Intramolecular homolytic substitution at the sulfur atom: an alternative way to generate phosphorus- and sulfur-centered radicals

Article abstract of DOI:10.1016/j.tet.2008.08.108

Two efficient procedures involving tin hydride or thiophenol-mediated intramolecular homolytic substitution at the sulfur atom are reported. They lead to the generation of varied P(V)-centered radicals from the corresponding aryl or alkyne thiophosphorus substrates. The radical formed can be trapped by an olefin via an intermolecular addition, leading to the construction of C-P bonds. Thiophosphination of triple bonds was also achieved using a radical cycloisomerization process. Extension of the methodology to sulfur-containing species was examined.

Full text of DOI:10.1016/j.tet.2008.08.108

Tetrahedron 64 (2008) 11865–11875
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Intramolecular homolytic substitution at the sulfur atom: an alternative way
to generate phosphorus- and sulfur-centered radicals
*
Paola Carta, Nicolas Puljic, Carine Robert, Anne-Lise Dhimane, Cyril Ollivier, Louis Fensterbank ,
*
*
ˆ
Emmanuel Lacote , Max Malacria
´
UPMC Univ Paris 06, Laboratoire de Chimie Organique (UMR CNRS 7611), Institut de chimie moleculaire (FR 2769), 4 place Jussieu, C. 229, 75005 Paris, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 July 2008
Accepted 29 August 2008
Available online 20 September 2008
Two efficient procedures involving tin hydride or thiophenol-mediated intramolecular homolytic sub-
stitution at the sulfur atom are reported. They lead to the generation of varied P(V)-centered radicals
from the corresponding aryl or alkyne thiophosphorus substrates. The radical formed can be trapped by
an olefin via an intermolecular addition, leading to the construction of C–P bonds. Thiophosphination of
triple bonds was also achieved using a radical cycloisomerization process. Extension of the methodology
to sulfur-containing species was examined.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Among the challenges we have faced to avoid the generation of
mixtures of compounds, three issues were especially trying. Design
The discovery of new, mild, and reliable methods for the con-
struction of carbon–heteroatom bonds is still an essential objective
for today’s organic chemists.1 Indeed, heteroatoms are first-rate
assets to modulate the properties of matter and/or to lead to mo-
lecular recognition. Nature has made abundant use of this oppor-
tunity. Thus, the periodic table offers significant opportunities to go
beyond naturally occurring structures and chemical functions. But
heavier elements have unique properties that are still not fully
explored and that one needs to master in order to devise efficient
methodologies leading to new motifs.
For the last decade, we have been involved in designing new
radical processes in which heteroatom-centered radicals play
a key-role. This has led us to investigate homolytic substitutions to
construct C–P bonds.2 In this article, we wish to give a full account
of this work, including an overview of its genesis.
of a successful asymmetric process requires a subtle yet strong
master plan, an efficient termination, and a source of chiral
information.
Tuning the different features of radical reactions allowed us to
introduce reactions previously considered to be forbidden (or very
rare), such as the 5-endo-trig7 and 4-exo-dig8 radical cyclizations,
and the 1,4-H translocation.9 Our take on the two other issues led
us to consider heteroatom-based processes. For example, b-elimi-
nation of a sulfonyl radical led to the triquinane framework in high
yields, a process that introduced five C–C bonds and five stereo-
genic elementsd including four quaternary carbonsdin one single
step (Scheme 1).10 On the other hand, chiral sulfoxides were our
entry point into asymmetric radical synthesis.11
Bu3SnH
AIBN cat.
90:10
1.1. Background of the present work
CN
CN
PhH, Δ
Following Julia’s,3 Stork’s,4 and Curran’s5 seminal contributions
to radical cascades, our group has been originally attracted by the
great potential those bio-inspired processes offer to organic syn-
thesis.6 We wished to use Nature’s lead to control reactivity toward
one pot assembly of enantiopure complex molecules from simple,
acyclic, achiral building-blocks.
Si
O
SO2Ph
O
Si
SO2Ph
50%
TMS
Br
TMS
CN
Si
O
* Corresponding authors. Tel.: þ33 1 44 27 70 68; fax: þ33 1 44 27 73 60 (L.F.);
tel.: þ33 1 44 27 25 47; fax: þ33 1 44 27 73 60 (E.L.); tel.: þ33 1 44 27 35 86; fax:
þ33 1 44 27 73 60 (M.M.).
TMS
E-mail addresses: louis.fensterbank@upmc.fr (L. Fensterbank), emmanuel.
Scheme 1. Radical cascade leading to linear triquinanes.
ˆ
lacote@upmc.fr (E. Lacote), max.malacria@upmc.fr (M. Malacria).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.108

11866
P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
This led us to craft a domino process using the sulfinyl moiety as
O
S
both chiral auxiliary and terminating trigger. In the process, we
devised an asymmetric intramolecular vinylation of prochiral rad-
icals (Scheme 2). Coordination of Lewis acids to the sulfoxide led to
a complete reversal of the stereochemical outcome of the vinyl-
ation.12 This work was part of a coordinated effort with the Renaud
group, who tailored a variation on that concept in which the sulf-
oxide led to desymmetrization during a 1,5-H transfer followed by
Bu3SnH, AIBN
PhH, reflux
X = O, NH
X
X
S
I
O
Scheme 4. Homolytic substitution at oxidized sulfur.
2. Construction of carbon–phosphorus bonds
the same
b
-sulfinyl radical elimination.13
2.1. Tin hydride-mediated homolytic substitution at sulfur/
phosphorus-centered radicals addition tandem reaction
R
E
E
E
R
H
S
S+
E
Generation of a wide range of phosphorus-centered radicals has
generally relied on homolytic cleavage of P–X bonds (X¼Se, S, P), or
hydrogen abstraction from P–H systems.21–23 We reasoned that
intramolecular homolytic substitution at sulfur might be an in-
teresting alternative to access the target intermediates.19c
In 1996, Crich showed that tin-mediated aryl radical cyclizations
onto thioesters derived from (iodoaryl)-thiols led to the formation
of acyl radicals.24 Taking inspiration from this approach, we de-
cided to examine the behavior of thiosphononate analogues 1a–c
toward generating P(V)-centered radicals. Evidence for formation
of the latter was sought from intramolecular trapping experiments
with alkenes (Scheme 5).
O-
H
O
E = CO2Me
without LA
approach on the O side
99% ee (93% yield)
E
E
OMe
OMe
with bulky LA
approach on the aryl side
92% ee (52% yield)
E
E
Bu3SnH
X
Scheme 2. Asymmetric intramolecular vinylation of prochiral radicals.
AIBN cat.
R
S
S
R2P
Br
P
X
R
PhH, Δ
Z
We next tried to extend the scope of the sulfinyl induction
to the 5-endo-trig process, which led us to the accidental
discovery of the first elimination of a P(V)-centered radical,
a process formerly thought impossible.14 We have examined
this interesting reaction more in-depth, and applied it to
radical vinylations (Scheme 3).15 Others have since introduced
, then red.
Z
R
R
R
P
X
+
P
X
R
S
related Pꢀ
b
-eliminations for allylations,16 carbonylations,17 or
X = O, S; R = Ph, OEt, (N(Me)CH2)2
arylations.18
Scheme 5. Generation of P-centered radicals via intramolecular homolytic
substitution.
Ts
N
Ts
N
O
2.2. Synthesis of the substrates
Cp2TiCl2, Mn
O
THF, rt
80%
HO
P
P(O)Ph2
Radical thiophosphonate precursors 1a–c were prepared in
moderate to good yields from sodium 2-(20-bromophenyl)ethane-
thiolate by nucleophilic substitution of the corresponding chloro-
phosphonate reagent. The starting thiol was obtained following
a known procedure,24a or a modified one (see Section 5).
Ph Ph
Ts
N
HO
Scheme 3. Radical vinylation via Pꢀ
2.3. Scope of the homolytic substitution/P-centered radicals’
radical addition tandem reaction
b
-elimination.
We examined the reactivity of thiophosphonates 1a–c. These
compounds were submitted to two different sets of conditions.
Method A involved standard syringe pump addition of tributyltin
hydride (TBTH) in the presence of AIBN and an olefin in refluxing
benzene. Method B is adapted from Stork’s catalytic conditions
((Bu3SnCl, 12 mol %), NaBH4, and the olefin in refluxing t-BuOH).
We selected an array of electronically different olefins (electron-
poor, -rich, and neutral) to get more data on the reactivity of the
phosphorus-centered radical (Table 1).
When employing Method A, substrates 1a–c efficiently led to
phosphinoyl, phosphonyl, and diaminophosphonyl radicals, which
added onto alkenes in moderate to good yields. Reactivity depen-
ded on the nature of the radical formed, as well as that of the olefin.
In a typical experiment, phosphine oxide 2a was formed in 84%
from 1a and 1-octene (Table 1, entry 1). 1-Octene (10 equiv) was
Our foray into the chemistry of S- and P-centered radicals led us
to consider homolytic substitutions as a promising territory to
uncover valuable new reactions. The former are highly versatile
because they can be used both to create selected bonds, or to
generate particular radicals.19
Facile extrusion of a cheap tert-butyl radical from sulfinates and
sulfinamides delivered interesting sulfur-containing heterocycles
(Scheme 4).20 To date, this is the highest oxidation state at sulfur
compatible with the homolytic substitution mechanism. Con-
versely, homolytic substitution at the sulfur atom in thio-
phosphorus compounds led us to devise a new way to generate
phosphorus-centered radicals, which formed the basis of a recent
communication from our group.2 We report herein the full scope of
this method.

P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
11867
Table 1
PhSH
X
R2P
AIBN cat.
R
S
P
X
R
PhH, Δ
Z
X
P
R
R
P
X
Conditions
S
+
R
R
Z
, then red.
Br
Z
Z
(n equiv.)
R
P
X
R
2a-c, Z = n-Hex
3a-c, Z = CN
4a-c, Z = O-tBu
R
R
1a X = O, R = Ph
1b X = O, R = OEt
1c X = O, R = (N(Me)CH2)2
+
S
PhS
P
X
S
SPh
2–4a
Yield (%)
X = O, S; R = Ph, OEt, (N(Me)CH2)2
Entry
1
Z
n
Condition
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
n-Hex
n-Hex
CN
10
2
2
A
B
A
B
A
B
A
B
A
B
A
B
A
A
2a
2a
3a
3a
4a
4a
2b
2b
3b
4b
2c
2c
3c
4c
84
58
39
Scheme 6. Thiophenol-mediated generation of phosphorus-centered radicals.
CN
2
50
O-t-Bu
O-t-Bu
n-Hex
n-Hex
CN
O-t-Bu
n-Hex
n-Hex
CN
10
10
10
10
10
10
10
10
2
71b
47c
75
synthesized from nucleophilic substitution of the mesylate of
pentynol with the ammonium salt of O,O-diethyl thiophosphate.
The reaction required strictly degassed DMF and an inert atmo-
sphere to avoid oxidation of the P]S bond to 1e.
70
9
74d
56
10
11
12
13
15
62e
48
O
82
1. NaH, THF
2. R2P(=X)Cl
40f
SH
P
R
O-t-Bu
10
S
R
Method A: Bu3SnH (1.2 equiv) AIBN (0.25 equiv), slow addition (0.2 mmol hꢁ1),
a
PhH, reflux. Method B: Bu3SnCl (12 mol %), NaBH4, t-BuOH, reflux.
1d R = Ph, 56%
1e R = OEt, 51%
b
Adduct was contaminated by approx. 20% of an unknown by-product.
Adduct was contaminated by approx. 10% of an unknown by-product.
Approx. 50% of oligomers.
Reduced S.M. (10–30%) was also observed.
c
1f R = (N(Me)CH2)2, 42%
d
e
S
f
OEt
P
Product is not stable.
1. MsCl, Et3N
2. (EtO)2P(=S)S-, NH4
OH
+
S
OEt
1g
76%
necessary to reach optimal yield. Phosphinoyl radicals are indeed
believed to be predominantly nucleophilic.21 Our results seem to
contradict this, since diphenylphosphinoyl radical addition gave
better yields with enol ethers than with acrylonitrile (compare
entries 3 and 5). However, this reading is skewed due to poly-
merization of acrylonitrile. Indeed, we performed competition ex-
periments between acrylonitrile and tert-butyl vinyl ether, and only
isolated 3a in 28% yield, which tends to confirm that phosphinoyl
radicals were predominantly nucleophilic.
The reaction proved quite general. Thiophosphonate 1b gener-
ated phosphonyl radical leading to the corresponding adducts 2b–
4b in good yields (Table 1, entries 7, 9, and 10). Diaminophosphonyl
radicals were investigated next. These intermediates had been
overlooked in the radical literature. We were pleased to observe
addition products from substrate 1c. Diaminophosphonates 2c–4c
were isolated after standard purification but proved unstable to
even short term storage. Method B was in most cases less efficient,
as the adducts were isolated in slightly lower yields.
Scheme 7. Preparation of 1d–g.
The substrates were refluxed in toluene in the presence of PhSH,
various alkenes, and slowly added AIBN (0.15 mmol hꢁ1). Com-
pound 1d proved to be an excellent precursor of phosphine oxide
adducts. Surprisingly, access to phosphonates following this pro-
tocol was poorly efficient, while diaminophosphonyl compounds
could not be isolated pure. The methodology was then extended to
the thiophosphonates, such as 1g, which proved to be an excellent
precursor of diethoxy phosphonothioyl radicals. 2-(Phenylthio-
methylene) tetrahydrothiophene25 was isolated in all cases as a by-
product (Table 2).
Smooth addition to 1-octene occurred, while the other alkenes
reacted only moderately. Hydrothiolated by-products (thiophenol
addition with no cyclization) were also isolated in variable
amounts, depending on the nature of the starting substrate. Fi-
nally, it is worthy of note that S-pentenyl thiophosphonate 1h,
with an alkene in lieu of the alkyne did not react under our con-
ditions. This lack of reactivity can be attributed either to the
lowered bond energy of an alkyl sp3 C–S bond relative to that of
a sp2 C–S bond, or to a greater reversibility of the addition step.
Both properties are expected to diminish the efficiency of the
homolytic substitutions.
2.4. Tin-free conditions: thiophenol as mediator
The Benati/Spagnolo group developed a tin-free methodology to
generate alkyl and acyl radicals.25 It relies on addition of the ben-
zenesulfanyl radical to the triple bond of alkyl or acyl 4-pentynyl
sulfides followed by homolytic substitution of the resulting tran-
3. Bis-heterofunctionalization of unsaturations
sient b-(phenylsulfanyl)vinyl radicals at the sulfur atom, leading to
the formation of the desired radical. We thus decided to extend the
scope of this procedure to the generation of P(V)-centered radicals
(Scheme 6).
Again, S-pentynyl thiophosphonates 1d–f were easily prepared
from pent-4-yne-1-thiol and the corresponding chlorophosphonate
reagent, as previously reported for thiophosphonates 1a–c(Scheme 7).
Pent-4-yne-1-thiol was obtained by nucleophilic displacement
with cesium thioacetate followed by saponification of the in-
termediate thioacetate. S-Pentynyl thiophosphonate 1g was readily
3.1. Thiophosphorylation of triple bonds involving
a cycloisomerization reaction
P-Centered radicals are known to add to alkynes.23i We
reasoned that the absence of alkene in the previous reaction
would guide the generated radicals toward addition onto the tri-
ple bond thus leading to a cycloisomerization of the starting
material, which amounts to hetero bis-functionalization of alkynes
(Scheme 8).

11868
P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
Table 2
Table 3
X
PR2
X
PPh2
X
R2P
PhSH
AIBN
PhSH
AIBN
R2P
X
+
Z
S
S
S
Z
(n equiv.)
2a-c, Z = n-Hex, X = O
2d, Z = n-Hex, X = S
3a-c, Z = CN, X = O
3d, Z = CN, X = S
4a-c, Z = O-tBu, X = O
4d, Z = O-tBu, X = S
1d X = O, R = Ph
5a X = O, R = Ph
1d X = O,R = Ph
1e X = O, R = OEt
5b X = O, R = OEt
5c X = O, R = (N(Me)CH2)2
5d X = S, R = OEt
1e X = O, R = OEt
1f X = O,R = (N(Me)CH2)2
1g X = S, R = OEt
1f X = O, R = (N(Me)CH2)2
1g X = S, R = OEt
Entry
1
PhSH (equiv)
5a
Yield (%)
E/Z
Entry
1
Z
n
2–4a
Yield (%)
1
2
3
4
5
6
7
8
1d
1d
1e
1e
1f
1f
1g
1g
1.1
0.4
1.1
0.4
1.1
0.4
1.1
0.4
5a
5a
5b
5b
5c
5c
5d
5d
72
72
3:7
3:7
d
1
2
3
4
5
7
8
9
10
11
12
15
1d
1d
1d
1d
1e
1e
1f
1f
1f
1g
1g
1g
n-Hex
n-Hex
CN
O-t-Bu
n-Hex
n-Hex
n-Hex
CN
10
2
2
5
10
2
10
4
5
10
5
5
2a
2a
3a
4a
2b
2b
2c
3c
4c
2d
3d
4d
87
57
Traces
Traces
Traces
Traces
78
66b
63c
d
d
58d
29e
w40f
w20f
w40f
93
d
1:1
1:1
65
a
Reactions were conducted according to the same procedure: PhSH, AIBN
(0.2 equiv), slow addition (0.15 mmol hꢁ1), Tol. reflux.
O-t-Bu
n-Hex
CN
48
61
O-t-Bu
match the behavior of the same substrates in the previous reaction.
We have no clear explanation to account for this reactivity differ-
ence. Moreover, the process could not be extended to the formation
of other ring sizes.
a
Method C: PhSH (1.1 equiv), AIBN (0.2 equiv), slow addition (0.15 mmol hꢁ1), Tol.
reflux.
b
Product was contaminated by approx. 30% of an undefined by-product.
Product was contaminated by approx. 40% of Ph2P(O)CH2CHO, a by-product
c
resulting from oxidation of the transient radical formed after addition.
d
3.2. Extension to thiosulfonylations
Hydrothiolation adducts (28%) were also isolated.
Hydrothiolation adducts (23%) were also isolated.
Yields are estimated based on the NMR ratios. Products were contaminated by
e
f
We had previously observed a dramatic change of the radical
reactivity upon switching from the phosphinate to sulfinate moiety.
The phosphorus tether in arylphosphinates would favor ipso-sub-
stitution and biaryl formation,18 while similar sulfinates (and sul-
finamides) would favor homolytic substitutions.20 We thus decided
to evaluate the behavior of thiosulfonates in the same
cycloisomerization.
unknown phosphorus-containing by-products.
R
S
P
X
R
AIBN
PhS
PhSH
PhS
S
Such a study was also stimulated by the scarce data available in
the literature for such a transformation. In a short communication,
R
P
R
ˆ
Da Silva Correa reported the first example of cycloisomerization of
X
alkenyl thiosulfonate 6a to tetrahydrothiophene 7a.27 Because
the reaction conditions involved peroxides, we can suppose the
mechanism of this rearrangement involves generation of the
methylphenylsulfonyl radical, followed by addition to the double
X
P
R
S
R
P
X
R
S
R
X
P
bond, intramolecular homolytic substitution of the formed b-(sul-
R
R
S
P
X
R
fonyl)alkyl radical at the sulfur atom, and simultaneous formation
of a new methylphenylsulfonyl radical, thus a mechanism remi-
niscent of our thiophosphination.28
R
Scheme 8. Mechanism of the proposed cycloisomerization.
Later, it was noticed that the reaction did not require initiation
by benzoyl peroxide and that leaving the samples exposed to light
for one month at rt was enough to convert all the starting material
to the cyclic product.29 These results prompted us to hypothesize
that the initiation step involved light-induced homolytic scission of
the S–SO2 bond, and not sacrificial addition of an initiator-derived
species to a fraction of the S.M. (Scheme 9). We thus decided to
reinvestigate the transformation of 6b and try to optimize the
conditions for the synthesis of the cyclic product.
Such concomitant thiophosphorylations of both ends of an al-
kyne are quite rare26 and, to the best of our knowledge, ours was
the first example of such a process in radical chemistry. Thiophenol
was only required to trigger formation of the initial P-centered
radicals, thus only a substoichiometric amount of mediator was
needed (Table 3).
In the absence of alkene and under the previously described
reaction conditions, S-pentynyl thiophosphine oxide 1d, as well as
The thiosulfonates 6a–d were prepared by nucleophilic sub-
stitution of the corresponding mesylates with the potassium salt of
p-toluenethiosulfonic acid (Scheme 10).
S-pentynyl dithiophosphonate 1g, underwent
a clean cyclo-
isomerization. Heterocycle 5a (respectively, 5d) was isolated in
good yield as a 70:30 (respectively, 50:50) mixture of Z/E isomers.
Assignment of the stereochemistry was determined by NOE.
Optimal conditions were found with 0.4 equiv of thiophenol
(Table 3). Replacement of toluene by tert-butanol was detrimental
to the reactivity. The cycloisomerizations of diethoxy- and dia-
minophosphonate derivatives 1e and 1f proceeded sluggishly and
only traces of the expected adducts were observed. This appears to
We first examined in more details the conditions required for the
radical cycloisomerization of alkene 6a. We carried out the cycli-
zations either in the presence of PhSH/AIBN in refluxing toluene, or
at rt in benzene under sunlamp irradiation. Tetrahydrothiophene 7a
was isolated in similarly high yields in both cases, which validate
our assumption that the S–SO2 bond is weak enough to be easily
cleaved by irradiation, and that this constitutes the initiation step
for the radical mechanism described above (Scheme 9).

P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
11869
4. Conclusion
( )n
hν
SSO2Ar
R1
R1
In summary we have devised two efficient approaches for the
formation of P(V)-centered radicals from aryl or alkyne thio-
phosphonates with and without tin hydride. The P-centered rad-
icals that were generated could be engaged in several bond
forming process, and efficient cycloisomerizations were carried
out, which led to the bis-functionalization of alkenes and alkynes.
The scope of the thiosulfonation of olefins was extended, while an
unprecedented thiophosphination of alkynes was introduced.
During the course of this work, we evidenced a complementary
reactivity of sulfur- and phosphorus-containing functions. We
believe these reactions to be of interest for the synthesis of sulfur
heterocycles.
( )n
S
SO2Ar
( )n
SSO2Ar
R1
S
ArO2S
R1
( )n
( )n
ArO2S
SSO2Ar
R1
Scheme 9. Thiosulfonation of olefins.
5. Experimental
( )n
SSO2Tol
5.1. General remarks
R1
( )n
or
Reagents and chemicals were purchased from commercial
sources and used as received. Reactions were carried out under
argon, with magnetic stirring and degassed solvents. CH2Cl2,
benzene, and toluene were dried and distilled from CaH2. Thin-
layer chromatography (TLC) was performed on Merck 60 F254 sil-
icagel. Merck Geduran SI 60 Å silicagel (35–70 mm) was used for
column chromatography. The melting points reported were mea-
sured with a Reichert hot-stage apparatus and are uncorrected. IR
spectra were recorded from a Bruker Tensor 27 ATR diamond PIKE
spectrometer. 1H NMR [13C NMR] spectra were recorded at rt with
OH
6a n = 1, R1 = H, 51%
6b n = 1, R1 = Me, 42%
6c n = 2, R1 = H, 63%
R1
1. MsCl, Et3N
2. TolSO2S- K+
OH
SSO2Tol
6d (ref. 29)
Scheme 10. Access to the thiosulfonates.
a
400 MHz [100 MHz] Bruker AVANCE 400 spectrometer or
a 200 MHz [50 MHz] Bruker AVANCE 200. Chemical shifts are
given in parts per million, referenced to TMS (
¼0 ppm) using the
solvent signals (
We next looked for the scope and limitation of this reaction
(Table 4). Quaternary centers could be installed (entry 4), as well
as six-membered rings (entry 5). Interestingly, the cyclo-
isomerization could also be carried out in tert-butanol albeit 7a
was produced in lower yield (entry 3). But the most surprising
feature came from the reaction of alkyne 6d. No conversion to the
desired cycloadduct was observed, 6d undergoing slow degrada-
tion.30 This result is quite surprising, since sulfonyl radicals are
known to add onto alkynes.31 Maybe the rate of addition of the
former cannot sustain a chain process, since it seems unlikely that
the homolytic substitution step should be an unfavorable process,
as was evident with thiophosphine oxides (see above). In any case,
we have evidenced a new complementarity between sulfur and
phosphorus. Unfortunately, it was not possible to extend this
particular cycloisomerization to the formation of small or me-
dium-sized rings.
d
d
¼7.28 or 77.16, respectively, for CDCl3). Coupling
constants (J) are given in hertz (Hz). 31P NMR spectra were
obtained at 298 K in 5 mm o.d. tube at 162 MHz, on a Bruker
AVANCE 400 spectrometer equipped with a QNP or BBFO probe at
a concentration of 100 mg/0.5 mL. External 85% H3PO4 in coaxial
tube was used as reference. Exact masses were recorded at the
Institut de chimie moleculaire (FR 2769) of our University (elec-
trospray source). Elemental analyses were performed by ICSN
(CNRS, Gif).
´
5.2. GP1: preparation of the thiophosphonates and related
compounds
To the starting thiol (5 mmol) in THF (30 mL) at 0 ꢂC was added
NaH (60% in mineral oil, 6 mmol, 240 mg). The R2P(]O)Cl de-
rivative (6 mmol) was added after 5 min and the reaction was left at
rt until completion, as monitored by TLC. The reaction mixture was
diluted with Et2O (15 mL), washed with satd aq NH4Cl, water, and
brine. The organic phase was dried over MgSO4, filtered, and con-
centrated in vacuo. The crude products were purified by flash col-
umn chromatography (silicagel).
Table 4
R1
MePhO2S
Conditions
( )n
( )n
SSO2PhMe
S
R1
6a n = 1, R1 = H
6b n = 1, R1 = Me
6c n = 2, R1 = H
7a n = 1, R1 = H
7b n = 1, R1 = Me
7c n = 2, R1 = H
5.3. GP2: preparation of the thiophosphonates from
sulfonates
Entry
6
Conditions
7a
Yield (%)
1
2
3
4
5
6a
6a
6a
6b
6c
A
B
C
B
B
7a
7a
7a
7b
7c
86
82
70
86
86
To the starting sulfonate (15 mmol) in degassed DMF (150 mL)
was added NH4SP(]S)(OEt)2 (18 mmol, 3.66 g) and the reaction
was heated overnight at 50 ꢂC. After completion (TLC monitoring),
the reaction mixture was diluted with CH2Cl2 (80 mL), washed with
water (ꢃ4), and brine. The organic phase was dried over MgSO4,
filtered, and concentrated in vacuo. The crude products were pu-
rified by flash column chromatography (silicagel).
Method A: PhSH (1.1 equiv), AIBN (0.2 equiv), slow addition (0.15 mmolꢁ1), Tol.
reflux. Method B: Sunlamp irradiation (300 W) for 1 h in PhH (0.03 mol/l). Method
C: same as Method B with t-BuOH (0.03 mol/l).
a

11870
P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
5.4. GP3: tributyltin hydride-mediated formation of C–P
bonds
concentrated in vacuo. The crude alcohol was isolated in 95% yield
(4.4 g) as a colorless oil. Spectral data corresponded to those
reported in the literature (CAS number: 1074-16-4).32
A degassed solution of AIBN (0.012 mmol, 15 mol %, 15 mg) and
Bu3SnH (0.6 mmol, 0.16 mL) in toluene (5 mL) was added via sy-
ringe pump (0.2 mmol hꢁ1) to a refluxed, degassed solution of the
thiophosphonyl substrate (0.5 mmol), the alkene (5 or 10 equiv),
and AIBN (0.04 mmol, 5 mol %, 5 mg) in toluene (12 mL). After
completion of the addition, the reaction mixture was refluxed for
an additional hour, and concentrated. Flash column chromatogra-
phy (silicagel) delivered the expected products.
5.10. 2-Bromophenethyl methanesulfonate
Methanesulfonyl chloride (2.7 mL, 35 mmol) was added drop-
wise over 5 min to a cooled (0 ꢂC) solution of 2-(20-bromophenyl)-
ethanol (4.5 g, 23 mmol) and triethylamine (6.5 mL, 46 mmol) in
CH2Cl2 (100 mL). The reaction mixture was further stirred at 0 ꢂC
for 5 min, then at rt for 2 h. It was quenched with H2O, and the
organic layer was washed with water (2ꢃ50 mL) and brine (50 mL),
dried over MgSO4 and concentrated in vacuo. The crude sulfonate
was used without further purification. Spectral data corresponded
to those reported in the literature (CAS number: 2183-83-7).32
5.5. GP4: catalytic tin conditions
A degassed solution of the thiophosphonyl derivative (0.5 mmol),
Bu3SnCl (0.06 mmol, 10 mol %, 0.16 mL), NaBH4 (1 mmol, 38 mg),
the alkene (1 mmol), and AIBN (0.05 mmol, 10 mol %, 9 mg) in tert-
butanol (25 mL) was refluxed for 5 h (AIBN (0.05 mmol, 10 mol %,
9 mg) was added again after 2.5 h.). After completion, the reaction
mixture was treated with satd aq NH4Cl. The aqueous phase was
extracted with Et2O (3ꢃ15 mL). The combined organics were
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo. The crude products were purified by flash column chroma-
tography (silicagel).
5.11. S-2-Bromophenethyl ethanethioate
To a solution of 2-(20-bromophenyl)ethanol (4.73 g, 23.4 mmol)
in 150 mL of THF were added successively PPh3 (9.26 g, 35.1 mmol)
and DEAD (40% in toluene, 16.2 mL, 35.1 mmol) at rt. After 5 min,
AcSH (3.36 mL, 46.8 mmol) was added dropwise to the solution,
which turned yellow (from light green). The mixture was stirred
overnight at rt. After partial evaporation of the solvent (to approx.
50 mL), n-pentane (100 mL) was added to precipitate triphenyl-
phosphine oxide. The white solid was filtered off and the filtrate
was concentrated in vacuo. The crude material was purified by flash
column chromatography (CH2Cl2/petroleum ether 1:3) to give the
5.6. GP5: thiophenol-mediated formation of C–P bonds, and
cycloisomerizations
A degassed solution of AIBN (0.1 mmol, 20 mol %, 16 mg) and
title compound in 72% yield. 1H NMR (CDCl3, 400 MHz):
d 2.36 (s,
thiophenol (0.55 mmol (or 0.2 mmol for cycloisomerizations), 56
m
l
3H, MeCO), 3.02 (m, 2H, CH2CH2S), 3.16 (m, 2H, CH2S), 7.11 (m, 1H
(respectively, 20 l) in toluene (8 mL)) was added via syringe pump
m
arom.), 7.28 (m, 2H arom.), 7.55 (dd, J¼8.0 Hz, 1.0 Hz, 1H arom.). 13C
(0.15 mmol hꢁ1) to a refluxed and degassed solution of the alkynyl
thiophosphonyl substrates (0.5 mmol) and alkene (0 for cyclo-
isomerizations, 5 or 10 equiv) in toluene (8 mL). After completion of
the addition, the reaction mixture was refluxed for an additional
hour, and concentrated. Flash column chromatography (silicagel)
delivered the expected products.
NMR (CDCl3, 100 MHz): d 28.8 (MeCO), 30.7 (CH2CH2S), 36.0 (CH2S),
124.4 (C arom.), 127.5 (CH arom.), 128.3 (CH arom.), 130.8 (CH
arom.), 132.9 (CH arom.), 139.1 (C arom.), 195.6 (CO).
The isolated sulfonate (6.14 g, 22 mmol) was added to cesium
thioacetate (23.1 mmol)dwhich was prepared by addition of
Cs2CO3 (7.9 g, 24.2 mmol) to a solution of freshly distilled thioacetic
acid (1.65 mL, 23.1 mmol) in MeOH (40 mL) followed by concen-
tration in vacuodin dry DMF (100 mL). The mixture was heated
with stirring at 50 ꢂC for 20 h, then cooled and diluted with CH2Cl2
(150 mL). DMF was removed by repeated washings with water
(4ꢃ50 mL). Filtration of the crude product through a short silicagel
plug gave the title compound in 70% yield (4 g, 15.4 mmol) as an oil.
5.7. GP6: preparation of the thiosulfonates
To the starting sulfonate (15 mmol) in degassed DMF (150 mL)
was added MePhSO2SK (18 mmol, 4.07 g) and the reaction mixture
was heated overnight at 50 ꢂC. After completion (TLC monitoring),
the reaction mixture was diluted with CH2Cl2 (80 mL), washed with
water (ꢃ4), and brine. The organic phase was dried over MgSO4,
filtered, and concentrated in vacuo. The crude products were pu-
rified by flash column chromatography (silicagel).
5.12. 2-(20-Bromophenyl)ethanethiol
To a solution of thioacetate (1.9 g, 7.3 mmol) in Et2O (50 mL) at
ꢁ78 ꢂC was added a solution of Dibal-H (1 M in hexanes, 18.3 mL,
18.3 mmol) over 15 min. The solution was allowed to warm to rt
and further reacted for two more hours. The reaction mixture was
quenched with 3 M HCl and the organic layer was washed with satd
aq NaHCO3, water and brine, then dried over MgSO4, filtered, and
concentrated in vacuo. The crude product was purified by flash
column chromatography (petroleum ether) to yield the thiol
5.8. GP7: light-promoted cycloisomerization of
thiosulfonates
A degassed solution of the thiosulfonate substrate (0.5 mmol) in
benzene (15 mL) was irradiated to reflux with a sunlamp (300 W).
After completion, the solvent was evaporated. Flash column chro-
matography (silicagel) delivered the expected products.
(1.44 g, 6.64 mmol, 91%). 1H NMR (CDCl3, 400 MHz):
d 1.43 (t,
J¼15.6 Hz, 1H, SH), 2.40 (m, 2H, CH2S), 3.10 (m, 2H, CH2CH2S), 7.12
5.9. 2-(20-Bromophenyl)ethanol
(m, 1H arom.), 7.27 (m, 2H arom.), 7.56 (d, J¼15.4 Hz, 1H arom.).
To a solution of 2-bromophenyl acetic acid (4.95 g, 23 mmol) in
THF (25 mL) was added dropwise at 5 ꢂC a BH3$SMe2 complex so-
lution 2 M in THF (25 mL, 25 mmol). The reaction mixture was left
at 5 ꢂC for 30 min, allowed to warm to rt overnight, and slowly
poured into ice-cold methanol (100 mL) with gentle swirling and
left to stand for at least 6 h. The clear solution was then concen-
trated and the residue was dissolved in Et2O (100 mL). The organic
layer was washed with satd NaHCO3 (3ꢃ50 mL), dried (MgSO4), and
5.13. Compound 1a
Following GP1 from 2-(20-bromophenyl)ethanethiol (1.06 g,
5 mmol) and diphenylphosphinic chloride (1.42 g, 6 mmol), sub-
strate 1a was isolated (petroleum ether/ethyl acetate 2:1, 1.71 g,
82%) as a colorless dense oil. IR (neat): 3056, 2927, 1589, 1568,
1113 cmꢁ1. 1H NMR (CDCl3, 400 MHz):
d
3.05–3.10 (m, 4H, CH2CH2),
7.05–7.10 (m, 1H arom.), 7.16–7.25 (m, 2H arom.), 7.47–7.60 (m, 7H

P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
11871
arom.), 7.88–7.92 (m, 4H arom.). 13C NMR (CDCl3, 100 MHz):
d
28.6
(180 mL) and extracted with CH2Cl2 (4ꢃ30 mL). The organic layer
was washed with aq NaCl, dried over MgSO4, filtered, and con-
centrated in vacuo. The crude product was used without
purification.
(d, J¼2.2 Hz, ArCH2), 37.3 (d, J¼4.4 Hz, SCH2), 124.3 (C arom.), 127.5
(CH arom.), 128.4 (CH arom.), 128.7 (d, J¼10.3 Hz, CH arom.), 131.1
(CH arom.), 131.5 (d, J¼10.3 Hz, CH arom.), 132.4 (d, J¼2.6 Hz, CH
arom.), 132.9 (CH arom.), 133.2 (d, J¼106.2 Hz, ]CP), 138.7 (C
arom.). 31P NMR (CDCl3,162 MHz):
d 44.6. Elemental analysis (%) for
5.17. Pent-4-ynyl methanesulfonate
C20H18BrOPS (417.30): calcd. C 57.56, H 4.35; found C 57.12, H 4.43.
81
HRMS calcd for C20
440.9840.
H
BrONaPS ([MþNa]þ): 440.9877, found
18
Starting from pent-4-yn-1-ol (2.52 g, 30 mmol), the corre-
sponding sulfonate was isolated without purification (4.87 g, >98%)
as a brown dense oil. Spectral data corresponded to those reported
in the literature (CAS number: 68275-03-6).33
5.14. Compound 1b
Following GP1 from 2-(20-bromophenyl)ethanethiol (1.06 g,
5 mmol) and diethyl chlorophosphate (1.035 g, 6 mmol), substrate
1b was isolated (petroleum ether/ethyl acetate 2:1, 1.16 g, 66%) as
5.18. Pent-4-enyl methanesulfonate
Starting from pent-4-en-1-ol (860 mg, 10 mmol), the corre-
sponding sulfonate was isolated without purification (1.64 g, >98%)
as a brown dense oil. Spectral data corresponded to those reported
in the literature (CAS number: 64818-35-5).34
a colorless oil. IR (neat): 2981, 2927, 1010 cmꢁ1 1H NMR (CDCl3,
.
400 MHz):
d
1.33 (t, J¼7.1 Hz, 6H, OCH2Me), 2.99–3.11 (m, 4H,
CH2CH2), 4.06–4.20 (m, 4H, OCH2Me), 7.04–7.10 (m, 1H arom.),
7.20–7.29 (m, 2H arom.), 7.49–7.51 (m, 1H arom.). 13C NMR (CDCl3,
100 MHz):
d
16.1 (d, J¼7.7 Hz, OCH2Me), 30.1 (ArCH2), 37.4 (d,
5.19. S-Pent-4-ynyl ethanethioate
J¼5.1 Hz, SCH2), 63.5 (d, J¼5.1 Hz, OCH2Me), 124.3 (C arom.), 127.6
(CH arom.), 128.5 (CH arom.), 131.0 (CH arom.), 132.9 (CH arom.),
Starting from pent-4-ynyl methanesulfonate (4.87 g, 30 mmol),
the corresponding thioacetate was isolated without purification
(3.41 g, 80%) as a clear oil. Spectral data corresponded to those
reported in the literature (CAS number: 64818-35-5).25a
138.6 (C arom.). 31P NMR (CDCl3, 162 MHz):
d 28.9. Elemental
analysis (%) for C12H18BrO3PS (353.21): calcd. C 40.81, H 5.14; found
C 40.65, H 5.26. HRMS calcd for C12
376.9775, found 376.9764.
81
H
18
BrO3NaPS ([MþNa]þ):
5.20. S-Pent-4-enyl ethanethioate
5.15. Compound 1c
Starting from pent-4-enyl methanesulfonate (3.28 g, 20 mmol),
the corresponding thioacetate was isolated without purification
Following GP1 from 2-(20-bromophenyl)ethanethiol (1.06 g,
5 mmol) and 1,3-dimethyl-2-oxo-1,3,2-diazaphospholidine (1.01 g,
6 mmol), substrate 1c was isolated (petroleum ether/ethyl acetate
1:1, 978 mg, 56%) as a whitish dense oil. IR (neat): 2986, 2928,
(2.51 g, 87%) as a clear oil. 1H NMR (400 MHz, CDCl3):
d 1.64 (quint.,
J¼6.9 Hz, 2H, CH2CH2CH2), 2.12 (q, J¼6.9 Hz, 2H,C]C–CH2), 2.32 (s,
3H, COMe), 2.87 (t, J¼6.8 Hz, 2H, CH2S), 5.00 (m, 2H, HC]CH2), 5.77
(m, 1H, HC]CH2).
1159 cmꢁ1. 1H NMR (CDCl3, 400 MHz):
d
7.56 (d, J¼8.3, 1H), 2.68 (s,
3H, NMe), 2.71 (s, 3H, NMe), 2.86–2.93 (m, 2H, CH2), 3.05–3.08 (m,
2H, CH2), 3.12–3.18 (m, 2H, CH2), 3.30–3.36 (m, 2H, NCH2), 7.10–7.14
(m, 1H arom.), 7.25–7.29 (m, 2H arom.), 7.54–7.56 (m, 1H arom.). 13C
5.21. Pent-4-yne-1-thiol
NMR (CDCl3, 100 MHz):
d
30.2 (d, J¼4.3 Hz, CH2Ar), 31.3 (d,
Starting from S-pent-4-ynyl ethanethioate (3.41 g, 24 mmol),
the corresponding thiol was isolated without purification (1.4 g,
56%) as a clear oil. Spectral data corresponded to those reported in
the literature (CAS number: 77213-88-8).25a
J¼6.0 Hz, NMe), 37.6 (d, J¼5.1 Hz, CH2S), 47.6 (d, J¼9.4 Hz, NCH2),
124.2 (C arom.), 127.6 (CH arom.), 128.4 (CH arom.), 131.1 (CH
arom.), 132.9 (CH arom.), 139.1 (C arom.). 31P NMR (CDCl3,
162 MHz):
d 42.1. Elemental analysis (%) for C12H18BrN2OPS
(349.23): calcd C 41.27, H 5.20, N 8.02; found C 40.94, H 5.22, N 7.94.
5.22. Pent-4-ene-1-thiol
5.16. Synthesis of the acyclic alkenyl or alkynyl thiols
Starting from S-pent-4-enyl ethanethioate (1.44 g, 10 mmol),
a 65:35 mixture of the corresponding thiol and disulfide was iso-
lated without purification (612 mg, 60%) as a clear oil. 1H NMR
Methanesulfonylchloride (3.48 mL, 45 mmol) was added over
5 min at 0 ꢂC to a stirred solution of alcohol (30 mmol) and tri-
ethylamine (8.43 mL, 60 mmol) in CH2Cl2 (200 mL). After 5 min at
0 ꢂC and 2 h at rt, the reaction mixture was washed with water
(2ꢃ50 mL) and brine (50 mL), dried over MgSO4, and concentrated
in vacuo.
(400 MHz, CDCl3):
CH2CH2CH2), 2.24–2.07 (m, 2H, ]CHCH2), 2.55 (td, J¼7.8 Hz, 7.8 Hz,
d
1.35 (t, J¼8.0 Hz, 1H, SH), 1.72 (m, 2H,
2H, CH2S), 5.0 (m, 2H), 5.8 (m, 1H) (CAS number: 17651-37-5).
The crude sulfonate (30 mmol) was used without purification. It
was added to cesium thioacetate (31.5 mmol)dwhich was pre-
pared by addition of Cs2CO3 (10.75 g, 33 mmol) to a solution of
freshly distilled thioacetic acid (2.25 mL, 31.5 mmol) in MeOH
(60 mL) followed by concentration in vacuodin dry DMF (190 mL).
The reaction mixture was heated at 50 ꢂC for 20 h, then diluted
with CH2Cl2 (200 mL). DMF was removed by repeated washings
with water (4ꢃ50 mL). The combined organics were concentrated
in vacuo. The crude product was filtered through a short plug of
silicagel, delivering the title compound as an oil.
5.23. Compound 1d
Following GP1 from pent-4-yne-1-thiol (500 mg, 5 mmol),
substrate 1d was isolated (petroleum ether/ethyl acetate 1:1,
978 mg, 56%) as a whitish dense oil. IR (neat): 3295, 3056, 2926,
2117, 1588, 1194 cmꢁ1 1H NMR (CDCl3, 400 MHz):
. d 1.85 (quint.,
J¼7.1 Hz, 2H, SCH2CH2), 1.90 (t, J¼2.7 Hz, 1H, ^CH), 2.25 (td, J¼7.1,
2.7 Hz, 2H, ^CCH2), 2.91 (dt, J¼11.4, 7.1 Hz, 2H, SCH2), 7.43–7.56 (m,
6H, arom.), 7.84–7.91 (m, 4H, arom.). 13C NMR (CDCl3, 100 MHz):
d
17.3 (SCH2CH2), 28.2 (^CCH2), 29.2 (d, J¼4.3 Hz, SCH2), 69.3
To a suspension of K2CO3 (11 mmol, 1.1 equiv) in MeOH (60 mL)
stirred 20 min at rt, was added the crude thioacetate (10 mmol).
The evolution of reaction was monitored by TLC. After 20 min of
stirring, the reaction mixture was quenched with 0.1 M HCl
(^CH), 82.7 (^CCH2), 128.7 (d, J¼12.8 Hz, CH arom.), 131.5 (d,
J¼10.3 Hz, CH arom.), 132.4 (d, J¼3.4 Hz, CH arom.), 133.2 (d,
J¼106.3 Hz, C arom.). 31P NMR (CDCl3, 162 MHz):
d 44.6 (CAS
number: 934538-84-8).

11872
P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
5.24. Compound 1e
CH2), 1.35–1.44 (m, 2H, CH2), 1.57–1.66 (m, 2H, CH2), 2.22–2.30 (m,
2H, CH2), 7.44–7.53 (m, 6H arom.), 7.71–7.78 (m, 4H arom.). 13C
NMR (CDCl3, 100 MHz):
Following GP1 from pent-4-yne-1-thiol (500 mg, 5 mmol),
d
14.1 (Me), 21.4 (d, J¼3.4 Hz, PCH2CH2CH2),
substrate 1e was isolated (petroleum ether/ethyl acetate 1:1,
22.6 (CH2), 29.0 (CH2), 29.7 (d, J¼71.1 Hz, PCH2), 31.0 (d, J¼14.6 Hz,
PCH2CH2), 31.8 (CH2), 128.6 (d, J¼12.0 Hz, CH arom.), 130.8 (d,
J¼9.4 Hz, CH arom.), 131.6 (d, J¼3.4 Hz, CH arom.), 133.2 (d,
602 mg, 51%) as a yellow oil. IR (neat): 3232, 2982, 2117, 1162 cmꢁ1
.
1H NMR (CDCl3, 400 MHz):
d
1.33 (t, J¼7.1 Hz, 6H, OCH2Me), 1.90
(quint., J¼7.1 Hz, 2H, SCH2CH2), 1.96 (t, J¼2.7 Hz, 1H, ^CH), 2.31 (td,
J¼7.1, 2.7 Hz, 2H, ^CCH2), 2.93 (dt, J¼11.4, 7.1 Hz, 2H, SCH2), 4.05–
J¼96.8 Hz, C arom.). 31P NMR (CDCl3, 162 MHz):
d 34.1. HRMS calcd
for C20H28OP (MHþ): 315.1878, found 315.1878.
4.22 (m, 4H, OCH2). 13C NMR (CDCl3, 100 MHz):
d
16.1 (d, J¼6.9 Hz,
OCH2Me), 17.3 (SCH2CH2), 29.4 (d, J¼4.8 Hz, SCH2 or ^CCH2), 29.6
5.29. Compound 2b
(d, J¼4.3 Hz, SCH2 or ^CCH2), 63.5 (d, J¼6.0 Hz, OCH2), 69.3 (^CH),
82.7 (^CCH2). 31P NMR (CDCl3, 162 MHz):
d
29.0 (CAS number:
Following GP3 from 1b (176 mg, 0.5 mmol) and 1-octene
(561 mg, 5 mmol, 10 equiv), or following GP4 from 1b (176 mg,
0.5 mmol) and 1-octene (561 mg, 5 mmol, 10 equiv), or following
GP5 from 1e (150 mg and 213 mg, 0.63 mmol and 0.96 mmol) and
1-octene (141 mg or 1.01 g, 1.26 mmol and 9 mmol, 2 equiv or
10 equiv), adduct 2b was isolated as a colorless oil (CH2Cl2/ethyl
acetate 50:50, 94 mg (respectively, 87 mg, 45 mg and 130 mg), 75%
(respectively, 70%, 29%, and 58%)). Its spectral data correspond to
those of commercial samples (CAS number: 1068-07-1).
934538-85-9).
5.25. Compound 1f
Following GP1 from pent-4-yne-1-thiol (500 mg, 5 mmol),
substrate 1f was isolated (CH2Cl2/MeOH 9:1, 488 mg, 42%) as
a yellow oil. IR (neat): 3213, 2928, 1475, 1160 cmꢁ1. 1H NMR (CDCl3,
400 MHz):
d
1.83 (quint., J¼7.1 Hz, 2H, SCH2CH2), 1.96 (t, J¼2.7 Hz,
1H, ^CH), 2.31 (td, J¼7.1, 2.7 Hz, 2H, ^CCH2), 2.68 (s, 3H, NMe),
2.71 (s, 3H, NMe), 2.73 (td, J¼11.4, 7.1 Hz, 2H, SCH2), 3.05–3.14 (m,
2H, NCH2), 3.27–3.37 (m, 2H, NCH2). 13C NMR (CDCl3, 100 MHz):
5.30. Compound 2c
d
17.4 (SCH2CH2), 29.5 (d, J¼5.1 Hz, SCH2 or ^CCH2), 29.6 (d,
Following GP3 from 1c (113 mg, 0.323 mmol) and 1-octene
(561 mg, 5 mmol, 10 equiv), or following GP4 from 1c (175 mg,
0.5 mmol) and 1-octene (561 mg, 5 mmol, 10 equiv), or following
GP5 from 1f (116 mg, 0.5 mmol) and 1-octene (561 mg, 5 mmol,
10 equiv), adduct 2c was isolated as a colorless oil contaminated by
approx. 50% of by-products (CH2Cl2/methanol 90:10, 50 mg (re-
spectively, 59 mg and 113 mg), 62% (respectively, 48% and w40%
J¼4.3 Hz, SCH2 or ^CCH2), 31.3 (d, J¼6.0 Hz, NCH2), 47.5 (d,
J¼10.3 Hz, NMe), 69.1 (^CH), 83.1 (^CCH2). 31P NMR (CDCl3,
162 MHz):
d 42.0 (CAS number: 934538-86-0).
5.26. Compound 1g
Following GP2 from pent-4-ynyl methanesulfonate (810 mg,
yield estimated by 1H NMR ratio)). IR (neat): 2923, 2853,1156 cmꢁ1
.
5 mmol), substrate 1g was isolated (petroleum ether/ethyl acetate
1H NMR (CDCl3, 400 MHz):
d
0.88 (t, J¼7.1 Hz, 3H, Me),1.18–1.37 (m,
9:1, 676 mg, 53%) as a yellow oil. 1H NMR (CDCl3, 400 MHz):
d
1.39
12H, CH2), 1.76–1.84 (m, 2H, CH2P), 2.66 (d, J¼9.4 Hz, 6H, NMe),
(t, J¼7.4 Hz, 6H, 2 CH3), 1.83 (quint., J¼7.4 Hz, 2H, SCH2CH2), 2.01 (t,
J¼2.7 Hz, 1H, ^CH), 2.34 (dt, J¼7.0, 1.3 Hz, 2H, ^CCH2), 3.00 (td,
J¼16.4, 7.4 Hz, 2H, SCH2), 4.23 (m, 4H, 2OCH2). 13C NMR (CDCl3,
3.04–3.08 (m, 2H, NCH2), 3.16–3.23 (m, 2H, NCH2). 13C NMR (CDCl3,
100 MHz):
d
14.1 (CH3), 22.6 (CH2), 23.0 (d, J¼4.3 Hz, CH2), 26.9 (d,
J¼115.7 Hz, PCH2), 29.0 (CH2), 29.1 (CH2), 30.7 (d, J¼17.1 Hz, CH2),
100 MHz):
d
15.9 (d, J¼8.6 Hz, CH3), 17.4 (SCH2CH2), 29.0 (d,
31.7 (CH2), 31.9 (d, J¼5.1 Hz, NMe), 48.3 (NCH2). 31P NMR (CDCl3,
J¼4.3 Hz, ^CCH2), 32.2 (d, J¼4.3 Hz, SCH2), 63.9 (d, J¼8.6 Hz, OCH2),
162 MHz):
found 247.1934.
d
43.3. HRMS calcd for C12H28N2OP ([MþH]þ): 247.1939,
69.4 (^CH), 82.7 (^CCH2). 31P NMR (CDCl3, 162 MHz):
d
96.8.
5.27. Compound 1h
5.31. Compound 2d
Following GP1 from pent-4-ene-1-thiol (612 mg, 6 mmol),
substrate 1h was isolated (petroleum ether/ethyl acetate 1:1,
800 mg, 44%) as a whitish dense oil. 1H NMR (CDCl3, 400 MHz):
Following GP5 from 1g (126 mg, 0.5 mmol) and 1-octene
(561 mg, 5 mmol, 10 equiv), adduct 2d was isolated as an oil (pe-
troleum ether/ethyl acetate 80:20, 123 mg, 93%). Spectral data
corresponded to those reported in the literature (CAS number:
100543-37-1).23e
d
1.70 (quint., J¼7.4 Hz, 2H, SCH2CH2), 2.08–2.12 (m, 2H, CH2CH]),
2.81 (dt, J¼10.6, 7.4 Hz, 2H, SCH2), 4.91 (m, 2H), 5.65 (m, 1H), 7.40–
7.56 (m, 6H arom.), 7.81–7.91 (m, 4H arom.). 13C NMR (CDCl3,
100 MHz):
d
28.6 (CH2CH2), 29.7 (CH2]CHCH2), 32.5 (d, J¼4.3 Hz,
5.32. Compound 3a
SCH2), 115.6 (CH2]CH), 128.6 (d, J¼12.8 Hz, CH arom.), 131.4 (d,
J¼10.3 Hz, CH arom.), 132.3 (d, J¼3.4 Hz, CH arom.), 133.1 (d,
J¼106.3 Hz, C arom.), 137.1 (CH2]CH). 31P NMR (CDCl3, 162 MHz):
Following GP3 from 1a (209 mg, 0.5 mmol) and acrylonitrile
(53 mg, 5 mmol, 10 equiv), or following GP4 from 1a (209 mg,
0.5 mmol) and acrylonitrile (53 mg, 1 mmol, 2 equiv), or following
GP5 from 1d (150 mg, 0.5 mmol) and acrylonitrile (53 mg, 1 mmol,
2 equiv), adduct 3a was isolated as an oil contaminated by approx.
20% of by-products (petroleum ether/ethyl acetate 50:50, 45 mg
(respectively, 64 mg and 85 mg), 39% (respectively, 50% and 66%
(contaminated by approx. 30% of an undefined product))). Spectral
data corresponded to those reported in the literature.35
d
44.5.
5.28. Compound 2a
Following GP3 from 1a (209 mg, 0.5 mmol) and 1-octene
(561 mg, 5 mmol, 10 equiv), or following GP4 from 1a (209 mg,
0.5 mmol) and 1-octene (112 mg, 1 mmol, 2 equiv), or following
GP5 from 1d (292 mg and 290 mg, 0.973 mmol and 0.966 mmol)
and 1-octene (217 mg and 1.09 g, 1.94 mmol and 9.73 mmol,
2 equiv and 10 equiv), adduct 2a was isolated as a white solid
(petroleum ether/ethyl acetate 50:50, 132 mg (respectively, 91 mg,
168 mg and 252 mg), 84% (respectively, 58%, 57%, and 87%)). Mp
5.33. Compound 3b
Following GP3 from 1b (176 mg, 0.5 mmol) and acrylonitrile
(265 mg, 5 mmol, 10 equiv), adduct 3b was isolated (ethyl acetate,
71 mg, 74%) as a colorless oil. Its spectral data corresponded to
those of commercial samples (CAS number: 10123-62-3).36
57–58.5 ꢂC. IR (neat): 3055, 2924, 2853, 1181, 1119 cmꢁ1
(CDCl3, 400 MHz):
.
1H NMR
d
0.86 (t, J¼7.1 Hz, 3H, Me), 1.18–1.31 (m, 8H,

P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
11873
5.34. Compound 3c
5.39. Compound 4d
Following GP3 from 1c (113 mg, 0.323 mmol) and acrylonitrile
(64 mg, 1 mmol, 2 equiv), or following GP5 from 1f (116 mg,
0.5 mmol) and acrylonitrile (106 mg, 2 mmol, 4 equiv), adduct 3c
was isolated as a white solid (CH2Cl2/methanol 90:10, 50 mg (re-
spectively, 42 mg), 82% (respectively, 45%)). Mp 112–115 ꢂC. IR
Following GP5 from 1g (126 mg, 0.5 mmol) and tert-butylvinyl-
ether (250 mg, 2.5 mmol, 5 equiv), adduct 4d was isolated as an oil
(petroleum ether/ethyl acetate 90:10, 77 mg, 61%). 1H NMR (CDCl3,
400 MHz):
(dt, J¼7.0, 1.6 Hz, 2H, CH2P), 3.67 (dt, J¼6.5, 1.6 Hz, 2H, OCH2CH2),
4.07–4.16 (m, 4H, 2OCH2). 13C NMR (CDCl3, 100 MHz):
16.2
(CH3CH2), 27.5 (CMe3), 35.5 (d, J¼70.6 Hz, PCH2), 56.3 (CH2CH2O),
62.3 (2OCH2), 73.4 (CMe3). 31P NMR (CDCl3, 162 MHz):
97.4. Mass
d
1.19 (s, 9H, CMe3), 1.29 (t, J¼7.5 Hz, 6H, CH3CH2), 2.25
(neat): 2912, 2866, 2361, 1168 cmꢁ1
.
1H NMR (CDCl3, 400 MHz):
d
d
2.16 (dt, J¼15.4, 7.8 Hz, 2H, CH2), 2.47 (dt, J¼15.6, 7.8 Hz, 2H, CH2),
2.67 (d, J¼9.6 Hz, 6H, NMe), 3.12–3.26 (m, 4H, NCH2). 13C NMR
d
(CDCl3, 100 MHz):
d
12.3 (d, J¼4.3 Hz, CH2CN), 22.4 (d, J¼120.0 Hz,
(MþNa): 277.1027. Elemental analysis (%) for C10H23O3PS: calcd C,
CH2P), 31.6 (d, J¼5.1 Hz, NMe), 47.9 (d, J¼9.4 Hz, NCH2), 119.0 (CN).
47.23; H, 9.12; found C 47.51, H 9.01.
31P NMR (CDCl3, 162 MHz):
d 37.4. HRMS calcd for C7H14N3OPNa
([MþNa]þ): 210.0772, found 210.0782.
5.40. Compound 5a
Following GP5 from 1d (190 mg, 0.63 mmol) and PhSH
(0.071 mL, 0.69 mmol) and from 1d (283 mg, 0.9 mmol) and PhSH
(0.036 mL, 0.36 mmol, 40 mol %), product 5a was isolated as a 70:30
E/Z mixture of isomers (petroleum ether/ethyl acetate 50:50,
5.35. Compound 3d
Following GP5 from 1g (126 mg, 0.5 mmol) and acrylonitrile
(133 mg, 2.5 mmol, 5 equiv), adduct 3d was isolated as a white solid
(petroleum ether/ethyl acetate 90:10, 50 mg, 48%). 1H NMR (CDCl3,
194 mg, 72%). IR (neat): 3051, 2928, 1565, 1174 cmꢁ1
.
1H NMR
(CDCl3, 400 MHz):
d
2.03 (quint., J¼6.6 Hz, 2H, CH2CH2S, Z), 2.10
400 MHz):
2H, CH2CN), 2.65 (dt, J¼15.4, 7.5 Hz, CH2P), 4.07–4.16 (m, 4H,
2OCH2). 13C NMR (CDCl3, 100 MHz):
11.6 (2 CH3CH2O), 15.8 (d,
d
1.30 (t, J¼7.5 Hz, 6H, 2CH3CH2), 2.25 (dt, J¼15.4, 7.5 Hz,
(quint., J¼6.6 Hz, 2H, CH2CH2S, E), 2.87 (tdd, J¼6.6, 3.0, 1.5 Hz, 2H,
]CCH2, Z), 2.98 (tdd, J¼6.6, 3.0,1.8 Hz, 2H, ]CCH2, E), 3.05–3.11 (m,
2H, SCH2, EþZ), 6.00 (br d, J¼21.0 Hz, 1H, ]CH, Z), 6.06 (dt,
J¼21.0 Hz, 1.8 Hz, 1H, ]CH, E), 7.41–7.53 (m, 6H, arom., EþZ), 7.69–
d
J¼6.5 Hz, CH2CN), 30.5 (d, J¼116.5 Hz, CH2P), 62.6 (d, J¼12 Hz,
2OCH2), 118.53 (d, J¼18.8 Hz, CN). 31P NMR (CDCl3, 162 MHz):
7.80 (m, 4H, arom., EþZ). 13C NMR (CDCl3, 100 MHz):
d 28.4
d
93.8. Its spectral data corresponded to those of commercial
samples (CAS number: 10123-62-3).37
(CH2CH2S, Z), 30.7 (CH2CH2S, E), 34.3 (SCH2, E), 35.9 (SCH2, Z), 36.1
(d, J¼19.7 Hz, ]CCH2, E), 42.0 (d, J¼14.6 Hz, ]CCH2, Z), 104.4 (d,
J¼109.7 Hz, ]CHP, Z), 105.3 (d, J¼108.0 Hz, ]CHP, E), 128.4
(d, J¼10.0 Hz, CH arom., Z), 128.5 (d, J¼11.1 Hz, CH arom., E), 130.9
(d, J¼9.4 Hz, CH arom., E), 131.1 (d, J¼10.3 Hz, CH arom., Z), 131.5 (br
s, CH arom., EþZ), 133.9 (d, J¼104.5 Hz, ]CP, Z), 134.7 (d,
J¼105.4 Hz, ]CP, E), 168.8 (]CS, Z), 170.4 (d, J¼5.1 Hz, ]CS, E). 31P
5.36. Compound 4a
Following GP3 or GP4 from 1a (209 mg, 0.5 mmol) and tert-
butylvinylether (500 mg, 5 mmol, 10 equiv) or following GP5 from
1d (150 mg, 0.5 mmol) and tert-butylvinylether (250 mg, 2.5 mmol,
5 equiv), adduct 4a was isolated (petroleum ether/ethyl acetate
50:50, 107 mg (respectively, 71 mg or 95 mg), 71% (contaminated
by approx. 20% of an undefined by-product) (respectively, 47%)
(contaminated by approx. 10% of an undefined by-product) or 63%
(contaminated by approx. 42% of Ph2P(O)CH2CHO)). IR (neat): 3055,
NMR (CDCl3, 162 MHz):
d 22.2 (E), 23.5 (Z). Elemental analysis (%)
for C17H17OPS (300.36): calcd C 67.98, H 5.70; found C 67.94, H 5.71.
5.41. Compound 5d
Following GP5 from 1g (126 mg, 0.5 mmol) and PhSH (0.056 mL,
0.55 mmol) and from 1g (126 mg, 0.5 mmol) and PhSH (0.02 mL,
0.2 mmol), product 5d was isolated as a 50:50 E/Z mixture of iso-
mers (petroleum ether/ethyl acetate 50:50, 99 mg (respectively,
82 mg), 78% (respectively, 65%)). Less polar isomer. 1H NMR (CDCl3,
2972, 1187, 1118 cmꢁ1 1H NMR (CDCl3, 400 MHz):
. d 1.07 (s, 9H,
CMe3), 2.53–2.66 (m, 2H, CH2P), 3.66–3.78 (m, 2H, CH2O), 7.45–7.55
(m, 6H arom.), 7.70–7.78 (m, 4H arom.). 13C NMR (CDCl3, 50 MHz):
d
27.7 (CMe3), 32.0 (d, J¼70.6 Hz, PCH2), 55.6 (CH2O), 73.9 (CMe3),
128.9 (d, J¼11.9 Hz, CH arom.), 131.1 (d, J¼9.6 Hz, CH arom.), 132.0
400 MHz):
d
1.32 (t, J¼7.3 Hz, 6H, Me), 2.17 (quint., J¼6.8 Hz, 2H,
(d, J¼2.9 Hz, CH arom.), 133.7 (d, J¼99.1 Hz, C arom.). 31P NMR
CH2CH2CH2), 3.00–3.04 (m, 2H, ]CCH2) 3.08 (td, J¼6.3, 0.7 Hz, 2H,
(CDCl3, 162 MHz):
d 33.2.
CH2S), 4.03–4.15 (m, 4H, OCH2), 5.79 (dt, J¼17.4, 2.0 Hz, 1H, CH]C).
13C NMR (CDCl3, 100 MHz):
d
16.2 (d, J¼6.8 Hz, 2Me), 30.8
5.37. Compound 4b
(CH2CH2CH2), 34.3 (CH2S), 35.7 (d, J¼6 Hz, CH2CH]), 62.1 (d,
J¼6 Hz, 2OCH2), 107.1 (d, J¼159.3 Hz, CH2CH]), 168.3 (d, J¼12 Hz,
SC]CH). 31P NMR (CDCl3, 162 MHz):
d
81.2. More polar isomer. 1H
Following GP4 from 1b (176 mg, 0.5 mmol) and tert-butylvinyl-
ether (500 mg; 5 mmol; 10 equiv), adduct 4b was isolated (CH2Cl2/
MeOH 90:10, 67 mg, 56%) as an oil. Spectral data corresponded to
those reported in the literature (CAS number: 19462-38-5).38
NMR (CDCl3, 400 MHz):
d
1.33 (t, J¼7.0 Hz, 2CH3, 6H), 2.06 (quint.,
J¼6.5 Hz, CH2CH2CH2, 2H), 2.77–2.82 (m, ]CCH2, 2H) 3.13 (t,
J¼6.5 Hz, CH2S, 2H), 4.07–4.16 (m, 4H, 2OCH2), 5.73 (dt, J¼16.6,
1.5 Hz, ]CH, 1H). 13C NMR (CDCl3, 100 MHz):
d
16.2 (d, J¼7.7 Hz,
5.38. Compound 4c
2CH3), 28.4 (CH2CH2CH2), 36.1 (CH2S), 41.6 (d, J¼18.8 Hz, CH2CH]),
62.2 (d, J¼6 Hz, 2OCH2), 106.7 (d, J¼161 Hz, CH2CH]), 168.4
Following GP3 from 1c (175 mg, 0.5 mmol) and tert-butylvinyl-
ether (500 mg, 5 mmol,10 equiv) or following GP5 from 1f (150 mg,
0.5 mmol) and tert-butylvinylether (250 mg, 2.5 mmol, 5 equiv),
adduct 4c was isolated as an unstable oil (ethyl acetate/methanol
90:10, 47 mg (respectively, 100 mg), 40% (respectively, w40% yield
(SC]CH). 31P NMR (CDCl3, 162 MHz):
d 82.5. Mixture of isomers.
Elemental analysis: C, 42.84; H, 6.79; found C, 43.17; H, 6.72.
5.42. 4-Methyl pent-4-enyl methanesulfonate
estimated by 1H NMR ratio)). 1H NMR (MeOD, 200 MHz):
d
1.23 (s,
Starting from 4-methyl pent-4-en-1-ol (550 mg, 5.5 mmol), the
expected sulfonate was isolated without purification as a brown
9H, CMe3), 2.13 (dt, J¼15.6, 6.4 Hz, 2H, CH2P), 2.68 (d, J¼9.8 Hz, 6H,
NMe), 3.16–3.26 (m, 4H, CH2N), 3.56 (dt, J¼18.6, 6.4 Hz, 2H, CH2O).
dense oil (922 mg, 94%). 1H NMR (CDCl3, 400 MHz):
d 1.64 (br s, 1H,
31P NMR (CDCl3, 162 MHz):
d
40.5. ES-MS (MeOH/CH2Cl2): 257.2
OH), 1.74 (s, 3H, ]C(CH3)CH2), 1.91 (quint., J¼7.0 Hz, 2H,
([MþNa]þ, 100), 235.2 (MHþ, 22).
CH2CH2CH2), 2.14 (t, J¼7.0 Hz, 2H, ]C(CH3)CH2), 3.02 (s, 3H,

11874
P. Carta et al. / Tetrahedron 64 (2008) 11865–11875
SO2CH3), 4.24 (t, J¼6.6 Hz, 2H, CH2O), 4.72 (s, 1H, ]CHH), 4.79 (m,
1H, ]CHH) (CAS number: 64818-36-6).
5.48. Compound 6d
Following the procedure described by Edwards from pent-4-
ynyl methanesulfonate. Spectral data corresponded to those
reported in the literature (CAS number: 178904-43-3).29
5.43. Hex-5-enyl methanesulfonate
Starting from hex-5-en-1-ol (860 mg, 10 mmol), the expected
sulfonate was isolated without purification (1.68 g, >98%) as
a brown dense oil. Spectral data corresponded to those reported in
the literature (CAS number: 64818-36-6).33
5.49. Compound 7a
Following GP5 from 6b (128 mg, 0.5 mmol) and PhSH
(0.056 mL; 0.55 mmol), or following GP7 from 6b (256 mg, 1 mmol)
in PhH (30 mL), or following GP7 from 6b (256 mg, 1 mmol) in
t-BuOH (30 mL), adduct 7b was isolated as a white solid (petroleum
ether/ethyl acetate 80:20, 110 mg (respectively, 211 mg and
180 mg), 86% (respectively, 82% and 70%)). Spectral data corre-
sponded to those reported in the literature (CAS number: 138643-
63-7).26 Mp :59–61 ꢂC. Elemental analysis (%) for C12H16O2S2
(256.38): calcd. C 56.22, H 6.29; found C 56.28, H 6.34.
5.44. Hept-6-enyl methanesulfonate
Starting from hept-6-en-1-ol (86 mg, 0.75 mmol), the corre-
sponding sulfonate was isolated without purification (90 mg, 94%)
as a brown dense oil. Spectral data corresponded to those reported
in the literature (CAS number: 64818-37-7).33
5.45. Compound 6a
5.50. Compound 7b
Following GP6 from pent-4-enyl methanesulfonate (1.98 g,
12 mmol) and MePhSO2SK (2.72 g, 12 mmol), substrate 6a was
isolated as an oil (petroleum ether/ethyl acetate 80:20, 1.57 g,
Following GP7 from 6c (135 mg, 5.18 mmol), adduct 7c was
isolated as a solid (petroleum ether/ethyl acetate 80:20, 116 mg,
86%). Mp 47 ꢂC. IR (neat): 2927, 1596, 1314, 1141, 1085, 814 cmꢁ1. 1H
51%). IR (neat): 2923, 1639, 1593, 1322, 1138, 914, 811 cmꢁ1 1H
.
NMR (CDCl3, 400 MHz):
d 1.71 (s, 3H, SC(CH3)CH2), 1.96–2.02 (m,
NMR (CDCl3, 400 MHz):
d
1.73 (quint., J¼7.3 Hz, 2H, CH2CH2CH2),
1H, CHHSC(CH3)CH2), 2.08–2.15 (m, 2H, CH2CH2S), 2.24–2.31 (m,
1H, CHHSC(CH3)CH2), 2.44 (s, 3H, ArMe), 2.86–2.98 (m, 2H,
CH2CH2S), 3.46 (d, J¼14.2 Hz, 1H, part A of AB system, CH2SO2), 3.53
(d, J¼14.2 Hz,1H, part B of AB system, CH2SO2), 7.36 (d, J¼8.3 Hz, 2H
arom.), 7.78 (d, J¼8.3 Hz, 2H arom.). 13C NMR (CDCl3, 100 MHz):
2.06–2.13 (m, 2H, ]CHCH2), 2.47 (s, 3H, Me), 3.00 (t, J¼7.3 Hz 2H,
CH2S), 5.01–4.96 (m, 2H, CH2]), 5.74–5.64 (m, 1H, CH]), 7.35 (dd,
J¼8.3, 0.5 Hz, 2H arom.), 7.83 (d, J¼8.3 Hz, 2H arom.). 13C NMR
(CDCl3, 100 MHz):
d 21.8 (ArMe), 27.8 (CH2CH2S), 32.4 (]CHCH2),
35.3 (CH2S), 116.2 (CH2]CH), 127.1 (2C arom.), 129.9 (2C arom.),
136.7 (CH2]CH), 142.0 (SSO2C), 144.8 (CMe) (CAS number:
138643-62-6).
d
21.7 (ArMe), 29.0 (SC(CH3)CH2), 29.8 (CH2CH2S), 33.2 (CH2CH2S),
43.2 (CH2SC(CH3)CH2), 54.7 (SC(CH3)CH2), 67.9 (CH2SO2), 127.8 (2C
arom.), 129.9 (2C arom.), 138.3 (CMe), 144.6 (CSO2). Elemental
analysis (%) for C13H18O2S2 (270.07): calcd. C 57.74, H 6.71; found C
57.76, H 6.88.
5.46. Compound 6b
Following GP6 from 4-methyl pent-4-enyl methanesulfonate
(922 mg, 5.18 mmol) and MePhSO2SK (2.36 g, 10.36 mmol), sub-
strate 6b was isolated as an oil (petroleum ether/ethyl acetate
80:20, 589 mg, 42%). IR (neat): 2921, 1648, 1593, 1322, 1138, 889,
5.51. Compound 7d
Following GP7 from 6d (270 mg, 1 mmol), substrate 7d was
isolated as a white solid (petroleum ether/ethyl acetate 80:20,
232 mg, 86%). Mp: 59–61 ꢂC. IR (neat): 2920, 1596, 1299, 1137, 1084,
811 cmꢁ1 1H NMR (CDCl3, 400 MHz):
. d 1.66 (s, 3H, ]C(CH3)CH2),
1.76 (quint., J¼7.4 Hz, CH2CH2CH2, 2H), 2.04 (t, J¼7.4 Hz 2H,
CH2S), 2.47 (s, 3H, ArCH3), 2.99 (t, J¼7.4 Hz, 2H, ]C(CH3)CH2),
4.66 (s, 1H, ]CHH), 4.72 (m, 1H, ]CHH), 7.35 (d, J¼8.3 Hz, 2H
arom.), 7.83 (d, J¼8.3 Hz, 2H arom.). 13C NMR (CDCl3, 100 MHz):
813 cmꢁ1 1H NMR (CDCl3, 400 MHz):
. d 1.36–1.47 (m, 1H,
CH2CHHCH2), 1.54–1.66 (m, 2H, CHHCH(CH2SO2PhMe)S and
CHHCH2S), 1.77–1.91 (m, 2H, CHHCH2S and CHHCH2CH2S), 2.26–
2.32 (m, 1H, CHHCH(CH2SO2PhMe)S), 2.46 (s, 3H, ArCH3), 2.54–2.60
(m, 1H, CH2CHHS), 2.65–2.72 (m, 1H, CH2CHHS), 3.15–3.30 (m, 3H,
CH(CH2SO2PhMe)S and CH(CH2SO2PhMe)S), 7.36 (d, J¼8.3 Hz, 2H
arom.), 7.80 (d, J¼8.3 Hz, 2H arom.). 13C NMR (CDCl3, 100 MHz):
d
21.7 (ArCH3), 22.1 (]C(CH3)CH2), 26.6 (CH2CH2CH2), 35.4
(CH2S), 36.4 (]C(CH3)CH2), 111.3 (CH2]), 127.1 (2C arom), 129.9
(2C arom.), 142.1 (SSO2C), 143.8 (]C(CH3)CH2), 144.8 (CH3C
arom.). HRMS calcd for C13H18O2NaS2 ([MþNa]þ): 293.0645,
found 293.0640.
d
21.7 (MeAr), 24.9 (CH2CH2CH2S), 26.5 (CH2CH2S), 29.1 (CH2CH2S),
33.6 (CH2CH(CH2SO2PhMe)S), 35.6 (CH(CH2SO2PhMe)S), 61.3
(CH2SO2PhMe), 128.0 (2C arom.), 130.0 (2C arom.), 136.8 (CMe),
144.9 (CSO2). Elemental analysis (%) for C13H18O2S2 (270.41): calcd
C 57.74, H 6.71; found C 57.59, H 6.79.
5.47. Compound 6c
Following GP6 from hex-5-enyl methanesulfonate (1.69 g,
9.5 mmol) and MePhSO2SK (3.65 g, 16.15 mmol), substrate 6c was
isolated as an oil (petroleum ether/ethyl acetate 80:20, 1.61 g, 63%).
Acknowledgements
IR (neat): 2924, 1639, 1593, 1323, 1138, 911, 811 cmꢁ1 1H NMR
.
We thank CNRS, IUF, UPMC, and ANR (grant BLAN0309, ‘Radi-
caux verts’) for financial support. Technical support from ICSN (Gif
sur Yvette, France) is gratefully acknowledged (HRMS and ele-
mental analyses).
(CDCl3, 400 MHz):
d
1.41 (quint., J¼7.3 Hz, CH2CH2CH2, 2H), 1.62
(quint., J¼7.3 Hz, CH2CH2CH2, 2H), 2.03–1.98 (m, 2H, ]CHCH2), 2.47
(s, 3H, CH3), 3.00 (t, J¼7.3 Hz 2H, CH2S), 4.99–4.94 (m, 2H, CH2]),
5.77–5.67 (m, 1H, CH]), 7.36 (d, J¼8.3 Hz, 2H arom.), 7.83 (d,
J¼8.3 Hz, 2H arom.). 13C NMR (CDCl3, 100 MHz):
d
21.7 (ArCH3), 27.7
References and notes
(CH2CH2CH2), 28.1 (CH2CH2CH2), 32.9 (]CHCH2), 35.9 (CH2S), 115.1
(CH2]CH), 127.1 (2C arom.), 129.9 (2C arom.), 137.9 (CH2]CH),
142.1 (SSO2C), 144.7 (CH3C arom.). HRMS calcd for C13H18O2NaS2
([MþNa]þ): 293.0645, found 293.0640.
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