Synthesis of optically pure 1,2-diaryl- and 1,2-alkylaryl-1,2-amino sulfides

Article abstract of DOI:10.1021/jo050129x

The reactions of the lithium (S)-α-(methylthio)-2-(p-toluenesulfinyl) benzyl carbanion with (S)-N-p-tolylsulfinyl aldimines evolve in a completely stereoselective manner providing a one-step synthesis of enantiomerically pure anti-1,2-disubstituted 1,2-am

Full text of DOI:10.1021/jo050129x

Synthesis of Optically Pure 1,2-Diaryl- and 1,2-Alkylaryl-1,2-amino
Sulfides
Yolanda Arroyo,*,† AÄ ngela Meana,† J. Fe´lix Rodr´ıguez,† Mercedes Santos,†
M. Ascensio´n Sanz-Tejedor,*,† and Jose´. L. Garc´ıa Ruano*,‡
Departamento de Quı´mica Orga´nica (ETSII), Universidad de Valladolid, Po. del Cauce s/n,
47011 Valladolid, Spain, and Departamento de Quı´mica Orga´nica (C-I), Universidad Auto´noma,
Cantoblanco, 28049 Madrid, Spain
atejedor@dali.eis.uva.es; joseluis.garcia.ruano@uam.es
Received January 21, 2005
The reactions of the lithium (S)-R-(methylthio)-2-(p-toluenesulfinyl)benzyl carbanion with (S)-N-
p-tolylsulfinyl aldimines evolve in a completely stereoselective manner providing a one-step synthesis
of enantiomerically pure anti-1,2-disubstituted 1,2-amino sulfide derivatives.
Introduction
such as diltiazem5a or the ecteinascidine family marine
alkaloids, an important group of anticancer agents.5b
1,2-Amino alchols, resulting in many cases from the
natural amino acids, are the most widely used starting
products for synthesizing vicinal amino sulfides. Their
stereoselective interconversion has been described ac-
cording to processes involving the ring opening of aziri-
dine intermediates, which in their term, were obtained
from 1,2-amino alcohols under Mitsunobu conditions.3a,6
A similar strategy is the base of an elegant asymmetric
synthesis of â-phenyl cysteine derivatives.7 1,2-Amino
sulfides1,4h and 1,2-amino thiols4b,e,f have also been pre-
pared by applying a mesylation of amino alcohol-thiolate
displacement sequence, via aziridinium salt intermediate
generated by neighboring group participation of the
nitrogen. Alternatively, the transformation of the amino
alcohols into iminocarbonates (instead of aziridines) and
their stereoselective thiolation has been used by Zhu’s
group8 to synthesize 1,2-amino sulfides. The usefulness
of all these strategies is mainly restricted by the incom-
plete regioselectivity in the opening reactions on the cyclic
intermediates. Additionally, all of them have the prob-
lems associated with the asymmetric synthesis of the
Enantiomerically pure 1,2-amino sulfides and 1,2-
amino thiols are structural subunits of undoubted syn-
thetic interest in organic chemistry. They have been
proven very successful as N,S-ligands in enantioselective
reactions such as palladium-catalyzed allylic substitu-
tion,1 addition of alkyllithium to aldehydes,2 iridium(I)-
catalyzed reduction of unsymmetrical ketones,3 and
addition of diethylzinc to aromatic aldehydes.4 Moreover,
chiral benzyl sulfides taking part in a 1,2-amino sulfide
subunit can be found in biologically active molecules5
† Universidad de Valladolid.
‡ Universidad Auto´noma.
(1) (a) Rassias, G. A.; Page, P. C. B.; Reignier, S.; Christie, S. D. R.
Synlett 2000, 379-381. (b) Page, P. C. B.; Heaney, H.; Reignier, S.;
Rassias, G. A. Synlett 2003, 22-27 and references therein.
(2) (a) Granander, J.; Sott, R.; Hilmersson, G. Tetrahedron: Asym-
metry 2003, 14, 439-447. (b) Sott, R.; Granander, J.; Dine´r, P.;
Hilmersson, G. Tetrahedron: Asymmetry 2004, 15, 267-274 and
references therein.
(3) (a) Petra, D. G. I.; Kamer, P. C. J.; Spek, A. L.; Schoemaker, H.
E.; van Leeuwen, P. W. N. M. J. Org. Chem. 2000, 3010-3017. (b)
Hage, A.; Petra, D. G. I.; Field, J. A.; Schipper, D.; Wijnberg, J. B. P.
A.; Kamer, P. C. J.; Reek, J. N. H.; van Leeuwen, P. W. N. M.; Wever,
R.; Schoemaker, H. E. Tetrahedron: Asymmetry 2001, 12, 1025-1034.
(4) (a) Hof, R. P.; Poelert, M. A.; Peper, N. C. M. W.; Kellog, R. M.
Tetrahedron: Asymmetry 1994, 5, 31-34. (b) Kang, J.; Lee, J. W.; Kim,
J. J. J. Chem. Soc, Chem. Commun. 1994, 2009-2010. (c) Jin, M. J.;
Ahn, S. J.; Lee, K. S. Tetrahedron Lett. 1996, 37, 8767-8770. (d)
Fulton, D. A.; Gibson, C. L. Tetrahedron Lett. 1997, 38, 2019-2022.
(e) Kang, J.; Kim, J. B.; Kim, J. W.; Lee, D. J. Chem. Soc., Perkin Trans.
2 1997, 189-194. (f) Anderson, J. C.; Cubbon, R.; Harding, M.; James,
D. S. Tetrahedron: Asymmetry 1998, 9, 3461-3490. (g) Kossenjans,
M.; Soeberdt, M.; Wallbaum, S.; Harms, K.; Martens, J.; Aurich, H.
G. J. Chem. Soc., Perkin Trans. 1 1999, 2353-2363. (h) Jimeno, C.;
Moyano, A.; Perica´s, M. A.; Riera, A. Synlett 2001, 1155-1157.
(5) (a) Schwartz, A.; Madan, P. B.; Mohacsi, E.; O’Brien, J. P.;
Todaro, L. J.; Coffen, D. L. J. Org. Chem. 1992, 57, 851-856 and
references therein. (b) Rinehart, K. L. Med. Res. Rev. 2000, 20, 1-27
and references therein.
(6) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Chem. Soc., Perkin Trans. 1 2001,
1314-1317.
(7) Xiong, Ch.; Wang, W.; Cai, Ch.; Hruby, V. J. J. Org. Chem. 2002,
67, 1399-1402.
(8) De Paolis, M.; Blankenstein, J.; Bois-Choussy, M.; Zhu, J. Org.
Lett. 2002, 4, 1235-1238.
10.1021/jo050129x CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/02/2005
3914
J. Org. Chem. 2005, 70, 3914-3920

Synthesis of 1,2-Diaryl- and 1,2-Alkylaryl-1,2-amino Sulfides
SCHEME 1
SCHEME 2. (a) 1. LDA, -78 °C; 2. Me2S2 (b) LDA,
-78 °C
TABLE 1. Lithiation and Subsequent Electrophilic
Substitution of (S)-2 and 2′ with Imines 3
starting 1,2-amino alcohols. A different approach was
used by Enders to prepare anti-1,2-amino sulfides,
involving the use of the SAMP/RAMP-hydrazone meth-
odology.9 It consists of the sequential formation of the
two chiral centers from optically pure 2-methylthio
acetaldehyde SAMP hydrazones, involving an R-alkyl-
ation followed by 1,2-addition to CdN bond. Both steps
are highly stereoselective, and in some cases, the moder-
ate yields in N,N bond cleavage is a real drawback.
Nevertheless, this procedure, which is more general than
the others previously cited, cannot be used to introduce
aryl residues at the alkylation step, and therefore, the
synthesis of the 1,2-diaryl-1,2-amino sulfides must be
done by some of the methods starting from 1,2-amino
alcohols or some of their most advanced heterocyclic
intermediates.
We have recently reported the almost completely
stereoselective transference of chiral benzyl groups to
different electrophiles from R-alkyl (and trimethylsililoxy)
2-p-tolylsulfinylbenzyl carbanions.10 In these reactions,
N-sulfinylimines worked as one of the most efficient
electrophiles for double-asymmetric induction processes10b,c
(Scheme 1). Bearing in mind these antecedents, we
thought that reactions of N-sulfinyl imines with R-thio-
2-p-tolylsulfinylbenzyl carbanions could provide a new
strategy, involving a short number of steps, for the
synthesis of 1,2-diaryl- and 1-alkyl-2-aryl-1,2-amino sul-
fides (Scheme 1). Although the configurational instability
of the R-lithio benzyl sulfides is well documented,11 some
examples concerning their highly diastereoselective12,13
and even enantioselective evolution have been recently
reported.14 These results prompted us to investigate the
influence of the o-sulfinyl group on the stereoselective
evolution of the benzyl carbanions in their reactions with
N-sulfinylimines. Herein we report the highly stereo-
entry
nucleophile
imine
products (ratio)
1
2
3
4
(S)-2
(S)-2
(S)-2
2′
(S)-3a
(R)-3a
3′a
4a (>98% de)
5a/5′a/5′′a (50:20:21)
complex mixture
6a/7a (80:20)
(S)-3a
selective reaction of the lithium (S)-R-methylthio-2-(p-
toluenesulfinyl)benzyl carbanion Li-(S)-2 with (S)-N-p-
tolylsulfinyl aldimines to afford the enantiomerically pure
anti-1,2-diaryl- and 1-alkyl-2-aryl-1,2-amino sulfide de-
rivatives.
Results and Discussion
(S)-R-Methylthio-2-(p-tolylsulfinyl)toluene (S)-2 was
prepared by deprotonation from enantiopure (S)-2-(p-
tolylsulfinyl)toluene10b (S)-1 with LDA and further reac-
tion with dimethyl disulfide, Me2S2, in 70% yield. The
subsequent formation of the R-thiocarbanion required 1.2
equiv of LDA solution (THF) to be stirred for 5 min with
(S)-2 at -78 °C before addition of the electrophile. Under
these conditions, the formation of a deeply purple solution
of Li-(S)-2 was observed (Scheme 2).15
To determine the role played by the sulfinyl group at
the nucleophile in the stereochemical course of the
addition reaction and to identify the matched pair, we
first studied the reactions of the R-sulfenyl carbanion Li-
(S)-2 with N-sulfinylimines (S)-3a and (R)-3a and their
corresponding sulfone 3′a. In this context, the reaction
of the achiral R-methylthio-2-(p-tolylsulfonyl)toluene 2′
was also investigated. In all experiments, the electrophile
(2 equiv) was added at -78 °C to the solution of the
carbanion. The reaction mixture was kept for 5-10 min
at this temperature, and subsequently, workup was
performed. The results are shown in Table 1.
(9) Enders, D.; Moll, A.; Schaadt, A.; Raabe, G.; Runsink, J. Eur. J.
Org. Chem. 2003, 3923-3938 and references therein.
(10) (a) Garc´ıa-Ruano, J. L.; Carren˜o, M. C.; Toledo, M. A.; Aguirre,
J. M.; Aranda, M. T.; Fischer, J. Angew. Chem., Int. Ed. 2000, 39,
2736-2737. (b) Garc´ıa-Ruano, J. L.; Alema´n, J.; Soriano, J. F. Org.
Lett. 2003, 5, 677-680. (c) Garc´ıa-Ruano, J. L.; Alema´n, J. Org. Lett.
2003, 5, 4513-4516. (d) Garc´ıa-Ruano, J. L.; Aranda, M. T.; Aguirre,
J. M. Tetrahedron 2004, 60, 5383-5392.
(11) Recent reviews: (a) Hoppe, D.; Hense, T. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2282-2316, (b) Basu, A.; Thayumanauan, S.
Angew. Chem., Int. Ed. 2002, 41, 716-738. (c) Toru, T. Nakamura, S.
Top. Organomet. Chem. 2003, 177-216.
Reactions carried out starting from 2′ and (S)-3a
evolved with a 60% de, giving rise to a mixture of two
diastereoisomers that have opposite configuration at the
two newly created stereogenic centers16 (Table 1, entry
4). A complex mixture of compounds was obtained in the
(12) (a) Hoppe, D.; Kaiser, B.; Stratmann, D.; Fro¨lich, R. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2784-2786. (b) Stratmann, D.; Kaiser,
B.; Fro¨lich, R.; Meyer, O.; Hoppe, D. Chem. Eur. J. 2001, 7, 423-435.
(13) For a review, see: (a) O’Brien. J. Chem. Soc., Perkin Trans. 1
1998, 1439-1457. For a more recent reference, see: (b) Gibson, S. E.
(ne´e Thomas); Reddington, E. G. Chem. Commun. 2000, 989-996.
(14) (a) Nakamura, S.; Nakagawa, R.; Watanabe, Y.; Toru, Angew.
Chem., Int. Ed. Engl. 2000, 39, 353-355. (b) Nakamura, S.; Nakagawa,
R.; Watanabe, Y.; Toru, T. J. Am. Chem. Soc. 2000, 112, 11340-11347.
(c) Nakamura, S.; Furutani, A.; Toru, T. Eur. J. Org. Chem. 2002,
1690-1695.
(15) A strict control of the temperature (-78 ( 5 °C) is required for
observing the formation of the carbanion.
(16) A enantiomeric pair was obtained when N-desulfinylation of
6a and 7a, with TFA/MeOH, was carried out (see the Experimental
Section).
J. Org. Chem, Vol. 70, No. 10, 2005 3915

Arroyo et al.
TABLE 2. Lithiation and Subsequent Electrophilic
The anti arrangement of the heteroatomic functions
assigned to compounds 4a-h is based on (a) the large
value observed for the vicinal coupling constants of their
CH-CH fragments (J g 9.5 Hz, see the Experimental
Section), which indicates a quite large conformational
preference of the rotamer exhibiting the anti arrange-
ment between such a protons. (b) The high value of the
vicinal coupling constant JH-N-C-H (7.5-10.4 Hz, see the
Experimental Section) reveals the predominance of rota-
mers exhibiting an anti relationship between these
protons, which is only possible by assuming that the
N-H proton is strongly associated by hydrogen bond with
the sulfinyl group. It requires a gauche arrangement
between the nitrogen function and the aryl group bearing
the sulfoxide, which in its term fix the anti arrangement
of the SMe and NHSOTol groups (Figure 1).
The configurational assignment of compounds 4i and
4′i could not be made by using these criteria. 4i exhibits
a very high JH-N-C-H value (9.9 Hz) which indicates that
NH must be associated by hydrogen bonds, but J1,2 ) 3.4
Hz, which evidences that H(1) and H(2) adopt a gauche
arrangement instead of an anti one characteristic for all
compounds 4. It could be explained by assuming that 4i
has the same configuration as 4a-h but with the tert-
butyl and arylsulfinyl groups adopting a gauche relation-
ship (Figure 1). The tendency of the tert-butyl groups to
reach a gauche arrangement with respect to phenyl rings
is not unexpected because it has been observed for many
compounds.20
This configurational assignment was unequivocally
confirmed in the case of 4a by X-ray analysis (Figure 1).
This study revealed that the absolute configurations of
4a at its stereogenic centers are 1R and 2S. This study
also proved the existence of an intramolecular hydrogen
bonding between the sulfinyl oxygen and the amidic
proton for compound 4a.
The similar behavior observed for all studied aromatic
and aliphatic aldimines (all of them evolve in a com-
pletely stereoselective manner) also suggests that the
absolute configuration for compounds 4b-h is identical
to that of 4a.
An additional check was made in the case of 4g, whose
absolute configuration at C-1 could be demonstrated to
be R by chemical correlation with amine 8 as previously
reported.10b Correlation was performed by N-desulfinyl-
ation of 4g with TFA followed by hydrogenolysis with
Ra-Ni of the two C-S bonds at the resulting free amine
to give optically pure 821 (Scheme 3).
Compounds 4 can be easily transformed into amino
sulfides or some of their thioderivatives by selective N-
or C-desulfinylation (Scheme 4). Hydrolysis of the N-S
bond can be made, without losing optical purity, by
reaction with TFA/MeOH, which affords optically pure
1,2-disubstituted-1,2-amino sulfides 922 in high yield. We
have illustrated this reaction by studying the transfor-
mation of 4a and 4g into 9a and 9g, respectively (Scheme
4). Otherwise, hydrogenolysis of the Ar-SOTol bond can
be made by reaction of the sulfoxides with organolithium
Substitution of (S)-2 with (S)-N-Sulfinylimines 3a-i
isolated
yield (%)
entry
products
R
de (%)
1
2
3
4
5
6
7
8
9
4a
Ph
85
78
72
60
70
50
65
70
70
>98
>98
>98
>98
>98
>98a
>98a
>98
52
4b
o-BrC6H4
p-MeOC6H4
p-CNC6H4
2-naphthyl
n-Pr
4c
4d
4e
4f
4g
n-Bu
4h
i-Pr
4i + 4′ib
t-Bu
a
See text and ref 18. b Unknown configuration.
reaction of (S)-2 with the more reactive sulfonamide 3′a
whose complete analysis was not possible in our hands
(Table 1, entry 3).17
Reaction of (S)-2 with (R)-3a afforded a mixture of
three amino sulfides, whose configurations have not been
unequivocally established, with low stereoselectivity (5a/
5′a/5′′a ) 50:29:21; Table 1, entry 2). By contrast, only
one diastereomeric 1,2-amino sulfide 4a (>98% de,
measured by 1H NMR) was obtained in high yield (85%)
in the reaction of (S)-2 with (S)-3a (Table 1, entry 1).
These results indicate that the matched pair of the
reagents is that formed by the sulfoxide and the imine
with identical configuration at sulfur, and a double-
induction process is necessary to attain a high stereo-
selectivity. This situation is consistent with that found
in other benzyl carbanions previously studied.10b,c Con-
sequently, the (S)-N-p-tolylsulfinylaldimines were chosen
as electrophiles for further studies with (S)-2. The results
of these reactions are collected in Table 2.
The reactions with arylaldimines 3b-e afforded
1,2-diaryl-1,2-amino sulfide derivatives 4b-e as single
stereoisomers (de >98%), regardless of the electronic
character of the substituents at the aryl group (entries
1-5). No other diastereoisomer could be detected by NMR
(300 MHz) from the reaction crudes. The isolated yields
ranged between 60 and 85%.
Alkylaldimines 3f-h were also studied with analogous
results (entries 6-8). It is remarkable that by using only
clear solutions of n-BuLi to prepare LDA one diastereo-
isomer was formed in reactions from 3f and 3g.18 Finally,
the reaction with the N-sulfinylimine derived from pival-
aldehyde has also been studied. It affords a 76:24 mixture
of two stereoisomers, 4i and 4′i, in 70% yield.19
(17) The signals of several amino sulfides, probably more than two,
could be recognized in the 1H NMR spectrum of the crude reaction
obtained from 3′a but they could not be isolated.
(18) Otherwise a 86:14 mixture of two diastereoisomers (4f + 4′f
from 3f and 4g + 4′g from 3g) were formed, presumably due to the
partial racemization at the benzyl carbon, as it has been previously
reported for other benzylthioethers in the presence of lithium salts
(lithium alcoholates or thiolates). See ref 12a and the Experimental
Section.
(20) Hirota, M.; Sekiya, T.; Abe, K.; Tashiro, H.; Karatsu, M.
Tetrahedron 1983, 39, 3091-3099.
(21) Specific rotation of compound 8: [R]20 ) -4.7 (c 0.5, MeOH)
D
[lit.10b [R]20 ) -4.5 (c 0.7, MeOH)].
D
(19) The configurational assignment of the minor isomer has not
been unequivocally established.
(22) De values higher than 98% were determined by using the
Mosher amides protocol.
3916 J. Org. Chem., Vol. 70, No. 10, 2005

Synthesis of 1,2-Diaryl- and 1,2-Alkylaryl-1,2-amino Sulfides
FIGURE 1. Values of the vicinal coupling constant for compounds 4 and X-ray structure for 4a.
SCHEME 3
SCHEME 4
FIGURE 2. Plausible transition states of the reaction of Li-
(S)-2 with (S)-N-sulfinylimines.
result in the two possible approaches of the (S)-imine to
the presumably most stable conformation of the nucleo-
philic carbanion derived from (S)-2, which is that depicted
in Figure 2. It displays the tolyl and SMe groups in a
pseudoaxial arrangement avoiding the benzylic strain
with their ortho protons. Moreover, the pseudoaxial
arrangement of the S-Me group must be favored be-
cause it allows the stabilization of the R-thio-substituted
carbanions by n-σS-C* overlapping which requires an
antiperiplanar arrangement of the S-CH3 and C-Li
bonds27 (such arrangement would be destabilized for
conformations with the SMe group in pseudoequatorial
orientation due to its steric interactions with the ortho
proton).28
compounds following reported procedures.23 Thus, de-
sulfinylation of 4a with t-BuLi (1.8 equiv) affords the
N-protected amino sulfide 10a in nearly quantitative
yield. It can be converted into the optically pure amino
sulfide 11a24 by reaction with TFA/MeOH. Reaction of
9a with t-BuLi yielded a complex reaction mixture.
These results suggest that compounds 4 can be used
for preparing the amino sulfides 11 and their N-protected
derivatives 10, able to act as a bidentate ligands. Also,
derivatives 9, containing an additional sulfinyl group, are
interesting since they could be used as tridentate chelat-
ing N,S,O-ligands exhibiting a different ability to coor-
dinate to metal transition ions.25 Moreover, manipulation
of the sulfide functionality allows interesting chemical
transformations of these compounds.26
On the basis on the steric interactions, TS-1 (affording
compounds anti) must be clearly favored with respect to
(25) (a) Abram, U.; Ortner, K.; Gust, R.; Sommer, K. J. Chem. Soc.,
Dalton Trans. 2000, 735-744. (b) Casas, J. S.; Castin˜eiras, A.;
Rodr´ıguez-Argu¨elles, M. C.; Sa´nchez, A.; Sordo, J.; Va´zquez-Lo´pez, A.;
Va´zquez-Lo´pez, E. M. J. Chem. Soc., Dalton Trans. 2000, 4056-4063.
(c) Kaasjager, V. E.; Broeke, J.; Henderson, R. K.; Smeets, W. J. J.;
Spek, A. L.; Driessen, W. L.; Bouwman, E.; Reedijk, J. Inorg. Chim.
Acta 2001, 316, 99-104. (d) Konno, T.; Shimazaki, Y.; Kawai, M.;
Hirotsu, M. Inorg. Chem. 2001, 40, 4250-4256. (e) Adams, H.; Clunas,
S.; Fenton, D. E.; Handley, G.; McHugh, P. E. Inorg. Chem. Commun.
2002, 5, 1044-1047. (f) Adams, H.; Clunas, S.; Cummings, L. R.;
Fenton, D. E.; McHugh, P. E. Inorg. Chem. Commun. 2003, 6, 837-
840. (g) Adams, H.; Clunas, S.; Fenton, D. E.; Grengson, T. J.; McHugh,
P. E. Spey, S. E. Inorg. Chem. Acta 2003, 346, 239-247. (h) Adams,
H.; Fenton, D. E.; McHugh, P. E. Inorg. Chem. Commun. 2004, 7, 147-
150.
The stereochemical outcome of this reaction can be
rationalized according to four-membered cyclic transition
states, TS-1 and TS-2, similar to those proposed for other
benzylcarbanions, both evolving with retention of the
configuration at benzylic carbon10a,b (Figure 2). They
(26) (a) Yang, X.-F.; Zhang, M.-J.; Hou, X.-L.; Dai, L.-X. J. Org.
Chem. 2002, 67, 8097-9003. (b) Aggarwal, V. K.; Charmant, J. P. H.;
Ciampi, C.; Hornby, J. M.; O’Brien, C. J.; Hynd, G., Parsons, R. J.
Chem. Soc., Perkin Trans. 1 2001, 3159-3166.
(27) (a) Wiberg, K. B.; Castejon, H. J. Am. Chem. Soc. 1994, 116,
10489-10497. (b) Kaiser, B.; Hoppe, D. Angew. Chem., Int. Ed. Engl.
1995, 34, 323-325. (c) Dress, R. K.; Ro¨lle, T.; Hoffmann, R. W. Chem.
Ber. 1995, 128, 673-677. (d) Lehn, J. M.; Wipff, G.; Demuynck, J. Helv.
Chim. Acta 1977, 60, 1239. (e) Brandt, P.; Haeffner, F. J. Am. Chem.
Soc. 2003, 125, 48-49.
(23) Clayden, J: Mitjans, D.; Youssef, L. H. J. Am. Chem. Soc. 2002,
124, 5266-5267.
(24) (()-11a had been previously reported. See: Carren˜o, C.; Car-
retero, J. C.; Garc´ıa Ruano, J. L.; Martinez, M. C. Org. Mass Spectrom.
1990, 25, 339-342 and references therein.
(28) For a more detailed discussion about this stereochemical model
see ref 10b.
J. Org. Chem, Vol. 70, No. 10, 2005 3917

Arroyo et al.
aqueous NH4Cl solution (2 mL) and extracted with CH2Cl2 (3
× 10 mL). The combined organic layers were dried over
MgSO4, and the solvent was removed under reduced pressure.
The residue was purified by flash column chromatography.
TS-2 (yielding the syn isomers) for the matched pair of
reagents. Changes in the configuration at the starting
N-sulfinylimine would decrease the stability difference
between TS-2 (it would become more stable) and TS-129
(it would be less stable), thus decreasing the stereo-
selectivity as observed for the mismatched pair. The
prevalent role of the sulfinyl group at the carbanion on
the stereoselectivity of these reactions is supported by
the moderated stereoselectivity observed when the sul-
fonyl carbanion derived from 2′ reacts with (S)-230 (Table
1, entry 4).
[1R,2S,(S)S]-N-{1-Phenyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4a): eluent for chromatography hexane/Et2O 1:4; yield 85%;
white solid; mp 107-108 °C (hexane/Et2O); [R]20 ) +78.3 (c
D
1.2, CHCl3); 1H NMR δ 7.88 (dd, 2H, J ) 7.6 and 1.4 Hz), 7.72
and 7.52 (2td, 2H, J ) 7.6 and 1.4 Hz), 7.42 (part of AA′BB′
system), 7.20-7.11 (m, 5H), 6.94 (bs, 4H), 6.10 (d, 1H, J ) 8.1
Hz), 4.66 (d, 1H, J ) 10.4 Hz), 4.35 (dd, 1H, J ) 10.4 and J )
8.1 Hz), 2.30 and 2.29 (two s, 6H), 0.87 (s, 3H); 13C NMR δ
141.9, 141.7, 141.6, 141.2, 140.7, 140.4, 133.1, 130.9, 129.3,
128,7, 128.5, 128.0, 127.8, 127.3, 125.8, 125.0, 61.9, 50.3, 21.2,
15.3. HRMS calcd for C29H29NO2S3 519.1361, found 519.1368.
Conclusion
In summary, we have described a highly stereoselective
reaction of the lithium (S)-2-(p-toluenesulfinyl)-R-(meth-
ylthio)benzyl carbanion, Li-(S)-2, with aromatic and
aliphatic (S)-N-sulfinylaldimines 3. This reaction pro-
vides an efficient method for the preparation of optically
pure anti-1,2-diaryl (with identical or different aromatic
residues) and 1-alkyl-2-aryl-1,2-amino sulfides deriva-
tives, 4, which can be transformed into interesting
bicoordinative S,N (10 and 11) or tricoordinative S,N,O
(9) ligands.
[(S)R]-N-{1-Phenyl-2-[(S)-2-(p-toluensulfinyl)phenyl]-
2-(methylthio)ethyl}-p-toluenesulfinamide (5a): eluent for
chromatography hexane/Et2O 1:4; yield 55%; colorless oil;
[R]20D ) -112.6 (c 0.5, CHCl3); 1H NMR δ 7.55 (d, 2H, J ) 7.7
Hz), 7.45-7.20 (m, 7H), 7.11, 6.99, 6.92 and 6.86 (two AA′BB′
system, 8H), 5.65 (d, 1H, J ) 3.2 Hz), 4.95-4.88 (m, 2H), 2.33
and 2.25 (two s, 6H), 1.82 (s, 3H); 13C NMR δ 143.8, 141.0,
140.9, 140.6, 140.1, 140.0, 139.3, 131.5, 129.7, 129.5, 128.9,
128.5, 127.9, 127.4, 126.9, 125.6, 125.5, 57.7, 51.8, 21.3 and
21.2, 13.5; MS (EI) m/z (relative intensity) 519 (3, M+), 380
(5), 211 (100), 139 (56), 106 (80).
[1R,2S,(S)S]-N-{1-(o-Bromophenyl-2-[(S)-2-(p-toluen-
sulfinyl)phenyl]-2-(methylthio)ethyl}-p-toluenesulfin-
amide (4b): eluent for chromatography hexane/Et2O 1:5; yield
78%; white solid; mp 153-154 °C (hexane/Et2O); [R]20D ) +75.0
(c 0.5, CHCl3); 1H NMR: δ 7.93 and 7.82 (two dd, 2H, J ) 7.6
and 0.9 Hz), 7.72, 7.63, 7.53 and 7.34 (four td, 4H, J ) 7.5
and 0.9 Hz), 7.42, 7.23, 6.99 and 6.92 (two AA′BB′ system, 8H),
7.05-7.00 (m, 2H), 6.56 (d, 1H, J ) 7.5 Hz), 5.04 (dd, 1H, J )
10.3 and 7.5 Hz), 4.69 (d, 1H, J ) 10.3 Hz), 2.31 and 2.27 (two
s, 6H), 0.84 (s, 3H); 13C NMR δ 141.7, 141.3, 141.2, 140.8,
140.5, 140.3, 133.3, 131.9, 131.3, 130.0, 128.8, 127.9, 126.6,
125.9, 124.8, 58.4, 51.2, 21.2, 14.1. calcd for C29H28 BrNO2S3
599.0445, found 599.0427.
Experimental Section
Synthesis of (S)-R-Methylthio-2-(p-tolylsulfinyl)tolu-
ene (2). A solution of n-BuLi 1.6 M in hexane (1.1 mL, 1.74
mmol, 1.2 equiv) was added over iPr2NH (0.37 mL, 2.61 mmol,
1.8 equiv) in THF (4 mL) at 0 °C. After 45 min of stirring, the
mixture was cooled at -78 °C, and then a solution of (S)-2-p-
tolylsulfinyltoluene10b (400 mg, 1.45 mmol, 1.0 equiv) in THF
(3 mL) was added. After 15 min of stirring, (CH3)2S2 (3.9 mmol,
2 equiv) was added at -78 °C. When the reaction was
completed (30 min), the mixture was hydrolyzed at that
temperature with saturated aqueous NH4Cl solution (2 mL)
and extracted with CH2Cl2 (3 × 10 mL). The combined organic
layers were dried over MgSO4, and the solvent was removed
under reduced pressure. The residue was purified by flash-
[1R,2S,(S)S]-N-{1-(p-Methoxyphenyl-2-[(S)-2-(p-toluen-
sulfinyl)phenyl]-2-(methylthio)ethyl}-p-toluenesulfin-
amide (4c): eluent for chromatography hexane/Et2O 1:5; yield
72%; white solid; mp 117-118 °C (hexane/Et2O); [R]20D ) +48.1
column chromatography (hexane/Et2O 1:1) to give pure com-
pound 2 (70%): [R]20 ) -147.6 (c 1.1, CHCl3); H NMR (300
1
1
D
(c 1.0, CHCl3); H NMR δ 7.87 (dc, 1H, J ) 7.6 and 1.1 Hz),
MHz, CDCl3) δ 7.87-7.82 (m, 1H), 7.54 and 7.23 (AA′BB′
7.71 and 7.54 (two td, 2H, J ) 7.6 and 1.1 Hz), 7.41, 7.15, 7.07,
6.98 and 6.92, 6.75 (three AA′BB′ system, 12H), 5.84 (d, 1H,
J ) 8.2 Hz), 4.66 (d, 1H, J ) 10.4 Hz), 4.33 (dd, 1H, J ) 10.4
and 8.2 Hz), 3.78 (s, 3H), 2.31 and 2.30 (two s, 6H), 0.95 (s,
3H); 13C NMR δ 158.8, 141.9, 141.8, 141.7, 141.3, 140.7, 140.3
and 134.0, 133.0, 130.7, 130.0, 128.7, 128.4, 127.8, 125.7, 125.1,
113.5, 61.8, 50.5, 55.1, 21.2, 14.3; calcd for C30H31NO3S3
549.1466, found 549.1453.
system, 4H), 7.44-7.31 (m, 3H), 3.84 (AB system, 2H, Jgem
)
13.8 Hz), 2.34 (s, 3H), 2.00 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 143.9, 141.4, 141.3, 136.5, 130.9, 130.0, 129.8, 128.4, 125.8,
125.5, 34.2 , 21.2, 15.1; HRMS calcd for C15H16OS2 276.0643,
found 276.0639.
General Procedure for the Reactions Summarized in
Tables 1 and 2. A solution of n-BuLi 1.6 M in hexane (0.60
mmol, 1.2 equiv) was added over iPr2NH (0.89 mmol, 1.8 equiv)
in THF (3 mL) at 0 °C. After 45 min of stirring, the mixture
was cooled at -78 °C and then a solution of the nucleophile
[(S)-2 or 2′; 0.50 mmol, 1.0 equiv] in THF (2 mL) was added.
After 5 min of stirring, the electrophile [sulfinylimine31 (3a-
i), 1.0 mmol, 2.0 equiv] dissolved in THF (4 mL) was added at
-78 °C. When the reaction was completed (5-10 min), the
mixture was hydrolyzed at that temperature with saturated
[1R,2S,(S)S]-N-{1-(p-Cyanophenyl-2-[(S)-2-(p-toluen-
sulfinyl)phenyl]-2-(methylthio)ethyl}-p-toluenesulfin-
amide (4d): eluent for chromatography hexane/Et2O 1:5; yield
60%; white solid; mp 135-136 °C (hexane/Et2O); [R]20D ) +59.0
1
(c 0.6, CHCl3); H NMR δ 7.92 and 7.83 (two dd, 2H, J ) 7.6
and 0.9 Hz), 7.77 and 7.56 (two td, 2H, J ) 7.6 and 0.9 Hz),
7.45, 7.39, 7.24, 7.22, 6.97 and 6.93 (three AA′BB′ system,
12H), 6.85 (d, 1H, J ) 7.6 Hz), 4.61 (d, 1H, J ) 10.7 Hz), 4.31
(dd, 1H, J ) 10.7 and 7.6 Hz), 2.33 and 2.29 (two s, 6H), 0.66
(s, 3H); 13C NMR δ 147.9, 141.4, 141.2, 141.1, 140.9, 140.7,
140.4, 133.6, 131.6, 131.4, 130.1, 129.6, 128.7, 128.3, 128.0,
125.8, 124.5, 59.9, 49.6, 21.2, 14.0; calcd for C30H28 N2O2S3
544.1313, found 544.1306.
(29) It can be easily deduced from Figure 2 by changing the relative
position of the O and Tol groups at the N-sulfinyl moiety, because the
interaction (Tol/H)1,3-parallel is higher than (O/H)1,3-parallel
.
(30) Benzylation of optically pure N-sulfinylimines with organo-
metallic does not usually evolve with complete stereoselectivity (see
ref 10b). The higher acidity of the benzyl protons at 6a and 7a could
have some role in the obtained 6a/7a ratio (Table 1, entry 4).
(31) (a) Davis, F. A.; Reddy, R. E.; Szewczyk, J. M.; Reddy, G. V.;
Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, T. R.; Zhou, P.; Carroll,
P. J. J. Org. Chem. 1997, 62, 2555-2563. (b) Davis, F. A.; Zhang, Y.;
Andemichael, Y.; Fang, T.; Fanelli, D. L.; Zhang, H. J. Org. Chem.
1999, 64, 1403-1406.
[1R,2S,(S)S]-N-{1-(2-Naphthyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4e): eluent for chromatography hexane/Et2O 1:5; yield 70%;
white solid; mp 101-102 °C (hexane/Et2O); [R]20D ) +122.0 (c
1
0.5, CHCl3); H NMR δ 7.94 and 7.88 (2dd, 2H, J ) 7.7 and
1.2 Hz), 7.79-7.40 (m, 9H), 7.45, 7.18, 6.97, and 6.77 (two
3918 J. Org. Chem., Vol. 70, No. 10, 2005

Synthesis of 1,2-Diaryl- and 1,2-Alkylaryl-1,2-amino Sulfides
AA′BB′ system, 8H), 6.37 (d, 1H, J ) 7.7 Hz), 4.78 (d, 1H, J )
10.6 Hz), 4.49 (dd, 1H, J ) 10.6 and 7.7 Hz), 2.29 and 2.10
(two s, 6H), 0.77 (s, 3H); 13C NMR δ 141.7, 141.5, 141.2, 140.8,
140.6, 140.4, 139.0, 132.7, 132.6, 133.3, 131.1, 130.0, 129.6,
128.8, 128.5, 128.1, 127.8, 127.5, 126.9, 125.8, 125.7 124.8,
124.6, 61.1, 49.7, 21.2, 20.9, 14.3; calcd for C33H31 NO2S3
569.1517, found 569.1515.
(s, 3H), 0.94 (s, 9H); 13C NMR δ 144.0, 142.1, 141.5, 141.3,
136.8, 131.7, 131.2, 130.0, 129.6, 128.8, 126.2, 124.9, 124.4,
69.3, 37.7, 28.2, 21.3, 15.7; calcd for C27H33 NO2S3 499.1674,
found 499.1688.
[(S)S]-N-{1-tert-Butyl-2-[(S)-2-(p-toluensulfinyl)phenyl]-
2-(methylthio)ethyl}-p-toluenesulfinamide (4′i): eluent
for chromatography hexane/Et2O 1:3; yield 18%; white syrup;
[R]20 ) +59 (c 1, CHCl3); 1H NMR δ 8.01 and 7.74 (two d,
[1R,2S,(S)S]-N-{1-Propyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4f): eluent for chromatography hexane/Et2O 1:1; yield 50%;
D
2H, J ) 7.8 Hz), 7.63-7.58 and 7.46-7.42 (two m, 2H), 7.61,
7.45, 7.29 and 7.27 (two AA′BB′ system, 8H), 4.98 (d, 1H, J )
7.8 Hz), 4.83 (d, 1H, J ) 3.1 Hz), 3.53 (dd, 1H, J ) 7.8 and 3.1
Hz), 2.42 and 2.38 (two s, 6H), 1.72 (s, 3H), 0.91 (s, 9H).
white solid; mp 80-81 °C (hexane/Et2O); [R]20 ) +50 (c 0.5,
D
CHCl3); 1H NMR δ 7.95 and 7.78 (two dd, 2H, J ) 7.6 and 1.3
Hz), 7.65-7.51 (m, 2H), 7.30, 7.07, 6.93 and 6.72 (two AA′BB′
system, 8H), 4.35 (d, 1H, J ) 9.6 Hz), 3.68-3.57 (m, 2H), 2.37
and 2.25 (two s, 6H), 1.62 (s, 3H), 1.60-1.21 (m, 4H), 0.93 (t,
3H, J ) 7.1 Hz); 13C NMR δ 143.3, 142.3, 141.8, 141.1, 140.8,
140.6, 132.2, 129.8, 129.5, 129.1, 127.8, 125.9,125.4, 125.2,
61.2, 49.5, 37.0, 17.7, 21.3, 14.2, 14.0; calcd for C26H31 NO2S3
485.1517, found 485.1496.
[(S)S]-N-{1-Phenyl-2-[2-(p-toluensulfonyl)phenyl]-2-
(methylthio)ethyl}-p-toluenesulfinamide (6a): eluent for
chromatography hexane/Et2O 1:4; yield 85%; white syrup;
1
[R]20 ) +113.5 (c 0.5, CHCl3); H NMR δ 8.02 and 7.83 (two
D
dd, 2H, J ) 7.1 and 0.9 Hz), 7.72-7.55 (m, 2H), 7.43 (t, 1H, J
) 7.1 Hz), 7.29-7.11 (m, 4H), 7.63, 7.09, 6.87 and 6.78 (two
AA′BB′ system, 8H), 5.23 (d, 1H, J ) 8.7 Hz), 4.85 (d, 1H, J )
10.5 Hz), 4.41 (dd, 1H, J ) 8.7 and 10.5 Hz), 2.25 and 2.20
(two s, 6H), 0.92 (s, 3H).
[(S)S]-N-{1-Propyl-2-[(S)-2-(p-toluensulfinyl)phenyl]-
2-(methylthio)ethyl}-p-toluenesulfinamide (4′f). This prod-
uct has only been detected when a cloudy solution of n-BuLi
was used in reaction with sulfinylimine 3f: eluent for chro-
Representative Procedure for C-S Desulfinylation.
To a stirred solution of 4a (0.12 mmol) in THF (2 mL) was
added t-BuLi (0.15 mL, 0.22 mmol, 1.5 M in hexane, 1.8 equiv).
When the reaction was completed (5 min), the mixture was
hydrolyzed with saturated aqueous NH4Cl solution (1 mL) and
extracted with CH2Cl2 (3 × 3 mL). The combined organic layers
were dried over MgSO4, and the solvent was removed under
reduced pressure. The residue was purified by flash column
chromatography (hexane/Et2O 1:1) to give pure 10a in quan-
titative yield: colorless syrup; [R]20D ) +155.8 (c 0.7, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.33-7.21 (m, 7H), 7.20-7.15
(m, 3H), 7.00-6.98 (m, 2H), 4.76 (dd, 1H, J ) 6.1 and 6.5 Hz),
4.75 (bs, 1H), 4.21 (d, 1H, J ) 6.5 Hz) 2.31 (s, 3H), 1.84 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 141.2, 141.0, 139.4, 138.4,
129.1, 128.4, 127.9, 127.6, 125.6, 61.2, 59.4, 21.2 , 14.9.
Representative Procedure for N-S Desulfinylation.
To a stirred solution of 4a, 4g, or 10a (0.05 mmol) in methanol
(1 mL) was added TFA (12.5 µL, 0.15 mmol, 3 equiv). After
the mixture was stirred for 3 h at 0 °C, the solvent was
evaporated, and the residue was purified by SCX column
chromatography to afford the corresponding amine.
matography hexane/Et2O 1:1; yield 10%; white syrup; [R]20
D
) -30 (c 0.3, CHCl3); 1H NMR δ 8.17 and 7.74 (two dd, 2H, J
) 6.3 and 1.4 Hz), 7.83, 7.61, 7.31 and 7.25 (two AA′BB′
system, 8H), 7.62-7.44 (m, 2H), 4.72 (d, 1H, J ) 4.2 Hz), 4.51
(d, 1H, J ) 10.4 Hz), 3.92-3.79 (m, 1H), 2.43 and 2.34 (two s,
6H), 1.61 (s, 3H), 1.61-1.15 (m, 4H), 0.84 (t, 3H, J ) 7.0 Hz).
[1R,2S,(S)S]-N-{1-Butyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4g): eluent for chromatography hexane/Et2O 1:1.5. yield 65%;
white solid; mp 96-97 °C (hexane/Et2O); [R]20D ) +49.5 (c 0.5,
CHCl3); 1H NMR δ 7.92 and 7.77 (two dd, 2H, J ) 7.6 and 1.3
Hz), 7.64-7.51 (m, 2H), 7.29, 7.06, 6.91 and 6.72 (two AA′BB′
system, 8H), 4.34 (d, 1H, J ) 9.8 Hz), 3.63 (d, 1H, J ) 9.3
Hz), 3.65-3.50 (m, 1H), 2.35 and 2.23 (two s, 6H), 1.60 (s, 3H),
1.59-1.12 (m, 6H), 0.92 (t, 3H, J ) 7.3 Hz); 13C NMR δ 143.2,
142.2, 141.8, 141,1, 140.8, 140.5, 132.1, 129.7, 129.0, 127.8,
127.0, 126.0, 125.4, 125.2, 61.1, 49.3, 34.4, 26.3, 22.5, 21.3, 14.1,
13.9; calcd for C27H33 NO2S3 499.1673, found 499.1675.
[(S)S]-N-{1-Butyl-2-[(S)-2-(p-toluensulfinyl)phenyl]-2-
(methylthio)ethyl}-p-toluenesulfinamide (4′g). This prod-
uct has only been detected when a cloudy solution of n-BuLi
was used in reaction with sulfinylimine 3g: eluent for chro-
(1S)-1-Phenyl-2-[(S)-2-(p-toluensulfinyl)phenyl]-2-
(methylthio)ethylamine (9a). This product was obtained
from 4a: yield 90%; yellow oil; [R]20 ) -155 (c 0.5, CHCl3);
matography hexane/Et2O 1:1.5; yield 10%; white syrup; [R]20
D
D
1H NMR (300 MHz, CDCl3): δ 7.84 and 7.72 (2dd, 2H, J ) 7.6
and 0.9 Hz), 7.57 and 7.28 (AA′BB′ system, 4H), 7.56 (d, 1H,
J ) 8.0 Hz), 7.50-7.31 (m, 6H), 4.69 and 4.13 (2d, 2H, J ) 8.5
Hz), 2.37 (s, 3H), 1.98 (bs, 2H), 1.41 (s, 3H).
) -36 (c 0.3, CHCl3); 1H NMR δ 8.16 and 7.73 (two dd, 2H, J
) 7.7 and 1.4 Hz), 7.56-7.46 (m, 2H), 7.80, 7.61, 7.32 and 7.25
(two AA′BB′ system, 8H), 4.72 (d, 1H, J ) 4.3 Hz), 4.52 (d,
1H, J ) 10.4 Hz), 3.92-3.79 (m, 1H), 2.43 and 2.34 (two s,
6H), 1.48 (s, 3H), 1.52-1.10 (m, 6H), 0.83 (t, 3H, J ) 7.1 Hz).
(1R)-1-[(S)-2-(p-Toluensulfinyl)-1-(methylthio)benzyl]-
pentylamine (9g). This product was obtained from 4g: Yield
[1R,2S,(S)S]-N-{1-Isopropyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4h): eluent for chromatography hexane/Et2O 1:5; yield 70%;
white solid; mp 77-78 °C (hexane/Et2O); [R]20D ) +32.1 (c 1.0,
CHCl3); 1H NMR δ 7.88 and 7.81 (two dd, 2H, J ) 7.6 and 1.2
Hz), 7.66 and 7.57 (two dt, 2H, J ) 7.6 and 1.2 Hz), 7.23, 7.01,
6.94 and 6.51 (two AA′BB′ system, 8H), 4.40 (d, 1H, J ) 10.9
Hz), 3.96 (d, 1H, J ) 10.4 Hz), 3.61-3.50 (m, 1H), 2.45-2.32
(m, 1H), 2.36 and 2.26 (two s, 6H), 1.44 (s, 3H), 1.15 and 0.86
(2d, 6H, J ) 6.8 Hz; 13C NMR δ 143.0, 142.9, 142.0, 141.7,
140.7, 140.3, 132.4, 130.0, 129.0, 127.6, 126.8, 125.6, 124.8,
68.0, 47.1, 29.1, 21.0, 15.1, 13.9; calcd for C26H31 NO2S3
485.1517, found 485.1502.
[1R,2S,(S)S]-N-{1-tert-Butyl-2-[(S)-2-(p-toluensulfinyl)-
phenyl]-2-(methylthio)ethyl}-p-toluenesulfinamide
(4i): eluent for chromatography hexane/Et2O 1:3; yield 60%;
white solid; mp 47-48 °C (hexane/Et2O); [R]20D ) -81.0 (c 0.5,
CHCl3); 1H NMR δ 8.12-8.01 (two m, 2H), 7.68, 7.65, 7.32 and
7.25 (two AA′BB′ system, 8H), 7.47 (dd, 2H, J ) 8.2 and 0.8
Hz), 4.73 (d, 1H, J ) 3.4 Hz), 4.52 (d, 1H, J ) 9.9 Hz), 3.82
(dd, 1H, J ) 9.9 and 3.4 Hz), 2.42 and 2.35 (two s, 6H), 1.64
1
90%; yellow oil; [R]20 ) -23.5 (c 0.5, CHCl3); H NMR (300
D
MHz, CDCl3) δ 7.88 and 7.66 (2dd, 2H, J ) 7.7 and 0.8 Hz),
7.52 and 7.24 (AA′BB′ system, 4H), 7.50-7.41 (m, 2H), 4.22
(d, 1H, J ) 8.4 Hz), 2.91 (dt, 1H, J ) 8.4 and 2.0 Hz) 2.35 (s,
3H), 1.70 (s, 3H), 1.45-1.16 (m, 6H), 1.40 (bs, 2H), 0.87 (t,
3H, J ) 7.0 Hz).
(1R,2S)-2-(Methylthio)-1,2-diphenylethylamine (11a).
This product was obtained from 10a: yield quantitative;
colorless oil; [R]20D ) +49.5 (c 0.5, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 7.42-7.29 (m, 10H), 4.29 (bs, 1H), 3.93 (d, 1H, J )
8.3 Hz) 2.03 (bs, 2H), 1.71 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 139.4, 137.0, 128.8, 128.6, 128.3, 127.9, 127.6, 127.3, 58.1,
49.9, 15.0.
1-Phenyl-2-[2-(p-toluensulfonyl)phenyl]-2-(methyl-
thio)ethylamine (12a). This product was obtained from 6a
1
and 7a: yield 90%; yellow oil; H NMR (300 MHz, CDCl3) δ
8.19 and 7.75 (2dd, 2H, J ) 8.0 and 1.1 Hz), 7.65 and 7.47
(2dt, 2H, J ) 8.0 and 1.1 Hz), 7.82 and 7.32 (AA′BB′ system,
4H), 7.40-7.29 (m, 5H), 4.92 and 4.01 (two d, 2H, J ) 9.1 Hz),
2.40 (s, 3H), 1.98 (bs, 2H), 1.07 (s, 3H).
J. Org. Chem, Vol. 70, No. 10, 2005 3919

Arroyo et al.
11a, and 12a and complete data of X-ray crystal structure of
4a. X-ray crystal structure of 4a (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We thank DGYCT (BQU2003-
04012) for financial support.
Supporting Information Available: 1H and 13C NMR
spectra of compounds 2, 4a-i, 4′f, 4′g, 4′i, 5a, 6a, 9a,g, 10a,
JO050129X
3920 J. Org. Chem., Vol. 70, No. 10, 2005