Vinylsulfones as nucleophiles and Michael acceptors in the same step: Stereoselective synthesis of amino acid precursors

Article abstract of DOI:10.1055/s-2005-870005

Several precursors of unnatural amino acids have been synthesized by addition of vinyl sulfones to an imine derived from (R)-glyceraldehyde. In these reactions the addition not only takes place in a stereoselective way, but a hydride transfer is also prod

Full text of DOI:10.1055/s-2005-870005

PAPER
3327
Vinylsulfones as Nucleophiles and Michael Acceptors in the Same Step:
Stereoselective Synthesis of Amino Acid Precursors
Vinylsulfones as
N
a
ucleophile
s
and Michae
i
l
A
cce
d
ptors inthe Sam
e
S
D
te
p
íez,*a Pilar García,a R. F. Moro,a Isidro S. Marcos,a Pilar Basabe,a Narciso M. Garrido,a
Howard B. Broughton,b Julio G. Uronesa
a
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, 37008 Salamanca, Spain
Fax +34(923)294574; E-mail: ddm@usal.es
Lilly, S.A., Avda de la Industria 30, 28108 Alcobendas, Madrid, Spain
b
Received 10 February 2005
This paper is dedicated to Prof. S. V. Ley on the occasion of his 60th birthday.
Abstract: Several precursors of unnatural amino acids have been
synthesized by addition of vinyl sulfones to an imine derived from
(R)-glyceraldehyde. In these reactions the addition not only takes
place in a stereoselective way, but a hydride transfer is also pro-
duced giving rise to the saturated sulfones and a new imine.
COOH
OR
O
NHBoc
O
NBn
OR
B
Key words: vinyl sulfones, hydride transfer, stereoselectivity,
synthesis, amino acids, molecular model, transition state
SO2Ph
I
Ref. 4
A
OH
COOMe
NH2
MeO
N
N
Sulfones are very useful compounds in organic synthesis,
and have been the object of many studies.1 In particular,
vinyl sulfones have been getting increasing attention in re-
cent years.2 Recently, we reported a new easy and practi-
cal method to synthesize cyclopropanol vinyl sulfones
and cyclopropylamine vinyl sulfones starting from readily
available starting materials.3 The cyclopropanol vinyl sul-
fones (I, Scheme 1) were used for the synthesis of glutam-
ic acid analogs using Schöllkopf’s methodology,4
employing the reactivity of vinyl sulfones as Michael ac-
ceptors (via A, Scheme 1). In order to increase the versa-
tility of these synthons (I), we decided to exploit another
important aspect of reactivity of vinyl sulfones, i.e. the
stabilization of an anion in the a position, enabling them
to act as nucleophiles.1a
OMe
Scheme 1
R
OR
1
2
MOM
I
SO2Ph
TBDMS
Ref. 3b
OR
OR
SO2Ph
SO2Ph
R
MOM
R
Cativiela, Díaz-de-Villegas and coworkers have de-
scribed the synthesis of amino acids by addition of orga-
nometallics to various imines derived from (R)-
glyceraldehyde.5 We decided to apply this methodology
to obtain protected amino acids or precursors, using vinyl
sulfones of the type I as the nucleophiles (via B,
Scheme 1).
3
5
4
6
MOM
70:30
30:70
TBDMS
TBDMS
Scheme 2
When compound 3 was treated with BuLi and then with 7
under various conditions as indicated in Table 1, only
three compounds, 8–10, were obtained (Scheme 3). The
organometallic addition was completely stereoselective
and followed the course found by Díaz-de-Villegas and
Galvez et al for the addition of benzyl magnesium chlo-
ride to 7,6 in contrast to the observed addition of other or-
ganometallics to the same imine by these authors.7 When
compound 8 was treated separately with BuLi a mixture
of 9 and 10 was obtained in moderate yield (Table 1, entry
8), confirming that the three compounds have the same
stereochemistry for the amino group, compound 10 being
the result of the hydrolysis of the imine 9. As can be seen,
compound 9 appears to be the result of an intramolecular
hydride transfer,8 opening a new field in the reactivity of
Initially, we prepared the starting materials following our
published methodology to obtain cyclopropanols.3a,b In a
previous paper we demonstrated that varying the protect-
ing group allowed for control of the diastereomeric ratio
in the desired cyclopropanes.3b Due to the ease with which
they could be prepared in large quantities compounds 3
and 6 were chosen as representatives to demonstrate the
viability of our approach (Scheme 2).
SYNTHESIS 2005, No. 19, pp 3327–3334
x
x.
x
x
.
2
0
0
5
Advanced online publication: 24.06.2005
DOI: 10.1055/s-2005-870005; Art ID: P01905SS
© Georg Thieme Verlag Stuttgart · New York

3328
D. Díez et al.
PAPER
the glyceraldehydes-derived imines. To the best of our We therefore sought a reasonable transition state for the
knowledge this is the first time that this kind of reaction of reaction with a view to provide a qualitative explanation
vinyl sulfones has been described. This reaction starts of the results. Examination of the 10 lowest-lying con-
with the addition of a nucleophile to a chiral imine (de- formers of 9a and 9b revealed that for 9b there were con-
rived from a chiral aldehyde) and ends with a chiral imine formers in which the imine carbon was close to the
derived from a chiral amine, opening new perspectives for methylene group. One of these, (the third-lowest energy
glyceraldehyde imine derivatives9 and related systems conformation found, MMFF94s energy 423.94 kJ/mol,
(Scheme 3).
top left in Figure 1) was imported into Sybyl11 (version
6.9, running under IRIX 6.5.18m on a Silicon Graphics
Octane), and the structure was modified by moving the
hydrogen involved in the proposed hydride transfer to
generate the lithium salt of structure 8 (lower left,
Figure 1). Distance constraints were set up so as to place
the transferring hydride at approximately 2 Å from the
carbon atom of origin and of destination. Several lithiated
sulfones, such as phenylsulfonylbenzyl lithium,12 have
been shown by X-ray crystallography to have the lithium
cation associated with the sulfone oxygen atoms, so we
chose to locate the lithium atom close to one sulfone oxy-
gen, the imine/amine nitrogen, and one of the oxygen at-
oms of the dioxolane, as a reasonable candidate for the
transition state.
We were intrigued by the apparent stereoselectivity of the
process, since the product of the hydride transfer, 9, is a
single diastereomer. Under the strongly basic conditions
of the reaction, it is reasonable to propose that the product
ratio could be controlled by the thermodynamic stability
of the two possible diastereomers 9a and 9b. To establish
whether there was a large difference in stability, a confor-
mational search was undertaken using Maestro and Mac-
romodel,10 with the MCMM/LowMode method. For each
diastereomer of 9, the automatic setup option in Maestro
was used to set up the molecule. The potential selected
was MMFF94S, with a limit of 5000 iterations of minimi-
zation using the TNCG algorithm, and 5000 attempts
were made to find conformers of each diastereomer of 9,
with a limit of 50 kJ/mol and default criteria for rejecting
conformers as duplicates of one another. The R-diastereo-
mer 9b at the sulfone-bearing carbon was only very slight-
ly less stable than the S-diastereomer 9a (421.02 kJ/mol
vs. 420.54 kJ/mol, respectively, for the lowest-energy
conformer found for each). While it is possible that the
search method failed to find a lower-lying conformer of
one of these species, or that solvent effects would give rise
to a more significant energy difference, these data do not
a priori support the idea that the diastereoselectivity of the
hydride transfer and subsequent protonation process is
thermodynamically controlled, though it may be that there
is a more significant difference in the energies of the lith-
ium salts of 9a and 9b which are the initially-formed prod-
ucts.
OMOM
O
O
NBn
SO2Ph
3
7
BuLi
THF
Ph
MOMO
O
O
O
O
O
O
MOMO
MOMO
NHBn
N
NH2
2'
R1
SO2Ph
SO2Ph
R2
10
8
9a (2'S) R1 = SO2Ph, R2 = H
9b (2'R) R1 = H, R2 = SO2Ph
Scheme 3 Reagents and conditions: see Table 1.
Table 1 Reaction of Compound 3 with BuLi and 7 under Various Conditions
Entry
3a
1
1
1
1
1
1
1
7a
8a
BuLia
1.1
1.3
1.1
1.5
1.1
1.3
1.3
1.3
Condition
8b
9b
10b
15
31
34
53
53
43
60
27
3b
1
1.5
1.5
1.5
1.5
1.5
1.1
1.5
A
A
B
B
C
D
E
42
41
57
45
27
29
40
21
2
3
4
5
13
15
25
28
6
15
7
8
1
C
28
a Equivalents.
b Isolated yield after chromatography on silica gel. Conditions: A: 15 min at –78 °C. B: 1 h at –78 °C. C: 7 h at –78 °C → 0 °C. D: 17 h at
–78 °C → r.t. E: 1 h at –78 °C, then 30 min at 0 °C and then left to warm to r.t.
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

PAPER
Vinylsulfones as Nucleophiles and Michael Acceptors in the Same Step
3329
Initially, the structure was minimized with MMFF94S in 12, and the N-Boc compound 13, in quantitative yield.
Sybyl, and the structure obtained after reaching default This compound was selectively deprotected by removal of
convergence was used to set up a semi-empirical quantum the acetonide to give diol 14, which upon treatment with
mechanical calculation in MOPAC93.13 In the first stage, NaH in THF led to the oxazolidinone 15. Examination of
the Li–N distance and the C–H distance for the transfer- the results of NOE experiments led to the assignment of
ring hydride were fixed to the values found by MMFF94S, the stereochemistry shown in Figure 2 for 15, thus demon-
while all other parameters were optimized with the EF strating that the addition of the organometallic reagent to
routine and PM3 Hamiltonian.14 The SCF criterion was 7 was the same as that observed by Díaz-de-Villegas and
set to 10–9 and the gradient norm criterion to 10–3. Full Galvez for the addition of benzyl magnesium chloride to
transition state optimization was then performed using the 7.6 The diol was transformed by treatment with excess of
TS algorithm, without any geometric variable constraints, sodium periodate in the presence of ruthenium trichloride
and with GNORM set to 10–2. The result of this operation according to the procedure described by Pericas et al17
(clearly shown to be a transitions state by analysis of vi- into the N-protected amino acid 16 (Scheme 4).
brational modes) is shown in the top right panel of
Figure 1.
O
O
MOMO
NHBoc
SO2Ph
a
10
76%
11
b
quant.
O
O
MOMO
MOMO
NHBoc
O
+
O
1:3
12
13
c
85%
Figure 1 Top left: MMFF94s conformation of 9b in which the re-
acting centers are close; lower left: PM3 conformation of the Li salt
of 8 which could achieve a transition state such as that shown top
right; lower right: conformation of the Li salt of 9b that could be pro-
duced by collapse of the transition state shown top right.
O
O
OH
OH
HO
MOMO
HO
MOMO
NH
MOMO
NHBoc
e
NHBoc
d
78%
O
92%
15
16
14
Conversion of this transition state to either the starting
material or the product could be achieved by varying
slightly the C–H bond length before initiating full EF op-
timization of the structure. It is interesting to note that in
the product (lower right panel in Figure 1), a fourth ligand
(such as water) might attach to the lithium during the
quench, permitting delivery of a proton from only one
face of the sulfone, in this case to give 9b as the expected
product. While this study is by no means a complete study
of the reaction, these preliminary results are consistent
with the observed diastereoselectivity of the reaction and
may provide a framework for anticipating the likely be-
havior of similar reactants.
Scheme 4 Reagents and conditions: (a) Boc2O, THF; (b) Na/Hg,
MeOH; (c) CF3COOH, MeOH–H2O (3:1); (d) NaH, THF; (e)
RuCl3·H2O, NaIO4, MeCN–CCl4–H2O (2:2:3).
HO
O
H
NH
O
H
H
H
H
NOE
H
OMOM
Figure 2 NOE in oxazolidinone 15.
The other vinyl sulfone chosen to test the viability of our
synthesis was 6. When this compound was subjected to
the reaction conditions shown in Table 2, the expected ad-
dition compound 17 and two diastereomeric compounds
18 and 19 (epimers at the carbon adjacent to the sulfone
group) were obtained (Scheme 5). Treatment of com-
pound 17 with BuLi gave the hydride transfer observed
previously for the trans cyclopropanes, but in lower yield
(Table 2, entry 4).
As can be seen, the best reaction conditions to obtain com-
pound 10 are those given in Table 1, entry 7. Hydrolysis
of compound 9 on silica gel gave 10 quantitatively. Once
compound 10 had been obtained in high yield we decided
to transform it into a protected amino acid and to establish
the configuration of the amino group. Compound 10 was
protected15 with Boc2O to give 11, which was desulfonyl-
ated under the usual conditions with sodium amalgam to
give, via a Julia type reaction,16 a 1:3 mixture of the olefin
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

3330
D. Díez et al.
PAPER
18
19
OTBDMS
O
a
a
78%
72%
O
NBn
SO2Ph
6
7
BuLi
THF
O
O
O
O
TBDMSO
TBDMSO
NHBoc
SO2Ph
NHBoc
SO2Ph
O
O
TBDMSO
NHBn
20
21
SO2Ph
17
b
b
21%:75%
O
O
O
O
O
TBDMSO
NH2
TBDMSO
O
NH2
TBDMSO
TBDMSO
NHBoc
O
SO2Ph
O
SO2Ph
18
19
1:3
22
23
Scheme 5 Reagents and conditions: see Table 2.
Scheme 6 Reagents and conditions: (a) Boc2O, THF; (b) Na/Hg,
MeOH.
Table 2 Reaction of Compound 6 To Give Compound 17–19
Entry 6a
7a
17a
BuLia Condi- 17b
18b
19b
H
SO2Ph
tion
H
NHBoc
TBDMSO
H
1
2
3
4
1
1
1
1.5
1.5
1.5
1.5
1.1
1.5
1.3
A
B
C
C
62
70
4
5
10
15
48
40
O
H
H
H
H
H
O
H
NOE
18
9
Figure 3 NOE in compound 20.
1
18
a Equivalents
b Isolated yield after chromatography on silica gel.
Conditions: A: 4 h at –78 °C → –30 °C. B: 7 h at –78 °C → 0 °C.
C: 15 h at –78 °C → 10 °C.
rived from chiral aldehydes, leading to chiral imines de-
rived from chiral amines.
1H NMR spectra were recorded in CDCl3 (reference peak at d =
7.26) at 200 MHz and 400 MHz on Varian 200 VX and BRUKER
DRX 400 instruments, respectively. 13C NMR spectra were record-
ed in CDCl3 (reference peak at d = 77.0) at 50 MHz and 100 MHz
on Varian 200 VX and BRUKER DRX 400 instruments, respective-
ly, and multiplicities were determined by DEPT experiments. IR
spectra were registered on a BOMEM 100 FT IR spectrophotome-
ter. Optical rotations were determined using a Perkin-Elmer 241 po-
larimeter and 1 dm cells. The electron impact (EI) mass spectra
were run on a VG-TS 250 spectrometer at 70 eV ionising voltage.
HRMS were recorded in a VG Platform (Fisons) spectrometer using
Chemical Ionisation (NH3 as gas) or Fast Atom Bombardment
(FAB) technique. Column chromatography was performed with
The predominance of 19 over 18 is in accord with the type
of mechanism suggested from our modeling studies for
the hydride transfer observed in the MOM derivatives 8
and 9. The stereochemistry of the addition step was de-
duced later on.
When compounds 18 and 19 were treated with Boc2O in
THF, the derivatives 20 and 21 were obtained. When
these compounds were desulfonylated separately they
gave the same mixture of compounds 22 and 23 in a 1:3
ratio, showing that 18 and 19 only differ in the configura-
tion of the carbon supporting the sulfone group. NMR Merck silica gel 60 (70–230 mesh). Solvents and reagents were gen-
erally distilled immediately prior to use: THF from sodium ben-
zophenone ketyl and CH2Cl2 from CaH2.
studies on compounds 20 and 21, especially NOE experi-
ments, led us to propose the stereochemistry shown in
Scheme 6 for these compounds, and so corroborate that
the addition step of the vinyl sulfones with a cis-cyclopro-
pane takes place with the same stereoselectivity as that
with the trans-cyclopropane vinyl sulfones (see Figure 3).
Compound 8
BuLi (1.6 M, 0.72 mL, 1.15 mmol) was added to a solution of 3 (205
mg, 0.76 mmol) in THF (3.5 mL) at –78 °C. After 15 min, imine 7
(250 mg, 1.14 mmol) was added to the reaction flask via cannula as
a solution in THF (3.5 mL). The reaction mixture was left to stir for
1 h at –78 °C under Ar before addition of sat. NH4Cl solution (2
mL). The product was extracted into EtOAc (3 ×). The organic ex-
tracts were combined, washed with brine, dried over anhyd Na2SO4,
filtered and the solvent removed in vacuo. The resultant oil was sub-
Hence, in this paper we have demonstrated the versatility
of cyclopropanol vinyl sulfone compounds of type I
(Scheme 1) for producing unnatural amino acids. We
have also described a new hydride transfer reaction that
can be used to exploit the reactivity of chiral imines de- mitted to flash silica column chromatography (hexane–EtOAc, 9:1)
to yield 8 (166 mg, 0.34 mmol, 45%) and 10 (160 mg, 0.40 mmol,
53%); [a]D22 –12.8 (c = 1.71, CHCl3).
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

PAPER
Vinylsulfones as Nucleophiles and Michael Acceptors in the Same Step
3331
IR: 2986, 2938, 1624, 1452, 1373, 1304, 1260, 1217, 1146, 1059,
924, 845, 733, 691 cm–1.
(m, 2 H, CH2OCH3), 5.52 (d, J = 9.8 Hz, 1 H, NH), 7.48, 7.64 (m, 3
H, Hmeta, Hpara in SO2Ph), 7.88–7.92 (m, 2 H, Hortho in SO2Ph).
1H NMR (400 MHz, CDCl3): d = 1.05 (q, J = 6.2 Hz, 1 H, Ha-3),
1.33 (s, 6 H, Me2C), 1.38 (ddd, J = 4.0, 6.2, 9.6 Hz, 1 H, Hb-3),
1.92–2.03 (m, 1 H, H-2), 2.38–2.47 (br s, 1 H, NH), 2.91, 3.24 (2 ×
d, J = 13.6 Hz, 2 H, CH2Ph), 3.34 (s, 3 H, CH2OCH3), 3.69 (ddd,
J = 2.4, 4.0, 6.4 Hz, 1 H, H-1), 3.74 (d, J = 8.4 Hz, 1 H, H-3¢), 3.82
(dd, J = 6.0, 8.8 Hz, 1 H, HA-5¢), 3.91 (dd, J = 6.0, 8.8 Hz, 1 H, HB-
5¢), 4.53–4.58 (m, 1 H, H-4¢), 4.56 (s, 2 H, CH2OCH3), 6.52 (d, J =
11.2 Hz, 1 H, H-1¢), 7.02 (d, J = 6.8 Hz, 2 H, Hortho in CH2Ph), 7.15–
7.23 (m, 3 H, Hmeta, Hpara in CH2Ph), 7.49–7.53 (m, 2 H, Hmeta in
SO2Ph), 7.57–7.61 (m, 1 H, Hpara in SO2Ph), 7.88–7.91 (m, 2 H,
Hortho in SO2Ph).
13C NMR (50 MHz, CDCl3): d = 13.5 (C-3), 18.3 (C-2), 25.2, 26.2
(Me2C), 28.0 (C-1¢), 28.5 [CO2C(CH3)3], 49.2 (C-3¢), 55.8
(CH2OCH3), 56.7 (C-1), 66.7 (C-5¢), 67.9 (C-2¢), 78.0 (C-4¢), 80.2
[CO2C(CH3)3], 96.5 (CH2OCH3), 109.8 (Me2C), 129.4 (Cortho, Cmeta
in SO2Ph), 134.0 (Cpara in SO2Ph), 138.1 (Cipso in SO2Ph), 156.0
[CO2C(CH3)3].
MS: m/z (%) = 522 (10) [M + Na]+, 500 (5) [M + 1]+, 400 (20), 354
(20), 136 (25), 101 (40).
HRMS: m/z [M + 1]+ calcd for C24H38NO8S: 500.2318; found:
500.2287.
13C NMR (100 MHz, CDCl3): d = 16.8 (C-3), 20.0 (C-2), 25.5, 26.9
(Me2C), 50.4 (CH2Ph), 55.8 (CH2OCH3), 59.4 (C-1, C-3¢), 66.6 (C-
5¢), 77.7 (C-4¢), 96.5 (CH2OCH3), 109.6 (Me2C), 126.8 (Cpara in
CH2Ph), 127.7 (Cortho in SO2Ph), 128.1 (C-2¢, Cmeta in CH2Ph), 128.5
(Cortho in CH2Ph), 128.9 (Cmeta in SO2Ph), 133.1 (Cpara in SO2Ph),
137.6 (Cipso in CH2Ph), 139.6 (Cipso in SO2Ph), 148.8 (C-1¢).
MS: m/z (%) = 488 (55) [M + 1]+, 386 (10), 245 (15), 91 (100).
HRMS: m/z [M + 1]+ calcd for C26H34NO6S: 488.2107; found:
Compound 12
A solution of 11 (267 mg, 0.53 mmol) in anhyd MeOH (3 mL) was
added to Na–Hg (5% amalgam, 800 mg) via cannula. The reaction
mixture was left to stir for 2 h at r.t. under Ar. The residue was fil-
tered and diluted with EtOAc. The mixture was washed with H2O
and brine, dried over anhyd Na2SO4, filtered and the solvent re-
moved. The crude product was submitted to flash silica column
chromatography (hexane–EtOAc, 9:1) to yield 12 (31 mg, 0.13
mmol, 24%) and 13 (143 mg, 0.40 mmol, 75%) as colorless oils;
[a]D22 –6.7 (c = 0.27, CHCl3).
488.2102.
Compound 10
IR: 2988, 2932, 1454, 1370, 1219, 1161, 1061, 995, 922, 858 cm–1.
[a]D22 +15.1 (c = 1.23, CHCl3).
1H NMR (200 MHz, CDCl3): d = 0.38 (q, J = 6.0 Hz, 1 H, Ha-3),
0.77 (ddd, J = 3.0, 5.8, 9.8 Hz, 1 H, Hb-3), 0.96–1.12 (m, 1 H, H-2),
1.38, 1.42 (2 × s, 6 H, Me2C), 1.80–2.12 (m, 2 H, H-1¢), 3.21 (dt,
J = 3.0, 3.0, 6.0 Hz, 1 H, H-1), 3.39 (s, 3 H, CH2OCH3), 3.56 (t, J =
8.0 Hz, 1 H, HA-5¢), 4.06 (dd, J = 6.2, 8.0 Hz, 1 H, HB-5¢), 4.42–4.53
(m, 1 H, H-4¢), 4.62 (s, 2 H, CH2OCH3), 5.52 (dd, J = 7.6, 15.4 Hz,
1 H, H-3¢), 5.81 (dt, J = 6.4, 6.4, 15.4 Hz, 1 H, H-2¢).
13C NMR (50 MHz, CDCl3): d = 11.5 (C-3), 17.2 (C-2), 25.3, 26.1
(Me2C), 33.4 (C-1¢), 55.0 (CH2OCH3), 55.6 (C-1), 68.9 (C-5¢), 76.6
(C-4¢), 95.8 (CH2OCH3), 108.5 (Me2C), 127.4 (C-2¢), 133.0 (C-3¢).
IR: 3399, 2986, 2934, 1449, 1371, 1306, 1262, 1217, 1148, 1059,
999, 918, 855, 735, 691, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.33 (q, J = 6.0 Hz, 1 H, Ha-3),
0.76 (ddd, J = 3.2, 6.0, 9.6 Hz, 1 H, Hb-3), 1.00–1.17 (m, 1 H, H-2),
1.31, 1.33 (2 × s, 6 H, Me2C), 1.59–1.73, 1.85–2.05 (2 × m, 2 H, H-
1¢), 3.06–3.15 (m, 2 H, H-1, H-2¢), 3.36–3.39 (m, 1 H, H-3¢), 3.38
(s, 3 H, CH2OCH3), 3.54–3.60 (m, 1 H, HA-5¢), 3.93–4.01 (m, 2 H,
HB-5¢, H-4¢), 4.56, 4.62 (2 × d, J = 6.4 Hz, 2 H, CH2OCH3), 7.56–
7.62 (m, 2 H, Hmeta in SO2Ph), 7.66–7.71 (m, 1 H, Hpara in SO2Ph),
7.92–7.94 (m, 2 H, Hortho in SO2Ph).
Compound 13
13C NMR (100 MHz, CDCl3): d = 13.4 (C-3), 18.1 (C-2), 25.1 (C-
1¢), 25.4, 26.3 (Me2C), 51.0 (C-3¢), 55.6 (CH2OCH3), 56.5 (C-1),
66.7 (C-5¢), 67.9 (C-2¢), 78.4 (C-4¢), 96.3 (CH2OCH3), 109.7
(Me2C), 128.7 (Cortho in SO2Ph), 129.3 (Cmeta in SO2Ph), 133.9 (Cpara
in SO2Ph), 137.8 (Cipso in SO2Ph).
MS: m/z (%) = 400 (100) [M + 1]+, 350 (10), 310 (25), 280 (20), 197
(10), 91 (60).
[a]D22 +15.5 (c = 0.86, CHCl3).
IR: 3366, 2932, 1715, 1505, 1454, 1368, 1248, 1219, 1161, 1059,
920 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.36 (q, J = 6.0 Hz, 1 H, Ha-3),
0.75 (ddd, J = 3.0, 5.8, 9.8 Hz, 1 H, Hb-3), 0.80–1.03 (m, 1 H, H-2),
1.21–1.28 (m, 2 H, H-1¢), 1.33, 1.41 (2 × s, 6 H, Me2C), 1.43 [s, 9
H, CO2C(CH3)3], 1.57–1.68 (m, 2 H, H-2¢), 3.17 (dt, J = 3.0, 3.0, 6.2
Hz, 1 H, H-1), 3.39 (s, 3 H, CH2OCH3), 3.61–3.68 (m, 1 H, H-3¢),
3.65 (dd, J = 7.4, 7.8 Hz, 1 H, HA-5¢), 3.97 (dd, J = 6.6, 8.0 Hz, 1 H,
HB-5¢), 4.08–4.14 (m, 1 H, H-4¢), 4.61 (s, 2 H, CH2OCH3).
13C NMR (50 MHz, CDCl3): d = 12.6 (C-3), 18.8 (C-2), 25.2, 26.4
(Me2C), 28.4 (C-1¢), 28.5 [CO2C(CH3)3], 33.0 (C-2¢), 50.4 (C-3¢),
55.8 (CH2OCH3), 56.6 (C-1), 66.5 (C-5¢), 77.7 (C-4¢), 79.4
[CO2C(CH3)3], 96.5 (CH2OCH3), 109.1 (Me2C), 156.3
[CO2C(CH3)3].
HRMS: m/z [M + 1]+ calcd for C19H30NO6S: 400.1794; found:
400.1763.
Compound 11
To a solution of 10 (510 mg, 1.28 mmol) in THF (6 mL) was added
Boc2O (340 mg, 1.56 mmol) as a solution in THF (6 mL). The mix-
ture was left to stir for 16 h before addition of 5% NaHCO3 solution
(2 mL). The product was extracted into EtOAc (3 ×). The organic
extracts were combined, washed with brine, dried over anhyd
Na2SO4, filtered and the solvent removed in vacuo. The resultant oil
was purified by flash silica column chromatography (hexane–
EtOAc, 8:2) to yield 11 (485 mg, 0.97 mmol, 76%); [a]D22 +27.2
(c = 1.04, CHCl3).
MS: m/z (%) = 360 (10) [M + 1]+, 304 (10), 260 (20), 214 (20), 184
(20), 101 (15).
HRMS: m/z [M + 1]+ calcd for C18H34NO6: 360.2386; found:
360.2412.
IR: 3372, 2982, 2934, 1711, 1503, 1449, 1370, 1306, 1248, 1219,
1161, 1059 cm–1.
Compound 14
1H NMR (200 MHz, CDCl3): d = 0.29 (q, J = 6.2 Hz, 1 H, Ha-3),
0.72–0.89 (m, 1 H, Hb-3), 1.07–1.20 (m, 1 H, H-2), 1.25, 1.33 (2 ×
s, 6 H, Me2C), 1.38 [s, 9 H, CO2C(CH3)3], 1.65–1.71, 1.83–1.97
(2 × m, 2 H, H-1¢), 3.13–3.17 (m, 1 H, H-1), 3.31–3.38 (m, 1 H, H-
2¢), 3.35 (s, 3 H, CH2OCH3), 3.53 (t, J = 7.8 Hz, 1 H, HA-5¢), 3.94
(t, J = 8.0 Hz, 1 H, HB-5¢), 4.27–4.33 (m, 2 H, H-4¢, H-3¢), 4.49–4.64
To a solution of 13 (130 mg, 0.36 mmol) in MeOH–H2O (3:1, 1.5
mL) was added CF3COOH (14 mL, 0.19 mmol), and the mixture
was left to stir for 14 h. The solution was then poured into a sepa-
rating funnel, extracted with CH2Cl2 (3 ×), dried over anhyd
Na2SO4, filtered and the solvent removed. The product was purified
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

3332
D. Díez et al.
PAPER
by flash silica column chromatography (hexane–EtOAc, 1:1) to
(C-1), 80.5 [CO2C(CH3)3], 96.6 (CH2OCH3), 156.0 [CO2C(CH3)3],
176.2 (C-4¢).
yield 14 (98 mg, 0.31 mmol, 85%); [a]D22 +15.4 (c = 0.57, CHCl3).
IR: 3600–3100, 2931, 1686, 1522, 1456, 1367, 1393, 1162, 1059,
921, 871 cm–1.
MS: m/z (%) = 304 (20) [M + 1]+, 216 (10), 91 (60).
HRMS: m/z [M+1]+ calcd for C14H26NO6: 304.1760; found:
1H NMR (200 MHz, CDCl3): d = 0.37 (q, J = 6.0 Hz, 1 H, Ha-3),
0.78 (ddd, J = 3.0, 5.8, 9.6 Hz, 1 H, Hb-3), 0.87–1.04 (m, 1 H, H-2),
1.21–1.35 (m, 2 H, H-1¢), 1.43 (s, 9 H, CO2C(CH3)3], 1.60–1.75 (m,
2 H, H-2¢), 3.17 (dt, J = 3.0, 3.0, 6.2 Hz, 1 H, H-1), 3.39 (s, 3 H,
CH2OCH3), 3.47–3.76 (m, 4 H, H-3¢, H-4¢, H-5¢), 4.62 (s, 2 H,
CH2OCH3), 4.70 (d, J = 9.0 Hz, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 12.8 (C-3), 18.8 (C-2), 28.5
[CO2C(CH3)3], 31.6 (C-1¢, C-2¢), 51.1 (C-3¢), 55.9 (CH2OCH3),
56.7 (C-1), 63.9 (C-5¢), 73.7 (C-4¢), 80.3 [CO2C(CH3)3], 96.7
(CH2OCH3), 157.4 [CO2C(CH3)3].
304.1783.
Compound 17
BuLi (1.6 M, 0.62 mL, 0.99 mmol) was added to a solution of 6 (312
mg, 0.92 mmol) in THF (4.5 mL) at –78 °C. After 15 min, imine 7
(293 mg, 1.34 mmol) was added to the reaction flask via cannula as
a solution in THF (7 mL). The reaction mixture was left to stir for 7
h at –78 °C → 0 °C under Ar before addition of sat. NH4Cl solution
(3 mL). The product was extracted into EtOAc (3 ×). The organic
extracts were combined, washed with brine, dried over anhyd
Na2SO4, filtered and the solvent removed in vacuo. The resultant oil
was submitted to flash silica column chromatography (hexane–
EtOAc, 9:1) to yield 17 (360 mg, 0.65 mmol, 70%), 18 (21.5 mg
(0.05 mmol, 5%) and 19 (65 mg, 0.14 mmol, 15%); [a]D22 –75.3
(c = 1.17, CHCl3).
MS: m/z (%) = 320 (5) [M + 1]+, 81 (80).
HRMS: m/z calcd for C15H30NO6 [M + 1]+: 320.2073; found:
320.2053.
Compound 15
IR: 3454, 3337, 2932, 1624, 1457, 1371, 1305, 1220, 1145, 1063,
839, 780, 689, 666 cm–1.
To a solution of 14 (26.5 mg, 0.083 mmol) in THF (3 mL) was add-
ed 60% NaH (80 mg, 2 mmol) under Ar at r.t. The reaction mixture
was left to stir for 1 h before addition of sat. NH4Cl solution (1 mL).
The mixture was poured into a separating funnel, diluted with
CH2Cl2 and washed with sat. NH4Cl, then dried over anhyd Na2SO4,
filtered and the solvent removed in vacuo. The resultant product
was purified by flash silica column chromatography (hexane–
EtOAc, 1:1) to yield 15 (16 mg, 0.065 mmol, 78%); [a]D22 +32.9
(c = 0.38, CHCl3).
1H NMR (200 MHz, CDCl3): d = 0.15 (s, 6 H, Me2Si), 0.86–0.96
(m, 1 H, Hb-3), 0.95 [s, 9 H, (CH3)3CSi], 1.12–1.24 (m, 1 H, Ha-3),
1.29, 1.31 (2 × s, 6 H, Me2C), 1.37–1.53 (m, 1 H, H-2), 2.89, 3.23
(2 × d, J = 13.8 Hz, CH2Ph, 2 H), 3.72–3.78 (m, 3 H, H-1, H-3¢, HA-
5¢), 3.90–3.96 (m, 1 H, HB-5¢), 4.56–4.66 (m, 1 H, H-4¢), 7.00–7.31
(m, 6 H, CH2Ph, H-1¢), 7.42–7.55 (m, 3 H, Hpara, Hmeta in SO2Ph),
7.89–7.95 (m, 2 H, Hortho in SO2Ph).
13C NMR (50 MHz, CDCl3): d = –4.8 (Me2Si), 18.3 [(CH3)3CSi],
18.7 (C-2), 19.2 (C-3), 25.7, 27.2 (Me2C), 26.0 [(CH3)3CSi], 50.6
(CH2Ph), 54.9 (C-1), 59.6 (C-3¢), 66.9 (C-5¢), 78.0 (C-4¢), 109.8
(Me2C), 127.0 (Cpara in CH2Ph), 128.2 (Cortho in SO2Ph), 128.3
(Cmeta in CH2Ph, C-2¢), 128.7 (Cortho in CH2Ph), 129.0 (Cmeta in
SO2Ph), 133.1 (Cpara in SO2Ph), 137.6 (Cipso in CH2Ph), 140.1 (Cipso
in SO2Ph), 149.1 (C-1¢).
IR: 3600–3100, 2929, 1750, 1456, 1160, 1060 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.38 (q, J = 6.0 Hz, 1 H, Ha-3),
0.79 (ddd, J = 3.2, 6.0, 10.0 Hz, 1 H, Hb-3), 0.92–1.00 (m, 1 H, H-
2), 1.13–1.22, 1.30–1.39 (2 × m, 2 H, H-1¢), 1.67–1.72 (m, 2 H, H-
2¢), 3.18 (dt, J = 3.2, 3.2, 6.2 Hz, 1 H, H-1), 3.39 (s, 3 H, CH2OCH3),
3.65 (dd, J = 4.4, 12.8 Hz, 1 H, HA-5¢), 3.76 (q, J = 6.0 Hz, 1 H, H-
3¢), 3.84 (dd, J = 3.2, 12.8 Hz, 1 H, HB-5¢), 4.21–4.25 (m, 1 H, H-
4¢), 4.60, 4.63 (2 × d, J = 6.4 Hz, 2 H, CH2OCH3), 6.21 (br s, 1 H,
NH).
MS: m/z (%) = 558 (10) [M + 1]+, 73 (100).
HRMS: m/z [M + 1]+ calcd for C30H44NO5SSi: 558.2709; found:
558.2689.
13C NMR (50 MHz, CDCl3): d = 12.6 (C-3), 18.5 (C-2), 27.8 (C-1¢),
35.0 (C-2¢), 53.7 (C-3¢), 55.9 (CH2OCH3), 56.7 (C-1), 62.9 (C-5¢),
82.7 (C-4¢), 96.6 (CH2OCH3), 159.5 (CO).
Compound 18
1H NMR (200 MHz, CDCl3): d = –0.29 to –0.22 (m, 1 H, Hb-3),
–0.02, 0.02 (2 × s, 6 H, Me2Si), 0.47–0.68 (m, 1 H, Ha-3), 0.81 [s, 9
H, (CH3)3CSi], 0.85–0.92 (m, 1 H, H-2), 1.38, 1.42 (2 × s, 6 H,
Me2C), 1.64–1.80, 1.95–2.17 (2 × m, 2 H, H-1¢), 3.03–3.11 (m, 1 H,
H-2¢), 3.26–3.36 (m, 2 H, H-1, H-3¢), 3.74 (dd, J = 7.0, 7.8 Hz, 1 H,
HA-5¢), 4.20 (dd, J = 6.6, 7.8 Hz, 1 H, HB-5¢), 4.71 (q, J = 6.6 Hz, 1
H, H-4¢), 7.50–7.67 (m, 3 H, Hmeta, Hpara in SO2Ph), 7.86–7.90 (m,
2 H, Hortho in SO2Ph).
13C NMR (50 MHz, CDCl3): d = –4.8, –4.7 (Me2Si), 12.9 (C-3),
14.8 (C-2), 18.2 [(CH3)3CSi], 24.5 (C-1¢), 25.6, 26.9 (Me2C), 26.0
[(CH3)3CSi], 50.9 (C-1), 54.7 (C-3¢), 66.5 (C-5¢), 68.4 (C-2¢), 77.9
(C-4¢), 109.7 (Me2C), 128.8 (Cortho in SO2Ph), 129.4 (Cmeta in
SO2Ph), 133.9 (Cpara in SO2Ph), 139.1 (Cipso SO2Ph).
Compound 16
To a solution of 14 (59 mg, 0.18 mmol) in MeCN–CCl4–H2O (2:2:3,
4 mL) was slowly added NaIO4 (158 mg, 0.74 mmol). The mixture
was vigorously stirred for 5 min before addition of RuCl3–H2O (5
mg, 0.024 mmol). It was then left to stir at r.t. for 1 h. CH2Cl2 was
then added and the product extracted with 1 M aq NaHCO3 solution
(3 ×). The aqueous extracts were combined, washed with Et2O, and
slowly acidified with solid KHSO4 until pH = 3. Product was then
extracted with Et2O, dried over anhyd Na2SO4, filtered and the sol-
vent removed in vacuo. It was purified by flash silica column chro-
matography (hexane–EtOAc, 1:1) to yield 16 (51 mg, 0.17 mmol,
92%); [a]D22 –24.5 (c = 0.44, CHCl3).
IR: 3333, 2928, 2856, 1716, 1519, 1456, 1393, 1249, 1220, 1161,
1061, 921 cm–1.
Compound 19
1H NMR (200 MHz, CDCl3): d = –0.02–0.06 (m, 1 H, Hb-3), 0.03,
0.07 (2 × s, 6 H, Me2Si), 0.53–0.63 (m, 1 H, Ha-3), 0.80–0.85 (m, 1
H, H-2), 0.86 [s, 9 H, (CH3)3CSi], 1.30, 1.32 (2 × s, 6 H, Me2C),
1.85–2.00, 2.07–2.25 (2 × m, 2 H, H-1¢), 3.09–3.16 (m, 1 H, H-2¢),
3.34 (dt, J = 3.2, 6.4, 6.4 Hz, 1 H, H-1), 3.51–3.58 (m, 2 H, H-3¢,
HA-5¢), 3.97 (dd, J = 6.4, 8.0 Hz, 1 H, HB-5¢), 4.16 (q, J = 6.4 Hz, 1
H, H-4¢), 7.52–7.69 (m, 3 H, Hmeta, Hpara in SO2Ph), 7.89–7.92 (m,
2 H, Hortho in SO2Ph).
1H NMR (200 MHz, CDCl3): d = 0.39 (q, J = 6.0 Hz, 1 H, Ha-3),
0.80 (ddd, J = 3.0, 5.8, 9.6 Hz, 1 H, Hb-3), 0.83–1.08 (m, 1 H, H-2),
1.21–1.40 (m, 2 H, H-1¢), 1.45 (s, 9 H, CO2C(CH3)3], 1.68–1.81,
1.92–2.05 (2 × m, 2 H, H-2¢), 3.18 (dt, J = 3.0, 3.0, 6.2 Hz, 1 H, H-
1), 3.42 (s, 3 H, CH2OCH3), 4.25–4.41 (m, 1 H, H-3¢), 4.64 (s, 2 H,
CH2OCH3), 5.00–5.09 (m, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 12.7 (C-3), 18.5 (C-2), 27.7 (C-1¢),
28.5 [CO2C(CH3)3], 32.0 (C-2¢), 53.3 (C-3¢), 55.8 (CH2OCH3), 56.7
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

PAPER
Vinylsulfones as Nucleophiles and Michael Acceptors in the Same Step
3333
Compound 20
128.9 (Cortho in SO2Ph), 129.2 (Cmeta in SO2Ph), 133.5 (Cpara in
SO2Ph), 139.1 (Cipso in SO2Ph), 156.3 [CO2C(CH3)3].
MS: m/z (%) = 570 (5) [M + 1]+, 470 (10), 398 (10), 324 (10), 136
(10), 101 (20), 73 (100).
HRMS: m/z [M + 1]+ calcd for C28H48NO7SSi: 570.2921; found:
570.2903.
To a solution of 18 (59 mg, 0.125 mmol) in THF (2 mL) was added
Boc2O (46 mg, 0.21 mmol) as a solution in THF (1.5 mL). The mix-
ture was left to stir for 7 h before addition of 5% NaHCO3 solution
(1 mL). The product was extracted into EtOAc (3 ×). The organic
extracts were combined, washed with 5% NaHCO3 solution and
brine, dried over anhyd Na2SO4, filtered and the solvent removed in
vacuo. The product was purified by flash silica column chromatog-
raphy (hexane–EtOAc, 9:1) to yield 20 (51.5 mg, 0.09 mmol, 72%);
[a]D22 +0.7 (c = 1.23, CHCl3).
Compound 22
A solution of 20 + 21 (129 mg, 0.23 mmol) in anhyd MeOH (1.5
mL) was added to 5% Na–Hg amalgam (800 mg) via cannula. The
reaction mixture was left to stir for 1 h at r.t. under Ar. The residue
was filtered and diluted with EtOAc. The mixture was washed with
H2O and brine, dried over anhyd Na2SO4, filtered and the solvent
removed. The crude product was submitted to flash silica column
chromatography (hexane–EtOAc, 9:1) to yield 22 (15 mg, 0.05
mmol, 21%) and 23 (73 mg, 0.17 mmol, 75%); [a]D22 –0.4 (c = 0.49,
CHCl3).
IR: 3443, 2957, 2932, 2857, 1718, 1498, 1369, 1305, 1252, 1222,
1150, 1078, 839, 779, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = –0.31 (dt, J = 2.8, 2.8, 6.0 Hz, 1
H, Hb-3), –0.04, 0.00 (2 × s, 6 H, Me2Si), 0.52 (dt, J = 6.0, 6.0, 9.6
Hz, 1 H, Ha-3), 0.80 [s, 9 H, (CH3)3CSi], 0.84–0.90 (m, 1 H, H-2),
1.36, 1.43 (2 × s, 6 H, Me2C), 1.43 [s, 9 H, CO2C(CH3)3], 1.54–1.68,
2.05–2.14 (2 × m, 2 H, H-1¢), 3.29 (dt, J = 3.3, 3.3, 6.4 Hz, 1 H, H-
1), 3.33–3.37 (m, 1 H, H-2¢), 3.72 (dd, J = 6.7, 8.2 Hz, 1 H, HA-5¢),
4.15 (dd, J = 6.7, 8.2 Hz, 1 H, HB-5¢), 4.45 (dt, J = 3.8, 3.8, 9.5 Hz,
1 H, H-3¢), 4.73–4.77 (m, 1 H, H-4¢), 5.22 (d, J = 9.6 Hz, 1 H, NH),
7.50–7.57 (m, 2 H, Hmeta in SO2Ph), 7.61–7.65 (m, 1 H, Hpara in
SO2Ph), 7.87–7.90 (m, 2 H, Hortho in SO2Ph).
13C NMR (100 MHz, CDCl3): d = –5.4, –5.2 (Me2Si), 12.6 (C-3),
14.5 (C-2), 17.9 [(CH3)3CSi], 23.6 (C-1¢), 25.3, 26.4 (Me2C), 25.8
[(CH3)3CSi], 28.3 [CO2C(CH3)3], 50.8 (C-3¢), 50.9 (C-1), 66.4 (C-
2¢), 67.1 (C-5¢), 75.2 (C-4¢), 79.7 [CO2C(CH3)3], 109.8 (Me2C),
128.4 (Cortho in SO2Ph), 129.2 (Cmeta in SO2Ph), 133.6 (Cpara in
SO2Ph), 139.0 (Cipso in SO2Ph), 155.5 [CO2C(CH3)3].
IR: 2986, 2956, 2929, 2857, 1476, 1370, 1260, 1224, 1063, 838,
781 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.09, 0.10 (2 × s, 6 H, Me2Si),
0.09–0.12 (m, 1 H, Hb-3), 0.63–0.71 (m, 1 H, Ha-3), 0.82–0.87 (m,
1 H, H-2), 0.89 [s, 9 H, (CH3)3CSi], 1.40, 1.43 (2 × s, 6 H, Me2C),
2.00–2.38 (m, 2 H, H-1), 3.42 (dt, J = 3.2, 6.4, 6.4 Hz, 1 H, H-1),
3.57 (t, J = 8.2 Hz, 1 H, HA-5¢), 4.07 (t, J = 8.2 Hz, 1 H, HB-5¢), 4.44–
4.55 (m, 1 H, H-4¢), 5.50 (dd, J = 8.0, 15.2 Hz, 1 H, H-3¢), 5.90 (dt,
J = 6.4, 6.4, 15.4 Hz, 1 H, H-2¢).
13C NMR (50 MHz, CDCl3): d = –4.8, –4.7 (Me2Si), 13.0 (C-3),
16.1 (C-2), 18.3 [(CH3)3CSi], 26.0 [(CH3)3CSi], 26.2, 27.0 (Me2C),
29.9 (C-1¢), 50.5 (C-1), 69.7 (C-5¢), 77.7 (C-4¢), 109.2 (Me2C),
127.2 (C-2¢), 136.1 (C-3¢).
MS: m/z (%) = 570 (5) [M + 1]+, 470 (10), 101 (20), 73 (100).
HRMS: m/z [M + 1]+ calcd for C28H48NO7SSi: 570.2921; found:
570.2942.
Compound 23
Compound 21
[a]D22 +11.8 (c = 0.83, CHCl3).
To a solution of 19 (96 mg, 0.204 mmol) in THF (2 mL) was added
Boc2O (80 mg, 0.37 mmol) as a solution in THF (1.5 mL). The mix-
ture was left to stir for 7 h before addition of 5% NaHCO3 solution
(1 mL). The product was extracted into EtOAc (3 ×). The organic
extracts were combined, washed with brine, dried over anhyd
Na2SO4, filtered and the solvent removed in vacuo. The resultant oil
was purified by flash silica column chromatography (hexane–
EtOAc, 9:1) to yield 21 (91 mg, 0.16 mmol, 78%); [a]D22 –5.0 (c =
0.86, CHCl3).
IR: 3452, 3365, 2981, 2930, 2858, 1717, 1499, 1368, 1251, 1222,
1172, 1070, 838, 777, 666 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.03–0.08 (m, 1 H, Hb-3), 0.08 (s,
6 H, Me2Si), 0.55–0.65 (m, 1 H, Ha-3), 0.85–0.90 (m, 1 H, H-2),
0.88 [s, 9 H, (CH3)3CSi], 1.11–1.26 (m, 2 H, H-1¢), 1.34–1.43 (2 ×
s, 6 H, Me2C), 1.43 [s, 9 H, CO2C(CH3)3], 1.45–1.75 (m, 2 H, H-2¢),
3.39 (dt, J = 3.2, 6.4, 6.4 Hz, 1 H, H-1), 3.62–3.70 (m, 1 H, H-3¢),
3.66 (dd, J = 7.4, 7.8 Hz, 1 H, HA-5¢), 3.99 (dd, J = 6.8, 7.8 Hz, 1 H,
HB-5¢), 4.12–4.18 (m, 1 H, H-4¢), 4.67 (d, J = 9.8 Hz, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = –4.8, –4.7 (Me2Si), 12.9 (C-3),
16.6 (C-2), 18.3 [(CH3)3CSi], 23.7 (C-1¢), 25.3, 26.5 (Me2C), 26.1
[(CH3)3CSi], 28.6 [CO2C(CH3)3], 33.7 (C-2¢), 50.7 (C-3¢), 50.8 (C-
1), 66.6 (C-5¢), 77.7 (C-4¢), 79.4 [CO2C(CH3)3], 109.2 (Me2C),
156.4 [CO2C(CH3)3].
IR: 3446, 3365, 2932, 2858, 1718, 1498, 1448, 1369, 1306, 1252,
1153, 1071, 840, 779, 733, 691, 665 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.04, 0.07 (2 × s, 6 H, Me2Si),
0.06–0.12 (m, 1 H, Hb-3), 0.62–0.68 (m, 1 H, Ha-3), 0.87 [s, 9 H,
(CH3)3CSi], 0.85–0.93 (m, 1 H, H-2), 1.31, 1.36 (2 × s, 6 H, Me2C),
1.42 [s, 9 H, CO2C(CH3)3], 1.76–1.83, 1.96-2.04 (2 × m, 2 H, H-1¢),
3.37–3.43 (m, 2 H, H-1, H-2¢), 3.63 (dd, J = 7.2, 8.2 Hz, 1 H, HA-
5¢), 4.02 (dd, J = 6.6, 8.4 Hz, 1 H, HB-5¢), 4.31 (dt, J = 2.8, 6.8, 6.8
Hz, 1 H, H-4¢), 4.50 (dt, J = 2.8, 2.8, 10.4 Hz, 1 H, H-3¢), 4.97 (d,
J = 10.4 Hz, 1 H, NH), 7.51–7.57 (m, 2 H, Hmeta in SO2Ph), 7.61–
7.64 (m, 1 H, Hpara in SO2Ph), 7.94–7.96 (m, 2 H, Hortho in SO2Ph).
MS: m/z (%) = 430 (5) [M + 1]+, 330 (20), 258 (25), 184 (20), 136
(10), 73 (100).
HRMS: m/z [M + 1]+ calcd for C22H44NO5Si: 430.2989; found:
430.2983.
13C NMR (100 MHz, CDCl3): d = –5.9, –5.8 (Me2Si), 13.6 (C-3),
14.8 (C-2), 18.0 [(CH3)3CSi], 23.8 (C-1¢), 25.2, 26.1 (Me2C), 25.8
[(CH3)3CSi], 28.3 [CO2C(CH3)3], 49.5 (C-3¢), 51.0 (C-1), 66.7 (C-
5¢), 68.1 (C-2¢), 77.5 (C-4¢), 79.7 [CO2C(CH3)3], 109.6 (Me2C),
Acknowledgment
The authors thank the CICYT (BQU 2001-1034), Junta de Castilla
y León, for financial support (SA 13-009) and Universidad de Sala-
manca for a doctoral fellowship to P.G.
Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York

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D. Díez et al.
PAPER
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Synthesis 2005, No. 19, 3327–3334 © Thieme Stuttgart · New York