Regio- and stereoselective synthesis of 1,3-aminoalcohol derivatives from allylamine derivatives via internal sulfinyl group participation

Article abstract of DOI:10.1016/j.tetasy.2003.11.036

The regio- and stereoselective preparation of 1,3-aminoalcohol derivatives from protected allylamines via intramolecular participation by the sulfinyl group is reported. A carbamate protecting group on nitrogen leads to products arising from nucleophilic

Full text of DOI:10.1016/j.tetasy.2003.11.036

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 365–379
Regio- and stereoselective synthesis of 1,3-aminoalcohol derivatives
from allylamine derivatives via internal sulfinyl group
participationq
Sadagopan Raghavan,a,* A. Rajender,a Suju C. Joseph,a M. Abdul Rasheeda
and K. Ravi Kumarb
aOrganic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
bX-ray Crystallography Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 5 November 2003; accepted 25 November 2003
Abstract—The regio- and stereoselective preparation of 1,3-aminoalcohol derivatives from protected allylamines via intramolecular
participation by the sulfinyl group is reported. A carbamate protecting group on nitrogen leads to products arising from nucleophilic
participation by both the sulfinyl and carbamate groups, while protection as the sulfonamide affords the product arising from
sulfinyl group participation alone.
ꢀ 2003 Elsevier Ltd. All rights reserved.
O
S
NHP R1
O
S
NHP R1
1. Introduction
NBS, H2O
Toluene
OH
R2
Ph
R2
Ph
1,3-Aminoalcohols are structural units present in many
synthetic1 and natural products2 possessing potent bio-
logical activity. Their potential as chiral auxiliaries and
ligands in asymmetric synthesis is also well recognized.3
Not surprisingly, 1,3-aminoalcohols have attracted the
attention of synthetic chemists with a number of differ-
ent strategies being devised for their construction.4 1,2-/
1,3-Stereocontrol, in the reaction of acyclic allylic and
homoallylically substituted olefins with electrophiles, by
asymmetric induction, constitutes a valuable synthetic
tactic.5 We report herein a novel methodology for the
regio- and stereoselective synthesis of 1,3-aminoalcohol
derivatives 2 from b-protected amino-c,d-unsaturated
sulfoxides 1, by 1,2-asymmetric induction via intramo-
lecular nucleophilic assistance by the sulfinyl group6
(Eq. 1).
Br
1
2
P = Boc, CO2Me, Ts
R
1 = H, Alkyl
R
2 = H, Alkyl, Aryl
ð1Þ
2. Results and discussion
The diastereomeric unsaturated sulfoxides 7–9 were
prepared in a short sequence of straightforward reac-
tions from acetonide 3.7 Thus deprotection of the acet-
onide group in 3 via treatment with cat. amounts of
camphor-10-sulfonic acid (CSA) in methanol afforded
the aminoalcohol 4. Compound 4 was further converted
into the sulfide 6 in a single step using the Hata proto-
col8 or in two steps by initial mesylation of the hydroxy
group followed by displacement of the mesylate with
9
thiophenol. Oxidation of the sulfide 6 with NaIO4
afforded an equimolar mixture of sulfoxides 7a and 7s,
which were separated by column chromatography
(Scheme 1). Deprotection of the carbamate group of 7a
and 7s individually with trifluoroacetic acid, followed by
reprotection of the resulting ammonium salt as the
q IICT Communication No. 030913.
* Corresponding author. Tel.: +91-40-27160123; fax: +91-40-271605-
12; e-mail: sraghavan@iict.ap.nic.in
0957-4166/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.036

366
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
R1
R1
BocHN
X
NBoc
a
e
O
R2
R2
4, X = OH
5, X = OMs
6, X = SPh
3
b
c
d
NHBoc
R1
NHBoc
O
S
O
S
R1
+
R2
Ph
Ph
R2
7a
7s
a, R1 = n-Bu, R2 = H
b, R1 = H, R2 = Ph
g or h
g or h
c, R1 = H, R2 = CH2OC(O)tBu
f
d, R1 = H, R2 = CH2OTBDPS
NHP
NHP
O
S
O
S
R1
R1
R2
Ph
R2
Ph
8a, P = CO2Me
9a, P = Ts
8s, P = CO2Me
9s, P = Ts
Scheme 1. Preparation of diastereomeric b-protected amino unsaturated sulfoxides. Reagents and conditions: (a) CSA (cat.), MeOH, rt, 16 h, 4a:
72%; 4b 75%; 4c: 70%; (b) MsCl, Et3N, CH2Cl2, rt, 30 min; (c) PhSH, DBU, PhH, rt, 30 min, 6a: 91%; 6b: 87%; (d) PhSSPh, PBu3P, THF, 72 ꢁC, 76 h,
6c: 63%; (e) NaIO4, MeOH, H2O, rt, 16 h, 7aa and 7as: 94%; 7ba and 7bs: 92%; 7ca and 7cs: 90%; (f) i. 0.5 M NaOH, MeOH, H2O, rt, 16 h, 95%; ii.
TBDPS–C1, imidazole, DMF, rt, 2 h, 80%; (g) i. TFA/DCM, 0 ꢁC, 30 min, 95%; ii. ClCO2Me, Et3N, 0 ꢁC to rt, 1 h, 86%; (h) i. TFA/DCM, 0 ꢁC,
30 min, 95%; ii. p-TsCl, Et3N, 0 ꢁC to rt, 1 h.
methyl carbamate or sulfonamide afforded sulfoxides
8a/8s and 9a/9s, respectively.
consequence of the inductive electron withdrawing nat-
ure of the allylic amino substituent, which would
destabilize any partial positive charge developing at C3.
(3) The reaction is general, stereoselective and proceeds
to afford a product in good yield. (4) The protecting
group on the amino substituent has very little influence
on the stereoselectivity of the reaction (i.e., compare
entries 1, 3, 5 and 2, 4, 6). (5) Opposite stereo- selectivity
is observed in products arising via carbamate and sul-
finyl group participation, indicating different reaction
pathways. The asymmetric induction in the pathway
proceeding via carbamate participation is very high. (6)
The sulfoxides with a relative syn-orientation of the
sulfinyl and amino substituents react more stereoselec-
tively than sulfoxides with an anti-disposition of sulfinyl
and amino substituents (compare entries 1, 3, 5, 7 and 9
with 2, 4, 6, 8 and 10). It is noteworthy that diastereo-
mers 7s–9s with the relative syn-disposition of the sul-
finyl and amino substituent can be selectively prepared
from 6 following the protocol reported by Lewanowicz
et al.11
The diastereomeric sulfoxides 7–9 were prepared in
order to study their reaction with N-bromosuccinimide
(NBS), which would allow us to understand the influ-
ence of the relative stereochemistry of the sulfinyl and
allylic amino substituent on the regio- and stereochem-
ical outcome of the reaction. The diastereomerically
pure sulfoxides were reacted at ambient temperature
with NBS in toluene as the solvent, in the presence
of water to afford the aminoalcohol derivatives (Table
1).
Sulfoxides 7a, wherein the allylic amino substituent was
protected as the tert-butyl carbamate, afforded products
arising from internal participation of both the carba-
mate10 and sulfinyl groups with the former pathway
being slightly favoured. The methyl carbamate moiety is
known to be a poorer nucleophile10e when compared to
the tert-butyl carbamate group. Thus sulfoxides 8a were
prepared and reacted with NBS. It is clear from entries 3
and 4 in Table 1 that the products resulting from the
sulfinyl group participation, although not formed
exclusively, are the predominant component of the
reaction mixture. The nucleophilicity of the sulfinyl
group can therefore be assumed to be inbetween that of
the tert-butyl and methyl carbamate group. In the
search for a protecting group for the amino substituent
that would not function as a nucleophile, the toluene-
sulfonamides 9 were prepared and treated with NBS.
Inspection of the table reveals the following trends: (1)
The products resulting from sulfinyl group participation
were formed exclusively in the reaction of 9 with NBS.
(2) The reaction is highly regioselective affording prod-
ucts from a 6-endo nucleophilic attack, probably as a
The regio- and stereoselectivity of the reaction can be
rationalized (as illustrated for sulfoxides 9b) by invoking
the sulfoxonium ion intermediate (I, II and III), formed
by the nucleophilic attack of the sulfinyl group on the
olefin p-complexed to the bromonium ion12 in a 6-endo
fashion followed by hydrolysis by the attack of water on
sulfur13 (Scheme 2). There is a net inversion of sulfur
configuration in going from the starting material to the
product.
The isomeric nature of products 10as/10aa, 11as/11aa,
12as/12aa, 13as/13aa, 13bs/13ba and 13ds/13da were
established by individually oxidizing the sulfoxides to
yield the identical sulfones.

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
Table 1. Regio- and stereoselective formation of bromohydrinsa
367
S. No. Allyl amino derivative
Product from sulfinyl
participation
C2/C3
syn/anti
Product from carba-
mate participation
C2/C3
syn/anti
Ratiob
(yield, %)c
O
S
NHBoc
NHBoc
O
O
O
OH
S
1
2
3
17:83
10:90
8:92
>95:<5
>95:<5
>95:<5
>95:<5
3:2 (81)
1:2 (78)
8:2 (70)
HN
O
Ph
Ph
2
Ph
Ph
4
S
Ph
Ph
Br
10as
Br
11aa
7aa
NHBoc
OH
O
S
O
NHBoc
O
S
O
S
HN
O
Br
Br
10aa
7as
11as
11aa
O
S
NHCO Me
2
NHCO Me
2
O
S
OH
Ph
Ph
Ph
Br
8aa
NHCO Me
12as
O
S
NHCO Me
2
2
OH
O
S
4
5
6
<5:>95
15:85
11as
8.5:1.5 (70)
100:0 (76)
100:0 (82)
Ph
Ph
Br
8as
NHTs
12aa
NHTs
O
S
O
S
OH
Ph
Ph
Ph
Br
13as
NHTs
9aa
NHTs
O
S
O
S
OH
<5:>95
Ph
Ph
Br
13aa
9as
NHTs
O
S
NHTs
OH
O
S
7
85:15
100:0 (75)
Ph
Ph
Ph
Br
13bs
9ba
NHTs
NHTs
O
S
O
S
OH
8
9
>95:<5
100:0 (80)
Ph
Ph
Ph
Ph
Ph
Br
9bs
NHTs
13ba
NHTs
O
S
O
S
OH
70:30d
100:0 (70)
Ph
Ph
Br
OTBDPS
OTBDPS
OTBDPS
9da
NHTs
13ds
NHTs
O
S
O
S
OH
10
85:15d
100:0 (70)
Br
OTBDPS
9ds
13da
aAll reactions were carried out on 0.5 mmol scale in the presence of 1.2 equiv of NBS and 1.5 equiv of water.
b Ratio refers to the products arising from sulfinyl versus carbamate participation, respectively.
c Yield refers to the combined yield of all the products resulting from the reaction.
d Approx. 10–15% of the regiomer was also formed.

368
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
NHTs
O
S
Ph
OH
Ph
H2O
O
S
Ph
TsHN
Ph
Ph
O
S
NHTs
Br
Br
13bs
m-CPBA
I
Ph
Ph
NHTs
Br
O
9ba
OH
Ph
O
S
NHTs
Br
OH
Ph
H2O
Ph
O
S
S
Ph
Ph
O
TsHN
Br
Sulfone
II
Stereomer of 13bs
m-CPBA
H2O
O
S
NHTs
O
S
NHTs
OH
Ph
O
S
Ph
TsHN
Ph
Ph
Ph
Ph
9bs
Br
Br
13ba
III
Scheme 2. Reaction pathways affording stereoisomeric products.
Suitable crystals were obtained from the p-nitrobenz-
enesulfonamide derivative 14bs, derived from 7bs (Eq.
2), with its structure deduced by X-ray diffraction14 (Fig.
1). Based on the crystal structure of 14bs, a structure
could be assigned to 9bs since it was also derived from
7bs. The relationship between the absolute configuration
of sulfoxides and the chiroptical properties is well
known.11;15 The positive sign observed for the primary
band (235–255 nm) in the Cotton effect curve of 9bs also
confirms the (R)-configuration for the sulfinyl group
(Fig. 2). The positive sign for the primary band in the
cotton effect curve of 9as and 9ds (Fig. 2) supports the
structure assigned to it. The CD spectra of 9aa, 9ba and
9da were almost mirror images of 9as, 9bs and 9ds,
respectively (Fig. 2).
of 7ba.16 The chemical shifts of the methine proton (C2-
H) of the diastereomeric sulfoxides are diagnostic;
the C2-H proton in the anti-series appears downfield.16
The structure of 10aa, the major stereoisomer arising
1
from 7as, was assigned by inspection of the H NMR
data of the derived oxazinone 1517 (Scheme 3). The C3
methine proton coupling with C2 and C4 methine pro-
1
tons were 8.7 and 3.5 Hz, respectively. The H NMR
data of oxazinone 11aa supported the structure assigned
to it as well. An NOE was observed between the methine
protons at C2 and C4. In addition the J values for C3
methine proton coupling with the C2 and C4 methine
protons were 3.5 and 2.5 Hz, respectively. The oxazi-
none derived from the minor isomer arising from 7as
was found to be identical to that of 11aa (Scheme 3).
This proves beyond doubt that there is inversion of
sulfur configuration6c;d in going from 7as to 10aa and its
minor stereoisomer due to intramolecular sulfinyl group
participation.18 Deprotection of the Boc group in 10as
and its subsequent treatment with methyl chloroformate
and p-toluenesulfonyl chloride in the presence of a base
afforded products identical to 12as and 13as, thus
proving their structure (Scheme 3). The relative orien-
tation of the substituents at C2–C4 in 13bs and 10aa was
proven by transforming them into tetrahydrofuran
derivatives 16 and 17, respectively.19 Compound 16
revealed NOEꢀs between the C2 and C4 methine protons
and C1 and C3 methine protons, thus proving the
assigned structure. Compound 17 revealed NOE
between C2 and C4 methine protons. The structure of
13ds/13da was assigned based on an analogy with 13bs/
13ba, respectively, since the trans-olefins 9b and 9d were
expected to react similarly.
1. TFA/CH2Cl2 (1:1), 90%
O
S
NHBoc
O
S
NHNs
Ph
Ph
Ph
Ph
2. p -NO2-C6H4-SO2Cl, Et3N
CH2Cl2, 79%
7bs
14bs
Ns = 4-nitrobenzene
sulfonyl
ð2Þ
Structures were assigned to 7as and 7ds by the
1
comparison of their H NMR data with 7bs.16 Similarly
the 1H NMR of 7aa and 7da were similar to the 1H NMR
3. Conclusion
In conclusion we have disclosed a methodology for the
regio- and stereoselective synthesis of 1,3-aminoalcohols
from allylamine derivatives via efficient asymmetric
induction and intramolecular nucleophilic participation
by the sulfinyl group. Highly functionalized products are
obtained, which can be further elaborated by carbon–
Figure 1. X-ray structure of 14bs.

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
369
P2O5 followed by CaH2 and toluene over P2O5. Com-
mercially available reagents were used without further
purification except NBS, which was freshly recrystal-
lized from hot water before use. Thin layer chroma-
tography was performed with precoated silica gel plates.
Column chromatography was carried out using silica gel
(60–120 mesh). NMR spectra were recorded on a 200,
CD-Spectra of 9aa and 9as
Light line = 9aa
5
4
Dark line = 9as
2
0
1
300 or 400 MHz spectrometer. H NMR and 13C NMR
samples were internally referenced to TMS (0.00 ppm).
Melting points are uncorrected.
-2
-3
200
220
220
220
240
260
280
300
4.1.1. Preparation of tert-butyl 4-[(Z)-1-hexenyl]-2,2-
dimethyl-(4S)-1,3-oxazolane-3-carboxylate, 3a..n-Pentyl-
phosphonium bromide (4.45 g, 11 mmol) was suspended
in dry THF (44 mL) in a round bottom flask under N2,
cooled to )78 ꢁC at which point n-BuLi (5 mL, 2 M in
hexane, 10 mmol) was added dropwise over 10 min. The
mixture was stirred for 30 min while gradually allowing
the temperature to reach 0 ꢁC after which stirring con-
tinued for a further period of 1 h at the same tempera-
ture. The resulting dark red solution was cooled to
)78 ꢁC and a solution of Garnerꢀs aldehyde (2.3 g,
10 mmol) in THF (10 mL) added dropwise over 10 min.
The reaction mixture was gradually allowed to return to
room temperature and stirred for a further period of 4 h
at room temperature. The reaction mixture was then
quenched with water and washed successively with an aq
1 M HCl solution, brine and dried over Na2SO4. Puri-
fication on a silica gel column using AcOEt/petroleum
ether (1:19, v/v) afforded 3a (1.26 g, 6.2 mmol) in 62%
Wavelength[nm]
CD-Spectra of 9ba and 9bs
6
4
2
0
Light line = 9ba
Dark line = 9bs
-2
-3
200
240
260
280
300
Wavelength[nm]
CD-Spectra of 9da and 9ds
1
5
4
yield. Liquid. H NMR (200 MHz, CDCl3) d 5.52–5.32
Light line = 9da
Dark line = 9ds
(m, 2H), 4.72–4.50 (br s, 1H), 4.02 (dd, J ¼ 9.0, 6.7 Hz,
1H), 3.61 (dd, J ¼ 9.0, 4.2 Hz, 1H), 2.24–1.98 (m, 2H),
1.56 (s, 3H), 1.54–1.24 (m, 16H), 0.91 (t, J ¼ 6.7 Hz, 3H).
IR (neat) m ¼ 3010–2830, 1695, 1375, 1250, 1175, 1090,
25
1050, 850. ½aꢀ ¼ +55.0 (c 0.95, CHCl3). MS (EI) 203
D
2
[M]þ. Anal. Calcd for C16H29NO3: C, 67.81; H, 10.31;
N, 4.94. Found: C, 67.75; H, 10.13; N, 4.72.
0
-1
200
240
260
280
300
4.1.2. Preparation of tert-butyl 2,2-dimethyl-4-[2-phenyl-
(E)-1-ethenyl]-1,3-oxazolane-3-carboxylate, 3b.. Benzyl-
phosphonium bromide (3.92 g, 11 mmol) was suspended
in dry THF (44 mL) in a round bottom flask under N2,
cooled to )78 ꢁC and n-BuLi (5 mL, 2 M in hexanes,
10 mmol) added dropwise over 10 min. The mixture was
stirred for 30 min gradually allowing the temperature to
reach 0 ꢁC and stirred further for a period of 1 h at the
same temperature. The resulting dark red solution was
cooled to )78 ꢁC and a solution of Garnerꢀs aldehyde
(2.3 g, 10 mmol) in THF (10 mL) added dropwise over
10 min. The reaction mixture was gradually allowed to
return to room temperature and then stirred for a fur-
ther period of 4 h. The reaction mixture was then
quenched with water and washed successively with aq
1 M HCl solution, brine and dried over Na2SO4.
1H NMR of the crude product revealed the presence of
cis- and trans-olefins in a ratio of 4:1. The product
mixture was subjected to isomerization following the
Wavelength[nm]
Figure 2. CD spectra. These were recorded in acetonitrile in the con-
centration range of 10ꢁ4–10ꢁ5 M.
carbon and carbon–heteroatom bond formations into
bioactive target molecules. The potential of the meth-
odology to synthesize natural products possessing the
1,3-aminoalcohol subunit is currently in progress and
shall be disclosed in due course.
4. Experimental section
4.1. General
All air or moisture sensitive reactions were carried out
under nitrogen atmosphere. Solvents were distilled
freshly, THF over Na/benzophenone ketyl, DCM over

370
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
NHBoc
OH
NHBoc
OH
O
S
H
O
S
H
O
S
O
S
O
O
H
N
H
H
N
2
2
2
4
2
4
Ph
Ph
Ph
Ph
Br
H
O
O
4
4
Br
10aa
Br
H
H
15
Br
11aa
Minor isomer
derived from 7as
NHCO2Me
OH
NHTs
NHBoc
OH
O
S
O
S
O
S
OH
Ph
2
4
Ph
Ph
B
13as
r
Br
12as
Br
10as
H
TsHN
Br
NHTs
OH
O
S
H
H
2
Ph
Ph
PhS
4
Br
13bs
O
16
Ph
H
H
TsHN
H
NHBoc
H
O
S
OH
2
Br
2
Ph
4
PhS
4
O
(CH2)3CH3
Br
10aa
H
= nOe
17
Scheme 3. Elucidation of the structure of aminoalcohols.
protocol previously reported by Schwarz et al.7a Thus,
PhSH (37 mg, 0.33 mmol) and AIBN (54 mg, 0.33 mmol)
were added to the olefin mixture (2.0 g, 6.6 mmol) in
benzene (25 mL) and refluxed for 16 h. The reaction
mixture was diluted with benzene and washed succes-
sively with 0.2 M NaOH soln, water, brine and dried
over Na2SO4. Evaporation of the volatiles under
reduced pressure followed by column chromatography
using AcOEt/petroleum ether (1:19, v/v) as the eluent
afforded 3b (2.0 g, 6.6 mmol) in 66% overall yield for 2
was removed by filtration. The filtrate was concentrated
and the residue purified by column chromatography
using AcOEt/petroleum ether (1:9, v/v) as the eluent to
afford the unsaturated ester (5.68g, 19mmol) in 95%
1
yield. Liquid. H NMR (200 MHz, CDCl3) d 6.83 (dd,
J ¼ 15.8, 8.7 Hz, 1H), 5.87 (d, J ¼ 15.8 Hz, 1H), 4.59–
4.34 (m, 1H), 4.20 (q, J ¼ 7.0 Hz, 2H), 4.12–3.98 (m,
1H), 3.73–3.68 (m, 1H), 1.68–1.39 (m, 15H), 1.25 (t,
J ¼ 7.0 Hz, 3H). IR (neat) m ¼ 2928, 1742, 1698, 1390,
1256, 1176. MS (LSIMS) 300 [M+H]þ..In a dry round
bottom flask containing dry toluene (32 mL), diiso-
butylaluminium hydride (47.5 mmol, 47.5 mL, 1 M soln
in toluene) was added, followed by n-BuLi (47.5 mmol,
23.75 mL, 2 M in hexanes) dropwise over a period of
10min at ambient temperature. The above prepared ate
complex was added to a solution of the unsaturated ester
(5.68g, 19 mmol) in toluene (38mL) and cooled at
)78 ꢁC, over a period of 10min. The reaction mixture
was stirred for 40min while gradually allowing it to
return to rt and then left to stir for a further period of
30 min. The reaction mixture was diluted with ether
(100mL) and small ice pieces added to quench the
reaction. The gel that precipitated out was filtered
through a sintered funnel and the gel washed with hot
ethyl acetate. Evaporation of the filtrate under reduced
pressure and column chromatography of the residue
using AcOEt/petroleum ether (3:7, v/v) afforded the
1
steps. Liquid. H NMR (200 MHz, CDCl3) d 7.35–7.10
(m, 5H), 6.49 (d, J ¼ 12.2 Hz, 1H), 5.68 (dd, J ¼ 12.2,
9.5 Hz, 1H), 4.91–4.75 (m, 1H), 4.23–4.08 (m, 1H), 3.86–
3.72 (m, 1H), 1.62 (s, 3H), 1.49 (s, 3H), 1.42 (s, 9H). IR
(neat) m ¼ 3060–2880, 1700, 1480, 1455, 1380, 1255,
25
1175, 1100. ½aꢀ ¼ )63.6 (c 1.0, CHCl3). MS (LSIMS)
D
304 [M+H]þ. Anal. Calcd for C18H25NO3: C, 71.26; H,
8.31; N, 4.62. Found: C, 70.97; H, 8.13; N, 4.83.
4.1.3. tert-Butyl 4-[3-(tert-butylcarbonyloxy)-(E)-1-prop-
enyl]-2,2-dimethyl-1,3-oxazolane-3-carboxylate, 3c. Ethyl-
(triphenylphosporanilidine)acetate (8.3 g, 20 mmol) was
added portionwise to a solution of Garner aldehyde
(4.6 g, 20 mmol) in benzene (60 mL) at room temperature
and then stirred for 30 min. After evaporation of the
solvent under reduced pressure, ether was added to the
residue and cooled to 0 ꢁC. Most of the triphenylphos-
phine oxide formed in the reaction precipitated out and
1
allylalcohol (3.55 g, 13.87 mmol) in 73% yield. Liquid. H
NMR (200 MHz, CDCl3) d 5.78–5.60 (m, 2H), 4.40–4.23
(m, 1H), 4.16–4.07 (m, 2H), 4.02–3.72 (m, 2H), 3.90 (br

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
371
25
s, OH), 1.61–1.42 (m, 15H). ½aꢀ ¼ +23.6 (c 0.75,
1170. MS (EI) 257 [M]þ.
NH), 4.57 (d, J ¼ 4.0 Hz, 2H), 4.26–4.22 (m, 1H), 3.72–
D
CHCl3). IR (neat) m ¼ 3445, 2980, 1696, 1392, 1255,
3.53 (m, 2H), 1.47 (s, 9H), 1.22 (s, 9H). IR (neat)
m ¼ 3369, 2975, 1712, 1699, 1518, 1367, 1284, 1163, 1059.
25
½aꢀ ¼ +3.6 (c 1.0, CHCl3). MS (LSIMS) 302 [M+H]þ.
D
To the stirred solution of allylalcohol (3.55 g,
13.9 mmol) in dry dichloromethane (56 mL) was added
successively Et3N (2.10 g, 20.8 mmol) and pivaloyl
chloride (1.81 g, 15 mmol) at 0 ꢁC. The reaction mixture
was gradually allowed to attain rt and stirred for a
further period of 25 min. The reaction mixture was
diluted with DCM, washed successively with water, 10%
aq citric acid soln, brine and dried over Na2SO4. The
organic layer was evaporated under reduced pressure,
and the crude residue purified by column chromato-
graphy using AcOEt/petroleum ether (1:9, v/v) as the
eluent to afford the ester 3c (3.91 g, 11.51 mmol) in 83%
yield (58% overall yield from Garner aldehyde). Liquid.
1H NMR (200 MHz, CDCl3) d 5.74–5.53 (m, 2H), 4.60–
4.47 (m, 2H), 4.30–4.16 (m, 1H), 4.02 (dd, J ¼ 8.9,
6.7 Hz, 1H), 3.72 (dd, J ¼ 8.9, 2.2 Hz, 1H), 1.59 (s, 3H),
1.51–1.31 (br s, 12H), 1.17 (s, 9H). IR (neat) m ¼ 3378,
Anal. Calcd for C16H29NO3: C, 59.78; H, 9.03; N, 4.65.
Found: C, 59.66; H, 9.14; N, 4.77.
4.1.5. General procedure for mesylation..To a solution of
4 (1 mmol) in dichloromethane (2 mL) cooled at 0 ꢁC
was added successively Et3N (131 mg, 1.3 mmol),
DMAP (cat.) and methanesulfonyl chloride (115 mg,
1 mmol) at 0 ꢁC and stirred for 10 min at the same
temperature. The reaction mixture was quenched by the
addition of water and then extracted into dichlorome-
thane. The organic layer was washed successively with
10% aq citric acid, aq NaHCO3, water, brine and dried
over Na2SO4. The solvent was removed under reduced
pressure and taken to the next step without further
purification.
4.1.5.1. 2-(tert-Butyloxycarbonylamido)-(Z)-3-octenyl
methanesulfonate, 5a. Viscous liquid, 95%. 1H NMR (200
MHz, CDCl3) d 5.63 (dt, J ¼ 10.8, 7.4 Hz, 1H), 5.31 (dd,
J ¼ 10.8, 8.8 Hz, 1H), 4.75–4.54 (m, 1H and NH), 4.23
(dd, J ¼ 9.7, 3.7 Hz, 1H), 4.14 (dd, J ¼ 9.7, 5.6 Hz, 1H),
2.99 (s, 3H), 2.23–2.02 (m, 2H), 1.54–1.22 (m, 13H), 0.92
(t, J ¼ 6.7 Hz, 3H).
2977, 2877, 1699, 1479, 1383, 1254, 1159, 1097.
25
½aꢀ ¼ +1.6 (c 1.0, CHCl3). MS (LSIMS) 342 [M+H]þ.
D
Anal. Calcd for C18H31NO5: C, 63.32; H, 9.15; N, 4.10.
Found: C, 63.49; H, 9.42; N, 3.87.
4.1.4. General procedure for the cleavage of the acetonide
group in 3 to yield 4.
.To the substrate 3 (5 mmol) in
methanol (20 mL) was added camphor-10-sulfonic acid
(62.5 mg, 0.25 mmol) at room temperature and stirred
for 16 h under N2 atmosphere. The reaction mixture was
quenched by the addition of a few drops of Et3N and the
solvent evaporated under reduced pressure. The crude
product mixture was chromatographed on a silica gel
column using AcOEt/petroleum ether (1:24, v/v) as the
eluent to afford the aminoalcohol 4.
4.1.5.2. 2-(tert-Butyloxycarbonylamido)-4-phenyl-(E)-
3-butenyl methanesulfonate, 5b. Liquid, 98%. H NMR
1
(200 MHz, CDCl3) d 7.38–7.18 (m, 5H), 6.63 (d,
J ¼ 15.6 Hz, 1H), 6.12 (dd, J ¼ 15.6, 6.2 Hz, 1H), 4.92 (d,
J ¼ 8.6 Hz, NH), 4.60–4.56 (m, 1H), 4.37 (dd, J ¼ 9.8,
4.4 Hz, 1H), 4.29 (dd, J ¼ 9.8, 5.1 Hz, 1H), 3.02 (s, 3H),
1.47 (s, 9H).
4.1.6. General procedure for preparation of sulfides..To a
solution of 5 (1 mmol) in benzene (2 mL) was added
successively PhSH (110 mg, 1 mmol) and DBU (228 mg,
1.5 mmol) under N2 and stirred for 30 min. The reaction
mixture was diluted with ether and washed successively
with 0.2 M aq NaOH solution, water, brine and dried
over Na2SO4. Evaporation of the solvent under reduced
pressure followed by purification on silica gel column
using AcOEt/petroleum ether (3:97, v/v) afforded the
thioether 6.
4.1.4.1. 2-(tert-Butyloxycarbonylamido)-(2R,3Z)-3-oct-
en-1-ol, 4a. Solid, 72%, mp 65–66 ꢁC. H NMR (200
MHz, CDCl3) d 5.57 (dt, J ¼ 10.9, 7.4 Hz, 1H), 5.25
(dd, J ¼ 10.9, 9.1 Hz, 1H), 4.72–4.53 (br s, NH), 4.52–
4.35 (m, 1H), 3.64–3.48 (m, 2H), 2.25–2.05 (m, 2H),
1.45 (s, 9H), 1.45–1.26 (m, 4H), 0.91 (distorted t, 3H).
1
IR (neat) m ¼ 3460–3380, 3040–2860, 1701, 1500, 1387,
25
1258, 1145. ½aꢀ ¼ +29.6 (c 1.0, CHCl3). MS (EI) 243
D
[M]þ. Anal. Calcd for C13H25NO3: C, 64.17; H, 10.35;
N, 5.76. Found: C, 64.21; H, 10.28; N, 5.72.
4.1.4.2. 2-(tert-Butyloxycarbonylamido)-4-phenyl-(2R,
3E)-3-buten-1-ol, 4b. Solid, 75%, mp 95–96 ꢁC. 1H NMR
(200 MHz, CDCl3) d 7.41–7.17 (m, 5H), 6.60 (d,
J ¼ 15.8 Hz, 1H), 6.14 (dd, J ¼ 15.8, 6.3 Hz, 1H), 4.95–
4.82 (br s, NH), 4.47–4.32 (m, 1H), 3.78 (dd, J ¼ 10.2,
4.1 Hz, 1H), 3.73 (dd, J ¼ 10.2, 4.9 Hz, 1H), 1.46 (s, 9H).
4.1.6.1. 1-Phenylsulfanyl-(2R,3Z)-3-octen-2-tert-butyl-
oxycarbonylamide, 6a. Viscous liquid, 91%. H NMR
1
(200 MHz, CDCl3) d 7.50–7.12 (m, 5H), 5.51 (dt,
J ¼ 10.8, 6.7 Hz, 1H), 5.34–5.27 (m, 1H), 4.65–4.45 (m,
1H and NH), 3.18 (dd, J ¼ 14.1, 4.7 Hz, 1H), 2.95 (dd,
J ¼ 14.1, 7.0 Hz, 1H), 2.12–1.96 (m, 2H), 1.43 (s, 9H),
1.36–1.20 (m, 4H), 0.88 (t, J ¼ 6.7 Hz, 3H). IR (neat)
IR (neat) m ¼ 3600–3280, 3005, 1700, 1500, 1270, 1170.
25
½aꢀ ¼ )40.6 (c 1.0, CHCl3). MS (EI) 263 [M]þ. Anal.
m ¼ 3312, 2927, 2897, 1698, 1503, 1400, 1245, 1163, 1023.
D
25
Calcd for C15H21NO3: C, 68.42; H, 8.04; N, 5.32.
Found: C, 68.32; H, 8.17; N, 5.70.
½aꢀ ¼ )4.0 (c 0.75, CHCl3). MS (LSIMS) 336 [M+H]þ.
D
Anal. Calcd for C19H29NO2S: C, 68.02; H, 8.71; N, 4.17;
S, 9.56. Found: C, 67.85; H, 8.43; N, 4.47; S, 9.23.
4.1.4.3. 4-(tert-Butyloxycarbonylamido)-5-hydroxy-(E,
4R)-2-pentenyl pivalate, 4c. Liquid, 70%. 1H NMR (200
MHz, CDCl3) d 5.82–5.60 (m, 2H), 4.78 (d, J ¼ 6.0 Hz,
4.1.6.2. 3-Phenyl-1-phenylsulfanylmethyl-(1R,2E)-2-
tert-butyloxycarbonylamide, 6b. Solid, 87%, mp 64–66 ꢁC.

372
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
1H NMR (200 MHz, CDCl3) d 7.40–7.10 (m, 4H), 7.33–
7.12 (m, 6H), 6.53 (d, J ¼ 15.6 Hz, 1H), 6.13 (dd, J ¼ 15.6,
5.9 Hz, 1H), 4.90–4.77 (br s, NH), 4.54–4.50 (m, 1H), 3.27
(dd, J ¼ 13.4, 5.2 Hz, 1H), 3.12 (dd, J ¼ 13.4, 5.9 Hz, 1H),
1.39–1.09 (m, 4H) 0.85 (distorted t, 3H). IR (neat)
25
m ¼ 3243, 2975, 2928, 1700, 1540, 1169. ½aꢀ ¼ +72.4 (c
D
1.0, CHCl3). MS (LSIMS) 353 [M+H]þ. Anal. Calcd for
C19H29NO3S: C, 64.92; H, 8.32; N, 3.98; S, 9.12. Found:
C, 64.73; H, 8.47; N, 3.73; S, 9.29.
1.46 (s, 9H). IR (neat) m ¼ 3375, 2928, 1696, 1500, 1366,
25
1247, 1167, 1022, 745. ½aꢀ ¼ +14.2 (c 1.1, CHCl3). MS
D
(LSIMS) 356 [M+H]þ. Anal. Calcd for C21H25NO2S: C,
70.95; H, 7.09; N, 3.94; S, 9.02. Found: C, 70.67; H, 7.19;
N, 3.73; S, 9.27.
4.1.8.3. 4-Phenyl-1-(SS)-phenylsulfinyl-(2R,3E)-3-but-
en-2-tert-butyloxycarbonylamide, 7ba. Solid, 46%, mp
1
147–148 ꢁC. H NMR (200 MHz, CDCl3) d 7.68–7.59
(m, 2H), 7.56–7.46 (m, 3H), 7.41–7.10 (m, 5H), 6.65 (d,
J ¼ 16.3 Hz, 1H), 6.37 (dd, J ¼ 16.3, 5.9 Hz, 1H), 5.90–
5.76 (br s, NH), 4.74 (quintet, J ¼ 5.9 Hz, 1H), 3.22–3.02
4.1.7. 4-(tert-Butyloxycarbonylamido)-5-phenylsulfanyl-
(E,4R)-2-pentenyl pivalate, 6c. .A hard glass tube con-
taining the alcohol 4 (2.41 g, 8 mmol), PhSSPh (5.2 g,
24 mmol) and PBu3 (6.46 g, 32 mmol) in dry THF
(32 mL) was sealed at the top at )78 ꢁC and after
attaining room temperature, heated to 72 ꢁC for 36 h.
After evaporating the solvent on a rotary evaporator the
crude product mixture was chromatographed on a silica
gel column using AcOEt/petroleum ether (1:9, v/v) as
the eluent to afford 6c in 63% yield. Low melting solid.
1H NMR (200 MHz, CDCl3) d 7.42–7.15 (m, 5H), 5.79–
5.77 (m, 2H), 4.75–4.65 (m, 1H), 4.52 (s, 2H), 4.43–4.32
(m, 1H), 3.12 (dd, J ¼ 14.1, 5.8 Hz, 1H), 2.98 (dd,
J ¼ 14.1, 5.8 Hz, 1H), 1.39 (s, 9H), 1.15 (s, 9H). IR (neat)
(m, 2H), 1.48 (s, 9H). IR (neat) m ¼ 3290, 2978, 2925,
25
1709, 1525, 1147, 1040. ½aꢀ ¼ )167.0 (c 1.04, CHCl3).
D
MS (LSIMS) 372 [M+H]þ. Anal. Calcd for
C21H25NO3S: C, 67.90; H, 6.78; N, 3.77; S, 8.63. Found:
C, 67.45; H, 7.04; N, 3.77; S, 8.53.
4.1.8.4. 4-Phenyl-1-(RS)-phenylsulfinyl-(2R,3E)-3-but-
en-2-tert-butyloxycarbonylamide, 7bs. Solid, 46%, mp
1
133–134 ꢁC. H NMR (200 MHz, CDCl3) d 7.72–7.61
(m, 2H), 7.58–7.46 (m, 3H), 7.36–7.15 (m, 5H), 6.55 (d,
J ¼ 15.2 Hz, 1H), 6.19 (dd, J ¼ 15.2, 7.0 Hz, 1H), 5.18–
5.04 (br s, NH), 4.63 (quintet, J ¼ 7.0 Hz, 1H), 3.16 (d,
m ¼ 3403, 2953, 1714, 1698, 1510, 1365, 1267, 1159, 1039.
J ¼ 7.0 Hz, 2H), 1.46 (s, 9H). IR (neat) m ¼ 3284, 2968,
25
½aꢀ ¼ +7.8 (c 1.0, CHCl3). MS (LSIMS) 394 [M+H]þ.
25
1710, 1523, 1157, 1037. ½aꢀ ¼ +13.5 (c 0.70, CHCl3).
D
D
MS (LSIMS) 372 [M+H]þ. Anal. Calcd for
C21H25NO3S: C, 67.90; H, 6.78; N, 3.77; S, 8.63. Found:
C, 67.73; H, 6.64; N, 3.84 S, 8.67.
Anal. Calcd for C21H31NO4S: C, 64.09; H, 7.94; N, 3.56;
S, 8.15. Found: C, 64.35; H, 7.63; N, 3.76; S, 8.53.
4.1.8. General procedure for the preparation of sulfoxides
from sulfides..To a solution of the substrate (1 mmol) in
methanol (10 mL) was added dropwise a solution of
NaIO4 (1 mmol) in water (5 mL) at 0 ꢁC and allowed to
attain room temperature during a period of 30 min.
After stirring for 16 h, the reaction mixture was filtered
and the resulting filtrate then evaporated to remove
most of methanol under reduced pressure. The aq resi-
due was extracted into ethyl acetate, dried over Na2SO4
and evaporated. The diastereomers were separated by
column chromatography using AcOEt/petroleum ether
(1:3, v/v) as the eluent.
4.1.8.5. 4-(tert-Butyloxycarbonylamido)-5-(SS)-phen-
ylsulfinyl-(E,4R)-2-pentenyl pivalate, 7ca. Liquid, 45%.
1H NMR (200 MHz, DMSO-d6) d 7.68–7.50 (m, 5H),
7.30 (d, J ¼ 8.4 Hz, NH), 5.76–5.62 (m, 2H), 4.57–4.32
(m, 3H), 3.0–2.80 (m, 2H), 1.40 (s, 9H), 1.12 (s, 9H). IR
(neat) m ¼ 3312, 2968, 1725, 1699, 1517, 1360, 1157,
25
1037. ½aꢀ ¼ )93.0 (c 0.75, CHCl3). MS (LSIMS) 410
D
[M+H]þ. Anal. Calcd for C21H31NO5S: C, 61.59; H,
7.63; N, 3.42; S, 7.83. Found: C, 61.23; H, 7.54; N, 3.57;
S, 7.87.
4.1.8.6. 4-(tert-Butyloxycarbonylamido)-5-(RS)-phen-
ylsulfinyl-(E,4R)-2-pentenyl pivalate, 7cs. Liquid, 45%.
1H NMR (200 MHz, CDCl3) d 7.73–7.46 (m, 5H), 5.92–
5.75 (m, 2H), 5.10–4.95 (br s, NH), 4.65–4.41 (m, 3H),
3.12–2.96 (m, 2H), 1.46 (s, 9H), 1.22 (s, 9H). IR (neat)
4.1.8.1. 1-(SS)-Phenylsulfinyl-(2R,3Z)-3-octen-2-tert-
Solid, 47%, mp 107–
butyloxycarbonylamide, 7aa.
1
109 ꢁC. H NMR (200 MHz, CDCl3) d 7.68–7.58 (m,
2H), 7.56–7.46 (m, 3H), 5.76–5.41 (m, 2H and NH),
4.90–4.70 (m, 1H), 3.17–3.03 (m, 1H), 2.89 (dd, J ¼ 13.5,
4.1 Hz, 1H), 2.25–2.01 (m, 2H), 1.60–1.28 (m, 13H), 0.91
m ¼ 3310, 2970, 1728, 1695, 1510, 1457, 1245, 1159, 1040.
25
½aꢀ ¼ +66.1 (c 0.66, CHCl3). MS (LSIMS) 410 [M+H]þ.
D
Anal. Calcd for C21H31NO5S: C, 61.59; H, 7.63; N, 3.42;
S, 7.83. Found: C, 61.42; H, 7.64; N, 3.33; S, 7.93.
(distorted t, 3H). IR (neat) m ¼ 3207, 2972, 2925, 2837,
MS (LSIMS) 353 [M+H]þ. Anal. Calcd for
C19H29NO3S: C, 64.92; H, 8.32; N, 3.98; S, 9.12. Found:
C, 65.13; H, 8.14; N, 3.63; S, 9.34.
25
D
1703, 1537, 1175, 1044. ½aꢀ ¼ )168.0 (c 1.0, CHCl3).
4.1.9. General procedure for the preparation of methyl
carbamates and sulfonamides from tert-butylcarba-
mates. .To a stirred solution of sulfoxide 7 (0.5 mmol)
in dichloromethane (0.5 mL) was added dropwise a
solution of trifluoroacetic acid/dichloromethane (1:1,
0.5 mL) at 0 ꢁC and stirred for 30 min. The solvent was
evaporated under reduced pressure, dried under vacuum
and without further purification, the ammonium salt
was taken into dichloromethane (2 mL) and treated with
triethylamine (101 mg, 1 mmol) followed by methyl-
chloroformate (47 mg, 0.5 mmol), p-TsCl (95 mg,
4.1.8.2. 1-(RS)-Phenylsulfinyl-(2R,3Z)-3-octen-2-tert-
butyloxycarbonylamide, 7as. Solid, 47%, mp 68–69 ꢁC.
1H NMR (200 MHz, CDCl3) d 7.76–7.66 (m, 2H), 7.56–
7.45 (m, 3H), 5.60–5.36 (m, 2H), 4.95–4.81 (br s, NH),
4.71 (quintet, J ¼ 6.9 Hz, 1H), 3.10 (dd, J ¼ 13.9, 6.9 Hz,
1H), 2.98–2.85 (m, 1H), 2.11–1.95 (m, 2H), 1.45 (s, 9H),

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
373
25
D
0.5 mmol) or p-nitrobenzenesulfonyl chloride (111 mg,
0.5 mmol) at 0 ꢁC. After stirring for 1 h at room tem-
perature, the reaction mixture was diluted with dichlo-
romethane and washed successively with aq citric acid,
water, brine and dried over Na2SO4. Evaporation of the
solvent under reduced pressure followed by purification
on a silica gel column using AcOEt/petroleum ether
(9:11, v/v) afforded the products 8, 9 or 14, respectively.
½aꢀ ¼ +168.7 (c 1.0, CHCl3). MS (LSIMS) 406 [M+H]þ.
Anal. Calcd for C21H27NO3S2: C, 62.19; H, 6.71; N,
3.45; S, 15.81. Found: C, 62.56; H, 6.38; N, 3.01; S,
16.13.
4.1.9.5. 1N-[3-Phenyl-1-(SS)-phenylsulfinylmethyl-(1R,
2E)-2-propenyl]-4-methyl-1-benzenesulfonamide, 9ba.
Solid, 80%, mp 177–178 ꢁC. 1H NMR (200 MHz,
CDCl3) d 7.74 (d, J ¼ 8.2 Hz, 2H), 7.62–7.43 (m, 5H),
7.38–7.11 (m, 7H), 6.45–6.40 (m, 1H and NH), 6.04 (dd,
J ¼ 16.3, 7.4 Hz, 1H), 4.52 (quintet, J ¼ 5.2 Hz, 1H),
2.98–2.92 (d, J ¼ 5.2 Hz, 2H), 2.34 (s, 3H). 13C NMR
(75 MHz, CDCl3) d 20.8, 51.4, 62.2, 123.4, 125.9, 127.4,
4.1.9.1. 1-(SS)-Phenylsulfinyl-(2R,3Z)-3-octen-2-meth-
1
oxycarbonylamide, 8aa. Solid, 78%, mp 115–117 ꢁC. H
NMR (200 MHz, CDCl3) d 7.65–7.58 (m, 2H), 7.54–7.45
(m, 3H), 5.93 (d, J ¼ 7.5 Hz, NH), 5.75–5.45 (m, 2H),
4.90–4.74 (m, 1H), 3.67 (s, 3H), 3.20–3.03 (m, 1H), 2.88
(dd, J ¼ 12.9, 2.8 Hz, 1H), 2.21–2.00 (m, 2H), 1.42–1.25
127.8, 128.9, 130.6, 131.8, 135.3, 142.5, 143.1. IR (neat)
25
D
m ¼ 3258, 2924, 2847, 1455, 1327, 1160. ½aꢀ ¼ )115.9 (c
0.5, CHCl3). MS (LSIMS) 426 [M+H]þ. Anal. Calcd for
C23H23NO3S2: C, 64.92; H, 5.45; N, 3.29; S, 15.07.
Found: C, 64.67; H, 5.66; N, 3.14; S, 14.90.
(m, 4H), 0.92 (t, J ¼ 6.7 Hz, 3H). IR (neat) m ¼ 3262,
25
2963, 2921, 1726, 1698, 1527, 1252, 1035. ½aꢀ ¼ )276.4
D
(c 1.16, CHCl3). MS (LSIMS) 310 [M+H]þ. Anal. Calcd
for C16H23NO3S: C, 62.11; H, 7.49; N, 4.53; S, 10.36.
Found: C, 61.98; H, 7.13; N, 4.43; S, 10.09.
4.1.9.6.
1N-[3-Phenyl-1-(RS)-phenylsulfinylmethyl-
(1R,2E)-2-propenyl]-4-methyl-1-benzenesulfonamide, 9bs.
Solid, 87%, mp 152–153 ꢁC. 1H NMR (200 MHz, CDCl3)
d 7.72 (d, J ¼ 8.2 Hz, 2H), 7.62–7.46 (m, 5H), 7.30–7.08
(m, 7H), 6.35 (d, J ¼ 16.3 Hz, 1H), 5.90 (dd, J ¼ 16.3,
9.2 Hz, 1H), 4.44–4.32 (m, 1H), 3.16 (dd, J ¼ 13.4, 7.4 Hz,
1H), 2.92 (dd, J ¼ 13.4, 5.9 Hz, 1H), 2.35 (s, 3H). 13C
NMR (75 MHz, CDCl3) d 21.3, 53.2, 62.3, 124.1, 125.8,
4.1.9.2. 1-(RS)-Phenylsulfinyl-(2R,3Z)-3-octen-2-meth-
1
oxycarbonylamide, 8as. Solid, 80%, mp 143–146 ꢁC. H
NMR (200 MHz, CDCl3) d 7.72–7.65 (m, 2H), 7.60–7.44
(m, 3H), 5.60–5.39 (m, 2H), 5.26 (d, J ¼ 7.1 Hz, NH),
4.75 (quintet, J ¼ 7.1 Hz, 1H), 3.64 (s, 3H), 3.12 (dd,
J ¼ 13.0, 7.1 Hz, 1H), 2.91 (dd, J ¼ 13.0, 5.7 Hz, 1H),
2.12–1.91 (m, 2H), 1.41–1.17 (m, 4H), 0.88 (distorted t,
127.4, 129.4, 129.5, 131.4, 133.2, 137.5, 143.2, 143.4. IR
25
D
(neat) m ¼ 3062, 2927, 1445, 1331, 1159. ½aꢀ ¼ +9.2 (c 0.7,
CHCl3). MS (LSIMS) 426 [M+H]þ. Anal. Calcd for
C23H23NO3S2: C, 64.92; H, 5.45; N, 3.29; S, 15.07.
Found: C, 65.07; H, 5.26; N, 3.55; S, 15.20.
3H). IR (neat) m ¼ 3310, 2970, 2923, 1716, 1520, 1040,
25
750, 683. ½aꢀ ¼ +89.4 (c 0.70, CHCl3). MS (LSIMS) 310
D
[M+H]þ. Anal. Calcd for C16H23NO3S: C, 62.11; H,
7.49; N, 4.53; S, 10.36. Found: C, 62.58; H, 7.33; N,
4.59; S, 10.77.
4.1.9.7.
1N-[3-Phenyl-1-(RS)-phenylsulfinylmethyl-
(1R,2E)-propenyl]-4-nitro-1-benzenesulfonamide, 14bs.
Solid, 88%, mp 164–165 ꢁC. 1H NMR (200 MHz,
4.1.9.3.
heptenyl]-4-methyl-1-benzenesulfonamide, 9aa.
1N-[1-(SS)-Phenylsulfinylmethyl-(1R,2E)-2-
Solid,
DMSO-d6)
d
8.05 (d, J ¼ 9.1 Hz, 2H), 7.89 (d,
1
J ¼ 9.1 Hz, 2H), 7.62–7.38 (m, 5H), 7.18–6.90 (m, 5H),
6.12 (d, J ¼ 15.6 Hz, 1H), 5.64 (dd, J ¼ 15.6, 8.2 Hz, 1H),
4.48–4.26 (br s, NH), 4.23–4.18 (m, 1H), 3.06 (dd,
J ¼ 12.6, 6.7 Hz, 1H), 2.83 (dd, J ¼ 12.6, 7.4 Hz, 1H). IR
(neat) m ¼ 3421, 2927, 1587, 1520, 1327, 1160. MS
(LSIMS) 457 [M+H]þ. Anal. Calcd for C22H20N2O5S2:
C, 57.88; H, 4.42; N, 6.14; S, 14.05. Found: C, 57.92; H,
4.57; N, 6.14; S, 14.12.
82%, mp 112–114 ꢁC. H NMR (200 MHz, CDCl3) d
7.72 (d, J ¼ 8.2 Hz, 2H), 7.55–7.40 (m, 5H), 7.28 (d,
J ¼ 8.2 Hz, 2H), 6.31 (d, J ¼ 5.9 Hz, NH), 5.45–5.30 (m,
2H), 4.49–4.40 (m, 1H), 3.03 (dd, J ¼ 13.4, 7.5 Hz, 1H),
2.69 (dd, J ¼ 13.4, 3.0 Hz, 1H), 2.44 (s, 3H), 1.81–1.69
(m, 2H), 1.23–1.10 (m, 4H), 0.86 (distorted t, 3H). 13C
NMR (75 MHz, CDCl3) d 13.8, 21.4, 22.2, 27.0, 31.1,
48.2, 60.4, 123.9, 127.1, 127.4, 129.2, 129.4, 131.2, 133.5,
137.6, 142.6, 143.2. IR (neat) m ¼ 3342, 2928, 2855, 1330,
[M+H]þ. Anal. Calcd for C21H27NO3S2: C, 62.19; H,
6.71; N, 3.45; S, 15.81. Found: C, 61.86; H, 6.97; N,
3.71; S, 16.10.
25
1159. ½aꢀ ¼ )118.8 (c 1.0, CHCl3). MS (LSIMS) 406
4.1.9.8. 4-(4-Methylphenylsulfonamido)-5-(SS)-phenyl-
sulfinyl-(E,4R)-2-pentenyl pivalate, 9ca. Viscous liquid,
79%. 1H NMR (200 MHz, CDCl3) d 7.75 (d, J ¼ 8.2 Hz,
2H), 7.55–7.44 (m, 5H), 7.26 (d, J ¼ 8.2 Hz, 2H), 6.50 (d,
J ¼ 8.2 Hz, NH), 5.72–5.65 (m, 2H), 4.43–4.38 (m, 3H),
D
2.94–2.74 (m, 2H), 2.43 (s, 3H), 1.18 (s, 9H). IR (neat)
4.1.9.4. 1N-[1-(RS)-Phenylsulfinylmethyl-(1R,2E)-2-
25
m ¼ 3325, 1732, 1332, 1159. ½aꢀ ¼ )90.1 (c 0.75, CHCl3).
heptenyl]-4-methyl-1-benzenesulfonamide, 9as.
Solid,
D
MS (LSIMS) 464 [M+H]þ. Anal. Calcd for
C23H29NO5S2: C, 59.59; H, 6.30; N, 3.02; S, 13.83.
Found: C, 59.69; H, 5.92; N, 3.27; S, 14.22.
84%, mp 114–116 ꢁC. 1H NMR (200 MHz, CDCl3)
d 7.75 (d, J ¼ 8.2 Hz, 2H), 7.70–7.45 (m, 5H), 7.28 (d,
J ¼ 8.2 Hz, 2H), 5.49–5.23 (m, 2H), 4.46–4.33 (m, 1H),
3.13 (dd, J ¼ 13.4, 6.7 Hz, 1H), 2.75 (dd, J ¼ 13.4,
6.7 Hz, 1H), 2.42 (s, 3H), 1.80–1.60 (m, 2H), 1.28–1.08
(m, 4H), 0.91 (distorted t, 3H). 13C NMR (75 MHz,
CDCl3) d 13.8, 21.4, 22.2, 27.1, 31.1, 48.0, 62.9, 124.0,
126.4, 127.4, 129.3, 129.5, 131.2, 134.7, 143.4, 143.7. IR
(neat) m ¼ 3258, 2924, 2847, 1455, 1327, 1160.
4.1.9.9. 4-(4-Methylphenylsulfonamido)-5-(RS)-phen-
ylsulfinyl-(E,4R)-2-pentenyl pivalate, 9cs.
Viscous
liquid, 81%. 1H NMR (200 MHz, CDCl3) d 7.73 (d,
J ¼ 8.2 Hz, 2H), 7.62–7.46 (m, 5H), 7.28 (d, J ¼ 8.2 Hz,
2H), 6.03 (d, J ¼ 5.9 Hz, NH), 5.62–5.58 (m, 2H), 4.38

374
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
(d, J ¼ 3.72 Hz, 2H), 4.23–4.20 (m, 1H), 3.03 (dd,
J ¼ 13.4, 7.4 Hz, 1H), 2.83 (dd, J ¼ 13.4, 5.9 Hz, 1H),
25
4.1.10.3. 1N-[4-Hydroxy-1-(SS)-phenylsulfinylmethyl-
(1R,2E)-2-butenyl]-4-methyl-1-benzenesulfonamide, 9da.
Solid, 83%, mp 115–116 ꢁC. 1H NMR (200 MHz,
CDCl3) d 7.70 (d, J ¼ 8.2 Hz, 2H), 7.62–7.54 (m, 4H),
7.48–7.45 (m, 5H), 7.38–7.28 (m, 6H), 7.18 (d,
J ¼ 8.2 Hz, 2H), 5.80–5.56 (m, 2H), 4.41–4.26 (m, 1H),
4.06 (s, 2H), 2.76 (d, J ¼ 5.2 Hz, 2H), 2.33 (s, 3H), 1.02
(s, 9H). 13C NMR (75 MHz, CDCl3) d 19.0, 21.2, 26.6,
51.6, 61.8, 63.0, 123.8, 126.1, 127.1, 127.5, 129.2, 129.3,
2.44 (s, 3H), 1.17 (s, 9H). IR (neat) m ¼ 3250, 1725, 1337,
1161. ½aꢀ ¼ +92.3 (c 0.25, CHCl3). MS (LSIMS) 464
D
[M+H]þ. Anal. Calcd for C23H29NO5S2: C, 59.59; H,
6.30; N, 3.02; S, 13.83. Found: C, 59.93; H, 6.08; N,
3.40; S, 13.62.
4.1.10. General procedure for the preparation of the silyl
ether from the pivaloyl esters. .To the pivaloyl ester 9ca
(820 mg, 2 mmol) in methanol (15 mL) cooled at 0 ꢁC
was added dropwise a solution of 0.2 M aq NaOH
(15 mL). The reaction mixture was allowed to attain
rt gradually and then stirred for 4 h. The solvent was
removed under reduced pressure and the product alco-
hol extracted into ethyl acetate. The organic layer was
washed with water, brine and dried over Na2SO4.
Evaporation of the solvent followed by column chro-
matography, using AcOEt/petroleum ether (2:3, v/v) as
the eluent, afforded the alcohol (589 mg, 1.9 mmol) in
95% yield.
129.5, 131.0, 132.4, 133.2, 135.2, 137.9, 142.9. IR (neat)
25
m ¼ 3421, 2927, 1451, 1168, 1109, 1043. ½aꢀ ¼ )75.8 (c
D
0.3, CHCl3). MS (LSIMS) 618 [M+H]þ. Anal. Calcd for
C34H39NO4S2Si: C, 66.09; H, 6.36; N, 2.27; S, 10.38.
Found: C, 66.29; H, 5.94; N, 2.63; S, 10.62.
4.1.10.4. 1N-[4-Hydroxy-1-(RS)-phenylsulfinylmethyl-
(1R,2E)-2-butenyl]-4-methyl-1-benzenesulfonamide, 9ds.
1
Low melting solid, 81%. H NMR (200 MHz, CDCl3) d
7.69 (d, J ¼ 8.2 Hz, 2H), 7.60–7.44 (m, 9H), 7.35–7.24
(m, 6H), 7.20 (d, J ¼ 8.2 Hz, 2H), 5.58–5.52 (m, 2H),
4.20–4.07 (m, 1H), 4.03 (s, 2H), 2.98 (dd, J ¼ 13.4,
7.4 Hz, 1H), 2.70 (dd, J ¼ 13.4, 5.9 Hz, 1H), 2.35 (s, 3H),
0.98 (s, 9H). 13C NMR (75 MHz, CDCl3) d 19.1, 21.4,
26.7, 52.4, 62.4, 63.1, 124.0, 126.3, 127.3, 127.6, 129.3,
129.5, 129.6, 131.3, 133.1, 135.3, 137.3, 143.3. IR (neat)
To the solution of the above alcohol (570 mg, 1.5 mmol)
in dichloromethane (6 mL) was added imidazole
(204 mg, 3 mmol) followed by TBDPSCl (453 mg,
1.65 mmol) and stirred at rt for 1 h. Dichloromethane
(10 mL) was added to the reaction mixture and the
organic layer washed with water, brine and dried over
Na2SO4. Column chromatography using AcOEt/petro-
leum ether (1:4, v/v) as the eluent afforded the 7da
(857 mg, 1.52 mmol) in 80% yield (76% overall yield for
2 steps).
m ¼ 3489, 2925, 2853, 1367, 1157, 1111, 1029.
25
D
½aꢀ ¼ +64.5 (c 0.55, CHCl3). MS (LSIMS) 618 [M+H]þ.
Anal. Calcd for C34H39NO4S2Si: C, 66.09; H, 6.36; N,
2.27; S, 10.38. Found: C, 65.78; H, 6.77; N, 2.23; S,
10.72.
4.1.11. General procedure for the reaction of the sulfox-
ides with NBS.
.To the solution of the sulfoxide (0.5
mmol) in toluene (2.5 mL) was added water (18 mg,
1 mmol) followed by freshly recrystallized N-bromo-
succinimide (0.107 g, 0.6 mmol) and stirred at rt under
nitrogen atmosphere. The progress of the reaction was
monitored by TLC. When no starting material could be
detected (30 min to 6 h), the reaction mixture was taken
into ethyl acetate (10 mL) and washed with aqueous
saturated sodium bicarbonate (10 mL), water
(2 · 10 mL) and brine (10 mL). The organic layer was
dried over sodium sulfate and evaporated under vacuum
to afford the crude product mixture. Purification of the
crude product by column chromatography on silica gel
using AcOEt/petroleum ether as eluent afforded prod-
ucts in 70–85% combined yield.
Following the similar procedure detailed for the con-
version of 9ca into 9da, 9cs yielded 9ds in 75% overall
yield for 2 steps.
4.1.10.1. Hydrolyzed product of 9ca: 1N-[4-hydroxy-1-
(SS)-phenylsulfinylmethyl-(1R,2E)-2-butenyl]-4-methyl-1-
1
benzenesulfonamide.
Solid, 76%, mp 143–145 ꢁC. H
NMR (200 MHz, CDCl3) d 7.74 (d, J ¼ 8.2 Hz, 2H),
7.50–7.44 (m, 5H), 7.28 (d, J ¼ 8.2 Hz, 2H), 6.30 (d,
J ¼ 8.9 Hz, NH), 5.86–5.64 (m, 2H), 4.31–4.29 (m, 1H),
4.08–3.96 (m, 2H), 2.92–2.78 (m, 2H), 2.43 (s, 3H). IR
25
D
(neat) m ¼ 3270, 1537, 1458, 1328, 1158. ½aꢀ ¼ )119.8 (c
0.25, CHCl3). MS (LSIMS) 380 [M+H]þ. Anal. Calcd
for C18H21NO4S2: C, 56.97; H, 5.58; N, 3.69; S, 16.90.
Found: C, 56.69; H, 5.52; N, 3.97; S, 16.85.
4.1.11.1. Products from 7aa
4.1.11.1.1. 2-(tert-Butyloxycarbonylamido)-3-bromo-
1-(RS)-phenylsulfinyl-(2S,3S,4S)-octan-4-ol, 10as. Vis-
4.1.10.2. Hydrolyzed product of 9cs: 1N-[4-hydroxy-1-
(RS)-phenylsulfinylmethyl-(1R,2E)-2-butenyl]-4-methyl-1-
benzenesulfonamide. Low melting solid, 75%. H NMR
1
cous liquid, 40%. H NMR (200 MHz, CDCl3) d 7.64–
1
7.54 (m, 2H), 7.50–7.40 (m, 3H), 5.38 (d, J ¼ 6.9 Hz,
NH), 4.13–3.89 (m, 2H), 3.75–3.63 (m, 1H), 3.40–3.10
(m, 2H), 1.51–1.10 (m, 15H), 0.82 (t, J ¼ 6.8 Hz, 3H). IR
(200 MHz, CDCl3) d 7.72 (d, J ¼ 8.2 Hz, 2H), 7.60–7.40
(m, 5H), 7.25 (d, J ¼ 8.2 Hz, 2H), 6.66 (d, J ¼ 6.7 Hz,
NH), 5.75–5.55 (m, 2H), 4.17–4.13 (m, 1H), 3.94–3.91
(m, 2H), 3.06 (dd, J ¼ 13.4, 6.7 Hz, 1H), 2.92 (dd, J ¼
(neat) m ¼ 3310, 2974, 2923, 1697, 1540, 1030.
25
½aꢀ ¼ +31.7 (c 0.8, CHCl3). MS (LSIMS) 448 [M+H]þ.
D
Anal. Calcd for C19H30BrNO4S: C, 50.89; H, 6.74; N,
13.4, 7.4, 1H), 2.38 (s, 3H). IR (neat) m ¼ 3145, 2926,
25
1460, 1330, 1159. ½aꢀ ¼ +112.6 (c 1.0, CHCl3). MS
(LSIMS) 380 [M+H]þD. Anal. Calcd for C18H21NO4S2:
C, 56.97; H, 5.58; N, 3.69; S, 16.90. Found: C, 57.11; H,
5.72; N, 3.47; S, 16.99.
3.12; S, 7.15. Found: C, 50.64; H, 6.99; N, 3.19; S, 6.89.
4.1.11.1.2. 2-(tert-Butyloxycarbonylamido)-3-bromo-
1-(RS)-phenylsulfinyl-(2S,3R,4R)-octan-4-ol, stereoiso-
1
mer of 10as. Liquid, 8%. H NMR (200 MHz, CDCl3)

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
375
d 7.72–7.60 (m, 2H), 7.58–7.45 (m, 3H), 5.12 (d,
J ¼ 7.2 Hz, NH), 4.41–4.23 (m, 2H), 3.72 (br s, 1H),
3.31–3.06 (m, 2H), 1.62–1.40 (m, 6H), 1.41 (s, 9H), 0.91
7.75–7.45 (m, 5H), 5.21 (d, J ¼ 8.9 Hz, NH), 4.84–4.65
(m, 1H), 3.85–3.61 (m, 4H), 3.60–3.44 (m, 1H), 3.29 (dd,
J ¼ 13.4, 8.9 Hz, 1H), 2.97 (dd, J ¼ 13.4, 5.1 Hz, 1H),
2.10–1.80 (m, 1H), 1.70–1.18 (m, 5H), 0.92 (distorted t,
(distorted t, 3H). IR (neat) m ¼ 3310, 2947, 1696, 1546,
25
1153, 1029. ½aꢀ ¼ +25.2 (c 0.64, CHCl3). MS (LSIMS)
3H). IR (neat) m ¼ 3289, 2927, 1708, 1465, 1524, 1032.
D
25
½aꢀ ¼ +28.4 (c 0.31, CHCl3). MS (LSIMS) 407 [M+H]þ.
448 [M+H]þ. Anal. Calcd for C19H30BrNO4S: C, 50.89;
H, 6.74; N, 3.12; S, 7.15. Found: C, 51.04; H, 6.39; N,
3.42; S, 7.08.
D
Anal. Calcd for C16H24BrNO4S: C, 47.30; H, 5.95; N,
3.45; S, 7.89. Found: C, 47.13 H, 5.88; N, 3.09; S, 8.16.
4.1.11.1.3.
methyl-(4S,5R,6R)-1,3-oxazinan-2-one, 11aa.
5-Bromo-6-butyl-4-(SS)-phenylsulfinyl-
Solid,
4.1.11.4. Products from 8as
1
33%, mp 129–130 ꢁC. H NMR (200 MHz, CDCl3) d
7.68–7.50 (m, 5H), 6.71–6.62 (br s, NH), 4.43 (dd,
J ¼ 3.5, 2.5 Hz, 1H), 4.14 (dt, J ¼ 9.3, 3.5 Hz, 1H), 4.02
(dt, J ¼ 10.4, 2.5 Hz, 1H), 3.32 (dd, J ¼ 12.7, 9.3 Hz,
1H), 2.91 (dd, J ¼ 12.7, 3.5 Hz, 1H), 1.90–1.12 (m, 6H),
4.1.11.4.1.
(SS)-phenylsulfinyl-(2S,3S,4S)-octan-4-ol, 12aa.
cous liquid, 59%. H NMR (200 MHz, CDCl3) d 7.73–
7.60 (m, 2H), 7.59–7.48 (m, 3H), 6.03 (d, J ¼ 7.3 Hz,
NH), 4.50–4.25 (m, 1H and OH), 4.20–3.83 (m, 2H),
3.72 (s, 3H), 3.47–3.10 (m, 2H), 2.10–1.83 (m, 2H), 1.70–
2-(Methoxycarbonylamido)-3-bromo-1-
Vis-
1
0.90 (t, J ¼ 6.9 Hz, 3H). IR (neat) m ¼ 3262, 2960,
25
2928, 2845, 1757, 1465, 1035. ½aꢀ ¼ )164.8 (c 1.0,
D
1.25 (m, 4H), 0.96 (t, J ¼ 6.8 Hz, 3H). IR (neat) m ¼ 3355,
CHCl3). MS (LSIMS) 375 [M+H]þ. Anal. Calcd for
C15H20BrNO3S: C, 48.14; H, 5.39; N, 3.45; S, 8.57.
Found: C, 48.33; H, 5.08; N, 3.49; S, 8.98.
25
2964, 2922, 2843, 1709, 1259, 1037. ½aꢀ ¼ )72.0 (c 0.55,
D
CHCl3). MS (LSIMS) 407 [M+H]þ. Anal. Calcd for
C16H24BrNO4S: C, 47.30; H, 5.95; N, 3.45; S, 7.89.
Found: C, 47.65; H, 6.28; N, 3.07; S, 7.54.
4.1.11.2. Products from 7as
4.1.11.2.1. 2-(tert-Butyloxycarbonylamido)-3-bromo-1-
(SS)-phenylsulfinyl-(2S,3S,4S)-octan-4-ol, 10aa. Liquid,
4.1.11.5. Products from 9aa
4.1.11.5.1. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-(RS)-
1
phenylmethylsulfinyl-(1S,2S,3S)-heptyl]-4-methyl-1-benz-
1
26%. H NMR (200 MHz, CDCl3) d 7.70–7.59 (m, 2H),
enesulfonamide, 13as.
Solid, 65%, mp 94–96 ꢁC. H
7.57–7.48 (m, 3H), 5.71–5.57 (br s, NH), 4.40–4.27 (m,
1H and OH), 4.07–3.87 (m, 2H), 3.42 (dd, J ¼ 13.4,
8.3 Hz, 1H), 3.17 (dd, J ¼ 13.4, 2.3 Hz, 1H), 2.08–1.85
(m, 2H), 1.49 (s, 9H), 1.45–1.28 (m, 4H), 0.91 (t,
NMR (200 MHz, CDCl3) d 7.76 (d, J ¼ 8.2 Hz, 2H),
7.69–7.47 (m, 5H), 7.29 (d, J ¼ 8.2 Hz, 2H), 6.62 (d,
J ¼ 7.4 Hz, NH), 4.08–3.88 (m, 1H and OH), 3.79–3.61
(m, 2H), 3.47 (dd, J ¼ 13.4, 2.2 Hz, 1H), 3.02 (dd, J ¼
13.4, 5.2 Hz, 1H), 2.45 (s, 3H), 1.98–1.74 (m, 1H), 1.74–
1.53 (m, 1H), 1.40–1.03 (m, 4H), 0.82 (t, J ¼ 6.7 Hz, 3H).
13C NMR (75 MHz, CDCl3) d 13.7, 21.4, 21.7, 29.6,
35.5, 54.3, 59.4, 60.0, 73.5, 124.1, 127.1, 129.3, 129.7,
J ¼ 6.7 Hz, 3H). IR (neat) m ¼ 3343, 2965, 2855, 1700,
25
1259, 1043. ½aꢀ ¼ )74.3 (c 1.9, CHCl3). MS (LSIMS)
D
448 [M+H]þ. Anal. Calcd for C19H30BrNO4S: C, 50.89;
H, 6.74; N, 3.12; S, 7.15. Found: C, 51.24; H, 6.42; N,
3.37; S, 7.49.
131.4, 137.3, 141.9, 143.7. IR (neat) m ¼ 3368, 2928,
4.1.11.2.2.
5-Bromo-6-butyl-4-(RS)-phenylsulfinyl-
Solid,
25
1331, 1159. ½aꢀ ¼ +109.7 (c 0.3, CHCl3). MS (LSIMS)
D
methyl-(4S,5R,6R)-1,3-oxazinan-2-one, 11as.
502 [M+H]þ. Anal. Calcd for C21H28BrNO4S2: C, 50.20;
H, 5.62; N, 2.79; S, 12.76. Found: C, 50.53; H, 5.22; N,
2.73; S, 12.52.
52%, mp 147–149 ꢁC. 1H NMR (200 MHz, CDCl3)
d 7.78–7.54 (m, 5H), 6.08–5.95 (br s, NH), 4.57 (dd,
J ¼ 3.4, 2.5 Hz, 1H), 4.46 (dt, J ¼ 7.6, 2.5 Hz, 1H), 4.26
(dt, J ¼ 9.5, 3.4 Hz, 1H), 3.25–3.02 (m, 2H), 2.04–1.86
(m, 2H), 1.79–1.59 (m, 2H), 1.55–1.32 (m, 2H), 0.98 (t,
4.1.11.5.2. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-(RS)-
phenylmethylsulfinyl-(1S,2R,3R)-heptyl]-4-methyl-1-benz-
1
enesulfonamide, stereoisomer of 13as. Liquid, 11%. H
J ¼ 6.7 Hz, 3H). IR (neat) m ¼ 3257, 2962, 2920, 1749,
25
NMR (200 MHz, CDCl3) d 7.64 (d, J ¼ 8.2 Hz, 2H),
7.56–7.44 (m, 5H), 7.28 (d, J ¼ 8.2 Hz, 2H), 6.16–6.07
(br s, NH), 4.60–4.55 (m, 1H), 3.77–3.68 (m, 1H), 3.50–
3.44 (m, 1H), 3.34 (dd, J ¼ 14.1, 7.0 Hz, 1H), 3.20 (dd,
J ¼ 14.0, 5.9 Hz, 1H), 2.42 (s, 3H), 2.04–1.80 (m, 2H),
1261, 1053. ½aꢀ ¼ +120.0 (c 1.0, CHCl3). MS (LSIMS)
D
375 [M+H]þ. Anal. Calcd for C15H20BrNO3S: C, 48.14;
H, 5.39; N, 3.45; S, 8.57. Found: C, 48.45; H, 5.78; N,
3.48; S, 8.33.
1.44–1.10 (m, 4H), 0.88 (t, J ¼ 6.7 Hz, 3H). IR (neat)
25
m ¼ 3281, 2925, 2854, 1367, 1158. ½aꢀ ¼ +78.4 (c 0.2,
D
4.1.11.3. Products from 8aa
CHCl3). MS (LSIMS) 502 [M+H]þ. Anal. Calcd for
C21H28BrNO4S2: C, 50.20; H, 5.62; N, 2.79; S, 12.76.
Found: C, 50.43; H, 5.98; N, 2.43; S, 12.99.
4.1.11.3.1.
(RS)-phenylsulfinyl-(2S,3S,4S)-octan-4-ol, 12as. Liquid,
2-(Methoxycarbonylamido)-3-bromo-1-
1
52%. H NMR (200 MHz, CDCl3) d 7.70–7.60 (m, 2H),
7.59–7.49 (m, 3H), 5.55 (d, J ¼ 7.6 Hz, NH), 4.22–4.05
(m, 2H), 3.86–3.60 (m, 4H), 3.40–3.20 (m, 2H), 2.05–1.70
(m, 2H), 1.60–1.24 (m, 4H), 0.90 (t, J ¼ 6.7 Hz, 3H). IR
4.1.11.6. Products from 9as
4.1.11.6.1. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-(SS)-
(neat) m ¼ 3334, 2924, 2360, 1700, 1444, 1528, 1027.
phenylmethylsulfinyl-(1S,2S,3S)-heptyl]-4-methyl-1-benz-
1
25
½aꢀ ¼ +47.3 (c 0.47, CHCl3). MS (LSIMS) 407 [M+H]þ.
enesulfonamide, 13aa.
Solid, 82%, mp 93–95 ꢁC. H
D
Anal. Calcd for C16H24BrNO4S: C, 47.30; H, 5.95; N,
3.45; S, 7.89. Found: C, 47.65; H, 6.08; N, 3.79; S, 7.96.
NMR (200 MHz, CDCl3) d 7.83 (d, J ¼ 8.2 Hz, 2H),
7.56–7.44 (m, 5H), 7.30 (d, J ¼ 8.2 Hz, 2H), 4.46–4.37
(m, 1H), 3.99–3.83 (m, 1H), 3.82 (d, J ¼ 8.2 Hz, 1H),
2.96 (dd, J ¼ 13.4, 5.2 Hz, 1H), 2.65 (dd, J ¼ 13.4,
2.3 Hz, 1H), 2.42 (s, 3H), 2.05–1.76 (m, 2H), 1.60–1.23
4.1.11.3.2.
(RS)-phenylsulfinyl-(2S,3R,4R)-octan-4-ol, stereomer
2-(Methoxycarbonylamido)-3-bromo-1-
1
of 12as.
Liquid, 4%. H NMR (200 MHz, CDCl3) d

376
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
25
1109, 1023. ½aꢀ ¼ +33.6 (c 0.25, CHCl3). MS (LSIMS)
(m, 4H), 0.91 (t, J ¼ 6.7 Hz, 3H). 13C NMR (75 MHz,
CDCl3) d 13.8, 21.4, 21.9, 29.6, 35.6, 54.5, 56.9, 61.0,
74.0, 123.7, 127.2, 129.3, 129.7, 131.3, 137.8, 143.2,
D
714 [M+H]þ.
25
143.6. IR (neat) m ¼ 3262, 2926, 1328, 1157. ½aꢀ ¼ )89.6
4.1.11.10. Products from 9ds
D
(c 0.3, CHCl3). MS (LSIMS) 502 [M+H]þ. Anal. Calcd
for C21H28BrNO4S2: C, 50.20; H, 5.62; N, 2.79; S, 12.76.
Found: C, 50.03; H, 5.87; N, 2.59; S, 12.53.
4.1.11.10.1. 1N-[2-Bromo-4-(tert-butyldiphenylsilyl-
oxy)-3-hydroxy-1-(SS)-phenylsulfinylmethyl-(1S,2R,3S)-
butyl]-4-methyl-1-benzenesulfonamide, 13da. Solid, 51%,
1
mp 173–175 ꢁC. H NMR (300 MHz, CDCl3) d 7.87–
4.1.11.7. Products from 9ba
4.1.11.7.1. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-(RS)-
phenylmethylsulfinyl-(1S,2S,3R)-propyl]-4-methyl-1-benz-
7.51 (m, 11H), 7.56–7.20 (m, 8H), 5.38 (d, J ¼ 11.7 Hz,
NH), 4.57–4.40 (m, 1H), 4.34–4.15 (m, 1H), 3.97–3.70
(m, 3H), 3.12 (dd, J ¼ 13.4, 3.0 Hz, 1H), 2.80–2.60 (m,
1
enesulfonamide, 13bs. Solid, 64%, mp 184–186 ꢁC. H
1H), 2.42 (s, 3H), 1.11 (br s, 9H). IR (neat) m ¼ 3465,
25
NMR (200 MHz, CDCl3) d 7.60 (d, J ¼ 8.2 Hz, 2H),
7.53–7.40 (m, 5H), 7.32–7.20 (m, 7H), 5.27 (d,
J ¼ 8.9 Hz, NH), 4.84 (d, J ¼ 8.9 Hz, 1H), 4.56 (d,
J ¼ 8.9 Hz, 1H), 4.24–4.13 (m, 1H), 3.26 (dd, J ¼ 14.1,
3054, 1458, 1327, 1156, 1111, 1024. ½aꢀ ¼ )108.4 (c 0.5,
D
CHCl3). MS (LSIMS) 714 [M+H]þ. Anal. Calcd for
C34H40BrNO5S2Si: C, 59.47; H, 5.87; N, 2.04; S, 9.34.
Found: C, 59.11; H, 6.20; N, 1.93; S, 9.45.
9.7 Hz, 1H), 2.78 (dd, J ¼ 14.1, 4.5 Hz, 1H), 2.44 (s, 3H).
4.1.11.10.2. 1N-[3-Bromo-4-(tert-butyldiphenylsilyl-
oxy)-2-hydroxy-1-(SS)-phenylsulfinylmethyl-(1R,2R,3S)-
25
IR (neat) m ¼ 3321, 2927, 1541, 1159. ½aꢀ ¼ +118.1 (c
0.75, CHCl3). MS (LSIMS) 523 [M+H]þD. Anal. Calcd
for C23H24BrNO4S2: C, 52.87; H, 4.63; N, 2.68; S, 12.27.
Found: C, 53.03; H, 4.92; N, 2.63; S, 12.52.
butyl]-4-methyl-1-benzenesulfonamide, regiomer of 13da.
1
Liquid, 10%. H NMR (300 MHz, CDCl3) d 7.68–7.40
(m, 11H), 7.38–7.18 (m, 8H), 5.18 (d, J ¼ 9.5 Hz, NH),
4.30–4.20 (m, 1H), 4.16–4.12 (m, 1H), 3.97 (dd, J ¼ 11.6,
2.0 Hz, 1H), 3.84 (dd, J ¼ 11.6, 4.1 Hz, 1H), 3.77–3.69
(m, 1H), 3.06 (dd, J ¼ 13.4, 8.2 Hz, 1H), 2.86 (dd,
J ¼ 13.4, 2.7 Hz, 1H), 2.32 (s, 3H), 0.98 (s, 9H). IR (neat)
4.1.11.8. Products from 9bs
4.1.11.8.1. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-(SS)-
phenylmethylsulfinyl-(1S,2S,3R)-propyl]-4-methyl-1-benz-
m ¼ 3502, 2928, 1458, 1320, 1155, 1109, 1021.
25
1
½aꢀ ¼ )28.4 (c 0.3, CHCl3). MS (LSIMS) 714 [M+H]þ.
enesulfonamide, 13ba. Solid, 80%, mp 172–174 ꢁC. H
D
NMR (200 MHz, CDCl3) d 7.78 (d, J ¼ 8.2 Hz, 2H),
7.56–7.46 (m, 5H), 7.38–7.14 (m, 7H), 5.40 (d,
J ¼ 10.4 Hz, NH), 4.84 (d, J ¼ 9.7 Hz, 1H), 4.71–4.61 (m,
1H), 4.11 (d, J ¼ 9.7 Hz, 1H), 2.99 (dd, J ¼ 13.4, 5.2 Hz,
1H), 2.73 (dd, J ¼ 13.4, 6.7 Hz, 1H), 2.41 (s, 3H). 13C
NMR (75 MHz, CDCl3) d 21.1, 49.9, 62.0, 62.5, 73.5,
123.7, 127.0, 127.5, 127.8, 128.0, 129.5, 129.7, 131.2,
Anal. Calcd for C34H40BrNO5S2Si: C, 59.47; H, 5.87; N,
2.04; S, 9.34. Found: C, 59.84; H, 6.04; N, 2.23; S, 9.65.
4.1.12. General procedure for the conversion of bro-
mohydrins to oxazinones..To a cooled )15 ꢁC solution of
the bromohydrin (0.1 mmol) in dichloromethane
(0.5 mL) was added trifluoroacetic acid (0.5 mL) drop-
wise and the mixture stirred gradually allowing to attain
rt and stirred further for a period of 30 min at the same
temperature. The volatiles were removed and the residue
taken into THF (0.5 mL). DABCO (0.3 mmol) and CDI
(0.2 mmol) were added and the reaction mixture stirred
at rt under nitrogen atmosphere for 24 h. The reaction
mixture was concentrated under vacuum and the residue
taken into ethyl acetate (15 mL). The organic layer was
washed successively with water (5 mL), brine (5 mL) and
dried over sodium sulfate. Evaporation of the solvent
afforded the crude product, which on purification by
chromatography on silica gel using AcOEt/petroleum
ether (1:1, v/v) as eluent afforded the oxazinone.
138.6, 142.6, 143.1, 144.2. IR (neat) m ¼ 3291, 2925,
25
1455, 1157. ½aꢀ ¼ )48.4 (c 1.0, CHCl3). MS (LSIMS)
D
523 [M+H]þ. Anal. Calcd for C23H24BrNO4S2: C, 52.87;
H, 4.63; N, 2.68; S, 12.27. Found: C, 52.63; H, 4.33; N,
2.93; S, 12.42.
4.1.11.9. Products from 9da
4.1.11.9.1. 1N-[2-Bromo-4-(tert-butyldiphenylsilyloxy)-
3-hydroxy-1-(RS)-phenylsulfinylmethyl-(1S,2R,3S)-butyl]-
1
4-methyl-1-benzenesulfonamide, 13ds. Liquid, 42%. H
NMR (300 MHz, CDCl3) d 7.73–7.42 (m, 11H), 7.40–
7.16 (m, 8H), 5.10 (d, J ¼ 11.7 Hz, NH), 4.46–4.42 (m,
1H), 4.28–4.10 (m, 1H), 3.82 (dd, J ¼ 12.4, 1.7 Hz, 1H),
3.76–3.43 (m, 2H), 3.16 (d, J ¼ 13.4, 8.2 Hz, 1H), 2.83
(dd, J ¼ 13.4, 2.7 Hz, 1H), 2.35 (s, 3H), 1.01 (br s, 9H).
IR (neat) m ¼ 3481, 3047, 1465, 1324, 1154, 1108, 1019.
4.1.12.1. 5-Bromo-6-butyl-4-(SS)-phenylsulfinylmethyl-
(4S,5S,6S)-1,3-oxazinan-2-one, oxazinone from 10aa.
Viscous liquid, 70%. 1H NMR (400 MHz, CDCl3)
d 7.66–7.52 (m, 5H), 6.27–6.23 (br s, NH), 4.58 (dd,
J ¼ 8.7, 3.6 Hz, 1H), 4.32–4.29 (m, 1H), 3.90 (dt,
J ¼ 10.3, 3.6 Hz, 1H), 3.78 (dd, J ¼ 13.4, 10.3 Hz, 1H),
2.84 (dd, J ¼ 13.4, 2.0 Hz, 1H), 2.33–2.29 (m, 1H), 2.05–
25
½aꢀ ¼ +89.1 (c 0.5, CHCl3). MS (LSIMS) 714 [M+H]þ.
D
Anal. Calcd for C34H40BrNO5S2Si: C, 59.47; H, 5.87; N,
2.04; S, 9.34. Found: C, 59.81; H, 5.62; N, 1.93; S, 9.45.
4.1.11.9.2. 1N-[3-Bromo-4-(tert-butyldiphenylsilyloxy)-
2-hydroxy-1-(RS)-phenylsulfinylmethyl-(1R,2R,3S)-
butyl]-4-methyl-1-benzenesulfonamide, regiomer of 13ds.
1
Liquid, 15%. H NMR (200 MHz, CDCl3) d 7.82–7.41
1.45 (m, 5H), 0.93 (distorted t, 3H). IR (neat) m ¼ 3456,
25
(m, 11H), 7.40–7.20 (m, 8H), 5.32 (d, J ¼ 8.2 Hz, NH),
4.60–4.51 (m, 1H), 4.37–4.10 (m, 1H), 4.04–3.80 (m,
2H), 3.70–3.58 (m, 1H), 3.24 (dd, J ¼ 13.4, 8.7 Hz, 1H),
2.88 (dd, J ¼ 13.4, 3.3 Hz, 1H), 2.41 (s, 3H), 1.08 (br s,
9H). IR (neat) m ¼ 3442, 3100, 2930, 1467, 1329, 1156,
1745, 1457, 1276, 1120. ½aꢀ ¼ +138.4 (c 0.5, CHCl3).
D
MS (LSIMS) 375 [M+H]þ. Anal. Calcd for
C15H20BrNO3S: C, 48.14; H, 5.39; N, 3.45; S, 8.57.
Found: C, 48.43; H, 5.08; N, 3.49; S, 8.78. Oxazinone
from minor stereomer of 10aa identical to 11aa.

S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
377
4.1.13. Preparation of sulfones from predominant sulfox-
ides formed during bromohydration. .To a solution of
NMR (200 MHz, CDCl3) d 7.73–7.40 (m, 7H), 7.37–7.13
(m, 7H), 5.27 (br s, NH), 4.82 (d, J ¼ 7.9 Hz, 1H), 4.62
(d, J ¼ 8.6 Hz, 1H), 4.16–4.09 (m, 1H), 3.54 (dd,
J ¼ 14.1, 10.2 Hz, 1H), 3.20 (d, J ¼ 14.1 Hz, 1H), 2.48 (s,
3H). IR (neat) m ¼ 3475, 3282, 2928, 1442, 1310, 1175.
MS (LSIMS) 539 [M+H]þ. Anal. Calcd for
C23H24BrNO5S2: C, 51.30; H, 4.49; N, 2.60; S, 11.91.
Found: C, 51.47; H, 4.34; N, 2.93; S, 12.23.
sulfoxide (0.05 mmol) in chloroform (0.2 mL) was added
m-CPBA (12 mg, 0.05 mmol) at 0 ꢁC and allowed to stir
for 10 min. The reaction mixture was diluted with ether
and washed successively with aq sodium thiosulfate
solution, aq NaHCO3 solution, water, brine and dried
over Na2SO4. Evaporation of the solvent under reduced
pressure followed by column chromatography using
AcOEt/petroleum ether afforded the sulfone.
4.1.13.6. 1N-[2-Bromo-4-(tert-butyldiphenylsilyloxy)-
3-hydroxy-1-phenylsulfonylmethyl-(1S,2R,3S)-butyl]-4-
methyl-1-benzenesulfonamide, sulfone of 13d. Solid, 78%,
4.1.13.1.
2-(tert-Butyloxycarbonylamido)-3-bromo-
1
1-phenylsulfonyl-(2S,3S,4S)-octan-4-ol, sulfone of 10a.
Liquid, 90%. 1H NMR (200 MHz, CDCl3) d 7.92 (d, J ¼
8.2 Hz, 2H), 7.75–7.50 (m, 3H), 5.20 (br s, NH), 4.43–
3.65 (m, 4H), 3.55–3.41 (m, 1H and OH), 2.08–1.78 (m,
2H), 1.70–1.13 (m, 13H), 0.90 (t, J ¼ 6.7 Hz, 3H). IR
m ¼ 3189, 2970, 2925, 1701, 1158, 1043. MS (LSIMS) 465
[M+H]þ. Anal. Calcd for C19H30BrNO5S: C, 49.14; H,
6.51; N, 3.02; S, 6.90. Found: C, 49.41; H, 6.24; N, 3.34;
S, 6.76.
mp 173–175 ꢁC. H NMR (200 MHz, CDCl3) d 7.89–
7.48 (m, 11H), 7.47–7.17 (m, 8H), 4.73 (d, J ¼ 10.4 Hz,
NH), 4.31–4.18 (m, 1H), 3.82 (br s, 2H), 3.65–3.26 (m,
2H), 3.28–2.99 (m, 2H), 2.40 (s, 3H), 1.08 (s, 9H). IR
(neat) m ¼ 3484, 2986, 1449, 1374, 1245, 1046. MS
(LSIMS)
730
[M+H]þ.
Anal.
Calcd
for
C34H40BrNO6S2Si: C, 58.11; H, 5.74; N, 1.99; S, 9.12.
Found: C, 58.34; H, 5.44; N, 1.93; S, 9.43.
4.1.14. Preparation of 12as and 13as from 10as. .To a
stirred solution of 10as (45 mg, 0.1 mmol) in dichloro-
methane (0.1 mL) was added dropwise a solution of
trifluoroacetic acid/dichloromethane (1:1, 0.1 mL) at
0 ꢁC and allowed to stir for 30 min. The solvent was
evaporated under reduced pressure, dried under vacuum
and without further purification the aminosulfoxide in
dichloromethane (0.4 mL) was treated with triethyl-
amine (20 mg, 0.2 mmol) followed by methyl chlorofor-
mate (9 mg, 0.1 mmol) or TsCl (16 mg, 0.1 mmol) at
0 ꢁC. After stirring for 1 h at room temperature, the
reaction mixture was diluted with dichloromethane and
washed successively with aq citric acid, water, brine and
dried over Na2SO4. Evaporation of the solvent under
reduced pressure followed by purification on a silica gel
column using AcOEt/petroleum ether (9:11, v/v) afford-
ed the products 12as/13as.
4.1.13.2. 2-(Methoxycarbonylamido)-3-bromo-1-phen-
ylsulfonyl-(2S,3R,4R)-octan-4-ol, sulfone of 12a. Liquid,
83%. 1H NMR (200 MHz, CDCl3) d 7.91 (d, J ¼ 8.2 Hz,
2H), 7.71–7.47 (m, 3H), 5.43 (d, J ¼ 9.4 Hz, NH), 4.48–
4.32 (m, 1H), 4.23 (ddd, J ¼ 11.2, 3.7, 1.1 Hz, 1H), 4.13–
3.94 (m, 1H), 3.89–3.45 (m, 5H and OH), 2.08–1.75 (m,
2H), 1.70–1.04 (m, 4H), 0.90 (t, J ¼ 6.7 Hz, 3H). IR
(neat) m ¼ 3289, 2955, 1699, 1543, 1034. MS (LSIMS)
423 [M+H]þ. Anal. Calcd for C16H24BrNO5S: C, 45.50;
H, 5.73; N, 3.32; S, 7.59. Found: C, 45.69, 5.98, 3.22,
7.89.
4.1.13.3.
5-Bromo-6-butyl-4-phenylsulfonylmethyl-
Solid,
(4S,5R,6R)-1,3-oxazinan-2-one, sulfone of 11a.
87%, mp 132–134 ꢁC. 1H NMR (200 MHz, CDCl3)
d 7.95 (d, J ¼ 8.6 Hz, 2H), 7.80–7.69 (m, 3H), 6.01 (br s,
NH), 4.48 (dd, J ¼ 4.5, 3.2 Hz, 1H), 4.34 (q, J ¼ 5.9 Hz,
1H), 4.12 (dt, J ¼ 10.2, 3.2 Hz, 1H), 3.40 (d, J ¼ 5.9 Hz,
2H), 2.06–1.21 (m, 6H), 0.93 (t, J ¼ 6.7 Hz, 3H). IR
(neat) m ¼ 3357, 2962, 2923, 2870, 1764, 1292, 1149. MS
(LSIMS) 391 [M+H]þ. Anal. Calcd for C15H20BrNO4S:
C, 46.16; H, 5.16; N, 3.59; S, 8.21. Found: C, 46.31; H,
5.04; N, 3.78; S, 8.60.
4.1.15. Procedure for the preparation of tetrahydrofuran
derivatives 16 and 17..To the bromohydrin (0.1 mmol) in
dry DMF (0.1 mL) was added imidazole (13 mg,
0.2 mmol) followed by TBDPSCl (27 mg, 0.1 mmol) at
room temperature under a N2 atmosphere. The reaction
mixture was stirred at rt until TLC revealed complete
consumption of the starting material. The reaction
mixture was diluted with ether and washed successively
with water, brine and dried over Na2SO4. The solvent
was evaporated under reduced pressure to afford the
crude product mixture. Purification by column chro-
matography using EtOAc/petroleum ether (1:24, v/v)
afforded the tetrahydrofurans.
4.1.13.4. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-phenyl-
methylsulfonyl-(1S,2R,3R)-heptyl]-4-methyl-1-benzene-
sulfonamide, sulfone of 13a. Solid, 82%, mp 128–129 ꢁC.
1H NMR (200 MHz, CDCl3) d 7.87–7.54 (m, 7H), 7.36
(d, J ¼ 8.2 Hz, 2H), 5.86 (d, J ¼ 10.5 Hz, NH), 4.24–4.01
(m, 2H), 3.85 (d, J ¼ 9.7 Hz, 1H), 3.58 (dd, J ¼ 14.1,
3.7 Hz, 1H), 3.21 (dd, J ¼ 14.1, 3.7 Hz, 1H), 2.48 (s, 3H),
2.18–1.73 (m, 2H), 1.62–1.24 (m, 4H), 0.93 (t,
J ¼ 6.7 Hz, 3H). IR (neat) m ¼ 3499, 3288, 2929, 1304,
1157. MS (LSIMS) 518 [M+H]þ. Anal. Calcd for
C21H28BrNO5S2: C, 48.65; H, 5.44; N, 2.70; S, 12.37.
Found: C, 48.91; H, 5.34; N, 2.73; S, 12.65.
4.1.15.1. 4-Bromo-3-(4-methylphenylsulfonamido)-5-
phenyl-2-phenylsulfanyl-(2S,3S,4R,5S)-tetrahydrofuran,
1
16. Viscous liquid, 86%. H NMR (200 MHz, CDCl3) d
7.82 (d, J ¼ 8.2 Hz, 2H), 7.38–7.13 (m, 12H), 6.07 (d,
J ¼ 8.2 Hz, NH), 5.30 (d, J ¼ 4.6 Hz, 1H), 5.06 (d,
J ¼ 8.9 Hz, 1H), 4.05 (ddd, J ¼ 8.2, 6.7, 4.6 Hz, 1H),
3.69 (dd, J ¼ 8.9, 6.7 Hz, 1H), 2.36 (s, 3H). IR (neat)
m ¼ 3268, 1591, 1451, 1331, 1218, 1161, 1015. MS
4.1.13.5. 1N-[2-Bromo-3-hydroxy-3-phenyl-1-phenyl-
methylsulfonyl-(1S,2S,3R)-propyl]-4-methyl-1-benzene-
sulfonamide, sulfone of 13b. Solid, 90%, mp 70–72 ꢁC. 1H

378
S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
M.; Jurgen, M. Tetrahedron: Asymmetry 1999, 10, 3409; (i)
(LSIMS) 382
C23H22BrNO3S2: C, 54.76; H, 4.40; N, 2.78; S, 12.71.
Found: C, 54.63; H, 4.52; N, 2.87; S, 12.62.
[M)STol]þ. Anal. Calcd
for
Kobayashi, S.; Kawamura, H. J. Am. Chem. Soc. 1998,
120, 5840.
5. Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321, and
references cited therein.
4.1.15.2. 4-Bromo-3-(4-methylphenylsulfonamido)-
5-phenyl-2-phenylsulfanyl-(2S,3S,4S,5S)-tetrahydrofuran,
17.
6. For nucleophilic assistance by the sulfinyl group in the
reaction of cyclic olefins, refer: (a) Montanari, F.; Danieli,
R.; Hogeveen, H.; Maccagnani, G. Tetrahedron Lett.
1964, 2685; (b) For nucleophilic participation by the
sulfinyl group in the reaction of acyclic olefins, refer:
Dalton, D. R.; Butta, V. P.; Jones, D. C. J. Am. Chem.
Soc. 1968, 90, 5468; (c) Raghavan, S.; Ramakrishna
Reddy, S.; Tony, K. A.; Naveen Kumar, Ch.; Varma, A.
K.; Nangia, A. J. Org. Chem. 2002, 67, 5838; (d)
Raghavan, S.; Rasheed, M. A.; Joseph, S. C.; Rajender,
A. J. Chem. Soc. 1999, 1845; (e) For nucleophilic
assistance by the sulfinyl group in the opening of epoxides
promoted by BF3ÆEt2O, refer: Westwell, A. D.; Thornton
Pett, M.; Rayner, C. M. J. Chem. Soc., Perkin Trans. 1
1995, 847.
1
Low melting solid, 90%. H NMR (300 MHz,
CDCl3) d 7.76 (d, J ¼ 8.2 Hz, 2H), 7.36–7.19 (m, 7H),
5.14 (d, J ¼ 10.5 Hz, 1H), 4.99 (d, J ¼ 8.2 Hz, 1H), 4.24
(dd, J ¼ 4.8, 2.2 Hz, 1H), 3.85 (ddd, J ¼ 10.5, 8.2, 4.8 Hz,
1H), 3.74 (td, J ¼ 6.7, 2.2 Hz, 1H), 2.48 (s, 3H), 1.80–
1.50 (m, 2H), 1.36–1.24 (m, 4H), 0.90 (t, J ¼ 6.7 Hz, 3H).
IR (neat) m ¼ 3310, 2927, 1457, 1329, 1211, 1159, 1020.
MS (LSIMS) 375 (Mþ)STol). Anal. Calcd for
C21H26BrNO3S2: C, 52.06; H, 5.41; N, 2.89; S, 13.24.
Found: C, 50.21; H, 5.72; N, 2.83; S, 13.54.
7. Reaction of Garner aldehyde with the ylid generated from
pentylphoshonium bromide, by treatment with n-BuLi,
afforded 3a exclusively in 62% yield. Reaction of Garner
aldehyde with the ylid derived from benzylphosphonium
bromide afforded a mixture of 3b along with the cis-
isomer. Without purification, treatment of this mixture
with catalytic amounts of PhSH7a and AIBN in THF
afforded olefin 3b exclusively in 66% overall yield. The
pivalate ester 3c was obtained in 83% yield from the
corresponding alcohol, which in turn was obtained from
Garner aldehyde following literature precedent.7b;c
(a) Schwarz, M.; Gaminski, G. F.; Waters, R. M. J. Org.
Chem. 1986, 51, 260; (b) Shimamoto, K.; Ohfune, Y.
Tetrahedron Lett. 1990, 31, 4049; (c) Kim, S.; Ahn, K. H.
J. Org. Chem. 1984, 49, 1717.
Acknowledgements
S.R. is thankful to Dr. J. S. Yadav, Director, IICT, for
constant support and encouragement; to Dr. A. C.
Kunwar for NMR spectra and Dr. M. Vairamani for
the mass spectra. A.R., S.C.J. and M.A.R. are thankful
to CSIR (New Delhi) for the senior research fellowship.
Financial assistance from DST is also gratefully
acknowledged.
References and notes
8. (a) Nakagawa, I.; Hata, T. Tetrahedron Lett. 1975, 1409;
(b) Nakagawa, I.; Aki, K.; Hata, T. J. Chem. Soc., Perkin
Trans. 1 1983, 1315.
1. (a) Friedrichs, E.; Christoph, T.; Buschmann, H. In
Ullmannꢀs Encyclopedia of Industrial Chemistry; McGuire,
J. L., Ed.; Wiley-VCH: Weinheim, 2000; (b) Gais, H.-J.;
Greibel, C.; Buschmann, H. Tetrahedron: Asymmetry
2000, 11, 917; (c) Carlier, P. R.; Lo, K. M.; Lo, M.
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S. Raghavan et al. / Tetrahedron: Asymmetry 15 (2004) 365–379
379
ber CCDC 223479. Copy of the data can be obtained, free
of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 11EZ, UK [fax: +44(0)-1223-336033] or
deposit@ccdc.cam.ac.uk.
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base in THF as the solvent afforded oxazinone 15.
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16.
25
D
25
D
Com-
pound
C2-H d ½aꢀ
Com-
pound
C2-H d ½aꢀ
(ppm)
(ppm)
7aa
7ba
7da
8aa
9aa
9ba
9ca
9da
4.81
4.74
4.58
4.83
4.45
4.52
4.40
4.34
)168.0
)167.0
)36.6
)276.4
)118.8
)115.9
)90.1
7as
7bs
7ds
8as
9as
9bs
9cs
9ds
4.71
4.63
4.44
4.75
4.38
4.38
4.21
4.15
+72.4
+13.5
+38.3
+89.4
+168.7
+9.2
+92.3
+64.5
)75.8