Synthesis of chiral ortho-thio-substituted phenyl phosphonodiamidates via a P-S to P-C rearrangement

Article abstract of DOI:10.1016/j.tetlet.2004.03.132

The ortho-lithiation of a phenyl phosphorodiamidothioate derived from an enantiopure C₂-symmetric diamine is studied. It is shown that the migration of the diaminophosphoryl group from sulfur to carbon, leading to an ortho-sulfanylated phenyl phosphonodiamidate, only occurs in the presence of an alkylating agent or a Lewis acid as BF₃·Et₂O. The influence of the chiral diaminophosphoryl group on the stereoselectivity of the oxidation of the ortho-sulfanyl or alkylsulfanyl group is also examined.

Full text of DOI:10.1016/j.tetlet.2004.03.132

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3855–3859
Synthesis of chiral ortho-thio-substituted phenyl
phosphonodiamidates via a P–S to P–C rearrangement
Christelle Mauger, Michel Vazeux and Serge Masson*
Laboratoire de Chimie Molꢀeculaire et Thio-organique (UMR CNRS 6507),Universit ꢀe de Caen––ENSICAEN,6 Boulevard Mar ꢀechal
Juin,14000 Caen,France
Accepted 22 March 2004
Abstract—The ortho-lithiation of a phenyl phosphorodiamidothioate derived from an enantiopure C2-symmetric diamine is studied.
It is shown that the migration of the diaminophosphoryl group from sulfur to carbon, leading to an ortho-sulfanylated phenyl
phosphonodiamidate, only occurs in the presence of an alkylating agent or a Lewis acid as BF3ÆEt2O. The influence of the chiral
diaminophosphoryl group on the stereoselectivity of the oxidation of the ortho-sulfanyl or alkylsulfanyl group is also examined.
ꢀ 2004 Elsevier Ltd. All rights reserved.
During the last three decades, the syntheses of a large
variety of chiral ligands have contributed to the con-
siderable development of asymmetric catalysis based
on organometallic chemistry.1 Among the bidentate
ligands, 1,2-difunctionalized aryl derivatives, in particular
chiral ortho-hydroxyaryl-substituted organophosphorus
derivatives, have been successfully used.2 One of the
more convenient ways to prepare such compounds is the
ortho-lithiation of an aryl phosphate3 or an aryl
phosphorodiamidate,4 which is usually followed by a
1,3-sigmatropic migration of the phosphorylated moiety
fromoxygen to carbon. More recently, a similar rear-
Like their 2-hydroxy analogues,2a 2-sulfanylarylphos-
phonodiamidates derived from chiral diamines could be
useful ligands for asymmetric synthesis provided that
they can be easily synthesized. Moreover, the sulfanyl
group can be readily alkylated into a sulfide and then
oxidized into a sulfoxide, another stereogenic center,
which has also good metal chelating properties. In
particular, recent studies by Hiroi et al. have shown
that an enantiopure 2-alkylsulfinylphenyl-diphenyl-phos-
phine can be used as chiral catalyst in a Tsuji–Trost
allylation reaction (ee up to 85%).11
rangement has been described through a halogen–lith-
5
Any investigation on the potential of 2-sulfanylaryl-
phosphonodiamidates or their derivatives as chiral
ligands in asymmetric synthesis needs an efficient
method to prepare them. Few years ago, our group has
demonstrated that the rearrangement aryl phosphoro-
thioate–ortho-sulfanylarylphosphonate is possible pro-
vided that the O,O0-alkyl substituents on phosphorus
are relatively bulky such as isopropyls, in order to avoid
the nucleophilic addition of the LDA to the phosphoryl
function.8 To our knowledge, as far as aryl phosp-
horodiamidothioates are concerned, only two examples
of such a 1,3-sigmatropic migration are mentioned in
the literature. The first one is connected to the synthesis
of the N,N-dimethyl 2-methylsulfanylphenyl phosphono-
diamidate by ortho-lithiation of the corresponding phen-
yl phosphorodiamidothioate at low temperature
()100 ꢁC) with subsequent addition of methyl iodide
(any attempt to prepare the corresponding thiol is not
mentioned).9 The second example is the ortho-lithiation
of a phenyl phosphorodiamidothioate derived from an
iumexchange froma 2-bromoarylphosphinite.
With a
chiral phosphorus center, a complete retention of con-
figuration was observed and the rearrangement was,
ꢀ
respectively, applied by the groups of Buono and Juge
to the asymmetric synthesis of a P-stereogenic 2-hy-
droxyarylphosphonamide and a 2-hydroxyarylphos-
phine–borane complex.5;6 Some applications of these
difunctional compounds (and of their methoxy ana-
logues) as ligands for asymmetric synthesis have already
been described, the stereogenic moiety being a diami-
nophosphoryl group derived froman asymmetric dia-
mine or aminoalcohol.7
Keywords: ortho-Lithiation; [1,3]-Sigmatropy; Phosphorodiamidothio-
ate; Phosphonodiamidate; Thiol; Sulfoxide.
* Corresponding author. Tel.: +33-0-2-31-45-28-91; fax: +33-0-2-31-
45-28-77; e-mail: serge.masson@ismra.fr
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.132

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C. Mauger et al. / Tetrahedron Letters 45 (2004) 3855–3859
enantiopure 2-anilinomethylpyrrolidine followed by a
protonation step, which actually leads to the prepara-
tion of the corresponding arylthiol but in a low yield
(20%).10 We report here our first results related to the
ortho-lithiation of a phenyl phosphorodiamidothioate
phosphonodiamidates 3, 4, and 5 were, respectively,
isolated in 58%, 68%, and 71% yields. The lower yield
was obtained with ethyliodide, the less efficient alkyla-
ting agent.
prepared froman enantiopure
trans-N,N0-dimethyl
In order to get a phenyl phosphonodiamidate ortho-
substituted by a thiol function, we then added a Lewis
acid to the solution of ortho-lithiated 1, with the aimto
increase the electrophilicity of the phosphorus. Four
Lewis acids were tested. ZnCl2 has no effect, TiCl4 and
ClSiMe3, respectively, produced degradation or incom-
plete conversion. Only the use of 2.5 equiv of BF3ÆEt2O
gave a complete transformation of 1 (this need of an
excess of Lewis acid being probably linked to the
2.5 equiv of LDA used for a complete ortho-lithiation).
Two products were isolated, both resulting fromthe
expected ortho-lithiation–1,3-migration sequence. The
main one was the expected 2-sulfanylphenyl phospho-
nodiamidate 6 (72%).15 The isolated by-product (17%) is
the corresponding disulfide 7 which, at roomtempera-
cyclohexane-1,2-diamine. This work demonstrates that,
with such a diamidothioate, the S fi C migration is not
spontaneous, as observed for their oxygen analogues,
and how it is possible to induce this rearrangement
by addition of an alkylating agent or a Lewis acid.
Moreover, procedures allowing the stereoselective pre-
paration of the corresponding 2-alkylsulfinylphenyl
phosphonodiamidate are also investigated.
The starting phenyl phosphorodiamidothioate 1 was
readily obtained in good yield (75%) by reaction of the
sodiumsalt of benzenethiol with a diaminophospho-
rochloridate, which was prepared from the commer-
cially available (1R,2R)-diaminocyclohexane, according
to known procedures.12;13 The ortho-lithiation of 1
(Scheme 1) by addition of 2.5 equiv of LDA in THF was
monitored by 31P NMR. At temperatures between )20
and +10 ꢁC, the signal of the starting material at 41 ppm
was replaced by a new signal at 44 ppm. However, after
protonation of the mixture, at room temperature, with
water (NH4Cl) or D2O, starting compound 1 or its
ortho-deuterated analogue was nearly quantitatively
recovered. This clearly indicates that, although the
ortho-lithiation occurred (the signal at 44 ppmcorre-
sponds to the ortho-lithiated derivative), no P–S to P–C
rearrangement took place.
ture, appears as a nearly 1:1 mixture of two rotamers 7a
31
and 7b (d
P
¼ 33.45 and 33.40) with a coalescence
DMSO
31
temperature of 50 ꢁC (d
slow rotation has already been observed for ortho-
substituted benzenedisulfides.17
P
¼ 33.12). Analogous
DMSO
The effect of an alkylating agent or of a Lewis acid on
the course of the reaction merits some comments.
Compared to the ortho-lithiated phenylthiophosphate
analogue, which rearranges spontaneously,8 initially
formed ortho-lithiated phenyl phosphorodiamidothioate
is probably more stabilized due to the electrondonating
effect of the two nitrogen atoms, which increases the
oxygen–lithiumchelation and reduces the electrophilic-
ity of the phosphorus. Therefore protonation gives back
the starting phosphorodiamidothioate 1. The addition
of an alkylating agent with a possible partial linkage of
its halogen to lithiummay destabilize this initial lithia-
ted species, which is then more easily converted into the
bipyramidal transition state suggested for the P–S to P–
C migration.6 Fromthis transition state, the cleavage of
the P–S bond to give the final rearranged product might
be also assisted by a simultaneous addition of the alkyl
group on the sulfur atom. The effect of the Lewis acid,
BF3ÆEt2O, can be interpreted by the chelation of the
oxygen of the P@O group, which both destabilizes the
Therefore, we examined the effect of the addition of an
alkylating agent (methyl iodide) to the ortho-lithiated
intermediate. Monitored by 31P NMR, this experiment
showed that, as soon as methyl iodide was added to
ortho-lithiated 1, the 44 ppmpeak disappeared com-
pletely and a new signal at 35 ppmwas observed. The
latter corresponds to the S-methylated rearranged
product, the 2-methylsulfanylphenyl phosphonodiami-
date 2, which was actually isolated in a 78% yield after
purification.14 No ortho-C alkylation of 1 could be de-
tected in the crude product. The same procedure was
repeated with ethyliodide, allylbromide, and benzyl-
bromide. Thus 2-(ethyl-, allyl-, and benzyl-sulfanyl)phenyl
°
1
1) T + 10 C
2) H3O+
O
P
N
N
SR
RX, 4 eq.
N
N
N
N
LDA, 2.5 eq.
°
P
T
+ 10 C
P
O
O
°
S
2 - 5
S
THF, -20 C
R = Me, Et, CH2 =CH-CH2, PhCH2,
Li
1
O
N
N
SH
BF3.Et2 O
2.5 eq.
P
+
7a,b
°
T
+ 10 C
6
Scheme 1.

C. Mauger et al. / Tetrahedron Letters 45 (2004) 3855–3859
3857
O
R
S
O
P
Me
O
P
S
N
N
[O]
N
N
2 dias :
8a,b
Yield (%)
81
[O]
R = Me
2
8a:8b (%)
58:42
NaIO4 , MeCOMe, r. t.
m-CPBA, CH2Cl2 , r. t.
H2 O2, MeOH, r. t.
60:40
80
63:37
80
Cl
Cl
N
Oxaziridine (+)
°
91:09
27:73
72
51
, CCl4, 0 C
S
O
O
O
°
1) MeLi, 1.1 eq., THF, -65 C
R = H
6
O
N
2)
Ph
racemic, 20 min.
SO2Ph
H3C
3) MeI
Scheme 2.
initial ortho-lithiated species and increases the electro-
philicity of the phosphorus atom, thus facilitating the
formation of the C–P bond.
interesting inversion of stereoselectivity has already been
observed for the two types of oxidation procedures
applied to (R)-2-(1-dimethylaminoethyl)benzenethiol
and to its S-methyl derivative.21
Then, in order to check if the asymmetric ortho-diamino-
phosphoryl group can be an efficient chiral inductor in
the oxidation of the sulfur atom, we examined the
reaction of sulfide 2 with NaIO4, m-chloroperbenzoic
acid, and hydrogen peroxide (Scheme 2). With such
achiral reagents, a mixture of diastereomers 8a and 8b
was obtained with poor diastereomeric excesses (up to
26%), as determined by 31P NMR (CDCl3, d ¼ 35:15
and 32.20, respectively).16 This clearly indicates a weak
asymmetric induction by the chiral phosphonamido
group. A similar conclusion can be drawn from the
reaction of sulfide 2 with the commercially available
enantiopure (+)-(2S,8aR)-8,8-dichloro-camphorsulfon-
yloxaziridine, which led also to 8a as the major dia-
stereomer. Although a much better diastereomeric
excess (very probably resulting froma match effect) was
obtained (82%), this de is relatively close to that we
previously observed for the oxidation of the achiral
2-methylsulfanylphenyl phosphonate (de ¼ 73%) using
the same enantiopure oxaziridine.18;19
In conclusion, this work describes efficient syntheses of a
new chiral ortho-sulfanylphenyl phosphonamide, and
some of its corresponding sulfides, derived from an
enantiopure trans-1,2-cyclohexane diamine by using the
ortho-lithiation–1,3-migration sequence. The procedures
described here and involving either a Lewis acid or an
alkylating agent open a way to the synthesis of a variety
of new potential mixed P,S-chiral bidentate ligands
prepared fromother C2-symmetric diamines. A rather
good diastereoisomeric excess of 82% was here observed
for the oxidation of the sulfide 2 into the corresponding
sulfoxide but this needed the use of an enantiopure
chiral oxaziridine. In order to get such ortho-difunc-
tionalized benzene derivatives (bearing both a phos-
phoramide and a sulfoxide as stereogenic centers) with
higher stereoselectivity, and without the requirement of
an enantiopure oxidizing agent, it will be worth studying
more extensively the synthesis and oxidation of ana-
logues of sulfide 2 and thiol 6 prepared fromother chiral
diamines, in particular those bearing more bulky sub-
stituents.
A method of direct oxidation of aromatic thiol into
sulfoxide, by
a deprotonation–oxidation–alkylation
sequence involving an intermediate lithium sulfenate,
has been described by Perrio and co-workers.20 Thiol 6
was oxidized according to this procedure, racemic N-
phenylsulfonyl tert-butyl methyl oxaziridine being used
for the oxidation step (Scheme 2). A mixture of the two
diastereomeric sulfoxides 8a, 8b was obtained in a ratio
27:73, isolated in a nonoptimized yield of only 51% due
to the formation of disulfide of the starting thiol
(disulfide 7 is isolated in 23% yield). The diastereomeric
excess for the sulfoxide 8 (46%) is still modest but the
stereoselectivity is opposite to that obtained for the
direct oxidation of sulfide 2 by achiral oxidants. Such an
Acknowledgements
This work has been performed within the ‘PUNCH-
^
Orga’ interregional network (Pole Universitaire de
Chimie Organique). We gratefully acknowledge finan-
ꢁ
cial support fromthe ‘Minist ere de la Recherche et des
Nouvelles Technologies’, CNRS (Centre National de la
ꢀ
Recherche Scientifique), the ‘Region Basse-Normandie’
and the European Union (FEDER funding) for finan-
cial support.

3858
C. Mauger et al. / Tetrahedron Letters 45 (2004) 3855–3859
is quenched by the addition of a saturated NH4Cl solution
References and notes
(5 mL) and extracted with diethyl ether (3 · 5 mL). The
organic phase was dried with MgSO4 and concentrated
under reduced pressure. The residue was purified by flash
chromatography on a silica gel column (ethyl acetate).
1. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. In Compre-
hensive Asymmetric Catalysis; Springer: Berlin, 1999; Vols.
1–3.
Compound 2 was isolated in 78% yield as colorless
2. (a) Brunel, J. M.; Buono, G. In New Chiral Organophos-
phorus Catalysts in Asymmetric Synthesis,Topics in
Current Chemistry; Majoral, J. P., Ed.; Springer: Berlin,
Heidelberg, 2002; Vol. 220, pp 79–105; (b) Molt, O.;
Schrader, T. Synthesis 2002, 18, 2633–2670.
3. (a) Melvin, L. S. Tetrahedron Lett. 1981, 22, 3375–3376;
(b) Dhawan, B.; Redmore, D. J. Org. Chem. 1984, 49,
4018–4021; (c) Dhawan, B.; Redmore, D. Synth. Commun.
1985, 15, 411–416; (d) Dhawan, B.; Redmore, D. Phos-
phorus Sulfur Silicon 1989, 42, 177–182.
20
D
crystals, mp 112 ꢁC; ½aꢀ )9.1 (c 1, CHCl3). 1H NMR
(CDCl3): d 1.22–1.45 (m, 2H), 1.78–1.92 (m, 2H), 1.97–
2.13 (m, 3H), 2.44 (d, J ¼ 11:1, 3H), 2.46 (s, 3H), 2.51 (d,
J ¼ 12:0, 3H), 2.52–2.63 (m, 1H), 2.88–3.09 (m, 2H), 7.17
(ddt, J ¼ 1:1, J ¼ 2:5, J ¼ 7:4, 1H), 7.24–7.29 (m, 1H),
7.43 (tt, J ¼ 1:5, J ¼ 7:4, 1H), 7.97 (ddd, J ¼ 1:5, J ¼ 7:4,
J ¼ 13:9, 1H). 13C NMR (CDCl3): d 16.37 (s), 24.72 (s),
24.85 (s), 28.55 (s), 28.70 (d, J ¼ 5:8), 28.91 (d, J ¼ 7:0),
29.38 (d, J ¼ 2:0), 64.84 (d, J ¼ 5:9), 64.89 (d, J ¼ 7:8),
124.15 (d, J ¼ 12:6), 125.23 (d, J ¼ 11:5), 127.44 (d,
J ¼ 151:3), 132.22 (d, J ¼ 2:6), 136.92 (d, J ¼ 8:9), 144.65
(d, J ¼ 8:4). 31P NMR (CDCl3): d 34.54. C15H23N2OPS:
calcd: C, 58.04; H, 7.47; N, 9.02; found: C, 58.48; H, 7.70;
N, 9.06.
4. (a) Jardine, A. M.; Vather, S. M.; Modro, T. A. J. Org.
Chem. 1988, 53, 3983–3985; (b) He, Z.; Modro, T. A.
Synthesis 2000, 4, 565–570.
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5. Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; Juge, S.
Tetrahedron: Asymmetry 2000, 11, 3939–3956.
6. Legrand, O.; Brunel, J. M.; Buono, G. Chem. Eur. J. 1998,
4, 1061–1105.
7. (a) Brunel, J. M.; Constantieux, T.; Legrand, O.; Buono,
G. Tetrahedron Lett. 1998, 39, 2961–2964; (b) Legrand, O.;
Brunel, J. M.; Buono, G. Tetrahedron Lett. 1998, 39,
9419–9422; (c) Brunel, J. M.; Buono, G. Tetrahedron Lett.
2000, 41, 2105–2108.
8. (a) Masson, S.; Saint-Clair, J. F.; Saquet, M. Synthesis
1993, 485–486; (b) Masson, S.; Saint-Clair, J. F.; Saquet,
M. Tetrahedron Lett. 1994, 3083–3084; (c) Masson, S.;
Saint-Clair, J. F.; Dore, A.; Saquet, M. Bull. Chem. Soc.
Fr. 1996, 133, 951–964.
9. Watanabe, M.; Date, M.; Kawanishi, K.; Akiyoshi, R.;
Furukawa, S. J. Heterocycl. Chem. 1991, 28, 173–176.
10. Legrand, O.; Brunel, J. M.; Buono, G. Tetrahedron 2000,
56, 595–603.
11. Hiroi, K.; Suzuki, Y.; Abe, I.; Kawagishi, R. Tetrahedron
2000, 56, 4701–4710.
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1992, 57, 1224–1237; (b) Bennani, Y. L.; Hanessian, S.
Tetrahedron 1996, 52, 13837–13866.
13. Synthesis of 1: Benzenethiol (3 mmol) was added at 0 ꢁC to
a suspension of sodium hydride (3.1 mmol) in dry THF
(5 mL) under nitrogen. The mixture was stirred for 30 min.
Then diaminophosphorochloridate12 (3 mmol) was added.
The solution was stirred for 12 h at roomtemperature,
quenched by the addition of a saturated NH4Cl solution
(10 mL) and extracted with diethyl ether (2 · 10 mL). After
drying and evaporation of the solvent, the residue was
purified by flash chromatography on a silica gel column
(ethyl acetate/petroleumether, 25/75) to give colorless
15. Synthesis of 6: To a stirred solution of LDA (2.5 mmol)
in dry THF (5 mL) under nitrogen, was slowly added
S-phenyl phosphorodiamidate 1 (1 mmol) at )20 ꢁC. The
mixture was allowed to warm to 10 ꢁC and BF3ÆEt2O
(2.5 mmol) was added dropwise at 0 ꢁC. The solution was
allowed to warmto rt, stirred for an hour and then added
to a saturated NH4Cl solution (5 mL). The product was
extracted with diethyl ether (3·5 mL). After usual work up,
the residue was purified by flash chromatography on a
silica gel column (ethyl acetate) to afford 6, as a green oil,
in 73% yield. 1H NMR (CDCl3): d 1.32–1.39 (m, 2H),
1.53–1.72 (m, 2H), 2.39 (d, J ¼ 11:5, 3H), 2.40–2.68 (m,
4H), 2.58 (d, J ¼ 11:7, 3H), 2.65–2.72 (m, 1H), 2.90–2.96
(m, 1H), 7.12–7.20 (m, 1H), 7.27–7.38 (m, 2H), 7.66 (ddd,
J ¼ 1:3, J ¼ 7:8, J ¼ 14:1, 1H). 13C NMR (CDCl3): d
24.59 (s), 24.70 (s), 28.52 (d, J ¼ 1:5), 28.82 (d, J ¼ 5:5),
28.90 (d, J ¼ 5:0), 29.27 (d, J ¼ 1:5), 64.39 (d, J ¼ 6:2),
65.55 (d, J ¼ 7:0), 124.65 (d, J ¼ 12:6), 126.08 (d,
J ¼ 151:2), 130.98 (d, J ¼ 12:3), 132.01 (d, J ¼ 2:7),
134.81 (d, J ¼ 9:0), 141.04 (d, J ¼ 8:6). 31P NMR
(CDCl3): d 37.62. C14H21N2OPS: calcd: C, 56.74; H,
7.14; N, 9.45; S, 10.82; found: C, 56.81; H, 7.16; N, 9.32; S,
10.96.
16. Characterization of the mixture of diastereomers 8a and
8b purified by flash chromatography (silica gel; ethyl
acetate) as a slightly brown solid. Compound 8a: 1H NMR
(CDCl3): d 1.19–1.45 (m, 4H), 1.87–1.92 (m, 2H), 2.09 (m,
3H), 2.35 (d, J ¼ 11:9, 3H), 2.58 (d, J ¼ 10:2, 3H), 2.89
(m, 1H), 2.96 (s, 3H), 7.55 (m, 2H), 7.77 (m, 1H), 8.36 (m,
1H). 13C NMR (CDCl3): d 24.60 (s), 24.77 (s), 28.27 (d,
J ¼ 8:0), 28.77 (d, J ¼ 4:9), 29.03 (s), 29.20 (d, J ¼ 2:9),
46.31 (s), 64.18 (d, J ¼ 6:7), 64.79 (d, J ¼ 7:7), 124.35 (d,
J ¼ 10:9), 128.11 (d, J ¼ 139:5), 130.64 (d, J ¼ 11:8),
132.75 (d, J ¼ 8:7), 133.12 (d, J ¼ 2:8), 153.27 (d,
J ¼ 10:6). 31P NMR (CDCl3): d 35.15. Compound 8b:
1H NMR (CDCl3): d 1.19–1.45 (m, 4H), 1.91–1.97 (m,
2H), 2.13 (m, 3H), 2.46 (d, J ¼ 10:6, 3H), 2.49 (d,
J ¼ 12:6, 3H), 2.87 (s, 3H), 3.10 (m, 1H), 7.54 (m, 1H),
7.59 (m, 1H), 7.78 (m, 1H), 8.35 (m, 1H). 13C NMR
(CDCl3): d 24.55 (s), 24.69 (s), 28.57 (d, J ¼ 5:7), 28.78 (d,
J ¼ 6:1), 29.12 (s), 29.48 (d, J ¼ 2:0), 45.64 (s), 64.98 (d,
J ¼ 5:5), 65.89 (d, J ¼ 7:6), 124.48 (d, J ¼ 10:9), 128.26
(d, J ¼ 153:3), 130.69 (d, J ¼ 12:3), 133.41 (d, J ¼ 2:8),
134.20 (d, J ¼ 9:4), 152.80 (d, J ¼ 10:1). 31P NMR
(CDCl3): d 32.20. C15H23N2O2PS: calcd: C, 55.20; H,
7.10; N, 8.58; S, 9.82; found: C, 55.85; H, 7.27; N, 8.83; S,
9.36.
20
D
1
crystals, mp 51 ꢁC; ½aꢀ )16.8 (c 2.55, CHCl3). H NMR
(CDCl3): d 0.73 (m, 1H), 0.94 (m, 1H), 1.06 (m, 1H), 1.23
(m, 1H), 1.59 (m, 1H), 1.71 (m, 3H), 1.90 (m, 1H), 2.63 (d,
J ¼ 13:0, 3H), 2.73 (m, 1H), 2.74 (d, J ¼ 11:6, 3H), 7.28–
7.36 (m, 3H), 7.53–7.56 (m, 2H). 13C NMR (CDCl3): d
24.35 (s), 24.44 (s), 28.07 (d, J ¼ 9:1), 28.34 (d, J ¼ 8:7),
28.40 (d, J ¼ 3:6), 28.68 (d, J ¼ 4:1), 63.80 (d, J ¼ 7:5),
64.80 (d, J ¼ 7:5), 129.07 (d, J ¼ 3, 2C), 129.10 (d,
J ¼ 7:1), 129.21 (s), 136.59 (d, J ¼ 2:7, 2C). 31P NMR
(CDCl3): d 44.65. C14H21N2OPS: calcd: C, 56.74; H, 7.14;
N, 9.45; S, 10.82; found: C, 56.95; H, 7.10; N, 9.60; S,
10.58.
14. Synthesis of 2 (typical procedure for the preparation of 2
to 5): Phenyl phosphorodiamidothioate 1 (1 mmol) was
slowly added to a stirred solution of LDA (2.5 mmol) in
dry THF (5 mL) under nitrogen at )20 ꢁC. The mixture
was allowed to warmto 10 ꢁC and alkyl halide (5 mmol)
was added. After 30 min at this temperature, the reaction
17. Kessler, H.; Rieker, A.; Rundel, W. Chem. Commun. 1968,
475–476.

C. Mauger et al. / Tetrahedron Letters 45 (2004) 3855–3859
3859
18. Mauger, C.; Masson, S.; Vazeux, M.; Saint-Clair, J. F.;
Midura, W. H.; Drabowicz, J.; Mikolajczyk, M. Tetra-
hedron: Asymmetry 2001, 12, 167–174.
19. The absolute configuration of the sulfoxide group for each
diastereomer 8a and 8b has not yet been determined. We
were not able to separate pure samples of these isomers, by
chromatography or crystallization, for a study by X-ray
diffraction. Moreover, our attempt to convert them into
the corresponding dimethyl phosphonates of known
configuration18 led us to a racemic mixture. Very proba-
bly, the strong acidic conditions needed to hydrolyse the
phosphonamido group racemized the sulfoxyde function.
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