Synthesis of enantiomerically enriched amino sulfide building blocks from acyclic chiral amino allylsilanes

Article abstract of DOI:10.1021/jo2010878

An efficient synthesis of various protected syn-β-sulfenyl amides is described. These are prepared from the corresponding enantiopure amino allylsilanes which are in turn obtained from naturally occurring amino acids. The key step for introduction of the

Full text of DOI:10.1021/jo2010878

ARTICLE
pubs.acs.org/joc
Synthesis of Enantiomerically Enriched Amino Sulfide Building Blocks
from Acyclic Chiral Amino Allylsilanes†
Gianna Reginato,*,‡ Bernardo Pezzati,‡,§ Andrea Ienco,‡ Gabriele Manca,‡ Andrea Rossin,‡ and
Alessandro Mordini‡,§
‡CNR - Istituto di Chimica dei Composti Organometallici (ICCOM), Via Madonna del Piano 50019 Sesto Fiorentino (FI), Italy
§Dipartimento di Chimica “Ugo Schiff”, Universitꢀa di Firenze, Via della Lastruccia 13 50019 Sesto Fiorentino (FI), Italy
S Supporting Information
b
ABSTRACT: An efficient synthesis of various protected syn-β-sulfe-
nyl amides is described. These are prepared from the corresponding
enantiopure amino allylsilanes which are in turn obtained from
naturally occurring amino acids. The key step for introduction of
the sulfur substituent is a diastereoselective electrophilic sulfodesilyla-
tion which is carried out with phthalimidesulfenyl chloride. The
resulting homochiral β-phthalimidesulfenyl amines with an allylic
sulforated stereogenic center are useful building blocks, as they
represent a starting point for subsequent functional manipulations.
Scheme 1. Electrophilic Fluorodesilylation of Amino Allyl-
’ INTRODUCTION
silanes with Selectfluor
Chiral β-sulfenyl amines of high diastereomeric and enantio-
meric purity are of great interest in synthetic organic chemistry;
in particular, they have gained considerable attention as N,S-
ligands in asymmetric catalysis.1,2 Heterobidentate N,S-ligands have
proved to be very effective in enantioselective palladium-catalyzed
allylic substitution reactions,3,4 for the enantioselective addition of
dialkylzinc reagents to prochiral carbonyl compounds,5 in the
enantioselective conjugate addition of organometallic reagents to
R,β-unsaturated carbonyl compounds,6 and in iridium(I)-catalyzed
asymmetric hydrogenation reactions.7,8 Furthermore, the β-sulfenyl
amine unit has been found in a number of important biologically
active molecules. For instance, it is a characteristic structural motif in
marine alkaloids of the Ecteinascidine family which have been
established as an important class of anticancer agents.9
Several methods for the synthesis of vic-sulfenyl amines have
been described in the literature,10ꢀ15 including those starting
from natural R-amino acids in an ex-chiral-pool synthesis,7,16ꢀ18
the simple regio- and stereoselective ring-opening of aziridines
with thiols,19ꢀ25 and the SAMP/RAMP-hydrazone methodol-
ogy which leads to both anti-configured enantiomers.26
As a part of a research program aimed at the synthesis of new
enantiomerically enriched building blocks via amino acids mod-
ification, we turned our interest to the development of a new
procedure to prepare new chiral units containing the vic-amino
sulfide moiety. Following our recent results,27 we focused on
chiral amino allylsilanes.
It is well recognized that allylsilanes are perhaps the most
useful type of silyl nucleophiles, as they react with a wide variety
of electrophiles,28 including sulfenyl halides.29 In addition, when
they are chiral, they can undergo asymmetric transformations
with a high degree of stereochemical control.30
As far as amino allylsilanes are concerned, we have shown that
they can react smoothly with electrophiles such as 1-chloro-
methyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoro-
borate) (Selectfluor) to give structurally diverse fluorinated
amines31 in high yield but in a roughly 1:1 diastereomeric mixture
(Scheme 1). This was in agreement with previous findings, as
electrophilic fluorodesilylation of chiral acyclic allylsilanes has been
reported as a high-yielding process, albeit with a poor level of
diastereocontrol.32,33 Likewise, we deemed that β-sulfenyl
amines could be obtained by electrophilic sulfodesilylation of
allylsilanes, and to prove this, the reactivity of phthalimidesul-
fenyl chloride with our substrates was tested.
Phthalimidesulfenyl chloride (PhthNSCl, Phth = phthaloyl) 2
can be easily obtained by the cleavage of N,N0-dithiobis-
(phthalimide) and displays a highly electrophilic character,
because of the presence of the phthalimide substituent. Although
it represents a convenient source of electrophilic sulfur,34ꢀ36 its
reactivity with allylsilanes has not been studied so far.
Herein, we describe the application of electrophilic sulfodesi-
lylation of acyclic homochiral amino allylsilanes 1, carried out
using phthalimidesulfenyl chloride 2, to prepare enantiopure
Received: June 6, 2011
Published: July 27, 2011
r
2011 American Chemical Society
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Scheme 2. Electrophilic Sulfodesilylation of Amino
Allylsilanes with Phthalimidesulfenyl Chloride
similar structures containing the phthalimidesulfenyl group
(mean values = 1.692 and 1.825 Å).35,38ꢀ41 The N1ꢀS1ꢀC9
bond angle equals 100.4(1)°, rather close to the mean literature
value of 102°. An intermolecular hydrogen bonding between
the amino proton H2 and the oxygen atom O2 from one
carbonyl moiety on the phthalimidesulfenyl substituent of the
neighboring molecule is present in the lattice, and a chain of
molecules is formed along the a axes.42 The synclinal conforma-
tion of the two substituents at C9 and C12 is confirmed by
the S1ꢀC9ꢀC12ꢀN2 torsion angle: 59.95(4)°. The absolute
configuration of the major diastereoisomer is thus determined as
(2S,3S).
The diastereotopic faces of the double bond in homochiral
allylsilanes have been reported to show a surprisingly high facial
selectivity in some reactions with electrophiles.43 For instance,
the electrophilic sulfodesilylation of (E)-trimethyl(4-phenyl-
pent-2-enyl)silane 7 with phenylsulfenyl chloride (PhSCl)29
has been found to occur with a high level of stereocontrol leading
to a 95/5 dr, according to a preferred anti attack of the
electrophile with respect to the bulkier substituent (Scheme 4).
In contrast, with our substrates the stereochemical course of
the reaction seems to be controlled by the presence of the amino
group since its ability at forming an intermolecular hydrogen
bonding (as found in the crystal lattice of 3b) may direct the
attack of the electrophile (Scheme 4), assisting the formation of
the diastereoisomer syn-(3aꢀc), where the amino and the sulfur
groups are on the same side.
Interactions between a substrate and reagent due to the
presence of functional groups are frequently responsible for
the stereochemical reaction outcome, particularly when polar
groups are present or hydrogen bond formation is possible.44
Accordingly, when N-methylated-t-Boc-amine 1e was prepared
by reaction of 1b with NaH in THF and methylation with MeI45
and used as starting material, almost no diastereoselectivity was
observed (Table 1, entry 6).
β-amino sulfides 3 with an allylic monosulforated stereogenic
center (Scheme 2). These novel compounds are valuable syn-
thetic intermediates, as several synthetic pathways for the sub-
sequent chemical manipulation of the sulfenimido group as well
as of the double bond can be exploited.
’ RESULTS AND DISCUSSION
The enantiopure chiral E-allylsilanes that we employed were
prepared as reported,27,31 starting from amino aldehydes 4aꢀd
by addition of vinylmagnesium bromide followed by esterifica-
tion with acetyl chloride, to obtain the corresponding acetates
5aꢀd with good yields. Silylcuprate displacement of the allylic
acetate afforded the desired E-amino allylsilanes 1aꢀd in good
yield and without racemization (Scheme 3).
Sulfodesilylation of allylsilanes 1aꢀd using phthalimidosulfe-
nyl chloride occurred smoothly in CH2Cl2 at ꢀ78 °C (Table 1),
affording the corresponding allylic phthalimidosulfenyl amines in
a 95/5 diastereomeric mixture with a good chemical yield. The
reaction takes place regioselectively: the site of attack of sulfur is
at C-γ (C-3), and the resulting intermediate undergoes rapid loss
of the silyl group, allowing for the formation of a product with a
net transposition of the double bond. A reaction temperature
increase (entry 2) caused a less clean reaction, significantly
lowering the final yield. A different N-protective group such as
the tosyl group in 1d did not change the stereochemical reaction
outcome (entry 5).
When the Z-allylsilane 1f (R = CH2Ph), prepared by the
reduction of the corresponding propargylamine,37 was used as a
substrate, a lower yield and stereoselectivity were observed
(entry 7). Finally, starting from the amino acid 1c, a new
unnatural sulfur-containing unsaturated amino acid, in its pro-
tected form (3c) was obtained and fully characterized.
The syn relative stereochemistry of the major diastereoisomer
was unambiguously determined by the X-ray crystallographic
analysis of 3b, which was crystallized from chloroform. Com-
pound 3b crystallizes in the orthorhombic crystal system (space
group P212121). N1ꢀS1 and S1ꢀC9 bond length of 1.690(2)
and 1.847(3) Å, respectively, fall in the typical range observed for
Table 1. Sulfodesilylation of Allylsilanes with Phthalimide-
sulfenyl Chloride
entrya
allylsilane
product
yield (%)b
dr anti/sync
1
2d
3
4
5
6
7
8
1a
1a
1b
1c
1d
1e
1ff
7
3a
3a
3b
3c
3d
3e
3a
8
62
35
80
42
87
67
31
74
5/95
5/95
<5/95
5/95
5/95
60/40e
30/70
90/10
a Reaction conditions: ꢀ78 °C, CH2Cl2, 1 h. b Isolated compound. c By
integration of 1H NMR signals. d RT, CH2Cl2. e The relative configura-
tion of major diastereoisomer was not determined. f Z-Allylsilane (Pg =
Boc, R = CH2Ph).
Scheme 3. Synthesis of Enantiopure E-Amino Allylsilanes 1aꢀd
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Scheme 4. Stereocontrol in the Sulfenylation Step
with Phenylsulfenyl Chloride and Phthalimidesulfenyl
Chloride
Figure 1. Intermediates syn-a+ and anti-b+. Isopropyl and t-Boc groups
are hidden for clarity. Color code: C, black; H, white; O, red; N, blue; Si,
orange; S, yellow.
difference between the two conformers is only 0.4 kcal/mol, the
latter being slightly more stable; consequently, both are acces-
sible at ꢀ78 °C. The charge distribution on the alkene carbon
atoms was determined by an NBO48 calculation on the transoid
optimized geometry. A slightly higher electron density on the
C-γ (C3) of the allylsilane moiety was found, this carbon being
indeed the one involved in the new CꢀS bond formation.
Furthermore, the NBO investigation confirms the well-known
ability of silanes at stabilizing adjacent negative charges.49ꢀ52 A
simplified model system, created by replacing the peripheral
aryl group on the phthalimide with a simpler alkene moiety was
taken into account for the following calculations, in order to
reduce the computational time. As it is well-known that the
electrophilic addition to a CdC double bond may occur
through a three-centered cyclic intermediate,53,54 a similar
process was envisaged to rationalize the sulfenylimide attack
on the alkene moiety of 1b. Under this perspective, in the
starting geometry for the optimization, the electrophile was
located at a distance of 3 Å from the CdC double bond,
investigating two possible routes: a syn- or a anti- attack with
respect to the NHBoc group, which would lead to the syn-a+
and anti-b+ intermediates and to the (3S,4S) and (3S,4R)
diastereomers, respectively (see Figure 1).
Scheme 5. Sulfodesilylation of Racemic (E)-2-Phenyl-5-tri-
methylsilyl-3-pentene rac-7 with Phthalimidesulfenyl
Chloride
However, sulfodesilylation of racemic 7, obtained from acetate
6 following the usual procedure (Scheme 5), led to the allyl
sulfide 8 with high anti diasteroselectivity (Table 1, entry 8), as
already observed in the known reaction with phenylsulfenyl
chloride.29
Syn-a+ was found to be the most stable intermediate (by 1.2
kcal/mol) where an intramolecular NH OdC hydrogen
3 3 3
Again, the relative stereochemistry of the major diastereoi-
somer was unambiguously determined as (3R4R)/(3S4S) by
X-ray diffraction of rac-8, which crystallizes in the centrosym-
metric space group P21/c as a pseudoracemate mixture. In the
asymmetric unit, both enantiomers are present in a disordered
manner. In particular it was possible to unambiguously locate the
phenylsulfenyl group, while the remaining organic parts are
disordered between two positions with a calculated occupancy
factor of almost 50%. The bond distances and angles fall in the
same range as those observed for 3b and are therefore not
discussed in detail.42
In order to rationalize the observed selectivities, we carried out
calculations using DFT methods, at the PBE1PBE46//6-31
+G(d,p) level of theory with the Gaussian 09 package.47 We
first performed geometry optimizations using allylsilane 1b as a
model substrate.
bond, which is responsible for such stabilization, is present.
Because the transition states are product-like, the difference in
energy between transition states (TS) can be inferred to be larger
or of the same order of the difference found for the intermediates.
Therefore, the presence of this hydrogen bond can be the driving
force that directs the electrophile approach to the CdC bond
and explains the regioselectivity observed experimentally. Finally,
the intermediates display a C1ꢀSi bond lengthening (from 1.90
Å in the starting conformer to 2.09 Å in both syn-a+ and anti-b+,
Figure 1) and the consequent adjacent C1ꢀC2 bond shortening
(from 1.49 to 1.38 Å), toward the formation of a new CdC
double bond. Remarkably, in both optimized geometries we
found that the C1ꢀH OdC distance is short (equal to 2.01 Å,
3 3 3
see Figure 1). The interaction between the oxygen and the
proton on C1 stabilizes the cationic character on the silicon atom,
being responsible for a more acidic character on the C1 atom with
the concomitant formation of a partially positive charge on the
SiMe3 group. To evaluate the strength of such an interaction with
a computational experiment, we optimized two conformers of a
simplified model of the addition product where the N-Boc
moiety was replaced by a hydrogen atom and one carbonyl
group of the imide was replaced with a methylene. The
Two different conformations were found as energy minima on
the potential energy surface (PES), considering the relative
orientation of the trimethylsilyl and t-Bu substituents: in the
first one the TMS and t-Bu substituents are in a cisoid con-
formation with respect to the CdC double bond, while in the
other one they are in a transoid spatial disposition. The energy
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Scheme 6. Sulfodesilylation of 1a with Phenylsulfenyl
Chloride
CꢀH OdC interaction is strong enough to favor the SiMe3
3 3 3
displacement because of its more cationic character.
Indeed, when allylsilane 1a was reacted with phenylsulfenyl
chloride, a different reactivity and selectivity was observed
compared with 2. A mixture of the two diastereoisomers corres-
1
ponding to the addition product 9 was found by H NMR
spectroscopic analysis of the crude mixture (Scheme 6) and no
elimination occurred, even over a longer reaction time. However,
when the crude was purified by flash chromatography, elimina-
tion took place55 and a 1:1 diastereomeric mixture of phenyl
sulfide 10 was finally recovered.
Finally, because allyl sulfides are valuable and versatile inter-
mediates, we decided to study the reactivity of the SꢀN bond of
phthalimidosulfides 3a and 8 with bases. The reaction was carried
out at ꢀ78 °C in THF using methyl-, 2-thienyl-, and phenyl-
lithium. The results obtained are collected in Table 2. In all cases,
a clean displacement of the phthalimide group was observed,
affording the corresponding unsymmetrical sulfides 10ꢀ14 in
high yield. This confirmed the labile nature of the SꢀN bond and
the ability of phthalimide to act as a sulfide “protecting group”.56
Table 2. Reactivity of Phthalimidosulfides 3a and 8 with
Nucleophiles
’ CONCLUSIONS
Syn-β-sulfenyl amines of high diastereomeric and enantio-
meric purity have been prepared from the corresponding en-
antiopure amino allylsilanes by electrophilic sulfodesilylation
with phthalimidesulfenyl chloride. The relative syn stereochem-
istry of the major diastereoisomer was determined unambigu-
ously by X-ray crystallographic analysis.
The stereochemical course of the reaction seems to be
controlled by the presence of the amino group in the substrate
and its ability to form an intermolecular hydrogen bond with the
carbonyl of the phthalimido group. The presence of such an
interaction has been confirmed by theoretical calculations.
Following this procedure, a new sulfur-containing unsaturated
amino acid has been obtained in its protected form and fully
characterized. Finally a clean displacement of the phthalimide
group has been accomplished by reaction with organolithium
nucleophiles, giving the corresponding unsymmetrical sulfides in
high yield.
’ EXPERIMENTAL SECTION
General. All air-sensitive reactions were performed using Schlenk
techniques.57 Tetrahydrofuran (THF) was distilled from sodium ben-
zophenone ketyl, and CH2Cl2 was stored under nitrogen over 4 Å
molecular sieves. HMPA was distilled from CaH2 at reduced pressure
and stored on KOH under nitrogen atmosphere. Petroleum ether, unless
specified, is the 40ꢀ70 °C boiling fraction. Allylsilanes 1aꢀc,27 acetate
6,43 aldehyde 4d,58 and Me3SiCuLi LiCN27 were prepared according to
3
literature methods.
1H NMR spectra were recorded at 200, 300, or 400 MHz, and 13
C
NMR spectra were recorded at 50.3, 75.5, or 100.6 MHz. Chemical shifts
were referenced to the residual solvent peak (CHCl3, δ 7.26 ppm, and
1
C6H6, δ 7.16 ppm, for H NMR; CHCl3, δ 77.0 ppm, and C6H6,
δ 128.06 ppm, for 13C NMR). When a diastereomeric mixture is present,
only the signals of the major diastereoisomer are reported. Mass spectra
were obtained at a 70 eV ionization potential and are reported in the
form m/z (intensity relative to base = 100). IR spectra were recorded in
CHCl3 solution on KBr and are expressed in cmꢀ1. Polarimetric
measurements were performed in CHCl3 solution at λ = 589 nm, and
the temperature is specified case by case.
a Isolated Compound.
conformer with the hydrogen bond was found to be more
stable by ca. 7.0 kcal/mol. Although probably overestimated
and based on a very simplified model, this value suggests that a
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X-ray. X-ray data were collected at ambient temperature (293 K) on
an Oxford Diffraction XCALIBUR 3 diffractometer equipped with a
CCD area detector using Mo KR radiation (λ = 0.7107 Å). The program
used for the data collection was CrysAlis CCD 1.171.59 Data reduction
was carried out with the program CrysAlis RED 1.17,60 and the
absorption correction was applied with the program ABSPACK 1.17.
Direct methods implemented in Sir9761 were used to solve the
structures, and the refinements were performed by full-matrix least-
squares against F2 implemented in SHELX97.62
Computational Details. The model systems were optimized at
the hybrid density functional theory (DFT) level, using the PBE1PBE
functional (known as PBE0).46 All the DFT calculations were carried out
using the Gaussian 09 package.47 For all of the fully optimized structures,
calculations of vibrational frequencies were performed to confirm their
nature as stationary point. The basis set was used for the 6-31G, with the
important addition of the polarization functions (d, p) for all atoms,
including the hydrogens. The intramolecular charge distribution was
determined by an NBO48 charges analysis carried out on the optimized
geometries.
THF (1 mL). After 30 min, the reaction mixture was hydrolyzed with
NH4Cl/NH4OH buffer solution and extracted with Et2O. The ethe-
real phase was then washed with brine, dried over Na2SO4, and
evaporated. The crude product was purified by flash chromatography.
Purification gave 1d (91 mg, 67%) as a 90/10 E/Z mixture of
diastereoisomrs. Colorless oil. Eluent: petroleum ether:ethyl acetate
5:1, Rf = 0.35. (1d, major diastereoisomer) 1H NMR (200 MHz,
CDCl3) δ: 7.64 (d, 2H, J = 8.4 Hz), 7.26ꢀ7.03 (m, 7H), 5.40ꢀ5.24
(m, 1H), 5.01 (dd, 1H, J = 15.2 Hz, J = 6.8 Hz), 4.69 (bd, 1H, J = 7.0
Hz), 3.98ꢀ3.87 (m, 1H), 2.82ꢀ2.70 (m, 2H), 2.39 (s, 3H), 1.28ꢀ1.16
(m, 2H), ꢀ0.14 (s, 9H); 13C NMR (50 MHz, CDCl3) δ: 142.7, 137.7,
136.7, 129.8, 129.3, 128.2, 127.0, 126.9, 126.8, 126.3, 57.2, 42.8, 22.7,
21.5, 2.0; MS (m/z): 372 (M+ ꢀ 15, 2), 73 (100). Elemental analysis:
Calcd for C21H29NO2SSi: C, 65.07; H, 7.54; N, 3.61. Found: C, 65.13;
H, 7.51; N, 3.63.
(S,E)-tert-Butyl Methyl(2-methyl-6-(trimethylsilyl)hex-4-en-3-yl)car-
bamate (1e). N-Boc-allylsilane 1b (42 mg, 0.15 mmol) and methyl
iodide (0.10 mL, 1.5 mmol) were dissolved in THF (1.5 mL) and
reacted with a 60% mineral oil dispersion of NaH (59 mg, 1.5 mmol),
under stirring. After 24 h at room temperature, the reaction was
quenched with ethyl acetate (2 mL) and H2O (8 mL). The aqueous
layer was extracted with Et2O (2 ꢁ 10 mL) and ethyl acetate (2 ꢁ
10 mL). The combined organic phases were washed with a saturated
solution of NaHCO3 (10 mL), a 5% solution of Na2S2O4 (15 mL), and
brine (10 mL) and then dried over Na2SO4. Purification by flash
chromatography gave 1e (41 mg, 93%) as a colorless oil. Eluent:
Synthesis of (S)-4-(4-Methylphenylsulfonamido)-5-phenylpent-1-
en-3-yl Acetate (5d). Aldehyde 4d (605 mg, 2.0 mmol) was dissolved
in THF (12 mL), cooled at 0 °C, and reacted with vinylmagnesium
bromide (1 M in ether, 5.0 mL, 5.0 mmol). The solution was stirred at
room temperature overnight and then diluted with ether (20 mL) and
hydrolyzed with a NH4Cl saturated aqueous solution (20 mL). After
extraction with ethyl acetate (3 ꢁ 10 mL), the organic phase was
collected, dried, and evaporated to afford the intermediate alcohol
(646 mg, 1.9 mmol, 97%) which was then dissolved into CH2Cl2
(15 mL) and reacted overnight with triethylamine (0.30 mL, 2.0 mmol),
acetic anhydride (0.20 mL, 2.0 mmol), and DMAP (15 mg, 0.01 mmol).
The reaction mixture was diluted with CH2Cl2 (15 mL), hydrolyzed
with a NaHCO3 saturated solution (30 mL), and extracted with CH2Cl2
(3 ꢁ 10 mL). The organic phase was dried over Na2SO4 and finally
evaporated to dryness. The crude product was filtered over a silica gel
column to afford a 2:1 diastereomeric mixture of 5d (391 mg, 54%) as a
white solid which was used for the subsequent step without further
purification. Eluent: petroleum etherꢀethyl acetate 1:1, Rf = 0.62. (5d,
major diastereomer) 1H NMR (200 MHz, CDCl3) δ: 7.61 (d, 2H, J =
8.2 Hz), 7.21ꢀ7.16 (m, 7H), 5.84ꢀ5.55 (m, 2H), 5.33ꢀ5.05 (m, 3H),
1
petroleum etherꢀethyl acetate 10:1, Rf = 0.45. (1e) H NMR (200
MHz, CDCl3) δ: 5.58ꢀ5.53 (m, 1H), 5.23 (dd, 1H, J = 8.1 Hz, J = 7.7
Hz), 4.11ꢀ3.87 (bm, 1H), 2.67 (bs, 3H), 1.80ꢀ1.65 (m, 1H), 1.44 (s,
9H), 1.25ꢀ1.19 (m, 2H), 0.86 (d, 3H, J = 3.7 Hz), 0.82 (d, 3H, J = 3.3
Hz), ꢀ0.02 (s, 9H); 13C NMR (50 MHz, CDCl3) δ: 155.9, 130.5, 126.0,
78.9, 65.2(b), 37.8 (b), 29.7, 28.6; 22.7, 20.3, 19.5, ꢀ1.9. MS (m/z): 284
(M+ ꢀ 15, 6), 73 (100). Elemental analysis: Calcd for C16H33NO2Si: C,
64.16; H, 11.10; N,4.68. Found: C, 64.18; H, 11.16; N, 4.65. [R]24
ꢀ32.3 (c = 2.8; CHCl3).
=
D
Sulfodesilylation of Allylsilanes: General Procdeure. Allylsilanes
1aꢀf (1 equiv) were dissolved in dry CH2Cl2 (0.1 M). The solution
was cooled at ꢀ78 °C, and then phthalimidesulfenyl chloride 2 (1.1
equiv) was added in portions. The reaction was left at ꢀ78 °C for 1 h,
and then the mixture was warmed up to room temperature and
quenched with water. The aqueous layer was extracted with CH2Cl2,
and the organic phases were collected, washed with a NaHCO3 saturated
solution, and then dried over Na2SO4. After solvent evaporation, the
crude product was purified by flash chromatography.
3.85ꢀ3.65 (m, 1H), 2.82ꢀ2.58 (m, 2H), 2.38 (s, 3H), 2.03 (s, 3H); 13
C
NMR (50 MHz, CDCl3) δ: 169.6, 142.9, 137.5, 136.3, 135.9, 129.3,
128.9, 128.5, 128.3, 126.8, 118.7, 73.9, 57.7, 38.2, 21.5, 20.9.
rac-(E)-Trimethyl(4-phenylpent-2-enyl)silane (7). Trimethylsilyl-
cyanocuprate was prepared using hexamethyldisilane (1.56 g, 10.7
mmol), HMPA (3.10 mL), MeLi (3.30 mL, 5.3 mmol), and CuCN
(261 mg, 2.9 mmol), cooled at ꢀ78 °C, and reacted with a solution of
4-phenylpent-1-en-3-yl acetate 6 (496 mg, 2.4 mmol) in THF (5 mL).
After 30 min, the reaction mixture was hydrolyzed with NH4Cl/
NH4OH buffer solution and extracted with Et2O. The ethereal phase
was then washed with brine, dried over Na2SO4, and evaporated. The
crude product was purified by flash chromatography. Purification gave 7
(447 mg, 84%) as a colorless oil. E/Z = 85/15. Eluent: petroleum
etherꢀethyl acetate 20:1, Rf = 0.41. (rac-7) 1H NMR (200 MHz,
CDCl3) δ: 7.39ꢀ7.18 (m, 5H), 5.52ꢀ5.47 (m, 2H), 3.53ꢀ3.42 (m,
1H), 1.44ꢀ1.40 (m, 2H), 1.33 (d, 3H, J = 7.3 Hz), ꢀ0.01 (s, 9H); 13C
NMR (50 MHz, CDCl3) δ: 146.8, 133.7, 128.3, 127.1, 125.8, 125.2,
42.7, 22.9, 22.0, ꢀ1.6; MS (m/z): 218 (M+, 7), 73 (100). Elemental
analysis: Calcd for C14H22Si: C, 76.99; H, 10.15. Found: C, 76.88;
H, 10.18.
(2S,3S)-3-[(1,3-Dioxoisoindolin-2-yl)sulfanyl]-1-phenylpent-4-en-
2-yl Carbamic Acid tert-Butyl Ester (3a). Allylsilane 1a (150 mg,
0.5 mmol) was reacted with phthalimidesulfenyl chloride 2 (106 mg,
0.5 mmol). Purification gave 3a (122 mg, 62%) as a 95/5 mixture of
diastereoisomers. Eluent: petroleum etherꢀethyl acetate: 5:1. Rf = 0.33
(3:1). White solid. Mp 178ꢀ179 °C. (3a) IR (KBr): ν 3420, 3022, 1785,
1740, 1715 cmꢀ1; 1H NMR (CDCl3 400 MHz) δ: 7.91ꢀ7.75 (m, 4H),
7.28ꢀ7.17 (m, 5H), 5.78ꢀ5.69 (dt, 1H, J = 16.8 Hz, J = 9.8 Hz),
5.06ꢀ4.90 (m, 3H), 4.16ꢀ4.05 (m, 2H), 3.06ꢀ3.00 (m, 1H),
2.84ꢀ2.79 (m, 1H), 1.37 (s, 9H); 13C NMR (CDCl3 100.6 MHz) δ:
168.4, 167.9, 154.9, 134.5, 134.2, 133.6, 132.0, 129.5, 126.6, 123.8, 123.5,
120.9, 79.6, 57.5, 53.4, 39.1, 28.3; MS m/z: 347 (1), 57 (100). Elemental
analysis: Calcd for C24H26N2O4S: C, 65.73; H, 5.98; N, 6.39. Found: C,
65.66; H, 6.03. N, 6.43. [R]26D = ꢀ22.1 (c = 1.0, CHCl3).
(3S,4S)-2-Methyl-4-[(1,3-dioxoisoindolin-2-yl)sulfanyl]hex-5-en-3-yl
Carbamic Acid tert-Butyl Ester (3b). Allylsilane 1b (131 mg, 0.5 mmol)
was reacted with phthalimidesulfenyl chloride 2 (108 mg, 0.5 mmol).
Purification gave 3b (144 mg, 80%). Eluent: petroleum etherꢀethyl
acetate: gradient (6:1ꢀ4:1) Rf = 0.44. White solid. Mp 145ꢀ148 °C. (3b)
IR (KBr): ν 3429, 3017, 1778, 1739, 1714, 1685 cmꢀ1; 1H NMR (CDCl3
(E,S)-4-Methyl-N-[1-phenyl-5-(trimethylsilyl)pent-3-en-2-yl]benze-
nesulfonamide (1d). Trimethylsilylcyanocuprate was prepared using
hexamethyldisilane (260 mg, 0.4 mmol), HMPA (0.45 mL), MeLi
(0.55 mL, 0.9 mmol), and CuCN (42 mg, 0.5 mmol) cooled at ꢀ78 °C
and reacted with a solution of allylacetate 5d (133 mg, 0.4 mmol) in
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400 MHz) δ: δ: 7.88ꢀ7.73 (m, 4H), 5.78ꢀ5.69 (dt, 1H, J = 16.8 Hz, J =
9.8 Hz), 4.89ꢀ4.82 (m, 3H), 4.17ꢀ4.12 (t, 1H, J = 9.8 Hz), 3.84ꢀ3.78
(m, 1H), 1.87ꢀ1.81 (m, 1H), 1.44 (s, 9H), 0.99 (d, 3H, J = 6.6 Hz), 0.85
(d, 3H, J = 6.6 Hz); 13C NMR (CDCl3 100 MHz) δ: 168.2, 155.4, 134.5,
134.3, 131.9, 123.5, 119.4, 79.4, 57.7, 56.6, 31.2, 28.4, 20.0, 16.6; MS m/z:
279 (11), 149 (100). Elemental analysis: Calcd for C20H26N2O4S: C,
61.52; H, 6.71; N, 7.17. Found: C, 61.46; H, 6.83; N, 7.13. [R]23D = +2.3
(c = 1.0, CHCl3).
(2S,3S)-Methyl 2-(tert-Butoxycarbonylamino)-3-(1,3-dioxoisoindo-
lin-2-ylthio)pent-4-enoate (3c). Allylsilane 1c (18 mg, 0.1 mmol) was
reacted with phthalimidesulfenyl chloride 2 (14 mg, 0.1 mmol).
Purification gave 3c (10 mg, 42%) as a 95/5 mixture of diastereoisomers.
Eluent: Petroleum ether:ethyl acetate: 5:1. Rf = 0.31. White solid. Mp
45ꢀ48 °C. (3c) 1H NMR (CDCl3, 400 MHz) δ: 7.95ꢀ7.91 (m, 2H),
7.81ꢀ7.66 (m, 2H), 5.93 (bd, 1H, J = 9.0 Hz), 5.75ꢀ5.69 (m, 1H), 5.38
(bd, 1H, J = 17.0 Hz), 5.27 (bd, 1H, J = 10.2 Hz), 4.74ꢀ4.69 (m, 1H),
4.65ꢀ4.60 (m, 1H), 3.46 (s, 3H), 1.48 (s, 9H); 13C NMR (CDCl3, 100
MHz) δ: 170.2, 167.8, 155.5, 134.6, 131.7, 130.3, 123.9, 122.2, 80.4,
54.8, 54.5, 52.5, 28.4. MS m/z: 347 (1), 57 (100). Elemental analysis:
Calcd for C19H22N2O6S: C, 56.15; H, 5.46; N, 6.89. Found: C, 56.21; H,
5.44; N, 6.93. [R]23D = ꢀ39.2 (c = 0.5, CHCl3).
135.5, 134.5, 132.1, 128.6, 127.7, 126.9, 123.7, 118.8, 61.0, 42.3, 19.9. MS
(m/z): 323 (M+, 1), 59 (100). Elemental analysis: Calcd for
C19H17NO2S, C, 70.56; H, 5.30; N, 4.33. Found: C, 70.47; H, 5.27.
N, 4.29.
General Procedure of Reaction of Phtalimido Sulfides with Nucleo-
philes. Phthalimidosulfide 3a or 8 (1 equiv) was dissolved in dry THF
(0.1 M). The solution was cooled at ꢀ78 °C, and then MeLi (1.6 M in
THF), 2-thienyllithium (1.0 M in THF), or phenyllithium (1.8 M in
nBu2O) was added with a syringe. After 30 min, at ꢀ78 °C the reaction
mixture was diluted with Et2O and quenched with a NH4Cl saturated
solution. The organic phase was extracted with Et2O (three times),
washed with fresh portions of the same solution and brine, and then
dried with Na2SO4. Solvent removal gave the crude product which was
purified by flash chromatography.
[(3S,4S),(3R,4R)]-Methyl(4-phenylpent-1-en-3-yl)sulfane (11). Fol-
lowing the general procedure, a solution of sulfide 8 (48 mg, 0.15 mmol)
in THF (1.5 mL) was reacted with MeLi (1.6 M in THF) (0.12 mL, 0.2
mmol). Purification gave a 90/10 diastereomeric mixture of racemic 11
(25 mg, 88%). Eluent: petroleum etherꢀethyl acetate 8:1, Rf = 0.69.
Colorless oil. (11) 1H NMR (200 MHz, CDCl3) δ: 7.33ꢀ7.17 (m, 5H);
5.47 (dt, 1H, J = 9.9 Hz, J = 16.8 Hz); 5.03ꢀ4.58 (m, 2H); 3.19 (dd, 1H,
J = 7.7 Hz, J = 9.9 Hz); 3.03ꢀ2.90 (m, 1H); 1.97 (s, 3H); 1.42 (d, 3H, J =
6.8 Hz). 13C NMR (50 MHz, CDCl3) δ: 143.8; 136.7; 128.0; 127.8;
126.4; 115.6; 57.8; 43.8; 19.7; 14.5. MS (m/z): 192 (M+, 8); 87 (M+ ꢀ
(2S,3S)-N-(3-(1,3-Dioxoisoindolin-2-ylthio)-1-phenylpent-4-en-2-
yl)-4-methylbenzenesulfonamide (3d). Following the general proce-
dure, allylsilane 1d (59 mg, 0.15 mmol) was reacted with phthalimide-
sulfenyl chloride 2 (36 mg, 0.2 mmol. Purification gave 3d (66 mg, 87%)
as a 95/5 mixture of diastereoisomers . Eluent: hexaneꢀethyl acetate:
gradient (4:1ꢀ2:1). Rf = 0.37 (2:1). White solid. Mp 168ꢀ170 °C. (3d):
IR (KBr): ν 3018, 1778, 1741, 1715, 1091 cmꢀ1; 1H NMR (400 MHz,
CDCl3) δ: 7.94ꢀ7.92 (m, 2H), 7.81ꢀ7.79 (m, 2H), 7.51ꢀ7.49 (m,
2H), 7.21ꢀ7.19 (m, 3H), 7.12ꢀ7.09 (m, 2H), 7.08ꢀ7.05 (m, 2H), 5.62
(ddd, 1H, J = 19.3 Hz, J = 10.2 Hz, J = 7.8 Hz), 5.16ꢀ5.11 (m, 2H), 4.02
(dd, 1H, J = 9.2 Hz, J = 4.7 Hz), 3.77ꢀ3.71 (m, 1H), 3.13 (dd, 1H, J =
13.9 Hz, J = 6.4 Hz); 2.66 (dd, 1H, J = 13.9 Hz, J = 6.9 Hz); 2.36 (s, 3H);
13C NMR (50 MHz, CDCl3) δ: 168.0, 143.2, 137.2, 136.1, 134.8, 131.9,
131.2, 129.6 (2C), 128.7, 126.9 (2C), 124.0, 122.1, 57.1, 38.2, 29.8, 21.6;
MS (m/z): 353 (9), 91 (100). Elemental analysis: Calcd for
C26H24N2O4S2: C, 63.39; H, 4.91; N, 5.69. Found: C, 63.45; H, 5.03;
N, 5.74. [R]30D = ꢀ62.0 (c = 2.3, CDCl3).
PhCH CH3, 100). Elemental analysis: Calcd for C12H16S: C, 74.94; H,
3
8.39. Found: C, 75.05; H, 8.43.
[(3S,4S,)(3R,4R)]-2-(4-Phenylpent-1-en-3-ylthio)thiophene
(12).
Following the general procedure, a solution of sulfide 8 (40 mg, 0.1
mmol) in THF (1.5 mL) was reacted with thiophen-2-yllithium (1.0 M
in THF, 0.15 mL, 0.15 mmol). Purification gave a 95/5 diastereomeric
mixture of racemic 12 (29 mg, 90%). Eluent: petroleum etherꢀethyl
acetate 10:1, Rf = 0.75. Yellow oil. (12) 1H NMR (400 MHz, CDCl3) δ:
7.35ꢀ7.18 (m, 6H); 7.07 (dd, 1H, J = 1.1 Hz J = 3.5 Hz); 6.97 (dd, 1H, J
= 1.1 Hz J = 5.3 Hz); 5.55 (dt, 1H, J = 10.0 Hz, J = 16.8 Hz); 4.83 (dd,
1H, J = 1.5 Hz, J = 10.0 Hz); 4.64 (dd, 1H, J = 16.8 Hz, J = 0.8 Hz); 3.54
(dd, 1H, J = 8.0 Hz, J = 9.6 Hz); 3.10ꢀ3.01 (m, 1H); 1.49 (d, 3H, J = 6.8
Hz). 13C NMR (75 MHz, CDCl3) δ: 143.4; 136.6; 135.3; 132.7; 129.9;
128.1; 128.1; 127.3; 126.6; 116.6; 62.9; 43.3; 20.0. MS (m/z): 260
[3S,4(R,S)]-tert-Butyl-4-(1,3-dioxoisoindolin-2-ylthio)-2-methylhex-
5-en-3-yl(methyl)carbamate (3e). Following the general procedure,
allylsilane 1e (45 mg, 0.15 mmol) was reacted with phthalimidesulfenyl
chloride 2 (34 mg, 0.2 mmol) for 1 h. Purification gave 3e (37 mg, 63%)
as a 60/40 mixture of diastereoisomers. Eluent: petroleum ether/ethyl
acetate = 8/1 Rf = 0.22. White gummy solid. (3e, major diastereoisomer)
IR (KBr): ν 3019, 1775, 1742, 1712 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
δ: 7.87ꢀ7.85 (m, 2H), 7.76ꢀ7.74 (m, 2H), 5.81ꢀ5.69 (m,1H),
4.88ꢀ4.73 (m, 2H), 4.22 (t, 1H, J = 9.7 Hz), 4.10ꢀ4.06 (m, 1H),
2.94 (s, 3H), 1.99ꢀ1.91 (m, 1H), 0.87 (d, 6H, J = 6.7 Hz) 1.46 (s, 9H).
13C NMR (CDCl3, 100 MHz) δ: 168.4, 155.9, 135.8, 134.3, 132.2,
123.5, 118.4, 79.7, 59.9, 56.8, 30.7, 29.6, 28.3, 20.5, 18.8. MS m/e:
331(1), 57 (100). Elemental analysis: Calcd for C21H28N2O4S: C,
62.35; H, 6.98; N, 6.93. Found: C, 62.42; H, 6.96. N, 6.88.
[(3S,4S),(3R,4R)]-2-(4-Phenylpent-1-en-3-ylthio)isoindoline-1,3-
dione (8). Following the general procedure, allylsilane 7 (146 mg, 0.7
mmol) was reacted with phthalimidesulfenyl chloride 2 (157 mg, 0.8
mmol). Purification gave 8 (160 mg, 74%) as a 90/10 racemic mixture of
diastereoisomers. Eluent: petroleum etherꢀethyl acetate 10:1, Rf = 0.18.
White oil. The relative configuration of the major diastereoisomer was
established by X-ray analysis. (rac,anti-8) 1H NMR (400 MHz, CDCl3)
δ: 7.89ꢀ7.87 (m, 2H), 7.75ꢀ7.73 (m, 2H), 7.31ꢀ7.25 (m, 2H),
7.21ꢀ7.16 (m, 3H), 5.56 (dt, 1H, J = 16.8 Hz, J = 10.2 Hz), 4.70 (dd,
1H, J = 0.4 Hz, J = 1.6 Hz), 4.61 (dd, 1H, J = 16.8 Hz, J = 1.6 Hz), 4.10
(dd, 1H, J = 10.2 Hz, J = 8.4 Hz), 3.12 (dq, 1H, J = 7.1 Hz, J = 1.4 Hz);
1.49 (d, 3H, J = 7.1 Hz); 13C NMR (50 MHz, CDCl3) δ: 168.0, 143.0,
(M+, 13); 155 (M+ ꢀ PhCH CH3, 100). Elemental analysis: Calcd for
3
C15H16S2, C, 69.18; H, 6.19. Found: C, 69.23; H, 6.21.
(2S,3S)-tert-Butyl 3-(Methylthio)-1-phenylpent-4-en-2-ylcarbamate
(13). A solution of phthalimidosulfide 3a (51 mg, 0.1 mmol) in THF
(1.5 mL) was reacted with MeLi (1.6 M in THF, 0.15 mL, 0.2 mmol).
Purification gave 13 (18 mg, 50%) as a single diastereoisomer. Eluent:
petroleum etherꢀethyl acetate 10:1, Rf = 0.30. Colorless oil. (13) IR
(KBr): ν 3434, 1689 cmꢀ1; 1H NMR (200 MHz, CDCl3) δ: 7.33ꢀ7.20
(m, 5H); 5.72 (dt, 1H, J = 9.9 Hz, J = 16.8 Hz); 5.21ꢀ5.00 (bd, 1H, J = 9.9
Hz); 5.67ꢀ4.21 (bd, 1H, J = 16.8 Hz); 4.64 (bd, 1H, J = 8.8 Hz);
4.17ꢀ4.02 (m, 1H);3.19(dd, 1H, J =5.1 Hz, J= 9.9 Hz); 3.05(dd, 1H, J=
6.0 Hz, J = 13.8 Hz); 2.76 (dd, 1H, J = 13.8 Hz, J = 7.7 Hz); 2.00 (s, 3H);
1.40 (s, 9H). 13C NMR (50 MHz, CDCl3) δ: 155.2; 137.8; 135.3; 129.3;
128.3; 126.3; 117.4; 79.3; 54.4; 53.7; 38.2; 28.3; 14.1. MS (m/z): 251 (M+
+
ꢀ t-Bu, 1); 91 (PhCH2 , 23); 57 (100). Elemental analysis: Calcd for
C17H25NO2S: C, 66.41; H, 8.20; N, 4.56. Found: C, 66.46; H, 8.23; N,
4.54. [R]24D = ꢀ31.1 (c = 0.9; CHCl3).
(2S,3S)-tert-Butyl 1-Phenyl-3-(thiophen-2-ylthio)pent-4-en-2-ylcar-
bamate (14). A solution of phthalimidosulfide 3a (27 mg, 0.1 mmol) in
THF (1.5 mL) was reacted with thiophen-2-yllithium (1.0 M in THF,
0.12 mL, 0.1 mmol). Purification gave 14 (18 mg, 78%) as a 95/5
diastereoisomeric mixture. Eluent: petroleum etherꢀethyl acetate 13:1,
Rf = 0.36. Colorless oil. (14) IR (KBr): ν 3646, 3081, 1635 cmꢀ1; 1H
NMR (200 MHz, CDCl3) δ: 7.37ꢀ7.20 (m, 6H); 7.13 (bd, 1H J = 3.3
Hz); 6.98 (dd, 1H, J = 3.3 Hz, J = 5.1 Hz), 5.78 (dt, 1H, J = 9.7 Hz, J =
16.9 Hz); 5.08 (bd, 1H, J = 9.7 Hz); 4.92ꢀ4.81 (m, 1H); 4.66 (bd, 1H,
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ARTICLE
J = 8.1 Hz); 4.17ꢀ4.02 (m, 1H); 3.56 (dd, 1H, J = 5.5 Hz, J = 9.5 Hz);
3.13 (dd, 1H, J = 13.5 Hz, J = 5.9 Hz); 2.79 (bdd, 1H, J = 13.5 Hz, J = 7.7
Hz); 1.39 (s, 9H). 13C NMR (50 MHz, CDCl3) δ: 155.1; 137.7; 135.8;
135.1; 130.4; 129.3; 128.3(2C); 127.6; 126.4; 118.3; 79.4; 58.9; 54.2;
38.4; 28.3. MS (m/z): 284 (M+ ꢀ Bn, 1.6); 91 (100). Elemental analysis:
Calcd for C20H25NO2S2: C, 63.96; H, 6.71; N, 3.73. Found: C, 64.03; H,
6.72; N, 3.76. [R]24D = +17.8 (c = 0.7; CHCl3)
(8) Ekegren, J. K.; Roth, P.; Kallstrom, K.; Tarnai, T.; Anderson,
P. G. Org. Biomol. Chem. 2003, 1, 358.
(9) Rinehart, K. L. Med. Res. Rev. 2000, 20, 1.
(10) Trost, B. M.; Shibata, T. J. Am. Chem. Soc. 1982, 104, 3225.
(11) Bewick, A.; Coe, D. E.; Mellor, J. M.; Owton, M. W. J. J. Chem.
Soc., Perkin Trans. 1 1985, 1033.
(12) Egli, M.; Hoesch, L.; Dreiding, A. S. Helv. Chim. Acta 1985,
68, 220.
(2S,3S)-tert-Butyl 1-Phenyl-3-(phenylthio)pent-4-en-2-ylcarbamate
(10). Phthalimido sulfide (3a) (22 mg, 0.05 mmol) in THF (1.5 mL) was
reacted with phenyllithium (1.8 M in n-Bu2O, 0.06 mL, 0.1 mmol).
Purification gave 10 (16 mg, 87%) as a single diastereoisomer. Eluent:
petroleum etherꢀethyl acetate 4:1, Rf = 0.51. White solid. Mp 54ꢀ58 °C.
(10) IR (KBr): ν 3433, 3063, 1706 cmꢀ1; 1H NMR (300 MHz, CDCl3)
δ: 7.39ꢀ7.17 (m, 10H); 5.80 (dt 1H, J = 9.3 Hz, J = 16.8 Hz); 5.05 (d,
1H, J = 9.6 Hz); 4.94 (d, 1H, J = 16.6 Hz); 4.69 (bd, 1H, J = 8.7 Hz);
4.19ꢀ4.11 (m, 1H); 3.76 (dd, 1H, J = 4.4 Hz, J = 8.9 Hz); 3.11 (dd, 1H,
J = 14.2 Hz, J = 6.2 Hz); 2.83ꢀ2.75 (m, 1H); 1.38 (s, 9H). 13C NMR
(100.6 MHz, CDCl3) δ: 155.2; 137.8; 135.6; 133.9; 132.8; 129.3; 128.9;
128.4; 127.3; 126.4; 117.8; 79.4; 55.7; 54.9; 38.3; 28.3. MS (m/z): 369
(1); 91 (30); 57 (100). Elemental analysis: Calcd for C22H27NO2S:
(13) Benati, L.; Spagnolo, P. C. Tetrahedron 1986, 42, 1145.
(14) Lucchini, V.; Modena, G.; Pasquato, L. J. Chem. Soc., Chem.
Commun. 1994, 1565.
(15) Ishibashi, H.; Uegaki, M.; Sakai, M. Synlett 1997, 915.
(16) Cran, G. A.; Gibson, C. L.; Handa, S. Tetrahedron: Asymmetry
1995, 6, 1553.
(17) Donner, B. G. Tetrahedron Lett. 1995, 36, 1223.
(18) Siedlecka, R.; Skarzewski, J. Synlett 1996, 757.
(19) Poindexter, G. S.; Owens, D. A.; Dolan, P. L.; E. Woo, J. J. Org.
Chem. 1992, 57, 6257.
(20) Poelert, M. A.; Hof, R. P.; Peper, N. C. M.; Kellogg, R. M.
Heterocycles 1994, 37, 461.
(21) Hayashi, M.; Ono, K.; Hoshimi, H.; Oguni, N. Tetrahedron
1996, 52, 781.
(22) Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.; Uneyama, K.
J. Org. Chem. 1999, 64, 7323.
C, 71.51; H, 7.36; N, 3.79. Found: C, 71.58; H, 7.34; N, 3.81. [R]23
ꢀ17.2 (c = 0.3; CHCl3)
=
D
(23) Bae, J. H.; Shin, S.-H.; Park, C. S.; Lee, W. K. Tetrahedron 1999,
55, 10041.
’ ASSOCIATED CONTENT
(24) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Chem. Soc., Perkin Trans. 1 2001,
1314.
(25) Ganesh, V.; Chandrasekaran, S. Synthesis 2009, 3267.
(26) Enders, D.; Moll, A.; Schaadt, A.; Raabe, G.; Runsink, J. Eur. J.
Org. Chem. 2003, 3923.
(27) Reginato, G.; Mordini, A.; Meffre, P.; Tenti, A.; Valacchi, M.;
Cariou, K. Tetrahedron: Asymmetry 2006, 17, 922.
(28) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97,
2063.
(29) Nativi, C.; Taddei, M.; Palio, G. Tetrahedron Lett. 1991,
32, 1583.
S
Supporting Information. X-ray data for 3b and 8, com-
b
putational details, and 1H and 13C NMR spectra of compounds 7,
1d, 1e, 3a, 3b, 3c, 3d, 3e, 8, 11, 12, 13, 14, and 10. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: gianna.reginato@iccom.cnr.it.
(30) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004,
15, 3173.
(31) Reginato, G.; Mordini, A.; Tenti, A.; Valacchi, M.; Broguiere, J.
Tetrahedron: Asymmetry 2008, 19, 2882.
(32) Tredwell, M.; Tenza, K.; Pacheco, M.; Gouverneur, V. Org. Lett.
2005, 7, 4495.
(33) Teare, H.; Huguet, F.; Tredwell, M.; Thibaudeau, S.; Luthra,
S. K.; Gouverneur, V. Arkivoc 2007, 232.
(34) Zibarev, A. V.; Miller, A. O.; Gatilov, Y. V.; Furin, G. G.
’ ACKNOWLEDGMENT
We thank Prof. Stefano Menichetti (University of Florence)
for helpful discussions and Dr. Enzo Perrotta (Chemper, Prato,
Italy) for providing a sample of N,N0-dithio-bis(phthalimide).
Financial support from CNR-RSTL(801) is gratefully acknowl-
edged. A.I. and G.M. appreciate the ISCRA-CINECA HP grant
“HP10BNL89W” for computational time.
J. Heterocycl. Chem. 1990, 1, 443.
(35) Capozzi, G.; Delogu, G.; Fabbri, D.; Marini, M.; Menichetti, S.;
Nativi, C. J. Org. Chem. 2002, 67, 2019 and refs cited therein.
(36) Srisailam, S. K.; Togni, A. Tetrahedron: Asymmetry 2006,
17, 2603.
(37) Reginato, G.; Mordini, A.; Messina, F.; Degl’Innocenti, A.; Poli,
G. Tetrahedron 1996, 52, 10985.
’ DEDICATION
†This work is dedicated to Prof. Alfredo Ricci in recognition of
his career as researcher, chemist, and teacher.
(38) Iwasaki, F.; Masuko, Y. Acta Crystallogr., Sect. C: Cryst. Struct.
Commun. 1986, 42, 124.
(39) Carle, A. B.; Bauer, J. A. K.; Wilson, R. M. Acta Crystallogr., Sect.
C: Cryst. Struct. Commun. 2000, 56, 97.
’ REFERENCES
(1) Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133.
(2) Pellissier, H. Tetrahedron 2007, 63, 1297.
(40) Brito, I.; Vargas, D.; Reyes, A.; Cardenas, A.; Lopez-Rodriguez,
M. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2005, 61, o234.
(41) Yazici, S.; Turkoz, N.; Kutuk, H.; Senel, I.; Buyukgungor, O.
Acta Crystallogr., Sect. E: Struct. Rep. Online 2007, 63, 804.
(42) Refer to the Supporting Information for the experimental
details and for the complete set of crystallographic data. CCDC
798991 and CCDC 814594 contain the supplementary crystallographic
data for 3b and 8, respectively. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif.
(3) Adams, H.; Anderson, J. C.; Cubbon, R.; James, D. S.; Mathias,
J. P. J. Org. Chem. 1999, 64, 8256 and refs cited therein.
(4) Niu, J.-L.; Wang, M.-C.; Kong, P.-P.; Chen, Q.-T.; Zhu, Y.; Song,
M.-P. Tetrahedron 2009, 65, 8869 and refs cited therein.
(5) Subirats, S.; Jimeno, C.; Pericꢀas, M. A. Tetrahedron: Asymmetry
2009, 20, 1413and ref. cited..
(6) Anderson, J. C.; Cubbon, R.; Harding, M.; James, D. S. Tetra-
hedron: Asymmetry 1998, 9, 3461.
(7) Petra, D. G. I.; Kamer, P. C. J.; Spek, A. L.; Schoemaker, H. E.;
Leeuwen, P. W. N. M. v. J. Org. Chem. 2000, 65, 3010 and refs cited
therein.
(43) Fleming, I.; Lewis, J. J. J. Chem. Soc., Perkin Trans. 1 1992, 3267.
7421
dx.doi.org/10.1021/jo2010878 |J. Org. Chem. 2011, 76, 7415–7422

The Journal of Organic Chemistry
ARTICLE
(44) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993,
93, 1307.
(45) Andrus, M. B.; Li, W.; Keyes, R. F. J. Org. Chem. 1997, 62, 5542.
(46) Adamo, C.; Barone, V. J. Chem. Phys. 1999, 110, 6158.
(47) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.; , J.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.;
Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.;
Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador,
P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman,
J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09 Revision B.01;
Gaussian, Inc., Wallingford, CT, 2010.
(48) Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.; Carpenter,
J. E.; Bohmann, J. A.; Morales, C. M.; Weinhold, F. NBO 5.0, Theoretical
Chemistry Institute, University of Wisconsin, Madison, WI, 2001.
(49) Roth, M.; Mayr, H. Angew. Chem., Int. Ed. 1995, 34, 2250.
(50) Burfeindt, J.; Patz, M.; M., M.; Mayr, H. J. Am. Chem. Soc. 1998,
120, 3629.
(51) Brinkman, E. A.; Berger, S; Brauman, J. I. J. Am. Chem. Soc.
1994, 116, 8304.
(52) Raguꢀe-Schleyer, P. v.; Clark, T.; Kos, A. J.; W-Spitznagel, G.;
Rohde, C.; Arad, D.; Houk, K. N.; Rondan, N. G. J. Am. Chem. Soc. 1984,
106, 6475.
(53) Huang, X.; Batchelor, R. J.; Einstein, F. W. B.; Bennet, A. J.
J. Org. Chem. 1994, 59, 7108.
(54) Bolster, J.; Kellogg, R. M.; Meijer, E. W.; Wynberg, H. Tetra-
hedron Lett. 1979, 20, 285.
(55) Porter, N. A.; Zhang, G.; Reed, A. D. Tetrahedron Lett. 2000,
41, 5773.
(56) Capozzi, G.; Gori, L.; Menichetti, S.; Nativi, C. J. Chem. Soc.,
Perkin Trans. 1 1992, 1923.
(57) Schlenk, W.; Bergann, E. Liebigs Ann. Chem. 1928, 22, 464.
(58) Golebiowski, A.; Izdebski, J.; Jacobsson, U.; Jurczak, J. Hetero-
cycles 1986, 24, 1205.
(59) Oxford Diffraction Ltd., CrysAlis CCD, Version 1.171.31.2
(release July 7, 2006, CrysAlis171.NET).
(60) Oxford Diffraction Ltd., CrysAlis RED, Version 1.171.31.2
(release July 7, 2006, CrysAlis171.NET).
(61) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna,
R. J. Appl. Crystallogr. 1999, 32, 115.
(62) Sheldrick, G. M. SHELXL, 1997
7422
dx.doi.org/10.1021/jo2010878 |J. Org. Chem. 2011, 76, 7415–7422