Enantiodivergent, catalytic asymmetric synthesis of γ-amino vinyl sulfones

Article abstract of DOI:10.1021/jo0268456

A set of diversely substituted N-Boc-γ-amino vinyl sulfones has been prepared by a four-step procedure from readily available, highly enantiopure anti-N-Boc-3-amino-1,2-alkanediols. This new route, which does not depend on the accessibility of α-amino acids as starting materials, is noteworthy for its efficiency, for its generality, and for the fact that both enantiomers of a given γ-amino vinyl sulfone can be obtained with equal ease.

Full text of DOI:10.1021/jo0268456

En a n tiod iver gen t, Ca ta lytic Asym m etr ic Syn th esis of γ-Am in o
Vin yl Su lfon es
Anna Pico´, Albert Moyano,* and Miquel A. Perica`s
Unitat de Recerca en S´ıntesi Asime`trica, Departament de Quı´mica Orga`nica, Facultat de Qu´ımica,
Universitat de Barcelona, Martı´ i Franque`s 1-11, 08028-Barcelona, Spain
amoyano@qo.ub.es
Received December 13, 2002
A set of diversely substituted N-Boc-γ-amino vinyl sulfones has been prepared by a four-step
procedure from readily available, highly enantiopure anti-N-Boc-3-amino-1,2-alkanediols. This new
route, which does not depend on the accessibility of R-amino acids as starting materials, is
noteworthy for its efficiency, for its generality, and for the fact that both enantiomers of a given
γ-amino vinyl sulfone can be obtained with equal ease.
In tr od u ction
Despite this remarkable biomedicinal significance,
synthetic routes to the requisite enantiopure γ-amino
vinyl sulfones are very limited, being invariably based
on stereospecific transformations of chiral nonracemic
R-amino acids.3a,7 In particular, these procedures involve
the preparation either of R-amino aldehydes3a (a class of
compounds that can be very prone to racemization)8 or
of R-amino diazoketones7 and are therefore not easily
amenable to scale up or to extensive structural modifica-
tions in the final products. We felt, accordingly, that the
development of a more general method that would not
rely on the availability of a precise R-amino acid and that
could afford with equal ease both enantiomers of a given
γ-amino vinyl sulfone was a worthy objective and could
be instrumental in the optimization of the pharmacologi-
cal properties of peptidyl vinyl sulfone-based drugs. We
wish to report in this paper full details of a short and
efficient synthesis of N-protected γ-amino vinyl sulfones
that fulfills the above requirements.
Cysteine proteases are a subclass of peptide bond
cleaving hydrolases that can be found in viruses, bacteria,
protozoa, fungi, plants, and mammals.1 The biological
activity spectrum of these enzymes is very broad: they
have been found to be involved in mammalian cellular
turnover and apoptosis, in the replication process of
human rhinovirus, and in the life cycle of many parasitic
protozoa and worms.2 Inhibition of cysteine proteases
constitutes therefore an important strategy to develop
new drugs for treatment of tumors, inflammatory dis-
eases, infections with viruses (common cold), and bacte-
rial and protozoa infections (malaria, Chagas’ disease,
leishmaniasis). In 1995, researchers from Khepri Phar-
maceuticals first reported the use of peptidyl vinyl
sulfones (Figure 1) as potent and selective inhibitors of
cysteine proteases.3 Further investigations led to the
development of a peptidyl vinyl sulfone inhibitor of
falcipain that markedly delayed the progression of mu-
rine malaria upon in vivo evaluation.4,5 Peptidyl vinyl
sulfones have also been shown to be useful inhibitors of
the proteasome and of its bacterial homologue HsIVU.6
Resu lts a n d Discu ssion
A simple retrosynthetic analysis of γ-amino vinyl
sulfones (Scheme 1) showed that they should be readily
accessed from anti-N-Boc-3-amino-1,2-alkanediols, by a
series of synthetic operations that imply the substitution
of the primary hydroxyl by an aryl or alkyl thiolate,
oxidation of the sulfide to the sulfone level, and elimina-
tion of the secondary hydroxyl. The starting 3-amino-1,2-
alkanediols, whose chemistry we have been exploring in
the past years,9 can be obtained in a highly enantiose-
lective fashion10 through catalytic asymmetric Sharpless
epoxidation of allylic alcohols11 and seemed to be ideally
suited to our purposes.
(1) For recent reviews on cysteine proteases and their inhibitors,
see: (a) Otto, H. H.; Schirmeister, T. Chem. Rev. 1997, 97, 133-171.
(b) Lecaille, F.; Kaleta, J .; Bro¨mme, D. Chem. Rev. 2002, 102, 4459-
4488. (c) Powers, J . C.; Asgian, J . L.; Ekici, O¨ . D.; J ames, K. E. Chem.
Rev. 2002, 102, 4639-4750.
(2) Robertson, C. D.; Combs, G. H.; North, M.; Mottram, J . C. In
Perspectives in Drug Discovery and Design; Anderson, P. S., Kenyon,
G. L., Marshall, G. R., Eds.; ESCOM Science: Leiden, 1996; Vol. 6, p
99.
(3) (a) Palmer, J . T.; Rasnick, D.; Klaus, J . L.; Bro¨mme, D. J . Med.
Chem. 1995, 38, 3193-3196. (b) Bro¨mme, D.; Klaus, J . L.; Okamoto,
K.; Rasnick, D.; Palmer, J . T. Biochem. J . 1996, 315, 85-89.
(4) Olson, J . E.; Lee, G. K.; Semenov, A.; Rosenthal, P. J . Bioorg.
Med. Chem. 1999, 7, 633-638.
(5) See also: (a) Scheidt, K. A.; Roush, W. R.; McKerrow, J . H.;
Selzer, P. M.; Hansell, E.; Rosenthal. P. J . Bioorg. Med. Chem. 1998,
6, 2477-2494. (b) Kong, J .; Venkatraman, S.; Furness, K.; Nimkar,
S.; Shepherd, T. A.; Wang, Q. M.; Aube´, J .; Hanzlik, R. P. J . Med.
Chem. 1998, 41, 2579-2587.
We decided to prepare a structurally diverse set of
N-Boc-γ-amino vinyl sulfones, to assess the generality of
our projected method. We selected therefore as starting
(6) (a) Bogyo, M.; McMaster, J . S.; Gaczynska, M.; Tortorella, D.;
Goldberg, A. L.; Ploegh, H. Proc. Natl. Acad. Sci. U.S.A. 1997, 94,
6629-6634. (b) Lee, D. H.; Goldberg, A. L. Trends Cell Biol. 1998, 397-
403. (c) Overkleeft, H. S.; Bos, P. R.; Hekking, B. G.; Gordon, E. J .;
Ploegh, H. L.; Kessler, B. M. Tetrahedron Lett. 1999, 41, 6005-6009.
(7) Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asymmetry
1998, 9, 2311-2316.
(8) For a recent example of the configurational lability of R-aminated
aldehydes, see: List, B. J . Am. Chem. Soc. 2002, 124, 5656-5657.
10.1021/jo0268456 CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/05/2003
J . Org. Chem. 2003, 68, 5075-5083
5075

Pico´ et al.
F IGURE 1. Representative peptidyl vinyl sulfone inhibitors.
SCHEME 1
CHART 1
demonstrate the applicability of the method to the
preparation of more functionalized compounds.
The required anti-N-Boc-3-amino-1,2-alkanediols 1a -e
were prepared in high enantiomeric purity (ee >95%)
according to our previously described procedure (Scheme
2), which involves the catalytic asymmetric Sharpless
epoxidation of an (E)-allylic alcohol followed by the regio-
and stereoselective oxirane ring opening by an ammonia
equivalent (azide ion or benzhydrylamine).10
The selective replacement of the primary hydroxyl
group in 1a -e by an alkyl- or arylsulfonyl moiety was
effected by a three-step sequence summarized in Scheme
3 and in Table 1.
materials the amino diols 1a -e and the thiols 2a -c
(Chart 1). Whereas most of the R1 and R2 residues were
chosen on the basis of their occurrence in known peptidyl
vinyl sulfone inhibitors (see Figure 1), the phenyl moiety
in R1 was specifically selected in order to provide an entry
to γ-aryl-γ-amino vinyl sulfones, a class of compounds
that is virtually unknown in the chemical literature,12
and whose enantioselective preparation through the
corresponding stereochemically labile R-amino-R-aryl al-
dehydes would be particularly challenging. Amino diol
1e, bearing an alkoxyalkyl residue, was selected to
In the first place, amino diols 1a -e were submitted to
Mitsunobu cyclization conditions (1.07 molar equiv of
triphenylphosphine and 1.07 molar equiv of diisopropyl
azodicarboxylate in refluxing chloroform) to afford the
anti-N-Boc-(1-aminoalkyl) epoxides 3a -e in good yields
after chromatographic purification.13 Subsequent reaction
of these epoxides with 1 molar equiv of thiophenol 2a in
the presence of triethylamine led to the selective forma-
tion of the hydroxy sulfides 4a a -ea . In a similar way,
the reaction of 3c with 2-naphthalenethiol (2-NpSH, 2c)
afforded the hydroxy sulfide 4cc. The introduction of a
thiomethyl group was achieved by treatment of the
epoxides with sodium methanethiolate in refluxing metha-
nol, to give the hydroxy sulfides 4a b-4d b. It is worth
noting here that the use of an excess of sodium meth-
anethiolate and of prolonged reaction times completely
diverts the course of the process, since in these conditions
the initially formed hydroxy sulfide cyclizes to an oxazo-
lidinone (Scheme 4).14 The oxidation of the hydroxy
sulfides 4 with 2.5 molar equiv of m-chloroperbenzoic
(9) (a) Catasu´s, M.; Bueno, A.; Moyano, A.; Maestro, M. A.; Mah´ıa,
J . J . Organomet. Chem. 2002, 642, 212-226. (b) Mart´ın, R.; Islas, G.;
Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron 2001, 57, 6367-
6374. (c) Medina, E., Moyano, A.; Perica`s, M. A.; Riera, A. Helv. Chim.
Acta 2000, 83, 972-988. (d) Catasu´s, M.; Moyano, A.; Perica`s, M. A.;
Riera, A. Tetrahedron Lett. 1999, 40, 9309-9312. (e) Aguilar, N.;
Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron Lett. 1999, 40, 3913-
3916. (f) Alco´n, M.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron:
Asymmetry 1999, 10, 4639-4651. (g) Aguilar, N.; Moyano, A.; Perica`s,
M. A.; Riera, A. J . Org. Chem. 1998, 63, 3560-3567 and references
therein.
(10) (a) Caron, M.; Carlier, P. R.; Sharpless, K. B. J . Org. Chem.
1988, 53, 5185-5187. (b) Canas, M.; Poch, M.; Verdaguer, X.; Moyano,
A.; Perica`s, M. A.; Riera, A. Tetrahedron Lett. 1991, 32, 6931-6934.
(11) (a) Hanson, R. M.; Sharpless, K. B. J . Org. Chem. 1986, 51,
1922-1925. (b) Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J . Am. Chem. Soc. 1987, 109, 5765-
5780. (c) Katsuki, T.; Mart´ın, V. S. Org. React. 1996, 48, 1-299.
(12) For the serendipitous formation of racemic γ-aryl-γ-amino vinyl
sulfones, see: Woodgate, P. D.; Sutherland, H. S. J . Organomet. Chem.
2001, 628, 155-168.
(13) Castejo´n, P.; Pasto´, M.; Moyano, A.; Perica`s, M. A.; Riera, A.
Tetrahedron Lett. 1995, 36, 3019-3022.
(14) For a related transformation, see: Luly, J . R.; Dellaria, J . F.;
Platter, J . J .; Soderquist, J . L.; Yi, N. J . Org. Chem. 1987, 52, 1487-
1492.
5076 J . Org. Chem., Vol. 68, No. 13, 2003

Enantioselective Synthesis of γ-Amino Vinyl Sulfones
SCHEME 2 a
a
Reagents and conditions: (i) cat. Ti(OiPr)4, cat. D-(-)-DIPT, tBuOOH, CH2Cl2, -20 °C, 80-90%; (ii) Ph2CHNH2, Ti(OiPr)4, CH2Cl2, rt,
70%; (iii) NaN3, LiClO4, CH3CN, reflux, 94% (R1 ) Ph); (iv) Ti(OiPr)2(N3)2, benzene, reflux, 100% (R1 ) PhCH2), 93% (R1 ) (CH3)2CHCH2),
55% (R1 ) TBDMSOCH2CH2CH2); (v) H2, cat. 10% Pd/C, Boc2O, EtAcO, rt, 82% (R1 ) Ph), 92% (R1 ) PhCH2), 80% (R1 ) (CH3)2CHCH2),
85% (R1 ) TBDMSOCH2CH2CH2); (vi) H2, cat. 10% Pd(OH)2/C, Boc2O, EtOAc, rt, 93%.
SCHEME 3 a
quantitative yield and in analytically pure form after a
rapid chromatographic purification on triethylamine-
pretreated silica gel. Under these optimized conditions,
the remaining γ-alkyl-γ-amino vinyl sulfones 6ba , 6bb,
6cb, 6cc, 6d a , 6d b, and 6ea were also readily accessed
from the corresponding hydroxy sulfones (Scheme 5). In
no cases could the presence of the isomer of (Z) config-
uration be detected.
However, when this synthetic protocol was applied to
the aryl-substituted hydroxy sulfone 5a a , the exclusive
product was the achiral â,γ-unsaturated sulfone 8, prob-
ably arising from base-catalyzed isomerization of the
expected vinyl sulfone 6a a . Even when 1 molar equiv of
triethylamine was used in the mesylate elimination step,
a 1:1 mixture of 6a a and of the rearranged product 8 was
obtained (Scheme 6).
a
Reagents and conditions: (i) PPh3, DIAD, CHCl3, reflux; (ii)
thiophenol or 2-naphthalenethiol, NEt3, CH3OH, reflux; (iii)
sodium methanethiolate (1.1 equiv), CH3OH, reflux; (iv) m-CPBA,
CH2Cl2, rt.
To avoid this unwelcome isomerization, a variety of
dehydration conditions that take place in the absence of
either strong bases or acids15 were investigated. Best
results were obtained by the use of the water-soluble
carbodiimide morpho-CDI in the presence of catalytic
amounts of copper(II) chloride.16 Under these conditions,
the phenyl-substituted hydroxy sulfones 5a a and 5a b
were converted into the corresponding vinyl sulfones 6a a
and 6a b in essentially quantitative yields (Scheme 7).17
In this way, γ-aryl-γ-amino vinyl sulfones have been
enantioselectively prepared for the first time.
In summary, we have developed a short (four steps)
and efficient (average yields from 87% to 98% for each
one of the steps) route to alkyl- or aryl-substituted N-Boc-
γ-amino vinyl sulfones 6 from readily available, highly
enantiopure N-Boc-3-amino-1,2-alkanediols 1, that takes
place without loss of optical purity.18 Moreover, since the
TABLE 1. Syn th esis of N-Boc-3-a m in o-2-h yd r oxy
Su lfon es 5 fr om N-Boc-3-a m in o-1,2-a lk a n ed iols 1
epoxide 3
(% yield)
sulfide 4 sulfone 5
R1
R2
(% yield)a (% yield)a
Ph
3a (86)
3b (75)
3c (92)
Ph
CH3
Ph
CH3
Ph
CH3
4a a (100) 5a a (100)
4a b (84)
5a b (100)
PhCH2
4ba (100) 5ba (81)
4bb (92)
4ca (78)
4cb (78)
5bb (80)
5ca (100)
5cb (79)
5cc (87)
5d a (97)
PhCH2CH2
2-naphthyl 4cc (87)
Ph
CH3
Ph
(CH3)2CHCH2
3d (95)
3e (81)
4d a (84)
4d b (86) 5d b (86)
4ea (89) 5ea (85)
TBDMSO(CH2)3
a
Isolated yields of analytically pure products.
acid took place uneventfully, and the corresponding
2-hydroxy sulfones 5 were obtained in good to excellent
yields.
(15) See: Bartoli, G.; Bellucci, M. C.; Petrini, M.; Marcantoni, E.;
Sambri, L.; Torregiani, E. Org. Lett. 2000, 2, 1791-1793, and refer-
ences therein.
(16) (a) Aggarwal, V. K.; Lightowler, M.; Lindell, S. D. Synlett 1992,
730-732. (b) Delouvrie´, B.; Na´jera, F.; Fensterbank, L.; Malacria, M.
J . Organomet. Chem. 2002, 643-644, 130-135.
(17) This dehydration procedure can also be applied to the alkyl-
substituted â-hydroxy sulfones. Thus, compound 5cc (3 molar equiv
morpho-CDI, cat. CuCl2, CH3CN, reflux, 11 h) afforded the correspond-
ing vinyl sulfone 6cc in 92% yield.
(18) Both the melting point and the rotatory power of the known
vinyl sulfone 6bb were higher than those reported in the literature.19
Moreover, HPLC analysis established a 95% ee for this compound (see
Experimental Section).
We next selected the hydroxy sulfone 5ca for the
evaluation of the reaction conditions for the dehydration
step. Contrary to the related precedent of Sengupta et
al.,7 we found that neither pyridine nor triethylamine
could effect, at room temperature, the elimination of the
mesylate formed in situ. On the other hand, when 5ca
was treated successively with mesyl chloride and 4-(dim-
ethylamino)pyridine in dichloromethane at room tem-
perature, the desired product 6ca was obtained in
J . Org. Chem, Vol. 68, No. 13, 2003 5077

Pico´ et al.
SCHEME 4
SCHEME 5
SCHEME 6
SCHEME 7
Exp er im en ta l Section
Gen er a l Ma ter ia ls a n d Meth od s. Melting points were
determined in an open capillary tube and are uncorrected.
Optical rotations were measured at room temperature (23 °C);
concentrations are given in g 100 mL-1. Infrared spectra were
recorded in a Fourier transform mode, using the NaCl film
technique. Unless otherwise stated, NMR spectra were re-
corded in CDCl3 solution. Chemical shifts are given in ppm
and referenced to TMS or CHCl3. Carbon multiplicities were
established by DEPT experiments. Elemental analyses were
performed by the “Servicios Xerais de Apoio a´ Investigacio´n,
Universidade da Corun˜a”. Exact mass measurements (HRMS)
were performed by the “Unidad de Espectrometr´ıa de Masas
de la Universidad de Santiago de Compostela”. Reactions were
generally run in flame- or oven-dried glassware under a N2
atmosphere. Commercially available reagents were used as
received. Diethyl ether used in the reactions was dried by
distillation over metallic sodium and benzophenone. Dichlo-
romethane, chloroform, acetonitrile, and triethylamine were
distilled from calcium hydride. N-Boc-3-amino-1,2-alkanediols
1a -e were prepared according to our previously described
procedures.10b,21
Typ ica l P r oced u r e for th e P r ep a r a tion of N-Boc-1-(1-
a m in oa lk yl)ep oxid es: (S)-[(S)-1-(ter t-Bu t oxyca r b on y-
la m in o)-3-p h en ylp r op yl]oxir a n e (3c). To a solution of
(2S,3S)-N-Boc-3-amino-5-phenylpentane-1,2-diol (1c) (0.10 g,
0.34 mmol) and of triphenylphosphine (95 mg, 0.36 mmol) in
anhydrous chloroform (2 mL), a solution of diisopropyl azodi-
carboxylate (71 µL, 0.36 mmol) in anhydrous chloroform (1 mL)
was added in one portion. The resulting mixture was heated
to reflux for 20 h, after which time TLC analysis showed the
complete disappearance of the starting product 1c. Elimination
of the solvent followed by chromatographic purification (silica
gel, hexanes-ethyl acetate mixtures as eluents) gave 86 mg
starting materials can be obtained from a variety of allyl
alcohols in both enantiomeric forms, the present proce-
dure is more flexible and general than those previously
described and is therefore particularly well suited for the
optimization of the pharmacological properties of peptidyl
vinyl sulfone-based protease inhibitors. Contrary to the
case of γ-hydroxy vinyl sulfones,20 the chemistry of
γ-amino vinyl sulfones remains practically unexplored.
Ongoing work in our laboratory is currently centered on
the study of these biologically interesting compounds.
(19) Thompson, S. A.; Andrews, P. R.; Hanzlik, R. P. J . Med. Chem.
1986, 29, 104-111.
(20) See, inter alia: (a) Fuchs, P. L.; Braish, T. F. Chem. Rev. 1986,
86, 903-917. (b) Isobe, M. In Perspectives in the Organic Chemistry of
Sulphur; Zwanenburg, D., Klunder, A. J . H., Eds.; Elsevier: New York,
1987; Vol. 28, pp 209-229. (c) Na´jera, C.; Yus, M. J . Org. Chem. 1989,
54, 1491-1499. (d) Trost, B. M.; Seoane, P.; Mignani, P.; Acemoglu, J .
J . Am. Chem. Soc. 1989, 111, 7487-7500. (e) Corey, E. J .; Bakshi, R.
K. Tetrahedron Lett. 1990, 31, 611-614. (f) Dom´ınguez, E.; Carretero,
J . L. Tetrahedron 1990, 46, 7197-7206. (g) Carretero, J . C.; Dom´ıngu-
ez, E. J . Org. Chem. 1993, 58, 1596-1600. (h) Enders, D.; J andeleit,
B.; von Berg, S. Synlett 1997, 421-431. (i) de Vicente, J .; Go´mez
Arraya´s, J .; Can˜ada, J . C.; Carretero, J . C. Synlett 2000, 53-56. (j)
Adrio, J .; Rodr´ıguez Rivero, M.; Carretero, J . C. Chem. Eur. J . 2001,
7, 2435-2448.
(21) (a) Pasto´, M.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron:
Asymmetry 1996, 7, 243-262. (b) Alco´n, M.; Poch, M.; Moyano, A.;
Perica`s, M. A.; Riera, A. Tetrahedron: Asymmetry 1997, 8, 2967-2974.
5078 J . Org. Chem., Vol. 68, No. 13, 2003

Enantioselective Synthesis of γ-Amino Vinyl Sulfones
(92% yield) of the title compound 3c as a colorless solid. Mp:
68-70 °C. [R]D23 ) -8.5 (c ) 1.02, CHCl3). IR (NaCl film): νmax
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-p h e-
n ylth io-2-p en ta n ol (4ca ). Obtained in 78% yield, after
chromatographic purification, from epoxide 3c (0.50 g, 1.8
mmol), thiophenol 2a (184 µL, 1.8 mmol), and triethylamine
(255 µL, 1.8 mmol) in refluxing methanol (18 mL, 4 h). Mp
) 2979, 1696, 1522, 1427, 1366, 1248, 1171 cm-1 1H NMR
.
(200 MHz, CDCl3): δ 1.46 (s, 9H), 1.70-1.80 (m, 1H), 1.90-
2.02 (m, 1H), 2.66-2.78 (m, 4H), 2.90 (m, 1H), 3.50 (m, 1H),
4.52 (br s, 1H), 7.18-7.28 (m, 5H) ppm. 13C NMR (50 MHz,
CDCl3): δ 28.4 (CH3), 31.9 (CH2), 33.8 (CH2), 46.1 (CH2), 52.1
(CH), 54.1 (CH), 79.8 (Cq), 126.0 (CH), 128.3 (CH), 128.4 (CH),
141.6 (Cq), 155.7 (Cq) ppm. MS (CI, NH3) m/e: 295 (M + 18,
45%), 278 (M + 1, 46%), 240 (M - 37, 100%). HRMS (CI, NH3)
C16H24NO3 (M + 1): calcd 278.1756, found 278.1760.
23
118-119 °C. [R]D ) -11.6 (c ) 0.7, CHCl3). IR (NaCl film):
νmax ) 3347, 1681, 1528, 1299, 1248, 1169, 1017 cm-1. 1H NMR
(200 MHz, CDCl3): δ 1.45 (s, 9H), 1.65-1.93 (m, 2H), 2.57-
2.92 (m, 2H), 3.02 (m, 1H), 3.13 (dd, J ) 13.6 Hz, J ′ ) 3.2 Hz,
2H), 3.72 (br s, 2H), 4.72 (br s, 1H), 7.19-7.36 (m, 10H) ppm.
13C NMR (50 MHz, CDCl3): δ 29.4 (CH3), 31.7 (CH2), 32.4
(CH2), 38.8 (CH2), 54.3 (CH), 72.4 (CH), 79.8 (Cq), 126.0 (CH),
126.7 (CH), 128.3 (CH), 128.4 (CH), 129.1 (CH), 130.1 (CH),
141.6 (Cq), 142.3 (Cq), 157.7 (Cq) ppm. MS (CI, NH3) m/e: 388
(M + 1, 100%), 349 (M - 38, 55%), 332 (M - 55, 34%). Anal.
(C22H29NO3S) (calcd, found): C (68.18, 68.30), H (7.54, 7.78),
N (3.61, 3.23), S (8.27, 7.81).
(S)-[(S)-1-(ter t-Bu toxycar bon ylam in o)-4-(ter t-bu tyldim -
et h ylsilyloxy)bu t yl]oxir a n e (3e). Obtained in 81% yield,
after chromatographic purification, from N-Boc-3-amino-1,2-
alkanediol 1e (0.29 g, 0.80 mmol), diisopropyl azodicarboxylate
(0.17 mL, 0.86 mmol), and triphenylphosphine (0.22 g, 0.86
23
mmol) in refluxing chloroform (4 mL, 7 h). Colorless oil. [R]D
) -5.15 (c ) 1.04, CHCl3). IR (NaCl film): νmax ) 2930, 2859,
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-p h e-
n ylth io-2-h exa n ol (4d a ). Obtained in 84% yield, after chro-
matographic purification, from epoxide 3d (0.30 g, 1.3 mmol),
thiophenol 2a (135 µL, 1.3 mmol), and triethylamine (185 µL,
1.3 mmol) in refluxing methanol (10 mL, 1 h). Mp 83-85 °C.
1702, 1522, 1254, 1173, 1100, 836 cm-1. H NMR (200 MHz,
1
CDCl3): δ 0.05 (s, 6H), 0.89 (s, 9H), 1.43 (s, 9H), 1.50-1.71
(m, 4H), 2.76 (d, J ) 3.6 Hz, 2H), 2.86 (m, 1H), 3.38 (m, 1H),
3.62 (t, J ) 5.4 Hz, 2H), 4.71 (br s, 1H, NH) ppm. 13C NMR
(50 MHz, CDCl3): δ -5.3 (CH3), 18.4 (Cq), 26.0 (CH3), 28.3
(CH2), 28.4 (CH3), 28.6 (CH2), 46.5 (CH2), 52.0 (CH), 54.1 (CH),
62.6 (CH2), 79.8 (Cq), 155.5 (Cq) ppm. MS (FAB+, NBA) m/e:
23
[R]D ) -25.3 (c ) 1.02, CHCl3). IR (NaCl film): νmax ) 1684,
1654, 1559, 1507, 1368, 1167, 737, 668 cm-1 1H NMR (200
.
MHz, CDCl3): δ 0.90 (d, J ) 6.6 Hz, 3H), 0.92 (d, J ) 6.6 Hz,
3H), 1.30-1.40 (m, 2H), 1.43 (s, 9H), 1.56-1.74 (m, 1H), 2.84-
2.96 (m, 1H), 3.00-3.20 (m, 1H), 3.68 (br m, 2H), 4.62 (br s,
1H, NH), 7.21-7.39 (m, 5H) ppm. 13C NMR (50 MHz, CDCl3):
δ 21.6 (CH3), 23.7 (CH3), 24.7 (CH), 28.4 (CH3), 38.6 (CH2),
38.9 (CH2), 52.9 (CH), 72.8 (CH), 79.8 (Cq), 126.5 (CH), 129.0
(CH), 129.9 (CH), 135.4 (Cq), 156.2 (Cq) ppm. MS (CI, NH3)
m/e: 340 (M + 1, 6%), 339 (M, 32%), 284 (M - 55, 100%).
HRMS (CI, NH3) C18H30NO3S (M + 1): calcd 340.1946, found
340.1936.
346 (M + 1, 100%), 468 (M + 23, 61%). HRMS (FAB+) C17H36
NO4Si (M + 1): calcd 346.2413, found 346.2397.
-
The known N-Boc-1-(1-aminoalkyl)epoxides 3a 13 (86% yield,
0.4 mmol scale), 3b22 (77% yield, 7.1 mmol scale), and 3d 14
(95% yield, 5.3 mmol scale) were obtained in a similar way.
Typ ica l P r oced u r e for th e P r ep a r a tion of N-Boc-3-
a m in o-1-p h en ylth io-2-a lk a n ols: (2S,3S)-3-(ter t-Bu toxy-
ca r bon yla m in o)-3-p h en yl-1-p h en ylth io-2-p r op a n ol (4a a ).
To a solution of the epoxide 3a (0.10 g, 0.40 mmol) in
anhydrous methanol (4 mL), triethylamine (57 µL, 0.40 mmol)
and thiophenol 2a (41 µL, 0.40 mmol) were added sequentially
via syringe. The resulting mixture was heated to reflux until
TLC analysis showed the complete disappearance of the
starting product (1 h). Elimination of the solvent followed by
chromatographic purification (triethylamine-pretreated silica
gel, 2.5% v/v, hexanes-ethyl acetate mixtures as eluents) gave
143 mg (100% yield) of the title compound 4a a as a colorless
(2S,3S)-3-(ter t-Bu toxycar bon ylam in o)-6-(ter t-bu tyldim -
eth ylsiloxy)-1-p h en ylth io-2-h exa n ol (4ea ). Obtained in
89% yield, after chromatographic purification, from epoxide
3e (0.17 g, 0.50 mmol), thiophenol 2a (51 µL, 0.50 mmol) and
triethylamine (71 µL, 0.51 mmol) in refluxing methanol (5 mL,
23
1.5 h). Colorless oil. [R]D ) -10.0 (c ) 1.1, CHCl3). IR (NaCl
film): νmax) 2931, 1696, 1654, 1507, 1252, 1169, 1100, 836
cm-1. 1H NMR (200 MHz, CDCl3): δ 0.05 (s, 6H), 0.89 (s, 9H),
1.43 (s, 9H), 1.50-1.71 (m, 4H), 2.91 (dd, J ) 13.4 Hz, J ′ )
9.0 Hz, 1H), 3.16 (dd, J ) 13.4 Hz, J ′ ) 3.4 Hz, 1H), 3.62 (t, J
) 5.5 Hz, 2H), 3.70 (br m, 1H), 4.84 (br s, 1H, NH), 7.18-7.40
(m, 5H) ppm. 13C NMR (50 MHz, CDCl3): δ -5.3 (CH3), 18.4
(Cq), 26.0 (CH3), 26.3 (CH2), 28.4 (CH3), 29.1 (CH2), 38.7 (CH2),
54.6 (CH), 62.7 (CH2), 72.5 (CH), 79.7 (Cq), 126.5 (CH), 129.0
(CH), 129.5 (CH), 135.7 (Cq), 156.2 (Cq) ppm. MS (FAB+,
NBA) m/e: 456 (M + 1, 100%), 478 (M + 23, 39%). HRMS
(FAB+) C23H42NO4SSi (M + 1): calcd 456.2604, found 456.2626.
23
solid. Mp 119-120 °C. [R]D ) +6.4 (c ) 1.02, CHCl3). IR
(NaCl film): νmax ) 1684, 1497, 1457, 1368, 1167 cm-1 1H
.
NMR (200 MHz, CDCl3): δ 1.39 (s, 9H), 2.54-2.65 (m, 1H),
2.98-3.10 (m, 1H), 3.98 (m, 1H), 4.76 (br s, 1H), 5.50 (br s,
1H), 7.23-7.33 (m, 10H) ppm. 13C NMR (50 MHz, CDCl3): δ
28.6 (CH3), 39.0 (CH2), 58.1 (CH), 72.0 (CH), 80.1 (Cq), 127.0
(CH), 128.1 (CH), 128.2 (CH), 128.8 (CH), 129.4 (CH), 130.4
(CH), 135.0 (Cq), 138.2 (Cq), 155.8 (Cq) ppm. MS (CI, NH3)
m/e: 360 (M + 1, 22%), 359 (M, 100%), 321 (M - 38, 56%),
304 (M - 55, 43%). Anal. (C20H25NO3S) (calcd, found):
(66.82, 66.99), H (7.01, 7.18), N (3.90, 3.64), S (8.92, 8.60).
C
(2S,3S)-3-(ter t-Bu toxycar bon ylam in o)-5-ph en yl-2-n aph -
th ylth io-2-p en ta n ol (4cc). To a solution of the epoxide 3c
(0.50 g, 1.80 mmol) in anhydrous methanol (18 mL), triethy-
lamine (255 µL, 1.82 mmol) and 2-naphthalenethiol 2c (0.29
g, 1.80 mmol) were added sequentially via syringe. The
resulting solution was heated to reflux for 4 h, at which point
TLC analysis showed that no starting epoxide 3c was present
in the reaction mixture. Elimination of the solvent and
chromatographic purification (triethylamine-pretreated silica
gel, 2.5% v/v, hexanes-ethyl acetate mixtures as eluents)
afforded 0.68 g (87% yield) of the title compound 4cc as a
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-4-p h en yl-1-p h e-
n ylth io-2-bu ta n ol (4ba ). The known N-Boc-3-amino-2-hy-
droxy sulfide 4ba 23 (100% yield, 0.8 mmol scale) was obtained
23
in a similar way. Mp 148-149 °C. [R]D ) -26.6 (c ) 1.0,
CHCl3). IR (NaCl film): νmax ) 3747, 3359, 1686, 1654, 1559,
1522, 1457, 1173, 741 cm-1 1H NMR (200 MHz, CDCl3): δ
.
1.34 (s, 9H), 2.83-3.02 (m, 2H), 3.16-3.30 (m, 2H), 3.30 (br s,
1H, OH), 3.68 (m, 1H), 3.87 (m, 1H), 4.60 (br s, 1H, NH), 7.16-
7.36 (m, 10H) ppm. 13C NMR (50 MHz, CDCl3): δ 28.3 (CH3),
35.8 (CH2), 38.8 (CH2), 55.9 (CH), 71.6 (CH), 80.0 (Cq), 126.4
(CH), 126.7 (CH), 128.4 (CH), 129.3 (CH), 129.5 (CH), 130.1
(CH), 138.0 (Cq), 141.4 (Cq), 156.0 (Cq) ppm.
23
colorless solid. Mp 125-127 °C. [R]D ) -23.0 (c ) 1.01,
CHCl3). IR (NaCl film): νmax ) 3357, 1683, 1524, 1297, 1248,
1
1173, 1021 cm-1. H NMR (200 MHz, CDCl3): δ 1.44 (s, 9H),
1.62-1.96 (m, 2H), 2.58-3.27 (m, 5H), 3.72 (br s, 2H), 4.71
(br s, 1H), 7.15-7.81 (m, 12H) ppm. 13C NMR (50 MHz,
CDCl3): δ 28.4 (CH3), 31.8 (CH2), 32.4 (CH2), 38.6 (CH2), 54.4
(CH), 72.5 (CH), 79.8 (Cq), 125.9 (CH), 126.6 (CH), 127.1 (CH),
127.6 (CH), 128.1 (CH), 128.3 (CH), 128.4 (CH), 128.7 (CH),
131.4 (Cq), 133.6 (Cq), 141.4 (Cq), 156.1 (Cq) ppm. MS (CI,
NH3) m/e: 455 (M + 18, 69%), 438 (M + 1, 36%), 437 (M,
(22) Barrish, J . C.; Gordon, E.; Alam, M.; Liu, P.-F.; Disacchi, G.
S.; Chen, P.; Cheng, P. T. W.; Fritz, A. W.; Greytok, J . A.; Hermsmeier,
M. A.; Humphreys, W. G.; Lis, K. A.; Marella, M. A.; Merchant, Z.;
Mitt, T.; Morrison, R. A.; Obermeier, M. T.; Pluscec, J .; Skoog, M.;
Slusarchyk, W. A.; Spergel, S. H.; Stevenson, J . M.; Sun, C.; Sundeen,
J . E.; Taunk, P.; Tino, J . A.; Warrack, B. M.; Colonno, R. J .; Zahler, R.
J . Med. Chem. 1994, 37, 1758-1768.
(23) Romeo, S.; Rich, D. H. Tetrahedron Lett. 1993, 34, 7187-7190.
J . Org. Chem, Vol. 68, No. 13, 2003 5079

Pico´ et al.
100%). Anal. (C26H31NO3S), (calcd, found): C (71.36, 71.47),
H (7.14, 7.29), N (3.20, 2.97), S (7.33, 7.48).
sodium methanethiolate (80 mg, 1.15 mmol) in anhydrous
methanol (10 mL) was heated to reflux. After 1 h, TLC analysis
showed that no starting epoxide remained and that the
hydroxy sulfide 4bb was the almost exclusive product; at this
point, only a trace of 7 was present in the reaction mixture.
The reflux was maintained for 4 h, after which time the
conversion of 4bb to 7 was essentially complete. Elimination
of the solvent and chromatographic purification (triethylamine-
pretreated silica gel, 2.5% v/v, hexanes-ethyl acetate mixtures
as eluents) afforded 0.16 g (89% yield) of the title compound 7
Typ ica l P r oced u r e for th e P r ep a r a tion of N-Boc-3-
a m in o-1-m eth ylth io-3-a lk a n ols: (2S,3S)-3-(ter t-Bu toxy-
ca r bon yla m in o)-3-p h en yl-1-m eth ylth io-2-p r op a n ol (4a b).
A solution of epoxide 3a (0.10 g, 0.40 mmol) and of sodium
methanethiolate (34 mg, 0.50 mmol) in anhydrous methanol
(5 mL) was heated to reflux until TLC analysis showed the
disappearance of the starting epoxide (4 h). Elimination of the
solvent and chromatographic purification (triethylamine-pre-
treated silica gel, 2.5% v/v, hexanes-ethyl acetate mixtures
as eluents) afforded 0.10 g (84% yield) of the title compound
23
as a colorless dense oil. [R]D ) -112.5 (c ) 1.0, CHCl3). IR
(NaCl film): νmax ) 3286, 2921, 1758, 1495, 1457, 1366, 1233,
1
1081 cm-1. H NMR (200 MHz, CDCl3): δ 2.24 (s, 3H), 2.58-
23
4a b as a colorless solid. Mp 129-130 °C. [R]D ) +29.2 (c )
3.04 (m, 4H), 4.06 (m, 1H), 4.81 (q, J ) 7 Hz, 1H), 5.15 (br s,
1H, NH), 7.16-7.35 (m, 5H) ppm. 13C NMR (50 MHz, CDCl3):
δ 16.6 (CH3), 32.7 (CH2), 36.0 (CH2), 56.5 (CH), 78.5 (CH), 127.2
(CH), 128.9 (CH), 129.0 (CH), 136.2 (Cq), 157.9 (Cq) ppm. MS
(CI, NH3) m/e: 255 (M + 18, 100%), 238 (M + 1, 28%). HRMS
(CI, NH3) C12H17NO2S (M + 1): calcd 238.0902, found 238.0903.
1.05, CHCl3). IR (NaCl film): νmax ) 3377, 1684, 1654, 1522,
1
1457, 1246, 1171, 1015 cm-1. H NMR (200 MHz, CDCl3): δ
1.41 (s, 9H), 2.09 (s, 3H), 2.16-2.28 (m, 1H), 2.56-2.62 (m,
1H), 4.03 (m, 1H), 4.72 (br m, 1H), 5.53 (br s, 1H), 7.31-7.33
(m, 5H) ppm. 13C NMR (50 MHz, CDCl3): δ 15.8 (CH3), 28.4
(CH3), 38.6 (CH2), 58.1 (CH), 72.0 (CH), 80.1 (Cq), 127.7 (CH),
127.9 (CH), 128.3 (CH), 138.1 (Cq), 155.4 (Cq) ppm. MS (CI,
NH3) m/e: 315 (M + 18, 9%), 298 (M + 1, 100%), 259 (M - 38,
75%), 242 (M - 55, 23%). Anal. (C15H23NO3S) (calcd, found):
C (60.58, 60.61), H (7.79, 7.78), N (4.71, 4.24), S (10.78, 10.41).
Typ ica l P r oced u r e for th e P r ep a r a tion of N-Boc-3-
a m in o-1-a r yl(a lk yl)su lfon yl-2-a lk a n ols: (2S,3S)-3-(ter t-
Bu toxyca r bon yla m in o)-3-ph en yl-1-ph en ylsu lfon yl-2-p r o-
p a n ol (5a a ). To a solution of the sulfide 4a a (0.107 g, 0.30
mmol) in dry dichloromethane (6 mL), a solution of m-
chloroperbenzoic acid (0.130 g, 0.75 mmol) in dry dichlo-
romethane (6 mL) was added dropwise. Stirring was main-
tained at rt until TLC analysis showed that the reaction was
complete (3 h). The reaction mixture was then cooled to 0 °C
and treated with 10% aqueous sodium sulfite (4 mL). After
15 min of stirring, the aqueous layer was separated. The
organic phase was then washed with saturated aqueous
sodium bicarbonate (5 mL) and with brine (5 mL) and dried
over magnesium sulfate. Elimination of the solvent and
chromatographic purification (triethylamine-pretreated silica
gel, 2.5% v/v, hexanes-ethyl acetate mixtures as eluents)
afforded 0.115 g (100% yield) of the title compound 5a a as a
colorless solid. Mp 158-160 °C. [R]D23 ) +3.2 (c ) 1.1, CHCl3).
IR (NaCl film): νmax ) 3504, 1702, 1497, 1366, 1308, 1153
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-4-p h en yl-1-m e-
th ylth io-2-bu ta n ol (4bb). 4bb was obtained in 92% yield,
after chromatographic purification, from epoxide 3b (0.20 g,
0.76 mmol) and sodium methanethiolate (60 mg, 0.84 mmol)
in refluxing methanol (10 mL, 0.5 h). Mp 134.5-135.5 °C.
23
[R]D ) -7.0 (c ) 1.0, CHCl3). IR (NaCl film): νmax ) 3357,
1
1685, 1527, 1316, 1250, 1171, 1015, 702 cm-1. H NMR (200
MHz, CDCl3): δ 1.35 (s, 9H), 2.11 (s, 3H), 2.49-3.03 (m, 4H),
3.20 (m, 1H), 3.71 (m, 1H), 3.88 (br s, 1H), 4.59 (br s, 1H),
7.20-7.30 (m, 5H) ppm. 13C NMR (50 MHz, CDCl3): δ 15.5
(CH3), 28.3 (CH3), 35.7 (CH2), 38.8 (CH2), 55.3 (CH), 70.6 (CH),
80.0 (Cq), 126.3 (CH), 128.3 (CH), 129.4 (CH), 137.7 (Cq), 155.6
(Cq) ppm. MS (CI, NH3) m/e: 312 (M + 1, 76%), 273 (M - 38,
100%), 256 (M - 55, 99%). HRMS (CI, NH3) C16H26NO3S (M
+ 1): calcd 312.1633, found 312.1631.
1
cm-1. H NMR (200 MHz, CDCl3): δ 1.37 (s, 9H), 2.87-3.25
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-m e-
th ylth io-2-p en ta n ol (4cb). 4cb was obtained in 78% yield,
after chromatographic purification, from epoxide 3c (0.50 g,
1.8 mmol) and sodium methanethiolate (150 mg, 2.2 mmol) in
refluxing methanol (20 mL, 4 h). Mp 108-109 °C. [R]D23 ) -7.6
(c ) 1.02, CHCl3). IR (NaCl film): νmax ) 3357, 1685, 1522,
(m, 2H), 3.48 (m, 1H, OH), 4.45-4.58 (m, 2H), 5.50 (br s, 1H,
NH), 7.26-7.32 (m, 5H), 7.56-7.70 (m, 3H), 7.86-7.91 (m, 2H)
ppm. 13C NMR (50 MHz, CDCl3): δ 28.3 (CH3), 58.2 (CH), 59.7
(CH2), 68.2 (CH), 80.2 (Cq), 127.9 (CH), 128.1 (CH), 128.6 (CH),
129.4 (CH), 134.0 (CH), 134.1 (CH), 137.8 (Cq), 138.8 (Cq),
155.0 (Cq) ppm. MS (CI, NH3) m/e: 409 (M + 18, 100%), 354
(M - 37, 74%), 335 (M - 55, 82%). Anal. (C20H25NO5S) (calcd,
found): C (61.36, 61.08), H (6.44, 6.43), N (3.58, 3.37), S (8.19,
8.08).
1248, 1173, 1019, 699 cm-1 1H NMR (200 MHz, CDCl3): δ
.
1.46 (s, 9H), 1.70-1.92 (m, 2H), 2.09 (s, 3H), 2.49-2.78 (m,
4H), 3.02 (m, 1H), 3.68 (br s, 2H), 4.78 (br s, 1H), 7.18-7.28
(m, 5H) ppm. 13C NMR (50 MHz, CDCl3): δ 15.4 (CH3), 28.4
(CH3), 31.5 (CH2), 32.4 (CH2), 38.6 (CH2), 54.2 (CH), 71.5 (CH),
80.0 (Cq), 125.9 (CH), 128.3 (CH), 128.4 (CH), 141.6 (Cq), 156.0
(Cq) ppm. MS (CI, NH3) m/e: 343 (M + 18, 100%), 326 (M +
1, 15%), 325 (M, 83%), 287 (M - 38, 32%). Anal. (C17H27NO3S)
(calcd, found): C (62.74, 62.85), H (8.36, 8.49), N (4.30, 4.14),
S (9.85, 9.96).
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-3-p h en yl-1-m e-
th ylsu lfon yl-2-p r op a n ol (5a b). Obtained in 100% yield, after
chromatographic purification, from sulfide 4a b (55 mg, 0.3
mmol). IR (NaCl film): νmax ) 1719, 1685, 1507, 1366, 1283,
1
1121, 1071 cm-1. H NMR (200 MHz, CDCl3): δ 1.42 (s, 9H),
3.00 (s, 3H), 3.02-3.33 (m, 2H), 3.32 (br s, 1H, OH), 4.53 (m,
1H), 4.69 (m, 1H), 5.29 (br s, 1H, NH), 7.33-7.39 (m, 5H) ppm.
13C NMR (50 MHz, CDCl3): δ 28.6 (CH3), 43.0 (CH3), 58.4
(CH2), 59.3 (CH), 69.7 (CH), 80.9 (Cq), 127.9 (CH), 128.8 (CH),
129.3 (CH), 137.8 (Cq), 156.0 (Cq) ppm. MS (CI, NH3) m/e: 347
(M + 18, 9%), 330 (M + 1, 88%), 291 (M - 38, 18%), 274 (M -
55, 100%). HRMS (CI, NH3) C15H24NO5S (M + 1): calcd
330.1375, found 330.1363.
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-m e-
th ylth io-2-h exa n ol (4d b). 4d b was obtained in 86% yield,
after chromatographic purification, from epoxide 3d (0.30 g,
1.31 mmol) and sodium methanethiolate (101 mg, 1.44 mmol)
23
in refluxing methanol (20 mL, 1 h). Mp 109-110 °C. [R]D
)
-24.4 (c ) 1.0, CHCl3). IR (NaCl film): νma`x ) 3359, 2952,
1679, 1530, 1329, 1254, 1171, 1057 cm-1. H NMR (200 MHz,
1
CDCl3): δ 0.90 (d, J ) 6.6 Hz, 3H), 0.92 (d, J ) 6.6 Hz, 3H),
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-4-p h en yl-1-p h e-
n ylsu lfon yl-2-bu ta n ol (5ba ). Obtained in 81% yield, after
chromatographic purification, from sulfide 4ba (0.20 g, 0.55
1.25-1.37 (m, 2H), 1.45 (s, 9H), 1.61-1.76 (m, 1H), 2.12 (s,
3H), 2.45-2.71 (m, 2H), 3.68 (m, 2H), 4.63 (br s, 1H) ppm. 13
C
23
NMR (50 MHz, CDCl3): δ 15.5 (CH3), 21.6 (CH3), 23.7 (CH3),
24.7 (CH), 28.4 (CH3), 38.4 (CH2), 38.6 (CH2), 52.7 (CH), 72.0
(CH), 79.8 (Cq), 156.0 (Cq) ppm. MS (CI, NH3) m/e: 295 (M +
18, 8%), 278 (M + 1, 100%), 239 (M - 38, 23%), 223 (M - 54,
58%). Anal. (C13H27NO3S), (calcd, found): C (56.28, 56.48), H
(9.81, 9.80), N (5.05, 4.99), S (11.56, 11.49).
mmol). Mp 154-155 °C. [R]D ) +3.0 (c ) 1.04, CHCl3). IR
(NaCl film): νmax ) 3355, 1692, 1526, 1316, 1148, 1013, 739
1
cm-1. H NMR (200 MHz, CDCl3): δ 1.30 (s, 9H), 2.83-3.02
(m, 2H), 3.19-3.38 (m, 2H), 3.82 (br s, 1H, OH), 3.98 (m, 1H),
4.14 (m, 1H), 4.60 (br s, 1H, NH), 7.19-7.26 (m, 5H), 7.57-
7.72 (m, 3H), 7.89-7.93 (m, 2H) ppm. 13C NMR (50 MHz,
CDCl3): δ 28.2 (CH3), 35.9 (CH2), 55.3 (CH), 59.9 (CH2), 68.1
(CH), 80.2 (Cq), 126.6 (CH), 127.9 (CH), 128.5 (CH), 129.3
(4S,5S)-4-Ben zyl-5-(m eth ylth io)m eth yl-1,3-oxa zolid in -
2-on e (7). A solution of epoxide 3b (0.20 g, 0.76 mmol) and of
5080 J . Org. Chem., Vol. 68, No. 13, 2003

Enantioselective Synthesis of γ-Amino Vinyl Sulfones
23
(CH), 129.4 (CH), 134.1 (CH), 136.9 (Cq), 139.0 (Cq), 155.6 (Cq)
ppm. MS (CI, NH3) m/e: 423 (M + 18, 7%), 406 (M + 1, 5%),
405 (M, 19%), 366 (M - 39, 100%), 349 (M - 56, 41%). Anal.
(C21H27NO5S), (calcd, found): C (62.20, 62.10), H (6.71, 6.77),
N (3.45, 3.44), S (7.91, 7.78).
0.60 mmol). Mp 106-107 °C [R]D ) -16.2 (c ) 1.03, CHCl3).
IR (NaCl film): νmax ) 2960, 1962, 1521, 1449, 1368, 1304,
1144 cm-1. 1H NMR (200 MHz, CDCl3): δ 0.90 (d, J ) 6.6 Hz,
3H), 0.92 (d, J ) 6.6 Hz, 3H), 1.30-1.40 (m, 2H), 1.40 (s, 9H),
1.56-1.74 (m, 1H), 3.26 (d, J ) 5.5 Hz, 2H), 3.62 (m, 1H), 3.78
(br s, 1H, OH), 4.11 (m, 1H), 4.62 (br s, 1H, NH), 7.54-7.69
(m, 3H), 7.90-7.98 (m, 2H) ppm. 13C NMR (50 MHz, CDCl3):
δ 21.5 (CH3), 23.6 (CH3), 24.6 (CH), 28.3 (CH3), 38.9 (CH2),
52.9 (CH), 59.8 (CH2), 69.3 (CH), 80.1 (Cq), 127.9 (CH), 129.3
(CH), 133.9 (CH), 139.4 (Cq), 156.0 (Cq) ppm. MS (CI, NH3)
m/e: 372 (M + 1, 18%), 371 (M, 86%), 316 (M - 55, 100%).
HRMS (CI, NH3) C18H30NO5S (M + 1): calcd 372.1845, found
372.1842. Anal. (C18H29NO5S.0.25H2O) (calcd, found): C (57.50,
57.26), H (7.91, 7.72), N (3.73, 3.89), S (8.53, 8.97).
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-4-p h en yl-1-m e-
th ylsu lfon yl-2-bu ta n ol (5bb). Obtained in 80% yield, after
chromatographic purification, from sulfide 4bb (0.20 g, 0.64
23
mmol). Mp 155-156 °C. [R]D ) -23.1 (c ) 0.9, CHCl3). IR
(NaCl film): νmax ) 3359, 1686, 1521, 1301, 1254, 1169, 1129,
1
1013 cm-1. H NMR (200 MHz, CDCl3): δ 1.36 (s, 9H), 2.72-
2.95 (m, 2H), 3.03 (s, 3H), 3.18 (br d, 2H), 3.86 (br s, 1H, OH),
4.24 (m, 1H), 4.37 (br m, 1H), 4.65 (br s, 1H, NH), 7.20-7.33
(m, 5H) ppm. 13C NMR (50 MHz, CDCl3): δ 28.3 (CH3), 36.3
(CH2), 42.6 (CH3), 56.5 (CH), 58.4 (CH2), 69.2 (CH), 80.6 (Cq),
126.9 (CH), 128.7 (CH), 129.2 (CH), 136.7 (Cq), 156.6 (Cq) ppm.
MS (CI, NH3) m/e: 344 (M + 1, 2%), 343 (M, 11%), 305 (M -
38, 100%), 288 (M - 55, 19%). Anal. (C16H25NO5S), (calcd,
found): C (55.95, 55.85), H (7.34, 7.21), N (4.08, 3.96), S (9.34,
9.17). A 95% ee was determined for this compound by 1H NMR
spectroscopy of the corresponding Mosher’s ester.
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-m e-
th ylsu lfon yl-2-h exa n ol (5d b). 5d b was obtained in 86%
yield, after chromatographic purification, from sulfide 4d b
23
(0.10 g, 0.36 mmol). Mp 137-138 °C. [R]D ) -22.8 (c ) 1.0,
CHCl3). IR (NaCl film): νmax ) 2960, 1686, 1522, 1393, 1368,
1295, 1167, 1133 cm-1.1H NMR (200 MHz, CDCl3): δ 0.96 (d,
J ) 6.6 Hz, 3H), 0.92 (d, J ) 6.6 Hz, 3H), 1.29-1.37 (m, 2H),
1.45 (s, 9H), 1.58-1.75 (m, 1H), 2.98-3.23 (m, 2H), 3.05 (s,
3H), 3.74 (br s, 1H, OH), 4.17 (m, 1H), 4.29 (br m, 1H), 4.60
(br s, 1H, NH) ppm. 13C NMR (50 MHz, CDCl3): δ 21.6 (CH3),
23.3 (CH3), 24.8 (CH), 28.3 (CH3), 39.4 (CH2), 42.7 (CH3), 53.9
(CH), 58.1 (CH2), 70.5 (CH), 80.6 (Cq), 157.2 (Cq) ppm. MS
(CI, NH3) m/e: 327 (M + 18, 29%), 310 (M + 1, 23%), 271 (M
- 38, 100%), 254 (M - 55, 15%). Anal. (C13H27NO5S), (calcd,
found): C (50.46, 50.89), H (8.80, 8.92), N (4.53, 4.52), S (10.36,
10.35).
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-p h e-
n ylsu lfon yl-2-p en ta n ol (5ca ). 5ca was obtained in 100%
yield, after chromatographic purification, from sulfide 4ca
(0.155 g, 0.40 mmol). Mp 129-130 °C. [R]D23 ) -13.5 (c ) 1.0,
CHCl3). IR (NaCl film): νmax ) 2362, 2341, 1717, 1507, 1289,
1
1144 cm-1. H NMR (200 MHz, CDCl3): δ 1.42 (s, 9H), 1.71-
1.86 (m, 2H), 2.56-2.74 (m, 2H), 3.22 (d, J ) 5 Hz, 2H), 3.55
(br s, 1H, OH), 3.72 (m, 1H), 4.13 (m, 1H,), 4.71 (br s, 1H, NH),
7.13-7.92 (m, 10H) ppm. 13C NMR (50 MHz, CDCl3): δ 28.3
(CH3), 31.7 (CH2), 32.1 (CH2), 54.2 (CH), 60.0 (CH2), 68.8 (CH),
80.0 (Cq), 125.9 (CH), 127.8 (CH), 128.3 (CH), 128.4 (CH),
129.4 (CH), 134.0 (CH), 139.0 (Cq), 141.2 (Cq), 157.8 (Cq) ppm.
MS (CI, NH3) m/e: 437 (M + 18, 16%), 420 (M + 1, 15%), 381
(M - 38, 22%), 380 (M - 39, 100%). Anal. (C22H29NO5S) (calcd,
found): C (62.98, 62.84), H (6.97, 7.38), N (3.34, 3.28).
(2S,3S)-3-(ter t-Bu toxycar bon ylam in o)-6-(ter t-bu tyldim -
eth ylsilyloxy)-1-p h en ylsu lfon yl-2-h exa n ol (5ea ). 5ea was
obtained in 85% yield, after chromatographic purification, from
23
sulfide 4ea (80 mg, 0.18 mmol). Colorless oil. [R]D ) -4.1 (c
) 1.7, CHCl3). IR (NaCl film): νmax ) 2931, 1685, 1507, 1366,
1306, 1252, 1146, 1086, 836 cm-1 1H NMR (200 MHz,
.
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-m e-
th ylsu lfon yl-2-p en ta n ol (5cb). 5cb was obtained in 80%
yield, after chromatographic purification, from sulfide 4cb
CDCl3): δ 0.05 (s, 6H), 0.89 (s, 9H), 1.40 (s, 9H), 1.47-1.71
(m, 4H), 3.25 (m, 2H), 3.53 (br, 1H, OH), 3.60 (t, J ) 5.5 Hz,
2H), 3.82 (m, 1H), 4.10 (m, 1H), 4.88 (br s, 1H, NH), 7.54-
7.72 (m, 3H), 7.90-7.95 (m, 2H) ppm. 13C NMR (50 MHz,
CDCl3): δ -5.3 (CH3), 18.3 (Cq), 26.0 (CH3), 26.3 (CH2), 28.3
(CH3), 28.6 (CH2), 54.4 (CH), 60.0 (CH2), 62.5 (CH2), 69.0 (CH),
79.9 (Cq), 127.9 (CH), 129.3 (CH), 133.9 (CH), 139.2 (Cq), 156.1
(Cq) ppm. MS (FAB+, NBA) m/e: 488 (M + 1, 47%), 510 (M +
23, 100%). HRMS (FAB+) C23H42NO6SSi (M + 1): calcd
488.2502, found 488.2504.
Typ ica l P r oced u r e for th e P r ep a r a tion of N-Boc-γ-
a lk yl-γ-a m in o Vin yl Su lfon es: (3S,E)-3-(ter t-Bu toxyca r -
bon yla m in o)-4-p h en yl-1-p h en ylsu lfon yl-1-bu ten e (6ba ).
To a cold (0 °C) solution of the 2-hydroxy sulfone 5ba (85 mg,
0.21 mmol) and of 4-(N,N-dimethylamino)pyridine (105 mg,
0.86 mmol) in anhydrous dichloromethane (2 mL), a solution
of mesyl chloride (33 mL, 0.43 mmol) in anhydrous dichlo-
romethane (1 mL) was added via syringe. The resulting
mixture was stirred at rt for 30 min., at which time TLC
analysis showed that the reaction was complete. After dilution
with dichloromethane (3 mL), the reaction mixture was
successively washed with a cold (0 °C) 10% aqueous HCl
solution (10 mL) and with aqueous saturated sodium bicar-
bonate (2 × 5 mL). The organic phase was dried over
magnesium sulfate. Following evaporation of the solvent at
reduced pressure, column chromatography of the crude pro-
ducte (triethylamine-pretreated silica gel, 2.5% v/v, hexanes-
ethyl acetate mixtures as eluent) gave 76 mg (94% yield) of
23
(0.20 g, 0.62 mmol). Mp 125-127 °C. [R]D ) -11.6 (c ) 1.0,
CHCl3). IR (NaCl film): νmax ) 1685, 1522, 1457, 1299, 1129,
1
473 cm-1. H NMR (200 MHz, CDCl3): δ 1.46 (s, 9H), 1.67-
1.92 (m, 2H), 2.63-3.21 (m, 4H), 3.01 (s, 3H), 3.63 (m, 1H),
4.17 (br m, 1H), 4.69 (br s, 1H, NH), 7.18-7.31 (m, 5H) ppm.
13C NMR (50 MHz, CDCl3): δ 28.3 (CH3), 31.9 (CH2), 32.2
(CH2), 42.6 (CH3), 55.0 (CH), 58.2 (CH2), 70.0 (CH), 80.3 (Cq),
126.2 (CH), 128.3 (CH), 128.5 (CH), 140.6 (Cq), 156.7 (Cq) ppm.
MS (CI, NH3) m/e: 374 (M + 18, 100%). HRMS (CI, NH3)
C
17H28NO5S (M + 1): calcd 358.1688, found 358.1677. Anal.
(C17H27NO5S.0.5H2O) (calcd, found): C (55.72, 56.19), H (7.70,
7.58), N (3.82, 3.51), S (8.75, 8.93).
(2S,3S)-3-(ter t-Bu t oxyca r b on yla m in o)-5-p h en yl-1-(2-
n a p h th ylsu lfon yl)-2-p en ta n ol (5cc). 5cc was obtained in
87% yield, after chromatographic purification, from sulfide 4cc
(0.30 g, 0.69 mmol). M.p 158-159 °C. [R]D23 ) -17.7 (c ) 1.03,
CHCl3). IR (NaCl film): νmax ) 1696, 1507, 1368, 1304, 1246,
1144, 1127, 1019, 749 cm-1 1H NMR (200 MHz, CDCl3): δ
.
1.40 (s, 9H), 1.69-1.92 (m, 2H), 2.49-2.73 (m, 2H), 3.30 (d, J
) 4.6 Hz, 2H), 3.57 (br s, 1H, OH), 3.73 (m, 1H), 4.17 (m, 1H),
4.67 (br s, 1H, NH), 7.11-7.26 (m, 5H), 7.67-8.08 (m, 6H),
8.47 (s, 1H) ppm. 13C NMR (50 MHz, CDCl3): δ 28.3 (CH3),
31.7 (CH2), 32.1 (CH2), 54.3 (CH), 59.9 (CH2), 68.9 (CH), 80.1
(Cq), 122.3 (CH), 126.0 (CH), 127.8 (CH), 128.0 (CH), 128.3
(CH), 128.4 (CH), 129.4 (CH), 129.5 (CH), 129.8 (CH), 132.0
(Cq), 135.4 (Cq), 141.1 (Cq), 156.0 (Cq) ppm. MS (CI, NH3)
m/e: 487 (M + 18, 100%), 431 (M - 38, 5%). HRMS (CI, NH3)
the title compound 6ba as a colorless solid. Mp 139.0-140.5
23
°C. [R]D ) +3.2 (c ) 1.05, CHCl3). IR (NaCl film): νmax
)
1702, 1507, 1447, 1368, 1308, 1148, 1086, 753 cm-1. H NMR
(200 MHz, CDCl3): δ 1.34 (s, 9H), 2.90 (d, J ) 6.6 Hz, 2H),
4.53 (br m, 1H), 4.64 (br s, 1H, NH), 6.32 (dd, J ) 15.0 Hz,
J ′) 1.2 Hz, 1H), 6.94 (dd, J ) 15.0 Hz, J ′ ) 5.0 Hz, 1H), 7.13-
7.26 (m, 5H), 7.51-7.59 (m, 3H), 7.81 (m, 2H) ppm. 13C NMR
(50 MHz, CDCl3): δ 28.2 (CH3), 40.5 (CH2), 52.1 (CH), 80.2
1
C
26H32NO5S (M + 1): calcd 470.2001, found 470.2011. Anal.
(C26H31NO5S.0.5H2O), (calcd, found): C (65.25, 65.67), H (6.74,
6.72), N (2.93, 2.71), S (6.70, 6.74).
(2S,3S)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-p h e-
n ylsu lfon yl-2-h exa n ol (5d a ). 5d a was obtained in 97% yield,
after chromatographic purification, from sulfide 4d a (0.20 g,
J . Org. Chem, Vol. 68, No. 13, 2003 5081

Pico´ et al.
(Cq), 127.0 (CH), 127.5 (CH), 128.6 (CH), 129.2 (CH), 129.3
(CH), 130.7 (CH), 133.3 (CH), 135.5 (Cq), 140.0 (Cq), 145.7
(CH), 154.6 (Cq) ppm. MS (CI, NH3) m/e: 405 (M + 18, 100%),
(NaCl film): νmax ) 3363, 2959, 1702, 1517, 1368, 1308, 1148,
1086 cm-1. 1H NMR (200 MHz, CDCl3): δ 0.90 (d, J ) 6.6 Hz,
3H), 0.92 (d, J ) 6.6 Hz, 3H), 1.30-1.43 (m, 2H), 1.37 (s, 9H),
1.63-1.75 (m, 1H), 4.46 (br m, 2H), 6.42 (dd, J ) 15 Hz, J ′ )
1.4 Hz, 1H), 6.88 (dd, J ) 15 Hz, J ′ ) 5.0 Hz, 1H), 7.53-7.62
(m, 3H), 7.88 (dd, J ) 8.5 Hz, J ′ ) 1.8 Hz, 2H) ppm. 13C NMR
(50 MHz, CDCl3): δ 22.0 (CH3), 22.8 (CH3), 24.7 (CH), 28.2
(CH3), 43.3 (CH2), 49.4 (CH), 80.1 (Cq), 127.5 (CH), 129.2 (CH),
129.8 (CH), 133.4 (CH), 140.3 (Cq), 147.0 (CH), 154.8 (Cq) ppm.
MS (CI, NH3) m/e: 371 (M + 18, 100%), 315 (M - 38, 33%).
Anal. (C18H27NO4S) (calcd, found): C (61.16, 61.37), H (7.70,
7.78), N (3.96, 3.81), S (9.07, 8.93).
348 (M - 39, 30%). Anal. (C21H25NO4S), (calcd, found):
C
(65.09, 64.97), H (6.50, 6.55), N (3.61, 3.54), S (8.28, 8.25).
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-4-p h en yl-1-m eth -
ylsu lfon yl-1-bu ten e (6bb). 6bb was obtained in 100% yield,
after chromatographic purification, from sulfone 5bb (18 mg,
0.052 mmol). Mp 145-146 °C (lit. 143-144 °C).19 [R]D23 ) +8.4
(c ) 0.83, CHCl3) (lit: [R]D ) +6.7 (c ) 0.9, CHCl3)).19 1H
25
NMR (200 MHz, CDCl3): δ 1.40 (s, 9H), 2.87 (s, 3H), 2.92 (d,
J ) 6.2 Hz, 2H), 4.63 (br m, 2H), 6.37 (dd, J ) 15 Hz, J ′ ) 1.6
Hz, 1H), 6.89 (dd, J ) 15 Hz, J ′ ) 5.0 Hz, 1H), 7.15-7.19 (m,
2H), 7.27-7.35 (m, 3H) ppm. 13C NMR (50 MHz, CDCl3): δ
28.3 (CH3), 40.5 (CH2), 42.8 (CH3), 52.1 (CH), 80.2 (Cq), 127.1
(CH), 128.7 (CH), 129.3 (CH), 129.8 (CH), 135.5 (Cq), 147.2
(CH), 154.6 (Cq) ppm. A 95% ee was determined for this
compound by HPLC (Chiralpak AS column, 80:20 hexane/
isopropyl alcohol; tR(R) ) 25.3 min, tR(S) ) 29.2 min).
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-m eth -
ylsu lfon yl-1-h exen e (6d b). 6d b was obtained in 89% yield,
after chromatographic purification, from sulfone 5d b (50 mg,
23
0.16 mmol). Mp 69-70 °C. [R]D ) -20.3 (c ) 1.0, CHCl3). IR
(NaCl film): νmax ) 3357, 2960, 1702, 1521, 1393, 1368, 1310,
1252, 1169, 1136 cm-1. 1H NMR (200 MHz, CDCl3): δ 0.90 (d,
J ) 6.6 Hz, 3H), 0.92 (d, J ) 6.6 Hz, 3H), 1.40-1.44 (m, 2H),
1.45 (s, 9H), 1.60-1.75 (m, 1H), 2.95 (s, 3H), 4.41 (br m, 1H),
4.55 (br s, 1H, NH), 6.49 (dd, J ) 15 Hz, J ′ ) 1.4 Hz, 1H),
6.81 (dd, J ) 15 Hz, J ′ ) 5.2 Hz, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 21.9 (CH3), 22.7 (CH3), 24.7 (CH), 28.3 (CH3), 42.9
(CH3), 43.3 (CH2), 49.5 (CH), 80.2 (Cq), 128.9 (CH), 148.5 (CH),
154.9 (Cq) ppm. MS (CI, NH3) m/e: 309 (M + 18, 100%), 253
(M - 38, 97%). HRMS (CI, CH4) C13H25NO4S + C2H5: calcd
320.1895, found 320.1890.
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-p h e-
n ylsu lfon yl-1-p en ten e (6ca ). 6ca was obtained in 100%
yield, after chromatographic purification, from sulfone 5ca
23
(100 mg, 0.24 mmol). Mp 78-80 °C. [R]D ) -1.3 (c ) 0.9,
CHCl3). IR (NaCl film): νmax ) 1702, 1517, 1368, 1308, 1250,
1
1148, 1086 cm-1. H NMR (200 MHz, CDCl3): δ 1.40 (s, 9H),
1.67-1.99 (m, 2H), 2.67 (t, J ) 7.6 Hz, 2H), 4.37 (br m, 1H),
4.58 (br s, 1H, NH), 6.43 (dd, J ) 15.2 Hz, J ′ ) 1.2 Hz, 1H),
6.90 (dd, J ) 15.2 Hz, J ′ ) 5.0 Hz, 1H), 7.15-7.85 (m, 10H)
ppm. 13C NMR (50 MHz, CDCl3): δ 28.2 (CH3), 31.9 (CH2),
35.9 (CH2), 50.7 (CH), 80.1 (Cq), 126.3 (CH), 127.5 (CH), 128.2
(CH), 128.5 (CH), 129.2 (CH), 130.5 (CH), 133.4 (CH), 140.1
(Cq), 141.2 (Cq), 146.2 (CH), 154.8 (Cq) ppm. MS (CI, NH3)
m/e: 419 (M + 18, 100%), 363 (M - 38, 33%), 345 (M - 56,
19%). HRMS (CI, NH3) C22H28NO4S (M + 1): calcd 402.1739,
found 402.1736. Anal. (C22H27NO4S.0.5H2O) (calcd, found): C
(64.36, 64.42), H (6.87, 7.02), N (3.41, 3.27), S (7.81, 7.24).
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-6-(ter t-bu tyld im -
eth ylsilyloxy)-1-p h en ylsu lfon yl-1-h exen e (6ea ). 6ea was
obtained in 100% yield, after chromatographic purification,
23
from sulfone 5ea (67 mg, 0.17 mmol). Colorless oil. [R]D
)
-3.0 (c ) 1.2, CHCl3). IR (NaCl film): νmax ) 2931, 1702, 1507,
1252, 1148, 1086, 1017, 836 cm-1 1H NMR (200 MHz,
.
CDCl3): δ 0.05 (s, 6H), 0.89 (s, 9H), 1.38 (s, 9H), 1.52-1.74
(m, 4H), 3.62 (t, J ) 5.5 Hz, 2H), 4.35 (m, 1H), 4.96 (br s, 1H,
NH), 6.42 (dd, J ) 15.0 Hz, J ′ ) 1.6 Hz, 1H), 6.90 (dd, J )
15.0 Hz, J ′ ) 5.0 Hz, 1H), 7.48-7.62 (m, 3H), 7.85-7.90 (m,
2H) ppm. 13C NMR (50 MHz, CDCl3): δ -5.3 (CH3), 18.3 (Cq),
26.0 (CH3), 28.2 (CH3), 28.5 (CH2), 30.6 (CH2), 50.8 (CH), 62.3
(CH2), 79.9 (Cq), 127.5 (CH), 129.2 (CH), 130.2 (CH), 133.3
(CH), 140.2 (Cq), 146.8 (CH), 154.9 (Cq) ppm. MS (FAB+,
NBA) m/e: 492 (M + 23, 46%). HRMS (FAB+) C23H40NO5SSi
(M + 1): calcd 470.2396, found 470.2376.
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-5-p h en yl-1-m eth -
ylsu lfon yl-1-p en ten e (6cb). 6cb was obtained in 100% yield,
after chromatographic purification, from sulfone 5cb (100 mg,
23
0.28 mmol). Mp 118-120 °C. [R]D ) +5.6 (c ) 1.04, CHCl3).
IR (NaCl film): νmax ) 1700, 1521, 1310, 1248, 1167, 1135,
1048, 967, 668 cm-1 1H NMR (200 MHz, CDCl3): δ 1.46 (s,
.
9H), 1.77-1.98 (m, 2H), 2.71 (t, J ) 7.6 Hz, 2H), 2.93 (s, 3H),
4.38 (br m, 1H), 4.60 (br s, 1H, NH), 6.48 (dd, J ) 15.2 Hz, J ′
) 1.6 Hz, 1H), 6.85 (dd, J ) 15.2 Hz, J ′ ) 5.0 Hz, 1H), 7.15-
7.35 (m, 5H) ppm. 13C NMR (100 MHz, CDCl3): δ 28.3 (CH3),
31.9 (CH2), 35.8 (CH2), 42.9 (CH3), 50.6 (CH), 80.2 (Cq), 126.3
(CH), 128.3 (CH), 128.6 (CH), 129.5 (CH), 140.1 (Cq), 147.8
(CH), 154.8 (Cq) ppm. MS (CI, NH3) m/e: 357 (M + 18, 100%),
301 (M - 38, 9%). Anal. (C17H25NO4S) (calcd, found): C (60.15,
59.92), H (7.42, 7.53), N (4.13, 3.86), S (9.45, 9.82).
Typ ica l p r oced u r e for th e P r ep a r a tion of N-Boc-γ-
a m in o-γ-a r yl Vin yl Su lfon es: (3S,E)-3-(ter t-Bu toxyca r -
bon yla m in o)-3-p h en yl-1-p h en ylsu lfon yl-1-p r op en e (6a a ).
A solution of the 2-hydroxy sulfone 5a a (50 mg, 0.13 mmol),
of the carbodiimide morpho-CDI (110 mg, 0.26 mmol), and of
anhydrous cupric chloride (2 mg) in dry acetonitrile (2 mL)
was heated to 70 °C for 1 h. After cooling to rt, the reaction
mixture was filtered through a short pad of Celite and silica
gel, which was thoroughly washed with dichloromethane.
Elimination of the solvents at reduced pressure afforded the
title compound 6a a (48 mg, 100% yield) as a colorless solid.
(3S,E)-3-(ter t-Bu t oxyca r b on yla m in o)-5-p h en yl-1-(2-
n a p h th ylsu lfon yl)-1-p en ten e (6cc). 6cc was obtained in
100% yield, after chromatographic purification, from sulfone
23
23
Mp 88-89 °C. [R]D ) +31.5 (c ) 1.04, CHCl3). IR (NaCl
5cc (100 mg, 0.28 mmol). Mp 123-126 °C (dec). [R]D ) +0.6
1
film): νmax ) 1700, 1507, 1320, 1148, 1086, 753, 689 cm-1. H
(c ) 1.02, CHCl3). IR (NaCl film): νmax ) 3855, 1702, 1654,
1
1559, 1507, 1457, 1148, 1127, 668 cm-1. H NMR (200 MHz,
NMR (200 MHz, CDCl3): δ 1.38 (s, 9H), 4.89 (br s, 1H, NH),
5.47 (br m, 1H), 6.50 (dd, J ) 15 Hz, J ′ ) 1.8 Hz, 1H), 7.11
(dd, J ) 15 Hz, J ′ ) 5.0 Hz, 1H), 7.23-7.37 (m, 5H), 7.54-
7.62 (m, 3H), 7.86-7.91 (m, 2H) ppm. 13C NMR (50 MHz,
CDCl3): δ 28.2 (CH3), 55.0 (CH), 80.5 (Cq), 127.1 (CH), 127.6
(CH), 128.5 CH), 129.1 (CH), 129.2 (CH), 131.0 (CH), 133.4
(CH), 137.9 (Cq), 140.0 (Cq), 145.3 (CH), 154.4 (Cq) ppm. MS
(CI, NH3) m/e: 391 (M + 18, 99%), 374 (M + 1, 4%), 335 (M -
38, 100%), 318 (M - 55, 9%). HRMS (CI, NH3) C20H42NO4S
CDCl3): δ 1.37 (s, 9H), 1.77-1.97 (m, 2H), 2.67 (t, J ) 7.2 Hz,
2H), 4.38 (br m, 1H), 4.53 (br s, 1H, NH), 6.49 (dd, J ) 15 Hz,
J ′ ) 1.2 Hz, 1H), 6.95 (dd, J ) 15 Hz, J ′ ) 4.8 Hz, 1H), 7.11-
7.28 (m, 5H), 7.61-8.00 (m, 6H), 8.48 (s, 1H) ppm. 13C NMR
(50 MHz, CDCl3): δ 28.2 (CH3), 31.9 (CH2), 35.8 (CH2), 50.7
(CH), 80.1 (Cq), 122.4 (CH), 126.2 (CH), 127.6 (CH), 127.9
(CH), 128.2 (CH), 128.5 (CH), 129.1 (CH), 129.2 (CH), 129.3
(CH), 129.6 (CH), 130.6 (Cq), 132.1 (Cq), 135.1 (Cq), 136.8 (Cq),
146.2 (CH), 154.7 (Cq) ppm. MS (CI, NH3) m/e: 469 (M + 18,
100%). HRMS (CI, CH4) C26H29NO4S + C2H5: calcd 480.2208,
found 480.2200.
(M + 1): calcd 374.1426, found 374.1410. Anal. (C20H23
-
NO4S.0.25H2O) (calcd, found): C (63.55, 63.69), H (6.27, 6.25),
N (3.71, 3.26), S (8.48, 8.18).
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-5-m eth yl-1-p h e-
n ylsu lfon yl-1-h exen e (6d a ). 6d a was obtained in 94% yield,
after chromatographic purification, from sulfone 5d a (100 mg,
(3S,E)-3-(ter t-Bu toxyca r bon yla m in o)-3-p h en yl-1-m eth -
ylsu lfon yl-1-p r op en e (6a b). 6ab was obtained in 96% yield
from the 2-hydroxy sulfone 5a b (45 mg, 0.14 mmol). Mp 128-
23
23
0.28 mmol). Mp 74-75 °C. [R]D ) -6.0 (c ) 1.0, CHCl3). IR
130 °C. [R]D ) +50.3 (c ) 0.30, CHCl3). IR (NaCl film): νmax
5082 J . Org. Chem., Vol. 68, No. 13, 2003

Enantioselective Synthesis of γ-Amino Vinyl Sulfones
) 1702, 1654, 1559, 1507, 1457, 1312, 1165, 1135, 969, 700
cm-1. 1H NMR (200 MHz, CDCl3): δ 1.26 (s, 9H), 2.97 (s, 3H),
4.95 (br s, 1H, NH), 5.47 (br m, 1H), 6.51 (dd, J ) 15.0 Hz, J ′
) 1.8 Hz, 1H), 7.10 (dd, J ) 15.0 Hz, J ′ ) 4.5 Hz), 7.24-7.40
(m, 5H) ppm. 13C NMR (100 MHz, CDCl3): δ 29.7 (CH3), 42.9
(CH3), 55.2 (CH), 80.9 (Cq), 127.1 CH), 128.6 (CH), 129.2 (CH),
130.0 (CH), 138.8 (Cq), 146.9 (CH), 154.4 (Cq) ppm. MS (CI,
NH3) m/e: 329 (M + 18, 100%), 274 (M - 37, 13%). HRMS
(CI, NH3) C15H22NO4S (M + 1): calcd 312.1269, found 312.1263.
00050) for financial support. A.P. acknowledges a pre-
doctoral fellowship from the University of Barcelona.
We are grateful to Dr. Antoni Riera for his interest in
this work.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H-
and 13C NMR spectra of compounds 3c, 3e, 4d a , 4ea , 4bb,
7, 5a b , 5d a , 5ea , 6cc, 6d b , 6ea , and 6a b . This material
is available free of charge via the Internet at http://pubs.
acs.org.
Ack n ow led gm en t. We thank the Ministerio de
Ciencia y Tecnolog´ıa (BQU2000-0648) and the Direccio´
General de Recerca, Generalitat de Catalunya (2001SGR
J O0268456
J . Org. Chem, Vol. 68, No. 13, 2003 5083