
tonation was made with NH4Cl(aq) at room temperature. Pro-
tonation was made with NH4Cl(methanolic solution) at -78 °C.
We have also studied the reactions of compounds 1
with different metal enolates of methyl 3-butenoate in
the absence of Lewis acids (Scheme 3). The results are
collected in Table 2. When the reactions were conducted
at -78 °C and the final protonation was carried out with
aqueous NH4Cl at room temperature, only two products
(4 + 11) were isolated starting from 1, their relative
proportion depending on the base (entries 1, 3, and 4;
with KHMDS the reaction does not work) but independ-
ent of the reaction time. The (E)-configuration of the
double bond of compound 11 was established by NOE
spectroscopic studies (Scheme 3). Under identical condi-
tions lithium enolate of the ester, generated with LDA,
reacts with 2, yielding compound 12 as exclusive product
(entry 6) in very good yield (82%).
served starting from 1), we did the protonation of the
reaction mixtures obtained from 1 and 2 at -78 °C (with
methanolic solution of NH4Cl). In these conditions 4 +
5 + 11 and 6 + 7 + 12 mixtures were, respectively,
detected (entries 2 and 7), which showed a moderated
stereoselectivity of these additions, similar to that ob-
served in the presence of Lewis acids (Table 1). More-
over, these results suggest that the isomerization of the
epimer 5 into 11 must be faster than that of 4. Other-
wise, the isomerization of the double bond must not be
possible in the presence of the Lewis acids (conditions of
Table 1), precluding the formation of compounds 11 and
12.
Assuming that the reaction is under kinetic control,
the stereochemical results can be rationalized in terms
of six-membered cyclic transition states. The fact that
all the products obtained have the R configuration at C-3
indicates that the attack of dienolates on the CdN bond
must take place from the re face (Scheme 4), which could
easily be explained by assuming that the metal counter-
The formation of compounds 11 and 12 could be
explained as a consequence of the isomerization from
their precursors, R-vinyl-â-sulfinylamino esters 4-7. To
know if the nucleophilic addition to sulfinylimine was
completely stereoselective (only compound 4 was ob-

7160 J . Org. Chem., Vol. 63, No. 21, 1998
Garc´ıa Ruano et al.
Sch em e 4
ion, involved in a chairlike transition state, was addition-
ally stabilized by association with the sulfinyl oxygen,
according to the Davis’s proposal to explain the attack
of the ester enolate to sulfinylimines.4 In such a case,
the transition states resulting from the attack to the si
face would be sterically destabilized because the aromatic
substituent at sulfur would be placed inside the “chair”.
The energy differences of competing transition states TE1
and TE2 (Scheme 4), leading to anti- and syn-â-amino
esters, respectively, must be relatively small (thus ex-
plaining the formation of epimeric mixtures at C-2),
which have been rationalized in other additions of
dienolates to imines by assuming that the vinyl substitu-
ent is coplanar with the enolate double bond and thus
sterically not very demanding.9 Nevertheless, the pre-
dominance of the anti-4 isomer in reactions starting from
1 (see Table 1) is not easy to explain from a steric point
of view, which suggests that other factors such as the
nature of the metal and the structure of the aryl group
joined to sulfur must also have some role in determining
the configuration at C-2.11
The different course of the reaction, depending on the
metal involved, could be rationalized as follows. The
lithium N-sulfinyl amide resulting in the addition of
dienolates (Table 2) would be able to abstract the acidic
protons at C-2, making possible the migration of the
double bond. The high stereoselectivity of the isomer-
ization of the double bond (only the E-olefins, 11 or 12,
were detected) could be a consequence of the fact that
the N-sulfinylamino group is more efficient than the ester
group to stabilize the resulting allyllithium (Figure 1).
The formation of a 11 + 4 mixture starting from 1, the
composition of which is not dependent on the reaction
time, as well as the isolation of 12 as exclusive product
when 2 was used as starting product, suggests the
existence of an equilibrium between the R-ethylidene
derivatives and the mixture of R-vinyl-â-amino esters (the
F igu r e 1.
anti isomers being the most stable), which is completely
shifted toward the former in the case of Ar ) 2-OMe-
naphthyl. In the case of the reactions catalyzed by Lewis
acids (Table 1) the higher stability and/or the lower
basicity of the resulting metal amides could justify the
absence of the isomerization products.
Con clu sion
In summary, we have demonstrated that reactions of
different metal dienolates with N-arylsulfinylimines are
completely regioselective (only â-amino esters are formed).
The control of the stereoselectivity is complete at C-3 but
moderate or low at C-2. Mixtures of vinyl â-amino esters,
epimers at C-R, are obtained in reactions conducted
under Lewis acid catalysis, which can be transformed into
optically pure 2-alkylidene 3-amino esters in high yields
by desulfinylation with TFA and further treatment with
Na2CO3. Reactions with lithium enolates yielded the
optically pure 2-ethylidene-3-arylsulfinylamino esters as
the major or exclusive product.
Exp er im en ta l Section
Ad d ition of Dien ola te Meth yl 3-Bu ten oa te to N-Su lfin -
ylim in es Ca ta lyzed by Lew is Acid s (Ta ble 1). Gen er a l
P r oced u r e. To a solution of 1.26 mL of diisopropylamine (9.0
mmol, 2.2 equiv) in THF (8 mL) was added 3.5 mL of a 2.4 M
solution of n-butyllithium in hexane (8.6 mmol, 2.1 equiv) at
-78 °C. After 30 min, a solution of 0.82 g of methyl
3-butenoate (8.3 mmol, 2.0 equiv) in THF (4 mL) was added.
After stirring for 30 min at -78 °C, the enolate was trans-
metalated by addition of a solution of 8.2 mmol of the
appropriated Lewis acid (2.0 equiv) in THF (5 mL), followed
by another 30 min of stirring. Next, a solution of 4.1 mmol of
the N-sulfinylimine 1-3 (1.0 equiv) and 4.1 mmol of the Lewis
acid (1.0 equiv) in THF (10 mL) was added. Stirring was
continued for 8 h at -78 °C. The reaction was quenched by
addition of saturated NH4Cl solution (20 mL) at room tem-
perature (or 20 mL of methanolic solution of NH4Cl at -78
°C) and extracted with EtOAc (4 × 20 mL). The combined
organic layers were dried over Na2SO4 and evaporated under
(11) These results are in concordance with the high trans-selectivity
observed by other authors in the condensation of zinc enolate esters
with imines.9 These authors have also explained their results by
assuming a transition state, type TE1, involving an (E)-imine and a
(Z)-enolate. In our case ET1 would be even more favored because the
E-Z equilibrium of the starting dienolate must be shifted to the Z
form, as in other stabilized conjugated enolates.12 On the other hand,
the change of stereoselectivity, from anti to syn, observed in the
addition of dienolate to the sulfinylimine 2 can be explained by
considering the higher steric volume of the naphthyl group compared
with the p-tolyl group, together with the possible competition between
the sulfinylic oxygen and the OMe group for metal chelation.
(12) Ireland, R. E.; Willard, A. K. Tetrahedron Lett. 1975, 3975.

Enantiomerically Pure R-Alkylidene â-Amino Esters
J . Org. Chem., Vol. 63, No. 21, 1998 7161
1
vacuum to yield the addition products that were purified by
flash chromatography (hexane/EtOAc, 4/1). The Lewis acid
used and yields and ratio of products obtained are indicated
in Table 1.
Meth yl 3-[N-(p-Tolylsu lfin yl)a m in o]-3-p h en yl-2-vin yl-
p r op a n oa te. The product was obtained as a mixture of anti
and syn diastereomers, 4 and 5, respectively, from (+)-(S)-(E)-
N-benzylidene)-p-toluenesulfinamide 1. The diastereomer 4
was obtained optically pure by flash chromatography using
Et2O/hexane (3/2) as eluent.
3-butenoate. [R]25 ) +8 (c 0.5, CHCl3); H NMR (CDCl3) δ
D
8.62 (d, J ) 8.6 Hz, 1H), 7.86 (d, J ) 9.1 Hz, 1H), 7.73 (d, J )
8.1 Hz, 1H), 7.49-7.11 (m, 8H), 7.04 (q, J ) 7.2 Hz, 1H), 5.63
(d, J ) 10.4 Hz, 1H), 3.99 (s, 3H), 3.61 (s, 3H), 1.94 (d, J ) 7.2
Hz, 3H); 13C NMR (CDCl3) δ 166.9, 140.8, 139.7, 133.7, 133.1,
130.6, 129.0, 128.5, 128.2, 127.8, 126.9, 125.9, 124.3, 122.5,
113.5, 57.2, 56.8, 51.6, 14.2; IR (CHCl3, cm-1) 3300, 2980, 1700,
1590, 1420, 1300, 1280, 1260, 1100, 1060. Anal. Calcd for
C23H23NO4S: C, 67.46; H, 5.66; N, 3.42; S, 7.83. Found: C,
67.59; H, 5.49; N, 3.27; S, 7.40.
Dia ster eom er 4(SS,2S,3R). The product was obtained as
a white crystalline solid by recrystallization from hexane. Mp
Desu lfin yla tion of Meth yl 3-[N-(Ar ylsu lfin yl)a m in o]-
3-p h en yl-2-vin ylp r op a n oa tes. Gen er a l P r oced u r e. To a
solution of 0.14 mmol of N-(2-(methoxycarbonyl)-1-phenyl-3-
butenyl)sulfinamide (1 equiv) in 3 mL of MeOH, at 0 °C, was
added 42 mL of TFA (0.56 mmol, 4 equiv). After stirring 5 h
at 0 °C, the solvent was evaporated under vacuum, and the
residue was treated with 5 mL of water and extracted with
CH2Cl2 (2 × 5 mL). The aqueous phase was evaporated under
vacuum, yielding the corresponding trifluoroacetate.
1
95 °C; [R]25 ) +79 (c 1.0, CHCl3); H NMR (CDCl3) δ 7.57-
D
7.53 (m, 2H), 7.37-7.27 (m, 7H), 5.71 (ddd, J ) 8.7, 10.1, 16.8
Hz, 1H), 5.17-5.04 (m, 2H), 4.99 (d, J ) 6.7 Hz, 1H), 4.80(dd,
J ) 6.7, 7.1 Hz, 1H), 3.65 (s, 3H), 3.51 (dd, J ) 7.1, 8.7 Hz,
1H), 2.42 (s, 3H); 13C NMR (CDCl3) δ 172.0, 142.2, 141.4, 139.2,
131.9, 129.5, 128.5, 128.0, 127.5, 125.4, 120.2, 60.0, 56.9, 52.1,
21.3; IR (CHCl3, cm-1) 3280, 2980, 1720, 1420, 1220, 1180,
1100, 920.
Dia ster eom er 5(SS,2R,3R) (spectroscopic data taken from
a mixture of both diastereomers 4 and 5). 1H NMR (CDCl3,
D2O) δ 7.65-7.55 (m, 2H), 7.39-7.27 (m, 7H), 5.85 (ddd, J )
9.4, 10.2, 16.8 Hz, 1H), 5.31-5.18 (m, 2H), 4.76 (d, J ) 8.6
Hz, 1H), 3.47 (s, 3H), 3.36 (dd, J ) 8.6, 9.4 Hz, 1H), 2.41 (s,
3H).
(1R,2R)-1-P h en yl-2-(m eth oxycar bon yl)bu t-3-en ylam m o-
n iu m Tr iflu or oa ceta te, 8(1R,2R). It was obtained from
compound 7(SS,2R,3R). Yield: 90%; [R]25 ) +43 (c 1.2,
D
water); 1H NMR (D2O): 7.29-7.20 (m, 5H), 5.70 (ddd, J ) 11.6,
12.3, 20.9 Hz, 1H), 5.38 (dd, J ) 1.4, 12.3 Hz, 1H), 5.32 (dd, J
) 1.4, 20.1 Hz, 1H), 4.45 (d, J ) 9.6 Hz, 1H), 3.62 (dd, J )
9.6, 11.6 Hz, 1H), 3.28 (s, 3H); 13C NMR (D2O) δ 172.1, 133.8,
130.0, 129.9, 129.4, 127.4, 124.0, 55.5, 55.1, 52.9; IR (CHCl3,
Met h yl 3-[N-(p -Tolylsu lfin yl)a m in o]-3-p h en yl-2-et h -
ylid en ep r op a n oa te, 11(SS,2E,3S). The major product was
obtained from 1 equiv of the (S)-(E)-N-(benzylidene)-1-p-
toluenesulfinamide 1 and 2 equiv of the lithium dienolate of
methyl 3- butenoate. It was purified by flash chromatography
cm-1) 2890, 1660, 1515, 1425, 1140. Anal. Calcd for C14H16
-
using EtOAc/hexane (1/4) as eluent. [R]25 ) +158 (c 1.0,
NO4F3: C, 52.67; H, 5.05; N, 4.39. Found: C, 52.30; H, 4.87;
N, 4.38.
D
CHCl3); 1H NMR (CDCl3) δ 7.65-7.18 (m, 9H), 6.95 (q, J )
7.5 Hz, 1H), 5.73 (d, J ) 10.4 Hz, 1H), 5.46 (d, J ) 10.4 Hz,
1H), 3.62 (s, 3H), 2.40 (s, 3H), 1.57 (d, J ) 7.5 Hz, 3H); 13C
NMR (CDCl3) δ 166.5, 141.4, 141.1, 140.7, 139.4, 133.2, 129.5,
128.3, 127.0, 126.1, 126.0, 53.5, 51.6, 21.2, 13.6. Anal. Calcd
for C19H21NO3S: C, 66.45; H, 6.16; N, 4.08; S, 9.33. Found:
C, 66.33; H, 6.46; N, 3.91; S, 8.92.
(1R,2S)-1-P h en yl-2-(m eth oxyca r bon yl)bu t-3-en yla m o-
n iu m Tr iflu or oa ceta te, 9(1R,2S). It was obtained from
compound 4(SS,2S,3R). Yield: 90%; [R]25 ) -30 (c 0.7,
D
water); 1H NMR (D2O) δ 7.26-7.11 (m, 5H), 5.45 (ddd, J )
8.8, 10.6, 19.5 Hz, 1H), 5.04-4.95 (m, 2H), 4.57 (d, J ) 8.3
Hz, 1H), 3.66 (dd, J ) 8.8, 8.3 Hz, 1H), 3.51 (s, 3H); 13C NMR
(D2O) δ 172.7, 147.5, 129.6, 129.5, 127.5, 126.5, 124.0, 55.3,
53.1, 52.8; IR (CHCl3, cm-1) 2850, 1655, 1500, 1420, 1140.
Anal. Calcd for C14H16NO4F3: C, 52.67; H, 5.05; N, 4.39.
Found: C, 52.20; H, 4.85; N, 4.41.
Meth yl 3-[N-(2-Meth oxy-1-n a p h th ylsu lfin yl)a m in o]-3-
p h en yl-2-vin ylp r op a n oa te. The product was obtained as a
mixture of diastereomers, 6 and 7, from (S)-(E)-N-(ben-
zylidene)-2-methoxy-1-naphthalenesulfinamide 2. Both dia-
stereomers were separated by flash chromatography using
Et2O/hexane/CH2Cl2 (2/2/1) as eluent.
Dia ster eom er 6(SS,2S,3R). [R]25 ) +195 (c 1.0, CHCl3);
Meth yl (2E,3R)-2-(r-Am in oben zyl)-3-p r op en oa te, 10-
(2E,3S). To a solution of trifluoroacetate 9(1R,2S) in water
was added saturated Na2CO3 solution. After stirring for 1 h
at room temperature, the aqueous phase was extracted with
CH2Cl2, dried over Na2SO4, filtered, and evaporated to yield
the amine 10 in quantitative yield. The same product was
obtained starting from trifluoroacetate 8(1R,2R). [R]25D ) -40
(c 0.01, CHCl3); 1H NMR (CDCl3) δ 7.29-7.20 (m, 5H), 7.0 (q,
J ) 7.0 Hz, 1H), 5.11 (s, 1H), 3.64 (s, 3H), 2.14 (d, J ) 7.0 Hz,
3H); 13C NMR (CDCl3) δ 166.5, 143.7, 137.6, 136.0, 127.7,
126.0, 125.4, 51.4, 50.9, 13.9; IR (CHCl3, cm-1) 3280, 2910,
1680, 1425, 1240, 1130. Anal. Calcd for C14H16NO4F3: C,
70.22; H, 7.37; N, 6.82. Found: C, 69.73; H, 7.42; N, 6.60.
D
1H NMR (CDCl3) δ 8.38 (d, J ) 8.3 Hz, 1H), 7.91 (d, J ) 9.1
Hz, 1H), 7.75 (d, J ) 7.8 Hz, 1H), 7.50-7.10 (m, 8H), 6.85 (sb,
1H), 5.77 (ddd, J ) 8.8, 10.3, 17.0 Hz, 1H), 5.16 (dd, J ) 10.3,
0.8 Hz, 1H), 5.12 (dd, J ) 17.0, 0.8 Hz, 1H), 4.92 (dd, J ) 8.6,
1.2 Hz, 1H), 4.10 (s, 3H), 3.70 (s, 3H), 3.62 (dd, J ) 8.8, 8.6
Hz, 1H); 13C NMR (CDCl3) δ 172.2, 155.3, 138.5, 133.2, 132.0,
130.7, 128.9, 128.3, 128.2, 127.9, 124.4, 122.2, 120.2, 113.6,
60.7, 57.1, 56.8, 52.1; IR (CHCl3, cm-1) 3250, 2950, 1710, 1580,
1425, 1325, 1250, 1150, 1060. Anal. Calcd for C23H23NO4S:
C, 67.46; H, 5.66; N, 3.42; S, 7.83. Found: C, 67.35; H, 5.46;
N, 3.26; S, 7.46.
Dia ster eom er 7(SS,2R,3R). The product was obtained as
a white crystalline solid by recrystallization from hexane. Mp
1
129 °C; [R]25 ) +55 (c 1.0, CHCl3); H NMR (CDCl3) δ 8.16
D
(d, J ) 9.1 Hz, 1H), 7.94 (d, J ) 9.1 Hz, 1H), 7.78 (d, J ) 8.1
HZ, 1H), 7.48-7.23 (m, 8H), 6.63 (sb, 1H), 6.04 (ddd, J ) 9.6,
10.2, 17.0 Hz, 1H), 5.38 (dd, J ) 1.3, 10.2 Hz, 1H), 5.29 (dd, J
) 1.3, 17.0 Hz, 1H), 4.87 (dd, J ) 1.6, 9.1 Hz, 1H), 4.10 (s,
3H), 3.50 (s, 3H), 3.38 (dd, J ) 9.1, 9.6 Hz, 1H); 13C NMR
(CDCl3) δ 171.1, 155.5, 137.9, 133.3, 133.0, 130.8, 128.3, 127.9,
Ack n ow led gm en t. This work was supported by the
“Ministerio de Educacio´n y Ciencia” (Spain) under
DGICYT Grants PB95-210 and PB94-1431.
124.4, 122.0, 121.2, 113.5, 58.7, 56.7, 51.8; IR (CHCl3, cm-1
)
Su p p or tin g In for m a tion Ava ila ble: ORTEP representa-
tion of the X-ray structure of compound 7 and 1H NMR and
13C NMR spectra of compound 4 (10 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
3300, 2980, 1750, 1420, 1340, 1290, 1270, 1080. Anal. Calcd
for C23H23NO4S: C, 67.46; H, 5.66; N, 3.42; S, 7.83. Found:
C, 67.41; H, 5.59; N, 3.25; S, 7.52.
Meth yl 3-[N-(2-Meth oxy-1-n a p h th ylsu lfin yl)a m in o]-3-
p h en yl-2-eth ylid en ep r op a n oa te, 12(SS,2E,3S). The prod-
uct was obtained as a unique diastereomer from 1 equiv of
the (S)-(E)-N-(benzylidene)-2-methoxy-1-naphthalenesulfin-
amide 2 and 2 equiv of the lithium dienolate of methyl
J O972303Q