A convergent, modular access to complex amines

Article abstract of DOI:10.1016/j.tet.2010.05.107

Various xanthates can be added to N-vinyl phthalimide with little formation of oligomers, if the xanthate is used in excess and the medium slightly diluted. The adduct xanthates thus obtained can in turn undergo radical additions to numerous olefins, providing a convergent and modular access to densely functionalized amines.

Full text of DOI:10.1016/j.tet.2010.05.107

Tetrahedron 66 (2010) 6656e6666
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A convergent, modular access to complex amines
*
Béatrice Quiclet-Sire, Guillaume Revol, Samir Z. Zard
Laboratoire de Synthèse Organique associé au C.N.R.S., Département de Chimie, Ecole Polytechnique, F-91128 Palaiseau, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Various xanthates can be added to N-vinyl phthalimide with little formation of oligomers, if the xanthate
is used in excess and the medium slightly diluted. The adduct xanthates thus obtained can in turn un-
dergo radical additions to numerous olefins, providing a convergent and modular access to densely
functionalized amines.
Received 15 March 2010
Received in revised form 27 May 2010
Accepted 28 May 2010
Available online 8 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
This paper is dedicated with respect and
admiration to Professor Steven V. Ley, re-
cipient of the 2009 Tetrahedron Prize
Keywords:
Radical addition
Xanthates
Amines
Phthalimides
S
1. Introduction
O
S
R
O
S
R
OEt
2
S
The amino group occupies a central position in organic chem-
istry, and the synthesis of numerous natural products, such as
amino-acids or alkaloids, or medicinal compounds, the vast ma-
jority of which contain one or more nitrogen atoms, hinges heavily
on the ability to access functionalized amine intermediates or end
products. As a consequence, the development of new flexible routes
to amines remains a very worthwhile endeavor. We now report
what we believe is an exceedingly powerful extension of an earlier
approach, allowing the expedient assembly of highly functional
internal primary amines conveniently protected as their phthali-
mido derivatives.
Recently, we described a versatile, practical radical amino-
methylation of alkenes based on the degenerative xanthate transfer
reaction,1 namely the addition of xanthate 1 to alkene 2 to give
adduct 3, as summarized by the first equation in Scheme 1.2 We
later expanded this strategy to the arylaminomethylation of al-
kenes and to the synthesis of usefully functionalized amines
starting from aminoacids.3
N
N
OEt
(peroxide)
1
3
O
O
Scheme 1.
N-vinyl phthalimide 5 furnished mostly oligomers 7 and only a small
yield of the desired adducts 6 (Scheme 2; PhthN¼phthalimido
throughout). All three alkenes readily polymerize,4 yet no difficulties
were encountered in controlling the addition with the first two. In
only one case, namely addition of AIBN derived xanthate (Me2C(CN)
SCSOEt, 4a)5 could we secure a good yield of mono-adduct under the
usual conditions. Since xanthate additions to N-vinyl phthalimide 5
would constitute a simple, convergent, and flexible route to a vast
number of variously functionalized, phthalimido protected primary
amines 6, we decided to re-examine this addition.
The difference in the behavior of N-vinyl phthalimide 5, as
compared to that of vinyl acetate and N-vinyl pyrrolidone, was
attributed to the existence of resonance structures 8a and 8b,
which impart a certain degree of allylic character to the adduct
radical 8.6 Such conjugation is expected to be much less significant
in the case of an acetate or a pyrrolidone group. The deleterious
consequence of this stabilization in the present context can be
understood by examining the fragmentation tendency of key in-
termediate 9 in Scheme 2. The formation of desired addition
At the origin of our work inthisareawasa puzzlingand frustrating
observation: in contrast to additions to vinyl acetate or N-vinyl pyr-
rolidone, the corresponding radical additions of xanthates 4 to
* Corresponding author. Tel.: þ33 169335971; fax: þ33 169335972; e-mail
address: zard@poly.polytechnique.fr (S.Z. Zard).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.05.107

B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
6657
Table 1
NPhth
R
Etc.
Oligomers
NPhth
Xanthate 4
Radical adduct 6
Yielda (%)
7
Me
Me
SCSOEt
4a
CN
Me
Me
SCSOEt
CN NPhth
6a, 74
NPhth
5
O
O
EtO2C
EtO2C
SCSOEt
EtO2C
SCSOEt
NPhth
R
N
R
N
6b, 95
6c, 73
6d, 69
6e, 79
O
8a
O
EtO2C
4b
8b
O
NC
SCSOEt
NPhth
NPhth
5
NC
SCSOEt
4c
S
R
N
R
R
O
S
OEt
S
8
O
O
O
4
SCSOEt
SCSOEt
SCSOEt
NPhth
4
4d
R
R
NPhth
S
F
F
O
SCSOEt
S
+
R
S
R
NPhth
4e
Br
Br
OEt
PhthN
OEt
6
9
MeO
O
MeO
O
Scheme 2.
SCSOEt
SCSOEt
6f, 50
NPhth
4f
product 6 is favored when the collapse of this intermediate leads
preferentially to radical Rꢀ and not back to adduct radical 8. Un-
fortunately, the enhanced stabilization of 8 provided by the
phthalimido group promotes the unwanted back fragmentation.
This causes a build up in the concentration of 8 and encourages the
formation of oligomer 7 by further additions to N-vinyl phthalimide
5. In the case of AIBN derived xanthate 4a, the corresponding
radical (Me2C$(CN)) is sufficiently more stable than adduct radical 8
to shift the equilibrium in the right direction and allow clean
obtention of mono-adduct 6a (6, R¼(Me2C(CN)e)).
Br
Br
O
O
O
SCSOEt
SCSOEt
NPhth
(1:1)
6g, 87
6h, 64
4g
O
SCSOEt
SCSOEt
NPhth
4h
S
S
While decisive, the extra stabilization provided by the phthali-
mido group is nevertheless expected to be small in absolute energy
terms. It appeared therefore possible to curtail the unwanted
oligomerization by a modification of the experimental parameters.
The additions of xanthates are normally conducted under a high
concentration of 1e4 M and the olefinic partner is normally used in
1.5 to 3-fold and sometimes up to 5-fold excess, depending on its
reactivity and volatility. If, instead, xanthate 4 is used in excess, the
equilibrium should shift to increase the concentration of tertiary
radical 9 at the expense of adduct radical 8. This lowering of the
concentration of 8 would automatically cause a decrease in the rate
of oligomer formation. The rate of the bimolecular oligomerisation
pathway may be further diminished by diluting the reaction me-
dium. Thus, instead of using the usual two-fold excess of olefin,
a two-fold excess of the xanthate and a 0.5 M concentration were
employed instead.
O
O
Piv
N
Piv
N
SCSOEt
NPhth
6i, 72
6j, 62
SCSOEt
4i
O
O
EtO2C
Ts
SCSOEt
NPhth
EtO2C
SCSOEt
4j
Ts
N
SCSOEt
SCSOEt
NPhth
N
6k, 86
6l, 72
O
O
4k
O
O
Cl
SCSOEt
NPhth
Cl
SCSOEt
4l
We were gratified to find that these modified conditions worked
quite nicely for xanthates derived from for diethyl malonate, ace-
tonitrile, and functionalized ketones (Table 1, 6aem). The yield
remained modest or poor with simpler xanthates 4n and 4o derived
from cyclopropyl methyl ketone and from acetone, respectively. In
these twocases, the efficiency was significantlyimproved to72% and
82%, respectively, by increasing further the excess of xanthate to
four-fold and further decreasing the dilution to 0.25 M. The same
observation was made for N-acetyl oxazolidone derived xanthate
4p. For the N,O-dimethyl acetylhydroxamic acid xanthate 4q,
a three-fold excess and a 0.33 M concentration were sufficient to
secure a good yield (76%) of the desired adduct 6q. With acetate or
acetanilide xanthates, 4r and 4s, which otherwise add efficiently to
ordinary terminal alkenes (e.g., allyl acetate), the extensive forma-
tion of oligomers could not be avoided unfortunately.
MeO
MeO
MeO
Me
SCSOEt
NPhth
SCSOEt
MeO
Me
6m, 73
O
O
(1:1)
4m
O
O
6m, 23
SCSOEt
NPhth
SCSOEt
4n
57b
O
O
6o, 22
SCSOEt
NPhth
(continued on next page)
SCSOEt
72b
Me
Me
4o

6658
B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
Table 1 (continued)
Xanthate 4
Table 2
Radical adduct 6
Yielda (%)
R'
O
O
O
O
1)
6p, 45
SCSOEt
NPhth
SCSOEt
82b
R'
10
SCSOEt
N
(Lauroyl peroxide)
N
O
R
R
O
4p
NPhth
NPhth
6
2) (Me3Si)3SiH
(AIBN)
O
O
6q, 76c
MeO
EtO
SCSOEt
MeO
SCSOEt
N
N
Xanthate 6
Alkene
Radical adduct 6
4q
Me Me
Me Me NPhth
EtO2C
CO2Et
PO(OMe)2
10a, 54%
PO(OMe)2
O
O
6b
6r, dd
SCSOEt
NPhth
SCSOEt
EtO
PhthN
4r
OMe
OMe
10b, 84%
O
MeO
NC
O
6c
OMe
6s, dd
SCSOEt
NPhth
SCSOEt
4s
Ph2N
NPhth
Ph2N
a
Except for 6a, yields refer to reactions with 2 equiv of xanthate 4 with N-vinyl
phthalimide 5 in refluxing ethyl acetate at 0.5 M concentration.
O
b
Yield using 4 equiv of xanthate 4 at 0.25 M concentration.
Yield using 3 equiv of xanthate 4 at 0.33 M concentration.
NHBoc
10c, 61%
NHBoc
c
6d
d
Extensive oligomer formation.
F
NPhth
O
Notwithstanding these, ultimately rather minor limitations, the
access to xanthate adducts 6 to N-vinyl phthalimide opens up vast
opportunities for the synthesis of complex, highly functionalized
amines. The stabilizing effect of the phthalimide group, initially
the cause of the difficulties we faced, now becomes a tremendous
asset because its presence will facilitate considerably the addition
of xanthates 6 to various other olefins. Thus, to the functional
groups contributed by the first xanthate 4, additional functionality
can be brought in by the olefinic partner, resulting in a modular,
convergent approach to primary amines protected as their
phthalimido derivatives. A selection of such structures is compiled
in Table 2, where a number of adducts to N-vinyl phthalimide
were made to react with various olefins. To simplify the structural
determination and description, the xanthate group in the adduct
was reduced off using tris(trimethylsilyl)silane (TTMSS).7 The
overall yield for the two steps was good in most cases, and the
tolerance for functional groups quite broad and in line with our
earlier studies.
CO2Et
CO2Et
CO2Et
CO2Et
6e
6i
NPhth
Br
10d, 50%
O
Piv
N
OAc
OAc
NPhth
10e, 69%
O
O
Ph
EtO2C
O
6j
Ph
NPhth
10f, 71%
MeO
MeO
SiMe3
6m
SiMe3
The synthesis of any of the protected amines pictured in Table
2 using traditional methods would be very tedious at best. The
complexity of the structures accessible by the present, unique
modular approach may be further underscored by the sequence
displayed in Scheme 3. By starting with xanthate 6a, made by
addition of xanthate 4a to N-vinyl phthalimide 5, it is possible to
perform a second radical addition to vinylidene carbonate then
a third addition to allyl trimethylsilane to give finally 12. Thus,
one xanthate and three different olefins could be stitched to-
gether using the same radical process. To simplify character-
isation, the xanthate group was reduced off to give 13 in 50%
overall yield from 11. The latter was also cleanly reduced into 14.
Except in the addition to vinylidene carbonate, which not un-
expectedly, takes place in a trans fashion, the relative stereo-
chemistry cannot otherwise be controlled. This lack of
diastereoselectivity is inherent to the free radical nature of the
intermediates and not to the method itself.
NPhth
Me
O
O
10g, 77%
CO2Me
( )8
NPhth
6o
6p
Me
CO2Me
( )8
10h, 70%
O
O
N
N
N
N
O
N
NPhth
N
N
10i, 73%
O
MeO
PO(OMe)2
PO(OMe)2
6q
N
The xanthate group in the first adduct can also be used to con-
struct cyclic derivatives through an intramolecular radical addition.
While further treatment of compound 6d with stoichiometric
Me Me NPhth
10j, 58%
amounts of lauroyl peroxide furnished only
a small and

B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
6659
O
O
O
N
NPhth
S
S
X
NPhth
1) (Me3Si)3SiH
(AIBN)
O
S
S
NPhth
Me
Me CN
OEt
Me
Me CN
(lauroyl peroxide)
EtOAc, reflux
2) MeNH2 /EtOH
rt, 2 hr
O
OEt
O
6g, X = SCSOEt
17, X = H, 88%
18, 72%
11, 59%
6a
O
(1:1)
SiMe3
NHBoc
NHBoc
(Me3Si)3SiH
(AIBN)
(lauroyl peroxide)
EtOAc, reflux
O
MeNH2
N
F
NPhth
SiMe3
NPhth
EtOH
NPhth
S
S
rt, 2 hr
F
10c
Me
Me CN
Me
Me CN
19, 95%
OEt
O
O
O
O
O
Ph
O
O
O
12
Ph
14, 78%
(Me3Si)3SiH
(AIBN)
NPhth
O
SiMe3
(1:1)
O
O
O
MeNH2
EtO
N
EtO
Me
Me CN
EtOH
NPhth
rt, 2 hr
O
13, 50% (from 11)
10f
20, ~100%
O
Scheme 5.
Scheme 3.
functional group (FG or FG0) containing alkenes furnishes termi-
nal or internal amine derivatives 21 and 23, respectively, the
present addition of a xanthate 4 to N-vinyl phthalimide 5 is more
powerful as it provides access to both terminal and internal
amines (24 and 25, and reduction products thereof). In all cases,
a very broad variety of densely functionalized amines can be
rapidly assembled.
disappointing 19% yield of tetralone 15 (Scheme 4), the corre-
sponding reaction with thiophene adduct 6h gave a high yield
(81%) of ketone 16. The steric hindrance caused by the large
phthalimido group appears to be of lesser consequence in the latter
transformation, in addition to the fact that the temporary disrup-
tion of the aromaticity during the cyclization onto the thiophene
ring is energetically less costly.
FG
O
O
PhthN
SCSOEt
FG
Lauroyl
PhthN
SCSOEt
NPhth
S
peroxide
peroxide
1
21
S
EtOAc
reflux
F
F
Amino acids
OEt
NPhth
O
15, 19%
6d
FG'
PhthN
SCSOEt
PhthN
FG
FG'
O
S
Lauroyl peroxide
EtOAc, reflux
NPhth
S
S
SCSOEt
23
peroxide
FG
22
S
NPhth
FG
SCSOEt
16, 81%
OEt
6h
4
R
Scheme 4.
NPhth
peroxide
5
By exploiting the presence in the adducts of various functional
groups, such as ketones, esters, nitriles, masked aldehydes (as in
6m) etc., it is possible to construct nitrogen containing hetero-
cycles by combining the radical process with classical ionic ring-
closures. For example, reductive removal of the xanthate in 6g
gave 17 in 88% yield and release of the amine group resulted in
spontaneous ring closure to give pyrrolenine 18 (72%), whereas
deprotection of adducts 10c and 10f furnished, respectively,
pyrrolenines 19 and 20 in essentially quantitative yield
(Scheme 5). The other amino group in the 19 remained safely
protected as the Boc derivative.
R
R
FG'
FG
NPhth
FG
NPhth
FG'
peroxide
SCSOEt
24
25
SCSOEt
Scheme 6.
2. Experimental
In conclusion, we now have in hand a unified, flexible, and
convergent strategy for assembling primary aliphatic amines
consisting of three main routes summarised in Scheme 6. All
hinge on the hitherto unappreciated stabilising effect of the
phthalimido group (or imides more generally). Whereas addition
of the parent xanthate 1 or aminoacid derived xanthates 22 to
2.1. General conditions
Anhydrous dichloromethane was obtained by distillation from
calcium hydride under nitrogen. Anhydrous THF and diethyl ether
were obtained by distillation from sodium benzophenone ketyl

6660
B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
under nitrogen. Other solvents were used as supplied by com-
mercial sources. Petroleum ether refers to the fraction of light
petroleum ether, boiling between 40e60 ꢁC. Purification pro-
cedures were in accordance with the instructions in D.D. Perrin
and W.L.F. Armarego, Purification of Laboratory Chemicals, 4th ed.;
The Bath, Bath, 2002. All reactions were carried out under dry,
oxygen free nitrogen. Flash chromatography was performed on
4b (527 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (2 mL) and needed 7 mol % of DLP
to go to completion. Flash chromatography on silica gel (ethyl ac-
etate/petroleum ether, 0:10 to 3:7 v/v) afforded 6b (500 mg, 95%) as
a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.86 (dd, 2H, J¼3.0,
5.5 Hz), 7.75 (dd, 2H, J¼3.1, 5.4 Hz), 6.37 (dd, 1H, J¼6.8, 9.3 Hz), 4.62
(q, 2H, J¼7.1 Hz), 4.21 (dq, 2H, J¼1.8, 7.1 Hz), 4.08 (ddt, 2H, J¼3.6, 7.1,
J¼10.8 Hz), 3.43 (t, 1H, J¼7.3 Hz), 2.84 (m, 2H), 1.40 (t, 3H, J¼7.1 Hz),
1.27 (t, 3H, J¼7.2 Hz), 1.20 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 210.20, 168.06, 167.95, 166.56, 134.49, 131.59, 123.70, 70.64,
62.02, 61.92, 55.71, 49.57, 32.24, 14.04, 13.97, 13.72. IR (CDCl3): nmax
2927, 2855, 1784, 1754, 1726, 1469, 1377, 1227, 1111, 1048. HRMS
(EIþ): m/z calculated for C20H23O7NS2 M¼453.0916, found:
453.0919, calculated for C17H18O6N [MꢂSC(S)OEt]¼332.1134,
found: 332.1127.
silica gel (SDS, 60 Å C. C. 40e63 mm) as the stationary phase. Thin
Layer Chromatography (TLC) was performed on aluminum plates
pre-coated with silica gel (Merck silica gel, 60 F254), which were
visualized by the quenching of UV fluorescence when applicable
(lmax¼254 nm and/or 366 nm) and/or by staining with anisalde-
hyde or vanillin in acidic ethanol followed by heating. When
compounds could not be visualized with anisaldehyde or vanillin,
a solution of phosphomolybdic acid in ethanol or a potassium
permanganate aqueous solution was used. Infrared spectra were
recorded as solutions in CDCl3 using CaF2 cells, on a PerkineElmer
FT 1600 or FT 2000. Absorption maxima (nmax) are reported in
wave numbers (cmꢂ1) and only selected peaks are reported.
Magnetic resonance spectra were recorded at ambient tempera-
ture on either a Bruker AMX 400, or a Bruker Avance DPX 400
instruments. Proton magnetic resonance spectra (1H NMR) were
recorded at 400 MHz and coupling constants (J) are reported to
ꢃ0.5 Hz. The following abbreviations were utilized to describe
peak patterns when appropriate: br¼broad, s¼singlet, d¼doublet,
t¼triplet, q¼quartet and m¼multiplet. Carbon magnetic reso-
nance spectra (13C NMR) were recorded at 100 MHz. Chemical
2.2.3. S-[3-Cyano-1-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-
O-ethyl dithiocarbonate (6c). Following the general procedure, the
reaction was carried out with a solution of xanthate 4c (356 mg,
2.32 mmol) and N-vinyl phthalimide (200 mg, 1.16 mmol) in 1,2-
dichloroethane (2 mL) and needed 2 mol % of DLP to go to
completion. Flash chromatography on silica gel (ethyl acetate/
petroleum ether, 0:10 to 3:7 v/v) afforded 6c (283 mg, 73%) as
a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.89 (dd, 2H, J¼3.1,
5.5 Hz), 7.77 (dd, 2H, J¼3.0, 5.5 Hz), 6.38 (m, 1H), 4.66 (q, 2H,
J¼7.1 Hz), 2.66 (m, 1H), 2.54 (m, 3H), 1.43 (t, 3H, J¼7.1 Hz). 13C
NMR (100.6 MHz, CDCl3): 210.04, 166.76, 134.72, 131.46, 123.91,
118.01, 70.99, 55.44, 29.43, 15.06, 13.75. IR (CDCl3): nmax 2927,
2855, 1783, 1727, 1470, 1377, 1333, 1228, 1111, 1051. HRMS (EIþ):
m/z calculated for C15H14O3N2S2 M¼334.0446, found: 334.0447,
calculated for C12H9O2N2 [MꢂSC(S)OEt]¼213.0664, found:
213.0662.
shifts (dH, dC) are quoted in parts per million (ppm) and are ref-
erenced to the residual solvent peak (CDCl3: dH¼7.26 and dC¼77.0).
High-resolution mass spectra were recorded by positive electron
impact ionization (EIþ) at 70 eV on a JEOL JMS-GCmate II mass
spectrometer. The quoted masses are accurate to ꢃ5 ppm. DLP
corresponds to di-lauroyl peroxide (often sold under lauroyl per-
oxide or laurox).
2.2.4. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-(4-fluo-
rophenyl)-4-oxo-butyl]-O-ethyl dithiocarbonate (6d). Following the
general procedure, the reaction was carried out with a solution of
xanthate 4d (597 mg, 2.32 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and needed
15 mol % of DLP to go to completion. Flash chromatography on
silica gel (ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) afforded
xanthate 6d (342 mg, 69%) as a pale yellow oil. 1H NMR (400 MHz,
CDCl3): 7.92 (dd, 2H, J¼5.4, 8.9 Hz), 7.85 (dd, 2H, J¼3.0, 5.5 Hz),
7.74 (dd, 2H, J¼3.1, 5.5 Hz), 7.09 (t, 2H, J¼8.6 Hz), 6.38 (t, 1H,
J¼7.9 Hz), 4.60 (dq, 2H, J¼2.5, 7.1 Hz), 3.10 (m, 2H), 2.65 (ddd, 2H,
J¼2.7, 7.5, 14.6 Hz), 1.38 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 211.04, 196.24, 166.80, 165.83 (d, J¼257.3 Hz), 134.44,
132.99, 131.62, 130.72 (d, J¼9.3 Hz), 123.69, 115.75 (d, J¼21.8 Hz),
70.61, 57.49, 35.28, 30.94, 28.10, 23.73. IR (CDCl3): nmax 2985, 2938,
1780, 1718, 1687, 1599, 1380, 1232, 1111, 1048. HRMS (EIþ): m/z
calculated for C18H13O3NF [MꢂSC(S)OEt]¼310.0879, found:
310.0878.
2.2. General procedure for the addition xanthate 4aes to
N-vinyl phthalimide 5
A
magnetically stirred solution of N-vinyl phthalimide 5
(1 equiv) and xanthate (2 equiv to 4 equiv) in 1,2-dichloroethane
(2 mL/mmol to 4 mL/mmol of 5) was heated at reflux for 15 min.
DLP (2e5 mol %) was then added and additional DLP (5 mol %) was
added every 60 min until total consumption of 5. The mixture was
then cooled to room temperature and the solvent was evaporated
under reduced pressure. The residue was purified by flash chro-
matography on silica gel to yield the desired compounds 6.
2.2.1. S-3-Cyano-1-(1,3-dioxoisoindolin-2-yl)-3-methylbutyl O-ethyl
carbonodithioate (6a). The reaction was run with xanthate 4a
(1.5 mmol) and N-vinyl-phthalimide (1 mmol) in 1,2-di-
chloroethane (0.5 mL). The reaction was completed after addition
of 15 mol % of DLP. After evaporation of the solvent, the residue was
purified by chromatography on silica gel using a gradient (petro-
leum ether/ethyl acetate: 95/5) and the addition product was iso-
lated as a pale yellow oil in 74% yield. 1H NMR (400 MHz, CDCl3):
7.87 (m, 2H), 7.74 (m, 2H), 6.53 (dd, 1H, J¼3.4, 12.2 Hz), 4.66 (q, 2H,
J¼7.1 Hz), 3.08 (dd, 1H, J¼12.2, 14.5 Hz), 2.00 (dd, 1H, J¼3.4,
14.6 Hz), 1.54 (s, 3H), 1.40 (s, 3H), 1.43 (s, 3H). 13C NMR (100 MHz,
CDCl3): 210.8, 167.2, 134.6, 131.6, 123.9, 123.6, 70.7, 54.5, 42.7, 30.5
(Cq, CMe2), 28.7, 24.9, 13.8. IR (CDCl3): nmax 2235, 1781, 1724, 1371,
1224, 1051. HRMS (EIþ): m/z calculated for C14H13N2O2 [MꢂSC(S)
OEt]¼241.0977, found: 241.0976.
2.2.5. S-[4-(4-Bromo-phenyl)-1-(1,3-dioxo-1,3-dihydro-isoindol-2-
yl)-4-oxo-butyl]-O-ethyl dithiocarbonate (6e). Following the general
procedure, the reaction was carried out with a solution of xanthate
4e (737 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (2 mL) and needed 15 mol % of
DLP to go to completion. Flash chromatography on silica gel (ethyl
acetate/petroleum ether, 0:10 to 3:7 v/v) afforded xanthate 6e
(450 mg, 79%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.83
(dd, 2H, J¼3.0, 5.5 Hz), 7.73 (dd, 2H, J¼4.2, 7.5 Hz), 7.73 (d, 2H,
J¼8.6 Hz), 7.53 (d, 2H, J¼8.6 Hz), 6.36 (t, 1H, J¼7.9 Hz), 4.59 (dq, 2H,
J¼2.6, 7.1 Hz), 3.09 (dt, 2H, J¼5.3, 6.9 Hz), 2.63 (ddd, 2H, J¼3.4, 7.4,
J¼14.6 Hz), 1.36 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3):
210.99, 196.82, 166.77, 134.46, 131.95, 131.59, 129.58, 123.69, 70.61,
57.43, 35.31, 28.03, 13.75. IR (CDCl3): nmax 2985, 2962, 2902, 1780,
2.2.2. Diethyl
2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-ethox-
ythiocarbonylsulfanyl-ethyl]-malonate (6b). Following the general
procedure, the reaction was carried out with a solution of xanthate

B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
6661
1723, 1688, 1587, 1470, 1380, 1365, 1333, 1229, 1111, 1048. HRMS
(EIþ): m/z calculated for C21H18O4NS2Br M¼490.9861, found:
490.9866, calculated for C18H13O3NBr[MꢂSC(S)OEt]¼370.0079,
found: 370.0087.
HRMS (EIþ): m/z calculated for C19H17O4NS3 M¼419.0320, found:
419.0323, calculated for C16H12O3NS [MꢂSC(S)OEt]¼298.0538,
found: 298.0546.
2.2.9. S-[4-[1-(2,2-Dimethyl-propionyl)-1H-indol-6-yl]-1-(1,3-di-
oxo-1,3-dihydro-isoindol-2-yl)-4-oxo-butyl]-O-ethyl dithiocarbonate
(6i). Following the general procedure, the reaction was carried out
with a solution of xanthate 4i (807 mg, 2.32 mmol) and N-vinyl
phthalimide (200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and
needed 15 mol % of DLP to go to completion. Flash chromatography
on silica gel (ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) affor-
ded xanthate 6i (450 mg, 72%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): 9.12 (d, 1H, J¼0.6 Hz), 7.93 (d, 1H, J¼3.8 Hz), 7.92
(m, 1H), 7.89 (dd, 2H, J¼3.1, 5.5 Hz), 7.77 (dd, 2H, J¼3.0, 5.5 Hz), 7.61
(d, 1H, J¼8.2 Hz), 6.69 (d, 1H, J¼3.8 Hz), 6.40 (t, J¼7.89 Hz, 1H), 4.66
(m, 2H), 3.29 (t, 2H, J¼7.2 Hz), 2.73 (q, 2H, J¼7.1 Hz), 1.57 (s, 9H),
1.44 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3): 210.94, 197.88,
177.08, 166.80, 136.33, 134.31, 133.28, 131.71, 128.86, 123.66, 123.33,
120.54, 118.03, 108.09, 70.53, 57.32, 41.41, 35.30, 28.69, 13.76. IR
(CDCl3): nmax 2959, 2933, 1774, 1742, 1713, 1686, 1427, 1371, 1307,
1239, 1190, 1079, 1045. HRMS (EIþ): m/z calculated for
C28H28O5N2S2 M¼536.1440, found: 536.1442, calculated for
C25H23O4N2[MꢂSC(S)OEt]¼415.1658, found: 415.1664.
2.2.6. S-[4-(5-Bromo-2-methoxy-phenyl)-1-(1,3-dioxo-1,3-dihydro-
isoindol-2-yl)-4-oxo-butyl]-O-ethyl dithiocarbonate (6f). Following
the general procedure, the reaction was carried out with a solution
of xanthate 4f (806 mg, 2.32 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and needed
15 mol % of DLP to go to completion. Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) afforded xan-
thate 6f (300 mg, 50%) as a pale yellow oil. 1H NMR (400 MHz,
CDCl3): 7.85 (dd, 2H, J¼3.2, 5.2 Hz), 7.74 (dd, 2H, J¼3.0, 5.5 Hz), 7.70
(d, 1H, J¼1.5 Hz), 7.50 (dd, 1H, J¼1.6, 8.8 Hz), 6.81 (d, 1H, J¼8.9 Hz),
6.35 (t, 1H, J¼8.0 Hz), 4.61 (q, 2H, J¼7.1 Hz), 3.82 (s, 3H), 3.10 (m,
2H), 2.58 (m, 2H), 1.38 (t, 1H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 211.18, 198.51, 166.76, 157.69, 136.20, 134.43, 133.05, 131.62,
129.00, 123.64, 113.55, 70.54, 57.48, 55.86, 40.69, 28.20, 13.77. IR
(CDCl3): nmax 2927, 2855, 1782, 1724, 1685, 1481, 1378, 1269, 1225,
1112, 1049. HRMS (EIþ): m/z calculated for C22H20O5NS2Br
M¼520.9966, found: 520.9964, calculated for C19H15O4NBr[MꢂSC
(S)OEt]¼400.0184, found: 400.0184.
2.2.7. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-(5-oxo-6,7,8,9-
2.2.10. Ethyl 6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-6-ethoxythiocar-
bonylsulfanyl-3-oxo-hexanoate (6j). Following the general pro-
cedure, the reaction was carried out with a solution of xanthate 4j
(870 mg, 3.47 mmol) and N-vinyl phthalimide (300 mg, 1.73 mmol)
in 1,2-dichloroethane (4 mL) and needed 10 mol % of DLP to go to
completion. Flash chromatography on silica gel (ethyl acetate/pe-
troleum ether, 0:10 to 3:7 v/v) afforded xanthate 6j (456 mg, 62%)
as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.83 (m, 2H), 7.72
(m, 2H), 6.25 (t, 1H, J¼7.9 Hz), 4.59 (q, 2H, J¼7.1 Hz), 4.11 (q, 2H,
J¼7.1 Hz), 3.38 (s, 2H), 2.69 (m, 2H), 2.47 (dd, 2H, J¼7.2, 14.7 Hz),
1.37 (t, 3H, J¼7.1 Hz), 1,20 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 210.86, 200.51, 166.83, 166.73, 134.45, 131.59, 123.65, 70.57,
61.43, 57.093, 49.23, 39.58, 27.35,14.06, 13.70. IR (CDCl3): nmax 2983,
2959, 2928, 2855, 1782, 1724, 1469, 1378, 1227, 1112, 1049. HRMS
(EIþ): m/z calculated for C19H21O6NS2 M¼423.0810, found:
423.0784, calculated for C16H16O5N [MꢂSC(S)OEt]¼302.1028,
found: 302.1039.
tetrahydro-5H-benzocyclohepten-6-yl)-ethyl]-O-ethyl
dithiocar-
bonate (6g). Following the general procedure, the reaction was
carried out with a solution of xanthate 4g (615 mg, 2.32 mmol)
and N-vinyl phthalimide (200 mg, 1.16 mmol) in 1,2-di-
chloroethane (2 mL) and needed 15 mol % of DLP to go to com-
pletion. Flash chromatography on silica gel (ethyl acetate/
petroleum ether, 0:10 to 3:7 v/v) afforded xanthate 6g (440 mg,
87%) as
a
pale yellow oil. 1H NMR (400 MHz, CDCl3): Di-
astereoisomer 1: 7.84 (dd, 2H, J¼3.1, 5.4 Hz), 7.80 (dd, 2H, J¼3.1,
5.4 Hz), 7.62 (dd, 1H, J¼1.2, 7.6 Hz), 7.42 (dd, 1H, J¼0.9, 7.6 Hz),
7.26 (m, 1H), 7.17 (m, 1H), 6.36 (m, 1H), 4.55 (m, 2H), 2.90 (m, 2H),
2.34 (m, 1H), 2.08 (m, 2H), 1.68 (m, 2H), 1.40 (t, 3H, J¼7.1 Hz).
Diastereoisomer 2: 7.74 (dd, 2H, J¼3.0, 5.5 Hz), 7.70 (dd, 2H, J¼3.0,
5.5 Hz), 7.42 (dd, 1H, J¼0.9, 7.6 Hz), 7.33 (dt, 1H, J¼1.1, 7.4 Hz), 7.17
(m, 2H), 6.36 (m, 1H), 4.61 (q, 2H, J¼7.2 Hz), 2.90 (m, 4H), 2.34 (m,
1H), 2.08 (m, 2H), 1.68 (m, 2H), 1.35 (t, 3H, J¼7.1 Hz). 13C NMR
(100.6 MHz, CDCl3): Diastereoisomer 1: 211.20, 204.68, 166.71,
141.57, 139.27, 134.33, 131.72, 131.42, 130.03, 128.60, 126.24, 123.66,
70.44, 56.64, 47.06, 34.86, 33.70, 30.56, 25.46, 13.75. Di-
astereoisomer 2: 210.78, 205.25, 166.67, 142.50, 139.71, 134.33,
131.63, 131.29, 129.78, 128.73, 126.46, 123.61, 70.48, 55.85, 47.44,
34.57, 33.88, 30.88, 25.68, 13.72. IR (CDCl3): nmax 2930, 2857, 1779,
1720, 1682, 1470, 1380, 1364, 1230, 1112, 1047. HRMS (EIþ): m/z
calculated for C24H23O4NS2 M¼453.1069, found: 453.1088, calcu-
lated for C21H18O3N [MꢂSC(S)OEt]¼332.1287, found: 332.1284.
2.2.11. S-{1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-[4-oxo-1-(tolu-
ene-4-sulfonyl)-piperidin-3-yl]-ethyl}-O-ethyl dithiocarbonate (6k).
Following the general procedure, the reaction was carried out with
a solution of xanthate 4k (860 mg, 2.32 mmol) and N-vinyl
phthalimide (200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and
needed 15 mol % of DLP to go to completion. Flash chromatography
on silica gel (ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) affor-
ded xanthate 6k (540 mg, 86%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): Diastereoisomer 1: 7.87 (dd, 2H, J¼2.5, 5.4 Hz),
7.77 (dd, 2H, J¼3.2, 5.7 Hz), 7.69 (d, 2H, J¼8.2 Hz), 7.33 (d, 2H,
J¼8.4 Hz), 6.34 (t, 1H, J¼7.7 Hz), 4.65 (q, 2H, J¼7.0 Hz), 4.05 (ddd,
1H, J¼2.2, 5.1 Hz, J¼11.7 Hz), 3.94 (m, 1H), 2.86 (dt, 1H, J¼3.8,
11.6 Hz), 2.64 (m, 4H), 2.43 (s, 3H), 2.11 (m, 2H), 1.41 (t, 3H,
J¼7.1 Hz). Diastereoisomer 2: 7.87 (dd, 2H, J¼2.7, 5.5 Hz), 7.75 (dd,
2H, J¼3.2, 5.7 Hz), 7.61 (d, 2H, J¼8.2 Hz), 7.30 (d, 2H, J¼8.4 Hz), 6.38
(dd, 1H, J¼6.1, 9.7 Hz), 4.63 (q, 2H, J¼7.0 Hz,), 3.94 (m, 2H), 2.64 (m,
5H), 2.42 (s, 3H), 2.11 (m, 2H), 1.42 (t, 3H, J¼7.0 Hz). 13C NMR
(100.6 MHz, CDCl3): Diastereoisomer 1: 206.02, 166.86, 144.18,
134.45, 131.66, 129.00, 127.56, 123.75, 70.74, 56.10, 51.05, 47.02,
46.69, 40.48, 31.21, 21.57, 13.73. Diastereoisomer 2: 205.69, 166.70,
144.22, 134.53, 131.61, 129.00, 127.48, 123.79, 70.74, 50.93, 55.52,
46.60, 46.58, 40.41, 30.62, 21.57, 13.73. IR (CDCl3): nmax 2982, 2926,
2854, 1781, 1723, 1599, 1470, 1367, 1226, 1170, 1112, 1048. HRMS
(EIþ): m/z calculated for C25H26O6N2S3 M¼546.0953, found:
2.2.8. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-4-thiophen-
2-yl-butyl]-O-ethyl dithiocarbonate (6h). Following the general
procedure, the reaction was carried out with a solution of xanthate
4h (569 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (2 mL) and needed 45 mol % of
DLP to go to completion. Flash chromatography on silica gel (ethyl
acetate/petroleum ether, 0:10 to 3:7 v/v) afforded xanthate 6h
(200 mg, 64%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.86
(dd, 2H, J¼3.1, 5.4 Hz), 7.76 (dd, 2H, J¼3.0, 5.5 Hz), 7.68 (dd, 1H,
J¼0.9, 3.8 Hz), 7.62 (dd, 1H, J¼0.9, 4.9 Hz), 7.11 (dd, 1H, J¼3.9,
4.8 Hz), 6.39 (t, 1H, J¼7.9 Hz), 4.62 (m, 2H), 3.09 (dt, 2H, J¼2.3,
7.2 Hz), 2.67 (m, 2H), 1.40 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 210.86, 190.73, 166.75, 143.66, 134.47, 133.97, 132.20, 131.54,
128.19, 123.67, 70.62, 57.29, 36.01, 28.25, 13.74. IR (CDCl3): nmax
2928, 2856, 1780, 1720, 1666, 1470, 1380, 1356, 1236, 1111, 1047.

6662
B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
546.0929, calculated for C22H21O5N2S[MꢂSC(S)OEt]¼425.1171,
calculated for C18H19O4NS2 M¼377.0756, found: 377.0738, calcu-
lated for C15H14O3N [MꢂSC(S)OEt]¼256.0974, found: 256.0982.
found: 425.1162.
2.2.12. S-[5-Chloro-1-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-
pentyl]-O-ethyl dithiocarbonate (6l). Following the general pro-
cedure, the reaction was carried out with a solution of xanthate
4l (491 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (2 mL) and needed 15 mol % of
DLP to go to completion. Flash chromatography on silica gel
(ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) afforded xanthate
6l (320 mg, 72%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3):
7.84 (dd, 2H, J¼3.1, 5.3 Hz), 7.74 (dd, 2H, J¼3.1, 5.4 Hz), 6.26 (t,
1H, J¼7.8 Hz), 4.60 (q, 2H, J¼7.1 Hz), 4.05 (s, 2H), 2.75 (m, 2H),
2.51 (q, 2H, J¼7.1 Hz), 1.38 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 210.85, 200.72, 166.79, 134.53, 131.54, 123.73, 70.69,
57.08, 48.00, 36.43, 27.46, 13.74. IR (CDCl3): nmax 2984, 2959,
2928, 2956, 1782, 1721, 1470, 1379, 1226, 1112, 1050. HRMS (EIþ):
m/z calculated for C16H16O4NS2Cl M¼385.0209, found: 385.0216,
calculated for C15H14O3NCl [MꢂSC(S)OEt]¼264.0427, found:
264.0422.
2.2.15. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-pentyl]-O-
ethyl dithiocarbonate (6o). Method a: Following the general pro-
cedure, the reaction was carried out with a solution of xanthate 4o
(412 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg, 1.16 mmol)
in 1,2-dichloroethane (2 mL) and needed 7 mol % of DLP to go to
completion. Flash chromatography on silica gel (ethyl acetate/pe-
troleum ether, 0:10 to 3:7 v/v) afforded xanthate 6o (90 mg, 22%) as
a pale yellow oil. Method b: Following the general procedure, the
reaction was carried out with a solution of xanthate 4o (824 mg,
4.64 mmol) and N-vinyl phthalimide (200 mg, 1.16 mmol) in 1,2-
dichloroethane (4 mL) and needed 15 mol % of DLP to go to com-
pletion. Flash chromatography on silica gel (ethyl acetate/petro-
leum ether, 0:10 to 3:7 v/v) afforded xanthate 6o (290 mg, 72%) as
a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.86 (dd, 2H, J¼3.1,
5.4 Hz), 7.75 (dd, 2H, J¼3.0, 5.5 Hz), 6.26 (t, 1H, J¼7.8 Hz), 4.62 (q,
2H, J¼7.1 Hz), 2.61 (m, 2H), 2.47 (m, 2H), 2.12 (s, 3H), 1.39 (t, 3H,
J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3): 211.06, 166.82, 134.45,
131.60, 123.70, 70.59, 57.32, 40.22, 29.96, 27.49, 13.76. IR (CDCl3):
nmax 2927, 2855,1781,1724,1469,1378,1356,1225,1111,1047. HRMS
(EIþ): m/z calculated for C16H17O4NS2 M¼351.0599, found:
351.0596, calculated for C13H12O3N [MꢂSC(S)OEt]¼230.0817,
found: 230.0819.
2.2.13. S-[3-Dimethoxymethyl-4-oxo-1-(1-oxo-1,3-dihydro-isoindol-
2-yl)-pentyl]-O-ethyl dithiocarbonate (6m). Following the general
procedure, the reaction was carried out with a solution of xanthate
4m (583 mg, 2.32 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (2 mL) and needed 7 mol % of DLP
to go to completion. Flash chromatography on silica gel (ethyl ac-
etate/petroleum ether, 0:10 to 3:7 v/v) afforded xanthate 6m
(342 mg, 73%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): Di-
astereoisomer 1: 7.86 (dd, 2H, J¼3.0, 5.5 Hz), 7.75 (dd, 2H, J¼3.1,
5.5 Hz), 6.24 (t, 1H, J¼7.9 Hz), 4.62 (q, 2H, J¼7.2 Hz), 4.31 (d, 1H,
J¼7.4 Hz), 3.29 (s, 3H), 3.27 (s, 3H), 3.07 (ddd, 1H, J¼3.9, 7.2,
10.7 Hz), 2.67 (m, 1H), 2.52 (m, 1H), 2.12 (s, 3H), 1.39 (t, J¼7.1 Hz,
3H). Diastereoisomer 2: 7.84 (dd, 2H, J¼3.0, 5.4 Hz), 7.73 (dd, 2H,
J¼3.1, 5.5 Hz), 6.16 (dd, 1H, J¼6.0, 10.3 Hz), 4.60 (q, 2H, J¼7.2 Hz),
4.34 (d, 1H, J¼7.1 Hz), 3.36 (s, 3H), 3.32 (s, 3H), 2.85 (m, 1, H), 2.52
(m, 1H), 2.40 (ddd, J¼14.37, 7.41, 3.93 Hz, 1H), 2.24 (s, 3H), 1.42 (t,
J¼7.2 Hz, 3H), 1.38 (t, J¼7.1 Hz, 3H). 13C NMR (100.6 MHz, CDCl3):
Diastereoisomer 1: 210.91, 166.83, 134.52, 131.55, 123.72, 105.47,
70.54, 56.69, 55.80, 53.51, 52.57, 31.36, 13.74. Diastereoisomer 2:
210.33, 166.67, 134.45, 131.55, 123.67, 105.17, 70.64, 56.07, 55.70,
53.18, 53.12, 31.15, 13.71. IR (CDCl3): nmax 2928, 2855, 1779, 1720,
1380, 1231, 1111, 1048. HRMS (EIþ): m/z calculated for C19H23O6NS2
M¼425.0967, found: 425.0946, calculated for C13H11O3N [MꢂSC(S)
OEt/CH(OMe)2]¼229.0739, found: 229.0743.
2.2.16. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-oxo-4-(2-oxo-
oxazolidin-3-yl)-butyl]-O-ethyl dithiocarbonate (6p). Method a:
Following the general procedure, the reaction was carried out with
a solution of 4p (576 mg, 2.32 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and needed
10 mol % of DLP to go to completion. Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 0:10 to 4:6 v/v) afforded xan-
thate 6p (220 mg, 45%) as a pale yellow oil. Method b: Following the
general procedure, the reaction was carried out with a solution of
xanthate 4p (1.152 mg, 4.64 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (4 mL) and needed
15 mol % of DLP to go to completion. Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 0:10 to 4:6 v/v) afforded xan-
thate 6p (400 mg, 82%) as a pale yellow oil. 1H NMR (400 MHz,
CDCl3): 7.82 (dd, 2H, J¼3.1, 5.4 Hz), 7.71 (dd, 2H, J¼3.0, 5.5 Hz), 6.29
(t, 1H, J¼7.9 Hz), 4.58 (q, 2H, J¼7.1 Hz), 4.38 (ddd, 2H, J¼2.9, 7.4 Hz,
J¼8.6 Hz), 3.97 (m, 2H), 3.01 (m, 2H), 2.54 (q, 2H, J¼7.2 Hz), 1.36 (t,
3H, J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3): 210.83, 171.46, 166.84,
153.52, 134.47, 131.57, 123.65, 70.60, 62.30, 56.84, 42.56, 31.85,
28.02, 21.08, 13.74. IR (CDCl3): nmax 2988, 2926, 1782, 1720, 1387,
1364,1229,1112,1046. HRMS (EIþ): m/z calculated for C18H18O6N2S2
M¼422.0606, found: 422.0604, calculated for C15H13O5N2 [MꢂSC
(S)OEt]¼301.0824, found: 301.0819.
2.2.14. S-[4-Cyclopropyl-1-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-
oxo-butyl]-O-ethyl dithiocarbamate (6n). Method a: Following the
general procedure, the reaction was carried out with a solution of
xanthate 4n (472 mg, 2.32 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (2 mL) and needed
7 mol % of DLP to go to completion. Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 0:10 to 3:7 v/v) afforded xan-
thate 6n (100 mg, 23%) as a pale yellow oil. Method b: Following the
general procedure, the reaction was carried out with a solution of
4n (944 mg, 4.64 mmol) and N-vinyl phthalimide (200 mg,
1.16 mmol) in 1,2-dichloroethane (4 mL) and needed 15 mol % of
DLP to go to completion. Flash chromatography on silica gel (ethyl
acetate/petroleum ether, 0:10 to 3:7 v/v) afforded 6n (250 mg, 57%)
as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.86 (dd, 2H, J¼3.1,
5.4 Hz), 7.74 (dd, 2H, J¼3.0, 5.5 Hz), 6.28 (dd, 1H, J¼7.3, 8.6 Hz), 4.62
(q, 2H, J¼7.1 Hz), 2.72 (m, 2H), 2.51 (m, 2H), 1.86 (m, 1H), 1.39 (t, 3H,
J¼7.2 Hz), 0.96 (m, 2H), 0.83 (m, 2H). 13C NMR (100.6 MHz, CDCl3):
211.10, 208.41, 166.80, 134.42, 131.64, 123.67, 70.54, 57.40, 40.16,
27.66, 20.54, 13.77, 11.09, 10.99. IR (CDCl3): nmax 2957, 2927, 2855,
1782, 1724, 1469, 1379, 1361, 1224, 1112, 1051. HRMS (EIþ): m/z
2.2.17. S-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-(methoxy-
methyl-carbamoyl)-butyl]-O-ethyl dithiocarbonate (6q). Following
the general procedure, the reaction was carried out with a solu-
tion of xanthate 4q (515 mg, 2.32 mmol) and N-vinyl phthalimide
(200 mg, 1.16 mmol) in 1,2-dichloroethane (3 mL) and needed
15 mol % of DLP to go to completion. Flash chromatography on
silica gel (ethyl acetate/petroleum ether, 0:10 to 4:6 v/v) afforded
xanthate 6q (350 mg, 76%) as
a
pale yellow oil. 1H NMR
(400 MHz, CDCl3): Diastereoisomer 1: 7.84 (dd, 2H, J¼2.9, 5.6 Hz),
7.73 (dd, 2H, J¼3.1, 5.4 Hz), 6.30 (dd, 1H, J¼6.2, 9.5 Hz), 4.61 (q,
2H, J¼7.1 Hz), 3.55 (s, 3H), 2.97 (s, 3H), 2.91 (m, 1H), 2.74 (m, 1H),
2.13 (td, 1H, J¼6.1, 13.8 Hz), 1.39 (t, 3H, J¼6.8 Hz), 1.18 (d, 3H,
J¼7.0 Hz). Diastereoisomer 2: 7.84 (dd, 2H, J¼2.9, 5.6 Hz), 7.73 (dd,
2H, J¼3.1, 5.4 Hz), 6.23 (dd, 1H, J¼6.5, 9.9 Hz), 4.59 (q, 2H,
J¼7.1 Hz), 3.14 (s, 3H), 3.50 (s, 3H), 2.91 (m, 1H), 2.52 (m, 1H),
2.34 (m, 1H), 1.37 (m, 3H), 1.16 (d, 3H, J¼6.9 Hz). 13C NMR

B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
6663
(100.6 MHz, CDCl3): Diastereoisomer 1: 211.02, 166.66, 134.35,
131.68, 123.52, 70.43, 61.26, 60.43, 56.34, 36.67, 33.71, 17.33, 13.75.
Diastereoisomer 2: 210.42, 166.75, 134.35, 131.68, 123.50, 70.43,
61.37, 60.43, 55.45, 36.10, 33.71, 17.62, 13.72. IR (CDCl3): nmax
2976, 2938, 2856, 1780, 1720, 1655, 1469, 1380, 1355, 1230, 1112,
1046. HRMS (EIþ): m/z calculated for C18H18O6N2S2 M¼422.0606,
found: 422.0604, calculated for C15H13O5N2 [MꢂSC(S)OEt]¼
301.0824, found: 301.0819.
calculated for C17H20O4N2 M¼316.1423, found: 316.1420, calculated
for C16H17O3N2 [MꢂOMe]¼285.1239, found: 285.1232.
2.3.3. tert-Butyl [4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-7-(4-flu-
oro-phenyl)-7-oxo-heptyl]-carbamate (10c). Following the general
procedure, the reaction was carried out with a solution of xanthate
6d (300 mg, 0.70 mmol) and N-allyl-tert-butyl carbamate (210 mg,
1.40 mmol) in 1,2-dichloroethane (1.4 mL) and needed 20 mol % of
DLP to go to completion. The reduction was carried out on the crude
product with TTMSS (323 mL, 1.05 mmol), AIBN (23 mg, 0.14 mmol)
2.3. General procedure for radical addition of xanthates
6 to olefins
in toluene and cyclohexane (1 mL). Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10c
(200 mg, 61%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.83
(dd, 2H, J¼5.4, 8.7 Hz), 7.76 (dd, 2H, J¼3.1, 5.4 Hz), 7.67 (dd, 2H,
J¼3.0, 5.4 Hz), 7.01 (t, 2H, J¼8.6 Hz), 4.63 (s, 1H), 4.27 (m, 1H), 3.07
(s, 2H), 2.88 (m, 2H), 2.48 (m, 1H), 2.14 (m, 2H), 1.78 (ddd, 1H, J¼5.4,
10.6, 19.5 Hz), 1.36 (m, 2H), 1.36 (s, 9H). 13C NMR (100.6 MHz,
CDCl3): 197.30, 168.64, 165.71 (d, J¼254.7 Hz), 155.94 (br s), 134.07,
133.15 (d, J¼3.0 Hz), 131.70, 130.65 (d, J¼9.3 Hz), 123.29, 115.63 (d,
J¼21.9 Hz), 79.16 (br s), 51.56, 40.08 (br s), 35.40, 29.72, 28.42, 27.32,
26.96. IR (CDCl3): nmax 2981, 2933, 1773, 1710, 1508, 1393, 1368,
1239, 1157. HRMS (EIþ): m/z calculated for C26H29O5N2F
M¼468.2060, found: 468.2055, calculated for C21H20O3N2F[MꢂC
(O)OtBu]¼367.1458, found: 367.1450.
A magnetically stirred solution of xanthate 6 (1 equiv) and
olefin (2 equiv) in 1,2-dichloroethane or ethyl acetate (1 mL/mmol
of 6) was heated at reflux for 15 min. DLP (5 mol %) was then
added and additional DLP (5 mol %) was added every 60 min until
total consumption of 6. The mixture was then cooled to room
temperature and the solvent was evaporated under reduced
pressure. AIBN was added to a soltution of the crude product of
the previous addition with tris(trimethylsilyl)silane (TTMSS,
1.5 equiv) and a 1:1 mixture of toluene and cyclohexane under
a nitrogen atmosphere. The reaction mixture was then heated to
reflux for one hour. The mixture was then cooled to room tem-
perature and the solvent was evaporated under reduced pressure.
The residue was purified by flash chromatography on silica gel to
yield the desired products 10.
2.3.4. Diethyl 2-[7-(4-Bromo-phenyl)-4-(1,3-dioxo-1,3-dihydro-iso-
indol-2-yl)-7-oxo-heptyl]-malonate (10d). Following the general
procedure, the reaction was carried out with a solution of xanthate
2.3.1. Diethyl 2-[5-(dimethoxy-phosphoryl)-2-(1,3-dioxo-1,3-dihy-
dro-isoindol-2-yl)-pentyl]-malonate (10a). Following the general
procedure, the reaction was carried out with a solution of xanthate
6e (350 mg, 0.71 mmol) and allyl ethylmalonate (285 mL,
1.42 mmol) in 1,2-dichloroethane (1.4 mL) and needed 20 mol % of
DLP to go to completion. The reduction was carried out on the crude
6b (400 mg, 0.88 mmol) and dimethyl allylphosphonate (184
mL,
product with TTMSS (323 mL, 1.06 mmol), AIBN (23 mg, 0.14 mmol)
1.76 mmol) in 1,2-dichloroethane (1.9 mL) and needed 25 mol % of
DLP to go to completion. The reduction was carried out on the crude
product with TTMSS (407 mL, 1.32 mmol), AIBN (30 mg, 0.18 mmol)
in toluene and cyclohexane (1 mL). Flash chromatography on silica
gel (ethyl acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10d
(203 mg, 50%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.80
(dd, 2H, J¼3.0, 5.5 Hz), 7.71 (dd, 2H, J¼3.1, 5.4 Hz), 7.69 (d, 2H,
J¼8.8 Hz), 7.52 (d, 2H, J¼8.6 Hz), 4.27 (ddd, 1H, J¼4.8, 9.9, 15.1 Hz),
4.16 (m, 1H), 4.13 (q, 4H, J¼7.0 Hz), 3.25 (t, 1H, J¼7.5 Hz), 2.89 (m,
2H), 2.50 (m, 1H), 2.18 (m, 2H), 1.88 (m, 4H), 1.21 (t, 3H, J¼7.1 Hz),
1.19 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3): 197.87, 169.24,
168.61, 135.43, 134.06, 131.87, 131.70, 129.55, 128.22, 123.28, 61.35,
51.82, 51.51, 35.45, 32.10, 28.33, 26.89, 24.44, 14.06. IR (CDCl3): nmax
2984, 2963, 2939, 2870, 1772, 1720, 1709, 1587, 1469, 1395, 1178,
1071, 1011. HRMS (EIþ): m/z calculated for C28H30O7NBr
M¼571.1206, found: 571.1206, calculated for C21H20O3N2F
[MꢂOEt]¼526.0865, found: 526.0850.
in toluene and cyclohexane (1.8 mL). Flash chromatography on
silica gel (ethyl acetate/petroleum ether, 8:2 to 10:0 v/v) afforded
10a (230 mg, 54%) as a pale colorless oil. 1H NMR (400 MHz, CDCl3):
7.83 (dd, 2H, J¼3.1, 5.4 Hz), 7.73 (dd, 2H, J¼3.0, 5.5 Hz), 4.21 (m, 3H),
4.01 (m, 2H), 3.69 (d, 3H, J¼3.0 Hz), 3.67 (d, 3H, J¼3.0 Hz), 3.24 (dd,
1H, J¼5.7, 9.3 Hz), 2.71 (ddd, 1H, J¼5.7, 11.1, 14.4 Hz), 2.35 (m, 1H),
2.22 (m, 1H), 1.76 (m, 3H), 1.54 (m, 2H), 1.24 (t, 3H, J¼7.1 Hz), 1.16 (t,
3H, J¼7.1 Hz). 13C NMR (100.6 MHz, CDCl3): 166.72, 168.60, 168.32,
134.14, 131.70, 123.34, 61.79, 61.65, 52.32 (d, J¼6.7 Hz), 49.53, 49.29,
33.20 (d, J¼16.5 Hz), 31.16, 24.83, 23.44, 19.46 (d, J¼4.9 Hz), 14.01,
14.94. HRMS (EIþ): m/z calculated for C22H30O9NP M¼483.1658,
found: 483.1674, calculated for C15H19O5NP[MꢂCH(CO2Et)2]¼
324.1001, found: 324.0986.
2.3.5. Acetic acid 7-[1-(2,2-dimethyl-propionyl)-1H-indol-6-yl]-4-
(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-7-oxo-heptyl ester (10e). Fol-
lowing the general procedure, the reaction was carried out with
a solution of xanthate 6i (200 mg, 0.37 mmol) and allyl acetate
2.3.2. 4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-7,7-dimethoxy-hepta-
nenitrile (10b). Following the general procedure, the reaction was
carried out with a solution of xanthate 6c (250 mg, 0.75 mmol) and
(162
20 mol % of DLP to go to completion. The reduction was carried out
on the crude product with TTMSS (171 L, 0.56 mmol), AIBN
mL, 1.49 mmol) in 1,2-dichloroethane (600 mL) and needed
acrolein dimethylacetal (265
(1.8 mL) and needed 15 mol % of DLP to go to completion. The re-
duction was carried out on the crude product with TTMSS (234 L,
mL, 2.24 mmol) in 1,2-dichloroethane
m
m
(12 mg, 0.07 mmol) in toluene and cyclohexane (1 mL). Flash
chromatography on silica gel (ethyl acetate/petroleum ether, 10:0
to 3:7 v/v) afforded 10e (132 mg, 69%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): 9.03 (s, 1H), 7.86 (d, 1H, J¼3.8 Hz), 7.82 (dd, 1H,
J¼1.5, 8.2 Hz), 7.79 (dd, 2H, J¼3.0, 5.5 Hz), 7.69 (dd, 2H, J¼3.0,
5.4 Hz), 7.54 (d, 1H, J¼8.2 Hz), 6.62 (d, 1H, J¼3.9 Hz), 4.35 (tt, 1H,
J¼4.9, 10.0 Hz), 4.05 (t, 2H, J¼6.5 Hz), 3.05 (m, 2H), 2.54 (tdd, 1H,
J¼6.7, 10.1, 13.6 Hz), 2.24 (m, 2H), 2.01 (s, 3H), 1.90 (m, 1H), 1.64 (m,
2H),1.50 (s, 9H). 13C NMR (100.6 MHz, CDCl3): 198.98,177.03,171.10,
168.65, 136.32, 133.94, 133.87, 133.14, 131.81, 128.72, 123.29, 120.48,
118.01, 108.06, 63.95, 51.56, 41.38, 35.38, 29.02, 28.68, 27.17, 25.90,
20.98. IR (CDCl3): nmax 2959, 2933,1774,1742,1713,1686,1427,1371,
1.47 mmol), AIBN (25 mg, 0.15 mmol) in toluene and cyclohexane
(1.5 mL). Flash chromatography on silica gel (ethyl acetate/petro-
leum ether, 0:10 to 3:7 v/v) afforded 10b (200 mg, 84%) as a pale
yellow oil. 1H NMR (400 MHz, CDCl3): 7.81 (dd, 2H, J¼3.0, 5.2 Hz),
7.71 (dd, 2H, J¼3.1, 5.2 Hz), 4.31 (t, 1H, J¼5.5 Hz), 4.26 (m, 1H), 3.25
(s, 3H), 3.22 (s, 3H), 2.50 (m, 1H), 2.32 (dd, 2H, J¼5.3, 7.2 Hz), 2.16
(dtd, 1H, J¼5.3, 10.4, 15.5 Hz), 2.05 (td, 1H, J¼7.1, 13.8 Hz), 1.78 (ddd,
1H, J¼5.4, 10.7, J¼19.3 Hz), 1.52 (m, 2H). 13C NMR (100.6 MHz,
CDCl3): 168.51, 134.31, 134.28, 131.55, 123.47, 118.78, 103.78, 53.22,
52.76, 50.84, 29.41, 28.18, 27.15, 14.84. IR (CDCl3): nmax 2935, 2835,
1774, 1712, 1469, 1395, 1373, 1362, 1129, 1050. HRMS (EIþ): m/z

6664
B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
1307, 1239, 1190, 1079, 1045. HRMS (EIþ): m/z calculated for
C30H32O6N2 M¼516.2260, found: 516.2275.
1771, 1709, 1468, 1438, 1396, 1372, 1200, 1172, 1088. HRMS (EIþ): m/
z calculated for C24H33O5N M¼415.2359, found: 415.2355, calcu-
lated for C22H30O4N[MꢂCOMe]¼372.2175, found: 372.2177.
2.3.6. Ethyl 6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3,11-dioxo-11-
phenyl-undecanoate (10f). Following the general procedure, the
reaction was carried out with a solution of xanthate 6j (400 mg,
0.94 mmol) and 1-phenyl-pent-4-en-1-one (454 mg, 2.83 mmol) in
1,2-dichloroethane (1 mL) and needed 20 mol % of DLP to go to
completion. The reduction was carried out on the crude product
2.3.9. 2-[4-Oxo-4-(2-oxo-oxazolidin-3-yl)-1-(3-1,2,4-triazol-1-yl-
propyl)-butyl]-isoindole-1,3-dione (10i). Following the general
procedure, the reaction was carried out with a solution of xanthate
6p (141 mg, 0.33 mmol) and allyl triazole (73 mg, 0.67 mmol) in
1,2-dichloroethane (600
completion. The reduction was carried out on the crude product
with TTMSS (153 L, 0.50 mmol), AIBN (11 mg, 0.07 mmol) in tol-
mL) and needed 10 mol % of DLP to go to
with TTMSS (435 mL, 1.41 mmol), AIBN (28 mg, 0.18 mmol) in tolu-
ene and cyclohexane (2 mL). Flash chromatography on silica gel
(ethyl acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10f
(300 mg, 71%) as a paleyellowoil.1H NMR (400 MHz, CDCl3): 7.89 (d,
2H, J¼7.2 Hz), 7.81 (dd, 2H, J¼3.0, 5.3 Hz), 7.71 (dd, 2H, J¼3.0, 5.3 Hz),
7.52 (t, 1H, J¼7.3 Hz), 7.42 (dd, 2H, J¼7.3 Hz), 4.13 (m, 1H), 4.12 (m,
2H), 3.36 (s, 2H), 2.90 (t, 2H, J¼7.2 Hz), 2.50 (m, 2H), 2.33 (m, 1H),
2.25e1.95 (m, 2H), 1.72 (m, 3H), 1.27 (m, 2H), 1.14 (m, 3H). 13C NMR
(100.6 MHz, CDCl3): 201.66, 199.90, 168.63, 166.99, 136.90, 134.07,
134.03, 132.91, 131.66, 128.54, 127.98, 123.23, 61.31, 51.34, 49.27,
39.86, 38.27, 32.18, 26.28, 28.11, 23.75, 14.05. IR (CDCl3): nmax 2934,
2862,1772,1709,1686,1469,1372,1332,1248,1181,1115,1028. HRMS
(EIþ): m/z calculated for C27H29O6N M¼463.1995, found: 463.1997,
calculated for C25H24O5N [MꢂOEt]¼418.1654, found: 418.1656.
m
uene and cyclohexane (1 mL). Flash chromatography on silica gel
(ethyl acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10i (99 mg,
73%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 8.04 (s, 1H),
7.89 (s, 1H), 7.81 (dd, 2H, J¼3.0, 5.4 Hz), 7.72 (dd, 2H, J¼3.1, 5.4 Hz),
4.38 (m, 2H), 4.29 (m, 1H), 4.17 (t, 2H, J¼7.0 Hz), 3.98 (m, 2H), 2.96
(ddd, 1H, J¼6.8, 8.4, 16.8 Hz), 2.80 (td, 1H, J¼6.1, 17.5 Hz), 2.40 (m,
1H), 2.15 (m, 2H), 1.85 (m, 2H), 1.74 (m, 1H). 13C NMR (100.6 MHz,
CDCl3): 172.30, 168.70, 152.10, 143.04, 134.22, 131.60, 123.38, 62.15,
48.83, 42.52, 31.62, 29.07, 26.85, 26.81. IR (CDCl3): nmax 2254, 1781,
1709, 1389, 1373, 1334, 1275, 1224, 1112, 1088. HRMS (EIþ): m/z
calculated for C20H21O5N5 M¼411.1543, found: 411.1550, calculated
for C17H17O3N4 [M-C(O)OC2H4N]¼325.1301, found: 325.1303.
2.3.7. 2-[3-Dimethoxymethyl-4-oxo-1-(3-trimethylsilanylpropyl)-
pentyl]-isoindole-1,3-dione (10g). Following the general procedure,
the reaction was carried out with a solution of xanthate 6m
(300 mg, 0.74 mmol) and allyl trimethylsilane (234 mL, 1.47 mmol)
in 1,2-dichloroethane (1.5 mL) and needed 15 mol % of DLP to go to
completion. The reduction was carried out on the crude product
2.3.10. [3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-5-(methoxy-methyl-
carbamoyl)-hexyl]-phosphonic acid dimethyl ester (10j). Following
the general procedure, the reaction was carried out with a solution of
xanthate 6q (300 mg, 0.76 mmol) and dimethyl vinylphosphonate
(206 mg, 1.51 mmol) in 1,2-dichloroethane (1 mL) and needed
25 mol % of DLP to go to completion. The reduction was carried out
with TTMSS (342
mL, 1.11 mmol), AIBN (24 mg, 0.15 mmol) in tolu-
on the crude product with TTMSS (340 mL, 1.10 mmol), AIBN (24 mg,
ene and cyclohexane (2 mL). Flash chromatography on silica gel
(ethyl acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10g
(240 mg, 77%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): Di-
astereoisomer 1: 7.80 (dd, 2H, J¼3.1, 5.5 Hz), 7.70 (dd, 2H, J¼3.1,
5.4 Hz), 4.23 (d, 1H, J¼7.7 Hz), 4.20 (m, 1H), 3.23 (s, 3H), 3.18 (s, 3H),
2.76 (ddd, 1H, J¼2.7, 7.8 Hz, J¼10.9 Hz), 2.34 (ddd, 1H, J¼2.8, 11.9,
14.4 Hz), 2.14 (s, 3H), 2.05 (m, 1H), 1.90 (td, 1H, J¼4.5, 14.5 Hz), 1.64
(m, 1H), 1.16 (m, 2H), 0.42 (m, 2H), ꢂ0.15 (s, 9H). Diastereoisomer 2:
7.77 (dd, 2H, J¼3.5, 5.9 Hz), 7.67 (dd, 2H, J¼3.0, 5.5 Hz), 4.30 (d, 1H,
J¼7.5 Hz), 4.03 (m, 1H), 3.31 (s, 3H), 3.27 (s, 3H), 2.83 (m, 1H), 2.47
(m, 1H), 2.05 (m, 2H), 1.97 (s, 3H), 1.64 (m, 1H), 1.16 (m, 2H), 0.42 (m,
2H), ꢂ0.15 (s, 9H). 13C NMR (100.6 MHz, CDCl3): Diastereoisomer 1:
211.46, 170.42, 135.84, 133.43, 125.00, 107.32, 57.60, 55.60, 53.99,
52.23, 38.27, 34.23, 32.39, 22.53, 17.79, 0.00. Diastereoisomer 2:
210.29, 170.34, 135.76, 133.43, 124.91, 107.32, 57.17, 55.11, 53.99,
51.25, 37.91, 32.06, 25.19, 22.53, 17.79, 0.00. IR (CDCl3): nmax 2955,
2837,1772,1709,1393,1373,1360,1248,1118,1070. HRMS (EIþ): m/z
calculated for C22H33O5NSi M¼419.2128, found: 419.2134, calcu-
lated for C21H30O5NSi[MꢂMe]¼404.1893, found: 404.1875.
0.14 mmol) in toluene and cyclohexane (1.4 mL). Flash chromatog-
raphy on silica gel (ethyl acetate/petroleum ether, 10:0 to 3:7 v/v)
afforded 10j (180 mg, 58%) as a pale yellow oil. 1H NMR (400 MHz,
CDCl3): Diastereoisomer 1: 7.76 (m, 2H), 7.67 (dd, 2H, J¼3.3, 5.3 Hz),
4.06 (m, 1H), 3.64 (m, 6H), 3.34 (s, 3H), 3.07 (s, 3H), 2.72 (m,1H), 2.34
(m, 1H), 2.22 (m, 1H), 2.06 (m, 1H), 1.95 (m, 1H), 1.63 (m, 2H), 1.04 (d,
3H, J¼6.9 Hz). Diastereoisomer 1: 7.76 (m, 2H), 7.68 (dd, 2H, J¼3.3,
5.2 Hz), 4.21 (ddd, 1H, J¼4.6, 10.1, 15.0 Hz), 3.64 (m, 6H), 3.42 (s, 3H),
2.87 (s, 3H), 2.72 (m, 1H), 2.52 (ddd, 1H, J¼6.5, 10.7, 14.1 Hz), 2.22 (m,
2H), 1.95 (m, 1H), 1.63 (m, 2H), 1.07 (d, 3H, J¼6.8 Hz). 13C NMR
(100.6 MHz, CDCl3): Diastereoisomer 1: 169.05, 134.62, 132.26,
123.69, 61.77, 52.96 (br s), 51.42, 51.29, 36.07, 32.87, 26.48, 26.23,
23.32, 21.90, 17.66. Diastereoisomer 1: 168.91, 134.66, 132.26, 123.72,
61.66, 52.96 (br s), 51.23, 51.10, 36.21, 33.59, 26.44, 26.19, 23.32, 21.90,
18.94. IR (CDCl3): nmax 2955, 2940, 2853, 1773, 1744,1709, 1651, 1469,
1392, 1373, 1250, 1182, 1063, 103. HRMS (EIþ): m/z calculated for
C18H25O7N2P [MHþꢂCH3]¼412.1399, found: 412.1410, calculated for
C16H19O6N2P[MHþꢂ2CH3ꢂCH2O]¼366.0981, found: 366.0961.
2.3.11. S-{5-[3-Cyano-1-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3,3-
dimethyl-propyl]-2-oxo-[1,3]dioxolan-4-yl}-O-ethyl dithiocarbonate
(11). The reaction was run with xanthate 6a (0.29 mmol) and vi-
nylidene carbonate (1.16 mmol) in ethyl acetate (0.3 mL). The re-
action was completed after addition of 30 mol % of DLP. After
evaporation of the solvent, the residue was purified by chroma-
tography on silica gel using a gradient (petroleum ether/ethyl ac-
etate: 7/3) and the addition product was isolated as a glass in 59%
yield and as a mixture of diastereoisomers in a 1:1 ratio. 1H NMR
(400 MHz, CDCl3): 7.92 (m, 2H), 7.80 (m, 2H), 6.40, 6.30 (two d, 1H,
J¼5.5, 6.0 Hz), 5.31, 5.26 (two dd,1H, J¼6.0, 9.9, 5.5, 8.5 Hz), 4.78 (m,
2H), 4.52 (m, 1H), 2.95, 2.90 (two dd, 1H, J¼11.9 Hz, J¼14.7 Hz,
J¼11.6 Hz, J¼14.8 Hz), 1.96, 1.60 (two dd, 1H, J¼2.5, 14.8 Hz, J¼2.1,
14.8 Hz), 1.52, 1.35 (two t, 3H, J¼7.1 Hz), 1.50, 1.48, 1.45, 1.43 (4s, 6H).
13C NMR (100.6 MHz, CDCl3): 206.6, 205.8, 168.2 (br s), 151.8, 151.6,
134.8, 134.7, 131.3 (br s), 124.0 (br s), 123.7, 123.4, 85.5, 85.3, 78.8,
2.3.8. Methyl 12-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-15-oxo-hex-
adecanoate (10h). Following the general procedure, the reaction
was carried out with a solution of xanthate 6o (100 mg, 0.31 mmol)
and methyl 10-undecenoate (140
chloroethane (600 L) and needed 10 mol % of DLP to go to com-
pletion. The reduction was carried out on the crude product with
TTMSS (143 L, 0.47 mmol), AIBN (10 mg, 0.06 mmol) in toluene
mL, 0.62 mmol) in 1,2-di-
m
m
and cyclohexane (1 mL). Flash chromatography on silica gel (ethyl
acetate/petroleum ether, 10:0 to 3:7 v/v) afforded 10h (93 mg, 70%)
as a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.81 (dd, 2H, J¼3.0,
5.4 Hz), 7.70 (dd, 2H, J¼3.1, 5.3 Hz), 4.15 (m, 1H), 3.63 (s, 1H), 2.38
(m, 1H), 2.27 (m, 3H), 2.02 (s, 3H), 1.70 (s, 1H), 1.56 (m, 3H), 1.22 (m,
16H). 13C NMR (100.6 MHz, CDCl3): 174.37, 168.75, 134.01, 131.76,
123.23, 51.79, 51.47, 40.60, 34.14, 32.37, 29.99, 29.45, 29.41, 29.37,
29.22, 29.20, 29.15, 26.60, 26.41, 24.98. IR (CDCl3): nmax 2930, 2857,

B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
6665
77.1, 71.8, 71.4, 49.85, 49.84, 37.8, 36.5, 30.0, 29.5, 28.9, 28.4, 25.5,
25.0, 13.7, 13.4. IR (CDCl3): nmax 2237, 1839, 1778, 1721, 1375, 1244,
1049. HRMS (EIþ): m/z calculated for C20H20N2O6S2: 448.0763,
found: 448.0769, calculated for C17H15N2O5 [MꢂSCSOCH2CH3]:
327.0981, found: 327.0984.
of the solvent, the residue was purified by chromatography on silica
gel using a gradient (petroleum ether/ethyl acetate:1/1) and the
reduced product 14 was isolated as an oil in 78% yield and as about
1:1 mixture of two diastereoisomers.1H NMR (400 MHz, CDCl3) 7.87
(dd, 2H, J¼2.9, 5.1 Hz), 7.76 (m, 2H), 5.32 (m, 0.45H), 5.23 (q, 0.5H,
J¼7.7 Hz), 4.69 (m, 0.5H), 4.60 (m,1H), 4.46 (t, 0.45H, J¼8.4 Hz), 4.37
(m, 0.5H), 4.14 (dd, 0.45H, J¼6.6, 8.9 Hz), 2.82 (q,1H, J¼12.6 Hz),1.94
(dd,1H, J¼2.3,14.8 Hz),1.47,1.43 (overlapping ddþs, 3.5H, J¼2.1 Hz),
1.40 (s, 1.5H), 1.39 (s, 1.5H). 13C NMR (100 MHz, CDCl3) 168.3 (br s),
153.9, 153.7, 134.9, 134.7, 131.4, 131.2, 123.9 (br s), 123.6, 75.2, 74.4,
67.2, 67.0, 49.9, 49.4, 38.2, 36.2, 29.9; 29.4, 28.9, 28.3, 25.4, 24.8. MS
(CI, NH3) 329 (MH)þ, 346 (MHþNH3)þ. HRMS (EIþ): m/z calculated
for C17H16N2O5 328.10592, found: 328.10590.
2.3.12. S-(2-{5-[2-Cyano-1-(1,3-dioxo-indan-2-yl)-2,2-dimethyl-
ethyl]-2-oxo-[1,3]dioxolan-4-yl}-1-(trimethylsilanylmethyl)-ethyl)-
O-ethyl dithiocarbonate (12). The reaction was run with xanthate 11
(0.145 mmol) and allyl trimethylsilane (4 equiv, 0.58 mmol) in ethyl
acetate (0.5 mL). The reaction was complete after addition of 20 mol
% of DLP. After evaporation of the solvent, the residue was purified by
chromatography on silica gel using a gradient (petroleum ether/ethyl
acetate:8/2) and the addition product 12 was isolated as a colorless
oil in 60% yield.1H NMR (400 MHz, CDCl3): 7.87 (m, 2H), 7.76 (m, 2H),
4.88 (m, 1H), 4.76e4.45 (m, 3H), 4.38, 4.22, 3.96, 3.76 (4 m, 1H), 2.80
(m, 1H), 2.29e1.76 (5 m, 3H), 1.45e0.8 (m, 12H), 0.10, 0.09, ꢂ0.018
(3s, 9H). 13C NMR (100.6 MHz, CDCl3): 213.1, 212.9, 212.3, 168.3 168.2
(br s), 153.1, 153.0, 152.9, 152.8, 134.8, 134.7, 134.6, 131.5, 131.4, 124.1,
123.4, 123.9, 123.8, 79.6, 79.4, 78.8, 78.74, 78.71, 78.5, 77.7, 77.2, 70.3,
70.2, 69.9, 69.7, 50.1, 50.07, 49.97, 49.91, 45.5, 45.0, 44.9, 44.6, 44.2,
43.9, 41.6, 41.0, 38.4, 38.1, 36.57, 36.3, 29.9, 29.7, 29.46, 29.43, 29.0,
28.7, 28.4, 25.5, 25.4, 24.9, 23.6, 23.5, 21.6, 21.3,13.9,13.8,13.79,13.71,
ꢂ0.63, ꢂ0.72, ꢂ0.79. IR (CDCl3): nmax 2237, 1839, 1778, 1721, 1375,
1244, 1049. HRMS (EIþ): m/z calculated for C23H29N2O5Si
[MꢂSCSOCH2CH3]: 441.1846, found: 441.1844.
2.3.15. 2-(7-Fluoro-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-iso-
indole-1,3-dione (15). A magnetically stirred solution of xanthate 6d
(450 mg, 1.04 mmol) in 1,2-dichloroethane (10 mL) was refluxed for
15 min. DLP (20 mol %) was then added and additional DLP (20 mol %)
was added every 60 min until total consumption of 6d. The mixture
wasthencooled toroomtemperatureandthesolventwasevaporated
under reduced pressure. Flash chromatography on silica gel (ethyl
acetate/petroleum ether, 8:2 to 6:4 v/v) afforded 15 (61 mg, 19%). 1H
NMR(400 MHz,CDCl3):8.16(dd,1H, J¼8.6,6.0 Hz), 7.91(dd,2H, J¼5.1,
3.0 Hz), 7.8 (dd, 2H, J¼5.2, 3.0 Hz), 7.07 (dt,1H, J¼8.6, 2.3 Hz), 6.73 (dd,
1H, J¼9.2,1.2 Hz), 5.71(dd,1H, J¼10.9,4.2 Hz),2.96e2.91(m, 2H), 2.74
(ddd, 1H, J¼17.2, 13.8, 4.6 Hz), 2.30 (ddd, 1H, J¼13.3, 9.1, 4.5 Hz). 13C
NMR (100.6 MHz, CDCl3): 194.6,167.6,166.2 (d, J¼254.7 Hz),144.4 (d,
J¼8.3 Hz), 134.5, 131.7, 131.1 (d, J¼9.7 Hz), 129.0 (d, J¼2.5 Hz), 123.8,
115.6 (d, J¼21.8 Hz),112.2 (d, J¼22.9 Hz), 48.7, 37.5, 27.6. IR(CCl4):nmax
2927, 2854, 1779, 1720, 1695, 1383, 1368, 1264.
2.3.13. 4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-{5-[3-(ethyl-di-
methyl-silanyl)-propyl]-2-oxo-[1,3]dioxolan-4-yl}-2,2-dimethyl-bu-
tyronitrile (13). The reaction was run with xanthate 11 (1.27 mmol)
and allyl trimethylsilane (3 equiv, 0.6 mL) in ethyl acetate (1.27 mL).
The reaction was completed after addition of 10 mol % of DLP. After
evaporation of the solvent, the residue was taken up in a 1:1 mixture
of toluene/cyclohexane (10 mL) and tris(trimethylsilyl)silane
(1.5 equiv, 0.6 mL) and AIBN (0.25 mmol, 41 mg) was added. The
resulting mixture was refluxed under nitrogen until consumption of
the starting xanthate. After evaporation of the solvent, the residue
was purified by chromatography on silica gel using a gradient (pe-
troleum ether/ethyl acetate:8/2) and the reduced product 13 was
isolated in 50% yield over two steps and as about 1:1 mixture of two
diastereoisomers. A pure fraction of each diastereoisomer was iso-
lated and characterized. Less polar diastereioisomer: 1H NMR
(400 MHz, CDCl3): 7.86 (dd, 2H, J¼3.0, 5.4 Hz), 7.74 (dd, 2H, J¼3.0,
5.4 Hz), 4.76 (dd, 1H, J¼4.9, 8.2 Hz), 4.61 (m, 1H), 4.52 (m, 1H), 2.83
(dd, 1H, J¼11.7, 14.5 Hz), 1.81 (m, 1H), 1.72 (m, 1H), 1.51 (m, 2H), 1.46
(dd,1H, J¼1.9,14.6 Hz),1.42 (s, 3H),1.38 (s, 3H), 0.53 (m, 2H), ꢂ0.02 (s,
9H).13CNMR(100.6 MHz,CDCl3): 13CNMR(100 MHz, CDCl3)168.3(br
s), 153.4, 134.6, 131.4, 123.8 (br s), 123.5 (br s), 79.7, 79.1, 49.6, 38.6,
36.2, 29.9, 29.7, 28.3, 25.4,19.2,16.2,ꢂ1.7. Morepolardiastereoisomer:
7.86 (m, 2H), 7.77 (dd, 2H, J¼5.81, 3.33 Hz), 4.87 (dd, 1H, J¼5.05 Hz),
4.53 (dt, 1H, J¼10.99, 2.27 Hz), 4.30 (dt,1H, J¼5.81, 7.68 Hz), 2.85 (dd,
1H, J¼14.65,12.13 Hz),1.91(dd,1H, J¼14.65, 2.27 Hz),1.69(m,1H),1.41
(s, 3H),1.40(s, 3H),1.25(m,1H),0.86(m,1H),0.33(m,1H),0.19(m,1H),
0.12 (m, 1H), 0.00 (s, 9H). More polar diastereoisomer: 170.41 (br s),
155.42, 136.84, 133.18 (br s), 125.84 (br s), 81.59, 80.33, 51.94, 40.16,
39.77, 31.40, 30.97, 26.86, 20.66, 18.06, 0.00. IR (CDCl3): nmax 2955,
1806(br), 1717, 1384, 1367, 1185. HRMS (EIþ): m/z calculated for
C23H30N2O5Si 442.1924, found: 442.1920.
2.3.16. 2-(7-Oxo-4,5,6,7-tetrahydro-benzo[b]thiophen-4-yl)-iso-
indole-1,3-dione (16). A magnetically stirred solution of xanthate 6i
(120 mg, 0.29 mmol) in 1,2-dichloroethane (3 mL) was refluxed for
15 min. DLP (20 mol %) was then added and additional DLP (20 mol
%) was added every 60 min until total consumption of 6i. The
mixture was then cooled to room temperature and the solvent was
evaporated under reduced pressure. Flash chromatography on sil-
ica gel (ethyl acetate/petroleum ether, 8:2 to 6:4 v/v) afforded 16
(70 mg, 81%). 1H NMR (400 MHz, CDCl3): 7.86 (dd, 2H, J¼3.1,
5.4 Hz), 7.76 (dd, 2H, J¼3.0, 5.5 Hz), 7.59 (d, 1H, J¼5.0 Hz), 6.78 (d,
1H, J¼5.0 Hz), 5.66 (dd, 1H, J¼5.0, 10.9 Hz), 2.93 (m, 1H), 2.73 (m,
1H), 2.31 (m, 2H). 13C NMR (100.6 MHz, CDCl3): 190.46, 171.19,
167.56, 149.45, 137.17, 134.52, 134.46, 131.71, 125.94, 123.66, 47.30,
37.56, 29.14. IR (CDCl3): nmax 2961, 2929, 1779, 1716, 1665, 1425,
1383, 1363, 1329, 1292, 1110. HRMS (EIþ): m/z calculated for
C16H11NO3S: 297.0460, found: 297.0464.
2.3.17. 2-[2-(5-Oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)-
ethyl]-isoindole-1,3-dione (17). The reduction was carried out on 6h
(400 mg, 0.91 mmol) with TTMSS (421 mL, 1.37 mmol), AIBN
(30 mg, 0.18 mmol) in toluene and cyclohexane (1.8 mL). Flash
chromatography on silica gel (ethyl acetate/petroleum ether, 10:0
to 3:7 v/v) afforded the desired intermediate 17 (256 mg, 88%) as
a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.81 (dd, 2H, J¼3.0,
5.4 Hz), 7.69 (dd, 2H, J¼3.0, 5.4 Hz), 7.60 (dd, 1H, J¼0.8, 7.6 Hz), 7.36
(dt, 1H, J¼1.2, 7.4 Hz), 7.24 (m, 1H), 7.19 (d, 1H, J¼7.5 Hz), 3.75 (m,
2H), 2.95 (m, 3H), 2.36 (qd, 1H, J¼7.2, 14.2 Hz), 2.10 (m, 2H), 1.82 (dt,
1H, J¼6.4, 12.8 Hz), 1.64 (m, 2H). 13C NMR (100.6 MHz,
CDCl3):205.96,168.35,133.89,131.29,129.90,128.62,126.35,123.25,
47.35, 36.15, 33.81, 30.57, 30.05, 25.58. IR (CDCl3): nmax 2941, 2867,
1773, 1712, 1682, 1441, 1397, 1360, 1078. HRMS (EIþ): m/z calculated
for C21H19NO3: 333.1365, found: 333.1366.
2.3.14. 4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2,2-dimethyl-4-(2-
oxo-[1,3]dioxolan-4-yl)-butyronitrile (14). A solution of xanthate 11
(0.21 mmol) in a 1:1 mixture of toluene/cyclohexane (2 mL) were
added tris(trimethylsilyl)silane (0.42 mmol, 0.133 mL) and AIBN
(0.042 mmol, 7 mg). The resulting mixture was refluxed under ni-
trogen until consumption of the starting xanthate. After evaporation
2.3.18. 2,3,3a,4,5,6-Hexahydrobenzo[6,7]cyclohepta[1,2-b]pyrrole
(18). A solution of 17 (200 mg, 0.63 mmol) and methylamine (33%

6666
B. Quiclet-Sire et al. / Tetrahedron 66 (2010) 6656e6666
in ethanol, 1.5 mL) in ethanol (1.5 mL) was stirred at room tem-
perature for 12 h. The solvent was evaporated under reduced
pressure and the residue was purified by flash chromatography on
silica gel (ethyl acetate/petroleum ether, 8:2 to 2:8 v/v) afforded 18
(90 mg, 72%) contaminated by 12% of N-methylphthalimide as
a pale yellow oil. 1H NMR (400 MHz, CDCl3): 7.74 (dd, 1H, J¼1.1,
7.5 Hz), 7.26 (dt, 1H, J¼1.4, 7.3 Hz), 7.21 (dt, 1H, J¼1.1, 7.4 Hz), 7.12 (d,
1H, J¼7.3 Hz), 3.99 (m, 1H), 3.84 (m, 1H), 2.97 (ddd, 2H, J¼3.1, 9.4,
13.1 Hz), 2.73 (ddd, 1H, J¼2.9, 7.7 Hz, J¼14.8 Hz), 2.25 (dtd, 1H,
J¼5.9, 8.6, 14.4 Hz), 2.00 (m, 1H), 1.85 (m, 2H), 1.64 (tdd, 1H, J¼5.2,
5.9, 10.3 Hz), 1.56 (ddd, 1H, J¼3.0, 5.7 Hz, J¼13.0 Hz). 13C NMR
(100.6 MHz, CDCl3):179.43, 141.18, 135.58, 133.90, 129.88, 129.75,
128.84, 126.37, 123.20, 58.80, 48.98, 35.23, 32.17, 32.07, 26.22. IR
(CDCl3): nmax 2933, 2864, 1710, 1450, 1353, 1224. HRMS (EIþ): m/z
calculated for C13H14N MꢂHþ¼184.1126, found: 184.1121.
methylamine (33% in ethanol, 1.4 mL) in ethanol (1.4 mL) was stir-
red at room temperature for 5 h. The solvent was evaporated under
reduced pressure and the residue was purified by flash chroma-
tography on silica gel (ethyl acetate/petroleum ether, 10:2 to 7:3 v/
v) afforded 20 (200 mg, 100%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): 8.02 (s, 1H), 7.95 (d, 2H, J¼7.6 Hz), 7.56 (t, 1H,
J¼7.3 Hz), 7.46 (t, 2H, J¼7.6 Hz), 4.48 (s, 1H), 4.10 (q, 2H, J¼7.1 Hz),
3.76 (m, 1H), 2.99 (t, 2H, J¼7.3 Hz), 2.58 (m, 2H), 2.10 (m, 1H), 1.77
(m, 2H), 1.51 (m, 5H), 1.25 (t, 3H, J¼7.1 Hz). 13C NMR (100.6 MHz,
CDCl3): 200.03, 170.83, 165.92, 137.02, 133.02, 128.64, 128.06, 59.56,
58.45, 38.36, 36.21, 31.87, 28.37, 26.18, 24.15, 14.77. IR (CDCl3): nmax
2980, 2935, 2862, 1682, 1652, 1592, 1449, 1295, 1241, 1151, 1049.
HRMS (EIþ): m/z calculated for C19H25O3N M¼315.1834, found:
315.1835.
Acknowledgements
2.3.19. tert-Butyl {3-[5-(4-fluoro-phenyl)-3,4-dihydro-2H-pyrrol-2-
yl]-propyl}-carbamate (19). A solution of 10c (85 mg, 0.18 mmol)
and methylamine (33% in ethanol, 400 mL) in ethanol (400 mL) was
One of us (GR) thanks Ecole Polytechnique for a scholarship.
stirred at room temperature for 5 h. The solvent was evaporated
under reduced pressure and the residue was purified by flash
chromatography on silica gel (ethyl acetate/petroleum ether, 10:0
to 7:3 v/v) afforded 19 (55 mg, 95%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): 7.83 (dd, 2H, J¼5.5, 8.7 Hz), 7.08 (t, 2H, J¼8.7 Hz),
5.07 (br s, 1H), 4.15 (m, 1H), 3.19 (m, 2H), 3.00 (m, 1H), 2.85 (m, 1H),
2.22 (m, 1H), 1.70 (m, 3H), 1.59 (m, 2H), 1.44 (s, 9H). 13C NMR
(100.6 MHz, CDCl3): 171.03, 164.20 (d, J¼250.5 Hz), 156.12, 130.92
(d, J¼2.3 Hz), 129.76 (d, J¼8.5 Hz), 115.43 (d, J¼21.7 Hz), 78.97 (br s),
72.99, 40.82, 35.11, 34.16, 28.99, 28.52, 27.37. IR (CDCl3): nmax 2931,
2868, 1706, 1602, 1510, 1367, 1235, 1168, 1157. HRMS (EIþ): m/z
calculated for C18H25O2N2F M¼320.1900, found: 320.1907.
References and notes
1. Quiclet-Sire, B.; Zard, S. Z. Org. Lett. 2008, 10, 3279.
2. For reviews of the xanthate transfer chemistry, see: (a) Zard, S. Z. Angew. Chem.,
Int. Ed. 1997, 36, 672; (b) Zard, S. Z. In Radicals in Organic Synthesis; Renaud, P.,
Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, p 90; (c) Quiclet-Sire, B.;
Zard, S. Z. Chem.dEur. J. 2006, 12, 6002; (d) Quiclet-Sire, B.; Zard, S. Z. Top. Curr.
Chem. 2006, 264, 201; (e) Zard, S. Z. Org. Biomol. Chem. 2007, 5, 205.
3. (a) Lebreux, F.; Quiclet-Sire, B.; Zard, S. Z. Org. Lett. 2009, 11, 2844; (b) Quiclet-
Sire, B.; Revol, G.; Zard, S. Z. Org. Lett. 2009, 11, 3554.
4. N-Vinyl phthalimide has recently been polymerized using xanthates by what is
now called the RAFT/MADIX process: Maki, Y.; Mori, H.; Endo, T. Macromol.
Chem. Phys. 2007, 208, 2589.
5. (a) Bouhadir, G.; Legrand, N.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett. 1999,
40, 277; (b) Thang, S. H.; Chong, Y. K.; Mayadunne, R. T. A.; Moad, G.; Rizzardo, E.
Tetrahedron Lett. 1999, 40, 2435.
2.3.20. Ethyl [5-(5-oxo-5-phenyl-pentyl)-pyrrolidin-(2Z)-ylidene]-
6. For a more complete discussion of this point, see Ref. 2.
acetate (20). A solution of 10f (300 mg, 0.65 mmol) and
7. Chatgilialoglu, C. Chem. Rev. 1995, 95, 1229.