Scope and limitations of the aromatic anionic [1,3] P-O to P-C rearrangement in the synthesis of chiral o-hydroxyaryl diazaphosphonamides

Article abstract of DOI:10.1016/S0040-4020(99)00966-7

The influence of numerous parameters in the aromatic anionic [1,3] P-O to P-C rearrangement in the synthesis of chiral o-hydroxyaryl diazaphosphonamides has been envisaged. Various strong bases such as LDA, sec-BuLi, tert-BuLi have been conveniently used. The scope of the regioselectivity of the rearrangement has been particularly studied varying the nature of the phenoxy group implied in this reaction. A totally diastereoselective P-O to P-C migration rearrangement has been observed starting from a thiophosphonamide precursor. Moreover, starting from a phenylthio substituted phosphonamide, a totally diastereoselective P-S to P-C rearrangement of the diazaphosphonamide moiety has also been demonstrated. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)00966-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 595–603
Scope and Limitations of the Aromatic Anionic [1,3] P–O to P–C
Rearrangement in the Synthesis of Chiral o-Hydroxyaryl
Diazaphosphonamides
*
´
Olivier Legrand, Jean Michel Brunel and Gerard Buono
´
`
´ ´
´
´
´ ˆ
Ecole Nationale Superieure de Syntheses, de Procedes et d’Ingenierie Chimiques d’Aix Marseille, UMR CNRS 6516, Faculte de St Jerome,
Av. Escadrille Normandie Niemen, 13397 Marseille, Cedex 20, France
Received 4 August 1999; accepted 27 October 1999
Abstract—The influence of numerous parameters in the aromatic anionic [1,3] P–O to P–C rearrangement in the synthesis of chiral
o-hydroxyaryl diazaphosphonamides has been envisaged. Various strong bases such as LDA, sec-BuLi, tert-BuLi have been conveniently
used. The scope of the regioselectivity of the rearrangement has been particularly studied varying the nature of the phenoxy group implied in
this reaction. A totally diastereoselective P–O to P–C migration rearrangement has been observed starting from a thiophosphonamide
precursor. Moreover, starting from a phenylthio substituted phosphonamide, a totally diastereoselective P–S to P–C rearrangement of the
diazaphosphonamide moiety has also been demonstrated. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
diastereoselectivity of the anionic [1,3] P–O to P–C rear-
rangement depending on the base used and the nature of the
substrate.
In the last five years, numerous studies dealing with the use
of non-organometallic phosphorus reagents in enantioselec-
tive catalysis have been described.1 In the context of our
work, we have recently reported the synthesis of a new class
of chiral bi-functional compounds: the ortho-hydroxy-
arylphosphine oxides, and their successful use as catalysts2
or ligands3 in various asymmetric reactions. These
compounds were easily obtained from various chiral diols,
diamines or aminoalcohols through an original totally
stereospecific P–O to P–C rearrangement.4 An extension
of this study has also demonstrated that this reaction is
totally diastereoselective and regioselective (Scheme 1).5,6
Results and Discussion
Precursors 1a–g were easily available by exchange reaction
at 110ЊC in toluene between tris(dimethylamino)phosphine
2 and (S)-(ϩ)-2-anilinomethylpyrrolidine 3 followed by
addition of the desired phenol. Oxidation of crude phos-
phines 4 by tert-butyl hydroperoxide or sulphur afforded
the expected compounds 1a–h with chemical yields ranging
from 55 to 87% (Scheme 2). Moreover, in all cases nearly
Scheme 1.
In this paper, we will describe the scope and limitations of
such a procedure studying more particularly the regio- and
only one diastereomer has been obtained and characterized
as the thermodynamic anti diastereomer7 (Table 1).
Since the pioneering work reported by Melvin,8 lithium
diisopropylamide (LDA) has appeared to be the best
common base used in the rearrangement of arylphosphate
into o-hydroxyarylphosphonate and related compounds.
Only a few reports have mentioned the use of butyllithium
Keywords: non-organometallic phosphorous reagents; enantioselective
catalysis; stereoselectivity.
* Corresponding author. Fax: ϩ33-4-91-02-77-76;
e-mail: brunel@spi-chim.u-3mrs.fr
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)00966-7

596
O. Legrand et al. / Tetrahedron 56 (2000) 595–603
Scheme 2.
Table 1. Synthesis of precursors 1a–h
Entry
Product
Diastereomeric ratio (%)a
Yield (%)b
XˆC 1a
XˆN 1b
100/0
100/0
87
63
1
RˆH 1c
100/0
90/10
55
55
2
RˆMe 1d
RˆH 1e
95/5
70
63
3
RˆSiEt3 1f
90/10
RˆH 1g
RˆBr 1h
100/0
100/0
78
69
4
a Diastereomeric ratio determined by 31P NMR spectroscopy.
b Isolated yield after column chromatography of anti diastereomer.
in such a reaction but a lower selectivity has been generally
encountered. To our knowledge, neither study has been
achieved dealing with the influence of the nature of the
strong base used on the chemo- and stereoselectivity of
the P–O to P–C migration rearrangement. The results of
our investigations are summarized in Table 2 (Scheme 3).
LTMP led to low results in terms of conversion, respec-
tively, 0 and 11% (entries 3 and 4). The use of alkyllithium
base has been also studied. Thus, the use of n-butyllithium
or n-BuLi/TMEDA complex did not afford 5 and in these
cases, only a product resulting from nucleophilic attack of
the phosphorus atom by the base has been isolated in low
yields (entries 5 and 6). Bulkier alkyllithium bases such as
sec-BuLi or tert-BuLi led to the anionic [1,3] rearrangement
product in a totally diastereoselective manner in high
chemical yields (entries 7 and 8). Although these results
are quite similar to those obtained with LDA, we will use
this latter in the following parts.
Various amide bases have been tested in the rearrangement
but whatever the experimental conditions applied, only
LDA led to the expected product in excellent yields and
with total diastereoselectivity. Moreover, in this case, it
clearly appears that the amount of LDA used has dramatic
effects on the outcome of the reaction (entries 1 and 2). The
best results were obtained using 2 equiv. of LDA with
respect to the precursor at Ϫ78ЊC (entry 1, 92% yield,
100% e.d.). On the other hand, the use of LHMDS or
The second part of our study deals with the regioselectivity
of P–O to P–C migration rearrangement depending on the
nature of the substrate considered. In this area, we have

O. Legrand et al. / Tetrahedron 56 (2000) 595–603
597
substituted aromatic ring, the structure of the regiomer
obtained is controlled by electronic or steric effects of the
substituent. Thus, in order to generalize our assumptions, we
have examined the regio- and stereoselectivity of the
rearrangement of precursors possessing a heteroaromatic
ring such as compound 1b. The rearrangement of
precursor 1b was achieved using the standard conditions
(2 equiv. LDA, THF, Ϫ78ЊC) and led to the expected
product 6 in 75% yield. 31P NMR analysis of the crude
product demonstrates that only one isomer has been
formed and the structure of 6 has been unambiguously
determined by X-ray diffraction analysis (Scheme 4).9
Scheme 3.
Table 2. Influence of the nature of the base on the P–O to P–C migration
rearrangement
Entry
Strong
base
Yield
Diastereo-
(conversion) (%)a
selectivity (%)b
In this case, the relative configuration at the phosphorus
atom is seen to be retained during the rearrangement
implying that the steric course of the [1,3] migration from
O to C of the chiral phosphorus atom is homofacial.10 The
phenyl ring (C8–C11) is almost coplanar with the atoms N6,
1
2
3
4
5
6
7
8
LDA
92 (100)
44 (50)
0 (0)
11 (15)
0 (10)
0 (6)
91 (100)
93 (100)
100
100
–
100
–
–
100
100
LDAc
LHMDSd
LTMPe
n-BuLi
n-BuLi/TMEDAf
sec-BuLi
tert-BuLi
˚
P1, C14 and the bond distance N6–C8 is short (1.416 A)
suggesting an interaction between the lone pair of the
nitrogen atom and the aromatic system. Moreover, there is
evidently a strong hydrogen bond between the hydroxy
group and the oxygen atom attached to the phosphorus
moiety.
a Isolated yield after column chromatography.
b Diastereomeric ratio determined by 31P NMR spectroscopy.
c One equivalent of LDA was used.
d LHMDS: lithium hexamethyldisilazane.
e LTMP: lithium tetramethylpiperidine.
Diazaphospholidine oxide group has appeared to be an
excellent activator for the direct metallation of the ortho
position in an aromatic system. The efficiency of the
phosphoryl group as DMG (Directed Metallation Group)
could be due to the formation of a six-membered ring
involving a coordination of lithium atom by the PyO
group as outlined in I (Scheme 5). The driving force of
f TMEDA: tetramethylethylenediamine.
recently clearly demonstrated the total regioselectivity of
this process in the case of precursors bearing a substituent
on the para or meta position of the phenoxy group.5 More-
over, starting from precursors possessing a non-symmetrical
˚
Scheme 4. Bond length (A): P1–O2, 1.481(1); P1–N4, 1.621(1); P1–N6, 1.669(1); P1–C9, 1.796(1); O3–C15, 1.348(2); N6–C8, 1.416(1). Angles (Њ): O2–
P1–N4, 107.5(1); O2–P1–N6, 118.8(1); O2–P1–C9, 117.8(1); N4–P1–N6, 94.9(1); N4–P1–C9, 110.5(1); N6–P1–C9, 106.5(1); P1–N4–C21, 127.7(1);
P1–N4–C16, 114.2(1); C16–N4–C21, 111.9(1); C8–N6–C14, 120.4(2); P1–N6–C8, 125.3(2); P1–N6–C14, 113.3(1).

598
O. Legrand et al. / Tetrahedron 56 (2000) 595–603
Scheme 5.
Scheme 6.
the anionic [1,3] rearrangement could be the formation of
the stable chelate complex II in which both oxygen atoms
could interact with the lithium atom.
from nucleophilic attack of the base at the phosphorus
atom.
In order to explain these results, numerous attempts have
been achieved to demonstrate the formation or not of a
carbanion on the benzylic position. Thus, treatment of
these precursors with strong bases such as n-BuLi, tert-
BuLi and subsequent addition of various electrophiles did
not lead to the formation of the expected substituted
products. These results tend to probe the considerable
degree of stabilization of the organolithium six-membered
ring intermediate with respect to the other seven-membered
ring.
Nevertheless, possible competition between the lithiation of
the ortho position of an aromatic ring and another position
by formation of a seven or eight lithiated membered ring
may be envisaged. With this purpose, we aim to achieve the
rearrangement of various precursors bearing a methyl or a
phenyl group on the ortho position of the aromatic ring.
Thus, treatment of precursor 1c with 2 equiv. of LDA has
been achieved (Scheme 6). In this case, only the formation
of o-hydroxyaryl diazaphospholidine oxide 7 resulting from
an anionic [1,3] rearrangement in 73% yield has been
encountered and no trace of product 8 resulting from a
[1,4] migration of the phosphoryl group on the benzylic
position has been observed.
In the same area, Snieckus has demonstrated that in the
presence of a phenyl substituent on the ortho position of
the aromatic ring, an amide group can be transferred on
the 20 position of the biaryl system11 (Scheme 8).
Moreover, starting from precursor 1d, any products
resulting from a migration of the phosphoryl group have
not been encountered (Scheme 7). The use of bases
such as alkyllithium afforded only by-products resulting
On the basis of these results, we have envisaged this strategy
in the presence of the chiral diazaphospholidine group.
Although precursor 1e led as expected to the anionic [1,3]
rearrangement product 10 clearly characterized by X-ray
diffraction analysis12 in 82% yield, any product resulting
from a migration of the phosphoryl group on the 20 position
has been observed from the silylated compound 1f. More-
over, subsequent addition of various electrophiles did not
lead to a product resulting from lithiation of the 20 position.
These elements seem to indicate that the diazaphospholidine
oxide group could not favour a complex-induced proximity
effect (CIPE)13 (Scheme 9).
In the field of applications of phosphorus compounds such
as P-DMG, few studies have concerned the anionic [1,3]
Scheme 7.
Scheme 8.

O. Legrand et al. / Tetrahedron 56 (2000) 595–603
599
˚
Scheme 9. Bond length (A): P1–O2, 1.487(3); P1–N4, 1.660(3); P1–N6, 1.660(2); P1–C12, 1.785(3); O3–C5, 1.367(4). Angles (Њ): O2–P1–N4, 116.9(2);
O2–P1–N6, 117.4(2); O2–P1–C12, 107.7(3); N4–P1–N6, 94.6(2); N4–P1–C12, 110.2(2); N6–P1–C12, 109.5(3); P1–N4–C14, 113.3(3); P1–N4–C9,
125.2(3); C9–N4–C14, 120.7(3); C18–N6–C26, 106.7(3); P1–N6–C26, 118.1(3); P1–N6–C18, 111.8(3).
rearrangement of PyS derivatives.14 Due to the weaker
complexation of lithium atom by PyS group by comparison
with PyO group, the DoM (Directed ortho Metallation)
reactions are less favoured in these cases. Thus, we have
investigated the possibility of realizing such a rearrange-
ment using a precursor bearing a chiral diazaphospholidine
moiety and a PyS function. Treatment of 1g with 2 equiv. of
LDA or other strong bases, did not lead to the expected
product 12 whatever the conditions used. Presumably, due
to the presence of the PyS moiety, the ortho-lithiated
intermediate is not sufficiently stabilized to lead to the
product of rearrangement 12. In order to favour its
formation, the parent compound 1h has been prepared
and treated with BuLi (1 equiv., THF, Ϫ78ЊC to RT,
12 h) leading to the metallation of the C–Br bond
(Scheme 10).
As an extension of this study, Masson et al. have recently
described a P–S to P–C migration rearrangement to prepare
ortho-thiohydroxyarylphosphonates.15 Watanabe et al. have
also prepared various ortho-thiohydroxyarylphosphonamides
involving a rearrangement of the corresponding thioaryl-
ester.16 Despite these works, no studies have been devoted to
the diastereoselective P–S to P–C migration rearrangement.
Thus, we have considered the rearrangement of the
The desired product of rearrangement 12 has been obtained
in 88% yield and, as already observed for the OyP–O to
OyP–C migration, this rearrangement proceeds by a totally
diastereoselective reaction at the phosphorus atom.
Scheme 10.

600
O. Legrand et al. / Tetrahedron 56 (2000) 595–603
Scheme 11.
diastereoisomerically pure precursor 13 easily obtained from
an exchange reaction between phosphine 2, diamine 3 and
thiophenol, followed by a subsequent oxidation by tert-
BuOOH. A mixture of the two diastereomers 13 and 14 has
been obtained and separated by column chromatography in,
respectively, 65 and 11% yield (Scheme 11).
SDS and used without any further purification. Column
chromatography was performed on SDS silica gel (70–
230 mesh). 1H and 13C NMR spectra were recorded in
CDCl3 solution at 200.00 MHz and 50.30 MHz on a Bruker
AC200 instrument, 31P NMR spectra were recorded in
CDCl3 solution at 40.50 MHz on a Bruker AC100 (the
usual abbreviations are used: sˆsinglet, dˆdoublet, tˆtri-
plet, qˆquadruplet, mˆmultiplet). The positive chemical
shift values are given in ppm, the coupling constants in
Hertz. Specific rotations were determined with a Perkin
Elmer Polarimeter 341. Elemental analyses were performed
Under the standard conditions (2 equiv. LDA, THF,
Ϫ78ЊC), treatment of precursor 13 led to the expected
o-thioaryl diazaphospholidine oxide 15 in only 20% yield.
It is noteworthy that 31P NMR analysis of the crude product
indicates the presence of numerous by-products, but no
trace of the other epimer at the phosphorus atom has been
detected. Nevertheless, as already observed for the P–O to
P–C rearrangement, this migration proceeds with total
retention of configuration at the phosphorus atom.
´
by the ‘Service de Microanalyse de la Faculte des Sciences
´ ˆ
de St Jerome (Marseille)’. X-Ray diffraction analyses were
´
performed at the ‘Service de Cristallographie de la Faculte
´ ˆ
des Sciences de St Jerome (Marseille)’.
General procedure for the synthesis of precursors 1b–h
Conclusion
In a two-necked round flask an equimolar mixture of
tris(dimethylamino)phosphine 2 (5 mmol, 0.82 g) and (S)-
(ϩ)-2-anilinomethylpyrrolidine 3 (5 mmol, 0.88 g) were
placed in dry toluene (10 mL) under argon atmosphere
and warmed at 110ЊC for 3 h. Then 1 equiv. of desired phe-
nol was added at room temperature and the mixture was
warmed at 110ЊC for 1 h. The mixture was allowed to
cool to room temperature and the toluene was removed in
vacuo. The crude phosphine was diluted with dichloro-
methane (15 mL) and the mixture cooled to 0ЊC. tert-
Butyl hydroperoxide 0.9 mL (5.5 M, decane) (in the case
of precursors 1g–h, sulphur, 0.2 g (6.2 mmol)), was slowly
added and the mixture was stirred for 3 h. After removing
the solvent in vacuo, the crude product was purified by
column chromatography or crystallization.
The influence of numerous parameters in the aromatic anionic
[1,3] P–O to P–C rearrangement in the synthesis of chiral o-
hydroxyaryl diazaphosphonamides has been examined. The
regioselectivity of the rearrangement has been particularly
studied varying the nature of the phenoxy group implied in
this reaction. A total diastereoselective P–O to P–C migration
rearrangement has beenobservedstartingfrom a thiophospho-
namide precursor. Although a diastereoselective P–S to P–C
migration rearrangement of the diazaphosphonamide moiety
asP-DoMgrouphasbeenalsodemonstrated, it has beenestab-
lished that this latter is less effective with respect to P–O to P–
C rearrangement. Further studies implying these new
compounds as chiral ligands or catalysts in asymmetric reac-
tions are under current investigation.
(2R,5S)-2-(3-Pyridinoxy)-3-phenyl-1,3-diaza-2-phospha-
bicyclo-[3.3.0]-octane 2-oxide 1b. Purification by crystal-
lization (mixture of ethyl acetate and petroleum ether)
afforded 1b as a white solid in 63% yield. Mp: 126ЊC;
[a]2D0ˆϪ76.6 (cˆ0.15, CH2Cl2); 1H NMR (200 MHz,
CDCl3) dˆ1.63–1.74 (m, 1H), 1.87–2.06 (m, 3H), 3.04–
3.15 (m, 1H), 3.26–3.35 (m, 1H), 3.47–3.61 (m, 2H),
Experimental
Tetrahydrofuran (THF) and toluene were distilled from
sodium/benzophenone ketyl immediately prior to use. Ethyl-
acetate and petroleum ether (35–60ЊC) were purchased from

O. Legrand et al. / Tetrahedron 56 (2000) 595–603
601
3
3.76–3.87 (m, 1H), 7.00 (t, JHHˆ7.2 Hz, 1H), 7.11–7.37
(2R,5S)-2-(2-Phenyl-6-triethylsilylphenoxy)-3-phenyl-
1,3-diaza-2-phosphabicyclo-[3.3.0]-octane 2-oxide 1f.
Purification by column chromatography (silica gel; ethyl-
acetate/petroleum ether 67:33) afforded 1f as a white solid
in 70% yield (product obtained as a mixture of two
(m, 6H), 8.34 (s, 2H); 13C NMR (50 MHz, CDCl3) dˆ26.1
3
3
3
(d, JPCˆ 3.1 Hz), 32.5 (d, JPCˆ2.6 Hz), 46.8 (d, JPCˆ
2
2
2.6 Hz), 49.7 (d, JPCˆ17.9 Hz), 57.1 (d, JPCˆ10.2 Hz),
3
116.3 (d, JPCˆ 4.6 Hz, 2C), 122.0 (s), 124.0 (s), 128.5 (d,
3JPCˆ3.5 Hz), 129.5 (s, 2C), 140.8 (d, JPCˆ5.0 Hz), 143.4
diastereomers 90/10). H NMR (200 MHz) dˆ0.78–0.95
2
1
(d, JPCˆ4.4 Hz), 146.0 (s), 148.0 (d, JPCˆ9.7 Hz); 31P
NMR (40.5 MHz, CDCl3) dˆ16.8. C16H18N3O2P (315.23):
calcd. C 60.95, H 5.75, N 13.33, P 9.82; found C 60.89, H
5.72, N 13.44, P 9.78.
(m, 15H), 1.44–1.90 (m, 4H), 2.15–2.29 (m, 1H), 3.08–
3
2
3
3.40 (m, 4H), 6.98 (t, JHHˆ7.2 Hz, 1H), 7.12–7.38 (m,
3
4
11H), 7.62 (dd, JHHˆ8.0 Hz, JHHˆ1.4 Hz, 2H); 13C
3
NMR (50 MHz) dˆ5.6 (s, 3C), 7.7 (s, 3C), 26.1 (d, JPCˆ
4.5 Hz), 30.4 (d, 3JPCˆ2.7 Hz), 45.3 (d, 2JPCˆ2.7 Hz), 49.3
2
2
(2R,5S)-2-(2-Methylphenoxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo-[3.3.0]-octane 2-oxide 1c. Purification by
column chromatography (silica gel; ethylacetate/petroleum
ether 75:25) afforded 1c as a white solid in 55% yield. Mp:
(d, JPCˆ16.9 Hz), 56.2 (d, JPCˆ11.1 Hz), 116.1 (d,
3JPCˆ4.4 Hz, 2C), 121.3 (s), 122.6 (d, JPCˆ2.5 Hz), 125.4
3
(s), 126.8 (s), 127.8 (s), 128.0 (s, 2C), 128.4 (s), 129.0 (s),
3
129.4 (s, 2C), 130.7 (s), 134.8 (d, JPCˆ4.4 Hz), 138.1 (s),
1
2
2
128ЊC; [a]2D5ˆϪ24 (cˆ0.2, CH2Cl2); H NMR (200 MHz,
141.2 (d, JPCˆ5.5), 148.2 (d, JPCˆ9.1 Hz); 31P NMR
(40.5 MHz) dˆ16.7 (anti) and 11.0 (syn). C29H37N2O2PSi
(504.68): calcd. C 69.02, H 7.39, N 5.55, P 6.14, Si 5.57;
found C 68.95, H 7.22, N 5.45, P 6.12, Si 5.48.
CDCl3) dˆ1.66–2.06 (m, 4H), 2.22 (s, 3H), 3.02–3.11 (m,
1H), 3.31–3.35 (m, 1H), 3.55–3.66 (m, 2H), 3.82–3.87 (m,
1H), 6.69–7.21 (m, 5H), 7.22–7.37 (m, 4H); 13C NMR
3
(50 MHz, CDCl3) dˆ16.4 (s), 26.0 (d, JPCˆ3.8 Hz), 32.4
3
2
2
(d, JPCˆ2.7 Hz), 46.7 (d, JPCˆ2.6 Hz), 49.7 (d, JPCˆ
(2R,5S)-2-Phenoxy-3-phenyl-1,3-diazaphosphabicyclo-
[3.3.0]-octane 2-thioxide 1g. Purification by column chro-
matography (silica gel; ethylacetate/petroleum ether 25:75)
afforded 1g as a white solid in 78% yield. Mp: 122ЊC;
2
3
17.6 Hz), 56.9 (d, JPCˆ10.1 Hz), 116.3 (d, JPCˆ4.3 Hz,
3
2C), 120.3 (d, JPCˆ2.5 Hz), 121.5 (s), 124.6 (s), 126.7 (s),
3
129.3 (s, 2C), 130.3 (d, JPCˆ4.4 Hz), 131.1 (s), 141.2 (d,
2JPCˆ5.7 Hz), 149.6 (d, 2JPCˆ9.0 Hz); 31P NMR (40.5 MHz)
dˆ15.6. C18H21N2O2P (328.13): calcd. C 65.84, H 6.45, N
8.53, P 9.43; found C 65.89, H 6.72, N 8.33, P 9.48.
[a]2D5ˆϪ8.3 (cˆ1, CH2Cl2); H NMR (200 MHz, CDCl3)
1
dˆ1.48–1.62 (m, 1H), 1.73–2.00 (m, 3H), 2.91–3.09 (m,
1H), 3.13–3.31 (m, 1H), 3.41–3.56 (m, 2H), 3.80–3.97 (m,
1H), 6.93–7.36 (m, 10H); 13C NMR (50 MHz, CDCl3)
3
3
(2R,5S)-2-(2,6-Dimethylphenoxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo-[3.3.0]-octane 2-oxide 1d. Purification by
column chromatography (silica gel; ethylacetate/petroleum
ether 80:20) afforded 1d as a white solid in 55% yield
(product obtained as a mixture of two diastereomers
90/10). 1H NMR (200 MHz, CDCl3) dˆ1.68–2.12 (m,
4H), 2.24 (s, 6H), 2.89–3.07 (m, 1H), 3.35–3.41 (m, 1H),
3.68–3.85 (m, 3H), 6.89–7.34 (m, 8H); 13C NMR (50 MHz,
CDCl3) dˆ17.4 (s, 2C), 26.0 (d, 3JPCˆ4.2 Hz), 32.4 (s), 47.3
dˆ26.1 (d, JPCˆ4.8 Hz), 31.8 (d, JPCˆ3.9 Hz), 47.4 (d,
2JPCˆ6.1 Hz), 52.4 (d, JPCˆ13.3 Hz), 58.7 (d, JPCˆ
2
2
3
6.2 Hz), 117.0 (d, JPCˆ4.3 Hz, 2C), 121.6 (s), 121.8 (d,
3JPCˆ8.8 Hz, 2C), 125.0 (s), 129.1 (s, 2C), 129.3 (s, 2C),
141.3 (d, 2JPCˆ7.2 Hz), 151.3 (d, 2JPCˆ12.8 Hz); 31P NMR
(40.5 MHz, CDCl3) dˆ71.5. C17H19N2OPS (330.10): calcd.
C 61.80, H 5.80, N 8.48, P 9.38, S 9.71; found C 61.50, H
5.80, N 8.42, P 9.42, S 9.68.
2
2
(d, JPCˆ2.6 Hz), 49.9 (d, JPCˆ18.8 Hz), 56.8 (d,
(2R,5S)-2-(2-Bromophenoxy)-3-phenyl-1,3-diazaphospha-
bicyclo-[3.3.0]-octane 2-thioxide 1h. Purification by
column chromatography (silica gel; ethylacetate/petroleum
ether 25:75) afforded 1h as a pale yellow solid in 69% yield.
Mp: 88ЊC; [a]2D5ˆϪ9.2 (cˆ0.6, CH2Cl2); 1H NMR
(200 MHz, CDCl3) dˆ1.67–1.78 (m, 1H), 1.86–2.07 (m,
3H), 3.11–3.22 (m, 1H), 3.36–3.44 (m, 1H), 3.63–3.83
(m, 2H), 3.94–4.05 (m, 1H), 7.06–7.51 (m, 8H), 7.62 (d,
3JHHˆ7.9 Hz, 1H); 13C NMR (50 MHz, CDCl3) dˆ26.1 (d,
3JPCˆ5.4 Hz), 31.8 (d, 3JPCˆ3.2 Hz), 47.8 (d, 2JPCˆ6.7 Hz),
2JPCˆ10.2 Hz), 117.2 (d, JPCˆ4.3 Hz, 2C), 121.9 (s),
3
124.6 (s), 129.0 (s, 2C), 129.2 (s, 2C), 130.3 (d,
3JPCˆ3.0 Hz, 2C), 141.2 (d, JPCˆ5.7 Hz), 149.6 (d,
2
2JPCˆ9.0 Hz); 31P NMR (40.5 MHz, CDCl3) dˆ17.2 (anti)
and 9.4 (syn). C19H23N2O2P (342.13): calcd. C 66.65, H
6.77, N 8.18, P 9.05; found C 66.89, H 6.72, N 8.33, P 9.18.
(2R,5S)-2-(2-Phenylphenoxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo-[3.3.0]-octane 2-oxide 1e. Purification by
column chromatography (silica gel; ethylacetate/petroleum
ether 67:33) afforded 1e as a white solid in 70% yield
(product obtained as a mixture of two diastereomers 95/5).
1H NMR (200 MHz) dˆ1.44–1.90 (m, 4H), 2.15–2.29 (m,
2
2
52.6 (d, JPCˆ14.0 Hz), 58.7 (d, JPCˆ7.2 Hz), 116.8 (d,
3JPCˆ5.7 Hz), 117.5 (d, JPCˆ5.6 Hz, 2C), 121.9 (s), 122.6
3
3
(d, JPCˆ4.2 Hz), 126.1 (s), 128.2 (s), 129.1 (s, 2C), 133.6
(s), 141.1 (d, JPCˆ6.0 Hz), 148.9 (d, JPCˆ11.6 Hz); 31P
NMR (40.5 MHz, CDCl3) dˆ71.7. C17H18N2OPSBr
(408.04): calcd. C 49.89, H 4.43, N 6.84, P 7.57, S 7.83, Br
19.52; found C 50.95, H 4.52, N 6.78, P 7.63, S 7.78, Br 20.01.
2
2
3
1H), 3.08–3.40 (m, 4H), 6.98 (t, JHHˆ7.2 Hz, 1H), 7.12–
3
4
7.38 (m, 12H), 7.62 (dd, JHHˆ8.0 Hz, JHHˆ1.4 Hz, 2H);
13C NMR (50 MHz) dˆ26.0 (d, JPCˆ4.3 Hz), 30.5 (d,
3
3JPCˆ2.8 Hz), 45.5 (d, JPCˆ2.8 Hz), 49.5 (d, JPCˆ
2
2
2
3
17.4 Hz), 56.5 (d, JPCˆ11.3 Hz), 116.1 (d, JPCˆ4.3 Hz,
General procedure for the anionic [1,3] rearrangement
3
2C), 121.4 (s), 122.1 (d, JPCˆ2.8 Hz), 125.3 (s), 127.0
(s), 127.9 (s), 128.2 (s, 2C), 128.4 (s), 128.9 (s), 129.3 (s,
To a stirred solution of the corresponding compounds 1a–h
(2.5 mmol) in dry THF (25 mL) under argon atmosphere was
slowly added at Ϫ78ЊC a solution of LDA (5 mmol, 2 M in
THF, 2.5 mL). The mixture was allowed to warm to room
temperature and quenched by addition of a saturated solution
of NH4Cl (20 mL). The product was extracted with
3
2C), 130.9 (s), 134.8 (d, JPCˆ4.4 Hz), 138.1 (s), 141.3 (d,
2JPCˆ5.8 Hz), 148.0 (d, 2JPCˆ8.9 Hz); 31P NMR
(40.5 MHz, CDCl3) dˆ16.8 (anti) and 11.1 (syn).
C23H23N2O2P (390.15): calcd. C 70.76, H 5.94, N 7.18, P
7.93; found C 70.95, H 6.02, N 7.25, P 7.98.

602
O. Legrand et al. / Tetrahedron 56 (2000) 595–603
ethylacetate ꢀ3×10 mL†: The combined organic phases were
driedoverMgSO4, filteredandevaporatedunderreducedpres-
sure. The residue was purified by chromatography or crystal-
lization.
8.0 Hz); 31P NMR (40.5 MHz) dˆ33.9. C23H23N2O2P
(390.15): calcd. C 70.76, H 5.94, N 7.18, P 7.93; found C
70.91, H 6.02, N 7.12, P 7.98.
(2S,5S)-2-(2-Hydroxyphenyl)-3-phenyl-1,3-diazaphospha-
bicyclo-[3.3.0]-octane 2-thioxide 12. To a stirred solution
of 1g (530 mg, 1.3 mmol) in dry THF (15 mL) under argon
atmosphere was slowly added at Ϫ78ЊC a solution of
n-BuLi (1.4 mmol, 2.5 M in hexanes, 0.56 mL). The
mixture was allowed to warm to room temperature and
stirred overnight. After quenching by addition of a satu-
rated solution of NH4Cl (10 mL), the product was
extracted with dichloromethane (3×10 mL). The
combined organic phases were dried over MgSO4,
filtered and evaporated under reduced pressure. Purifi-
cation by column chromatography (silica gel; ethyl-
acetate/petroleum ether 50:50) afforded 12 as a white
solid in 88% yield. Mp: 147ЊC; [a]2D5ˆϩ95 (cˆ1.38,
CH2Cl2); 1H NMR (200 MHz, CDCl3) dˆ1.86–2.26
(m, 4H), 2.96–3.09 (m, 1H), 3.47–3.57 (m, 1H),
3.85–4.06 (m, 1H), 4.18–4.25 (m, 1H), 6.87–7.02 (m,
(2S,5S)-2-(2-Hydroxy-4-pyridinyl)-3-phenyl-1,3-diaza-
2-phosphabicyclo-[3.3.0]-octane 2-oxide 6. Purification by
crystallization in diethylether afforded 6 as a pale yellow
solid in 75% yield. Mp: 176ЊC; [a]2D5ˆϩ43.6 (cˆ0.28,
1
CH2Cl2); H NMR (200 MHz, CDCl3) dˆ1.74–1.87 (m,
1H), 1.94–2.23 (m, 3H), 2.95–3.04 (m, 1H), 3.53–3.60
(m, 1H), 3.68–3.79 (m, 1H), 3.91–4.11 (m, 2H), 6.90 (t,
3
3JHHˆ7.6 Hz, 1H), 6.96 (d, JHHˆ7.5 Hz, 2H), 6.96–7.20
3
3
(m, 1H), 7.21 (dd, JHHˆ7.6 Hz, JHHˆ7.5 Hz, 2H), 8.03
3
3
3
(dd, JHHˆ4.8 Hz, JPHˆ4.2 Hz, 1H), 8.37 (d, JPHˆ
7.4 Hz, 1H), 10.92 (s, OH); 13C NMR (50 MHz, CDCl3)
3
2
dˆ26.7 (d, JPCˆ2.5 Hz), 32.3 (s), 44.6 (s), 49.7 (d, JPCˆ
2
3
14.4 Hz), 60.1 (d, JPCˆ5.8 Hz), 116.7 (d, JPCˆ4.6 Hz),
1
2
120.7 (d, JPCˆ159.6 Hz), 122.6(s), 123.8 (d, JPCˆ
3
5.8 Hz), 129.5 (s, 2C), 140.1 (d, JPCˆ11.6 Hz), 140.5
2
3
(d, JPCˆ5.4 Hz), 141.5 (d, JPCˆ9.1 Hz), 157.6 (d,
2JPCˆ5.4 Hz); 31P NMR (40.5 MHz, CDCl3) dˆ30.0.
C16H18N3O2P (315.23): calcd. C 60.95, H 5.75, N
13.33, P 9.82; found C 60.92, H 5.82, N 13.44, P 9.88.
3
4
2H), 7.07 (dd, JHHˆ7.9 Hz, JHHˆ1.0 Hz, 2H), 7.27
3
3
(dd, JHHˆ7.6 Hz, JPHˆ7.3 Hz, 2H), 7.36–7.59 (m,
3H), 10.35 (s, OH); 13C NMR (50 MHz, CDCl3)
3
2
dˆ26.8 (d, JPCˆ3.0 Hz), 31.5 (s), 45.8 (d, JPCˆ
2
2
(2S,5S)-2-(2-Hydroxy-3-methylphenyl)-3-phenyl-1,3-
diaza-2-phosphabicyclo-[3.3.0]-octane 2-oxide 7. Purifi-
cation by column chromatography (silica gel; ethylacetate/
petroleum ether 80:20) afforded 7 as a white solid in 70%
yield. Mp: 202ЊC; [a]2D5ˆϩ37.7 (cˆ1.34, CH2Cl2); 1H NMR
(200 MHz, CDCl3) dˆ1.73–2.23 (m, 4H), 2.15 (s, 3H),
2.93–3.03 (m, 1H), 3.54–3.61 (m, 1H), 3.71–3.79 (m,
3.4 Hz), 51.7 (d, JPCˆ12.8 Hz), 61.1 (d, JPCˆ2.8 Hz),
1
3
101.0 (d, JPCˆ151.0 Hz), 118.1 (d, JPCˆ5.2 Hz, 2C),
3
3
118.8 (d, JPCˆ9.8 Hz), 119.6 (d, JPCˆ13.1 Hz), 122.1
2
(s), 129.0 (s, 2C), 131.4 (d, JPCˆ8.2 Hz), 134.3 (s),
141.4 (d, JPCˆ5.8 Hz), 160.7 (d, JPCˆ8.7 Hz); 31P
NMR (40.5 MHz, CDCl3) dˆ70.2. C17H19N2OPS
(330.10): calcd. C 61.80, H 5.80, N 8.48, P 9.38, S
9.71; found C 61.75, H 5.75, N 8.43, P 9.28, S 9.63.
2
2
3
3
1H), 3.88–4.08 (m, 2H), 6.67 (ddd, JHHˆ7.6 Hz, JHH
ˆ
4
3
7.4 Hz, JPHˆ3.4 Hz, 1H), 6.89 (t, JHHˆ7.2 Hz, 1H), 6.98
(d, 3JHHˆ8.4 Hz, 2H), 7.06 (d, 3JHHˆ7.6 Hz, 1H), 7.18 (dd,
3JHHˆ8.4 Hz, 3JHHˆ7.2 Hz, 2H), 7.15–7.26 (m, 1H), 11.26
(s, OH); 13C NMR (50 MHz, CDCl3) dˆ16.2 (s, CH3), 26.7
(s), 32.3 (s), 44.6 (s), 49.7 (d, 2JPCˆ13.3 Hz), 60.0 (d, 2JPCˆ
(2R,5S)-2-Phenylthio-3-phenyl-1,3-diazaphosphabicyclo-
[3.3.0]-octane 2-oxide 13 and (2S,5S)-2-phenylthio-3-
phenyl-1,3-diazaphosphabicyclo-[3.3.0]-octane 2-oxide 14.
In a two-necked round flask an equimolar mixture of
tris(dimethylamino)phosphine 2 (5 mmol, 0.82 g) and (S)-
(ϩ)-2-anilinomethylpyrrolidine 3 (5 mmol, 0.88 g) were
placed in dry toluene (10 mL) under argon atmosphere
and warmed at 110ЊC for 3 h. Then 1 equiv. of thiophenol
was added at room temperature and the mixture was
warmed at 110ЊC for 1 h. The mixture was allowed to
cool to room temperature and the toluene was removed
in vacuo. The crude phosphine was diluted with
dichloromethane (15 mL) and the mixture was cooled at
0ЊC. Then tert-butyl hydroperoxide 0.9 mL (5.5 M, decane),
was slowly added and the mixture was stirred for 3 h. After
removing the solvent in vacuo, the crude product was puri-
fied by chromatography (silica gel; ethylacetate/petroleum
ether 75:25) and afforded the two diastereomers 13 and 14
as white solids in, respectively, 68 and 11% chemical yield.
Analytical data for 13: mp: 222ЊC; [a]2D5ˆϪ155 (cˆ0.985,
1
3
5.9 Hz), 112.2 (d, JPCˆ162.9 Hz), 116.5 (d, JPCˆ5.4 Hz,
3
3
2C), 118.9 (d, JPCˆ14.9 Hz), 121.8 (s), 126.6 (d, JPCˆ
2
11.4 Hz), 128.9 (d, JPCˆ7.3 Hz), 129.3 (s, 2C), 135.1 (d,
4JPCˆ2.6 Hz), 141.2 (d, JPCˆ6.9 Hz), 161.1 (d, JPCˆ
7.2 Hz); 31P NMR (40.5 MHz, CDCl3) dˆ33.9.
C18H21N2O2P (328.13): calcd. C 65.84, H 6.45, N 8.53, P
9.43; found C 65.79, H 6.72, N 8.43, P 9.50.
2
2
(2S,5S)-2-(2-Hydroxy-3-biphenyl)-3-phenyl-1,3-diaza-2-
phosphabicyclo-[3.3.0]-octane 2-oxide 10. Purification by
column chromatography (silica gel; ethylacetate/petroleum
ether 50:50) afforded 10 as a white solid in 82% yield. Mp:
152ЊC; [a]2D0ˆϩ237 (cˆ0.18, CH2Cl2); 1H NMR
(200 MHz) dˆ1.80–2.20 (m, 4H), 3.00–3.05 (m, 1H),
3.58–3.65 (m, 1H), 3.77–3.85 (m, 1H), 3.94–4.15 (m,
2H), 6.81–6.93 (m, 2H), 7.06 (d, Jˆ8.2 Hz, 2H), 7.14–
3
1
7.26 (m, 3H), 7.35–7.49 (m, 4H), 7.62 (ddd, JHHˆ8.4 Hz,
CH2Cl2); H NMR (200 MHz, CDCl3) dˆ1.44–1.55 (m,
4
4JHHˆ2.0 Hz, JHHˆ1.6 Hz, 2H), 11.55 (s, OH); 13C NMR
1H), 1.86–2.03 (m, 3H), 2.70–2.77 (m, 1H), 3.02–3.20
(50 MHz) dˆ26.7 (d, 3JPCˆ2.3 Hz), 32.4 (s), 44.7 (d, 2JPCˆ
(m, 3H), 3.78–3.92 (m, 1H), 7.03 (t, JHHˆ7.2 Hz, 1H),
3
2
3
2.2 Hz), 49.7 (d, JPCˆ13.4 Hz), 60.0 (d, JPCˆ5.6 Hz),
7.16–7.21 (m, 5H), 7.22–7.37 (m, 4H); 13C NMR
1
3
3
113.3 (d, JPCˆ162.3 Hz), 116.6 (d, JPCˆ4.7 Hz, 2C),
(50 MHz, CDCl3) dˆ26.1 (d, JPCˆ2.4 Hz), 32.7 (d,
3
2
2
119.4 (d, JPCˆ14.6 Hz), 121.9 (s), 127.2 (s), 128.1 (s,
3JPCˆ2.7 Hz), 44.4 (d, JPCˆ2.6 Hz), 48.5 (d, JPCˆ
2C),129.4 (s, 2C) 129.5 (s, 2C), 130.3 (d, JPCˆ11.5 Hz),
13.0 Hz),
58.3
(d,
2JPCˆ6.5 Hz),
116.9
2
(d,
3
4
130.8 (d, JPCˆ7.3 Hz), 135.3 (d, JPCˆ2.3 Hz), 137.9 (d,
3JPCˆ4.4 Hz, 2C), 121.9 (s), 128.1 (d, JPCˆ6.5 Hz),
2
4JPCˆ2.7 Hz), 141.2 (d, JPCˆ5.8 Hz), 160.0 (d, JPCˆ
128.6 (d, JPCˆ2.6 Hz, 2C), 129.0 (s, 2C), 129.1 (s),
2
2
4

O. Legrand et al. / Tetrahedron 56 (2000) 595–603
603
3
2
136.1 (d, JPCˆ4.3 Hz, 2C), 140.8 (d, JPCˆ7.1 Hz); 31P
NMR (40.5 MHz, CDCl3) dˆ35.9. C17H19N2OPS
(330.10): calcd. C 61.80, H 5.80, N 8.48, P 9.38, S
9.71; found C 60.75, H 5.75, N 8.33, P 9.28, S 9.62.
Analytical data for 14: mp: 216ЊC; [a]2D5ˆϩ140
(cˆ0.93, CH2Cl2); 1H NMR (200 MHz, CDCl3)
membered phosphorus-containing ring, we call it a syn diastereo-
mer; otherwise, it is an anti diastereomer. (a) Cros, P.; Buono, G.;
Peiffer, G.; Denis, D.; Mortreux, A.; Petit, F. New J. Chem. 1987,
11, 573. (b) Arzoumanian, H.; Buono, G.; Choukrad, M’B.;
Petrignani, J. F. Organometallics 1988, 7, 59. (c) Brunel, J. M.;
Chiodi, O.; Faure, B.; Fotiadu, F.; Buono, G. J. Organomet. Chem.
1997, 529, 285.
3
dˆ1.72–2.03 (m, 4H), 2.55 (t, JHHˆ8.6 Hz, 1H),
3.20–3.28 (m, 1H), 3.52–3.70 (m, 2H), 3.87–3.94 (m,
8. Melvin, L. S. Tetrahedron Lett. 1981, 22, 3375.
1H), 6.95–7.45 (m, 10H); 13C NMR (50 MHz, CDCl3)
9. X-Ray analysis of 6:
A plate white monocrystal of
3
3
dˆ27.4 (d, JPCˆ6.8 Hz), 31.3 (d, JPCˆ4.2 Hz), 42.7
C16H18N3O2P, obtained by recrystallization in ethylacetate, with
approximate dimensions 0:5×0:4×0:4 mm was mounted on a
glass capillary. All the measurements were made on a Rigaku
diffractometer with Mo-Ka radiation. Cell constants and the orien-
tation matrix for data collection were obtained from a least-square
refinement using setting angles of 30 reflections in the range
uˆ1–25Њ; which corresponded to a monoclinic cell with dimen-
2
2
(d, JPCˆ6.6 Hz), 52.4 (d, JPCˆ10.9 Hz), 57.6 (d,
2JPCˆ10.3 Hz), 116.5 (d, JPCˆ4.7 Hz, 2C), 121.8 (s),
3
2
4
127.8 (d, JPCˆ7.2 Hz), 129.1 (d, JPCˆ2.3 Hz, 2C),
3
129.3 (s, 2C), 136.0 (d, JPCˆ4.5 Hz, 2C), 141.8 (d,
2JPCˆ7.0 Hz); 31P NMR (40.5 MHz, CDCl3) dˆ26.5.
C17H19N2OPS (330.10): calcd. C 61.80, H 5.80, N
8.48, P 9.38, S 9.71; found C 61.75, H 5.89, N 8.43,
P 9.50, S 9.63.
ꢀ
sions: aˆ23:2509ꢀ8†; bˆ9:9621ꢀ3†; cˆ16:1614ꢀ6† A: For Zˆ8 and
Mˆ315:31; rcalcdˆ1:25 g cmϪ3: The space group was determined
to be C2/c from the systemic absences. A total of 3098 reflections
were collected at Tˆ298 K: The standards were measured after
every 120 reflections. Among the first 200 pairs of reflections,
the signs of the corresponding calculated differences, establishing
that the molecule is described with the correct absolute configura-
tion S. CCDC 132971.
(2S,5S)-2-(2-Sulfanylphenyl)-3-phenyl-1,3-diazaphospha-
bicyclo-[3.3.0]-octane 2-oxide 15. Classical procedure has
been used for the preparation of 15 from diastereomerically
pure precursor 13. Purification by column chromatography
(silica gel; ethylacetate/petroleum ether 25:75) afforded 15
as a white solid in 20% yield. Mp: 104ЊC; [a]2D5ˆϩ22.1
10. Depending on the nature of the substituents bound to the phos-
phorus atom, the absolute configurations of both the substrate and
product are different. This absolute configuration was established
by considering the PyO bond as Pϩ–OϪ according to Mikolajczyk
et al.: (a) Mikolajczyk, M.; Omelanzuk, J.; Paru, M. Tetrahedron
1972, 28, 3855 and references cited therein. (b) Dowden, H. In
Organophosphorus Stereochemistry, Part II: P(V) Compounds;
McEwen, W. E.; Berlin, K. D., Eds., Pennsylvania, 1975. (c)
Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
Wiley: New York, 1994; pp 138–139.
1
(cˆ1, CH2Cl2); H NMR (200 MHz, CDCl3) dˆ1.86–2.26
(m, 4H), 2.96–3.09 (m, 1H), 3.47–3.57 (m, 1H), 3.85–4.06
(m, 1H), 4.18–4.25 (m, 1H), 6.87–7.02 (m, 2H), 7.07 (dd,
3JHHˆ7.9 Hz, JHHˆ1.0 Hz, 2H), 7.27 (dd, JHHˆ7.6 Hz,
3JPHˆ7.3 Hz, 2H), 7.36–7.59 (m, 3H), 10.35 (s, OH); 13C-
NMR (50 MHz, CDCl3) dˆ26.8 (s), 32.3 (s), 44.5 (s), 49.6
(d, 2JPCˆ11.5 Hz), 59.9 (s), 103.6 (d, 1JPCˆ162.0 Hz), 116.4
4
3
3
3
(d, JPCˆ5.4 Hz, 2C), 117.6 (d, JPCˆ11.6 Hz), 119.3 (d,
3JPCˆ14.1 Hz), 121.8 (s), 129.2 (s, 2C), 130.7 (d, JPCˆ
2
2
6.7 Hz), 131.3 (d, JPCˆ8.4 Hz), 134.3 (s), 141.4 (d,
11. Wang, W.; Snieckus, V. J. Org. Chem. 1992, 57, 424.
12. X-Ray analysis of 10: A plate white monocrystal of
C23H23N2O2P, obtained by recrystallization in ethylacetate, with
approximate dimensions 0:4×0:3×0:2 mm was mounted on a
glass capillary. All the measurements were made on a Rigaku
diffractometer with Mo-Ka radiation. Cell constants and the orien-
tation matrix for data collection were obtained from a least-square
refinement using setting angles of 30 reflections in the range
uˆ1–25Њ; which corresponded to an orthorhombic cell with dimen-
2JPCˆ5.7 Hz); 31P NMR (40.5 MHz, CDCl3) dˆ30.9.
C17H19N2OPS (330.10): calcd. C 61.80, H 5.80, N 8.48, P
9.38, S 9.71; found C 61.75, H 5.89, N 8.54, P 9.48, S 9.53.
References
1. For a review, see: Buono, G.; Chiodi, O.; Wills, M. Synlett
1999, 377.
2. (a) Brunel, J. M.; Constantieux, T.; Legrand, O.; Buono, G.
Tetrahedron Lett. 1998, 39, 2961. (b) Legrand, O.; Brunel, J. M.;
Buono, G. Tetrahedron Lett. 1998, 39, 9419.
3. Brunel, J. M.; Legrand, O.; Buono, G. Tetrahedron: Asymmetry
1999, 10, 1979.
4. Legrand, O.; Brunel, J. M.; Constantieux, T.; Buono, G. Chem.
Eur. J. 1998, 4, 1061.
ꢀ
sions: aˆ9:620ꢀ1†; bˆ9:675ꢀ1†; cˆ21:729ꢀ1† A: For Zˆ4 and
Mˆ390:42; rcalcdˆ1:25 g cmϪ3: The space group was determined
to be P212121 from the systemic absences. A total of 2278 reflec-
tions were collected at Tˆ298 K: The standards were measured
after every 120 reflections. Among the first 200 pairs of reflections,
the signs of the corresponding calculated differences, establishing
that the molecule is described with the correct absolute config-
uration S. CCDC 132970
5. Legrand, O.; Brunel, J. M.; Buono, G.; Eur. J. Org. Chem. 1999,
1099.
13. (a) Fu, J.-M.; Sharp, M. J.; Snieckus, V. Tetrahedron Lett.
1988, 29, 5459. (b) Fu, J.-M.; Zhao, B.-P.; Sharp, M. J.; Snieckus,
V. J. Org. Chem. 1991, 56, 1683.
14. (a) Yoshifuji, M.; Ishizuka, T.; Choi, Y. J.; Inamoto, N.
Tetrahedron Lett. 1984, 25, 553. (b) Craig, D. C.; Roberts, K. C.;
Transwell, J. L. Aust. J. Chem. 1990, 43, 1487.
15. (a) Masson, S.; Saint-Clair, J.-F.; Saquet, M. Synthesis 1993,
485. (b) Masson, S.; Saint-Clair, J.-F.; Dore, A.; Saquet, M. Bull.
Soc. Chim. Fr. 1996, 133, 951.
16. Watanabe, M.; Date, M.; Kawanishi, K.; Akiyoshi, R.;
Furukawa, S. J. Heterocycl. Chem. 1991, 28, 173.
6. On the other hand, treatment of such precursors prepared from
(S)-2-anilinomethyl pyrrolidine with an excess of LDA led to the
formation of products resulting from an original ring-expan-
sion reaction of the diazaphospholidine ring via a totally
stereospecific P–N to P–C migration rearrangement. Legrand,
O.; Brunel, J. M.; Buono, G. Angew. Chem., Int. Ed. Engl.
1999, 38, 1479.
7. The notations of the syn and anti diastereomers are according to
the methylene substituent of the pyrrolidine ring with respect to the
extracyclic aryl group. If they are at the same side of the five