Totally stereoselective P-O to P-C migration rearrangement: Application to the synthesis of new chiral O-hydroxyaryl phosphine oxides

Article abstract of DOI:10.1002/(SICI)1521-3765(19980615)4:6<1061::AID-CHEM1061>3.0.CO;2-V

The synthesis of a novel class of chiral o-hydroxyaryl phosphine oxides by the rearrangement of a P-O to a P-C bond is described. This reaction proceeds with excellent yields (75-95%) and total retention of the configuration on the phosphorus atom. In the case of the treatment of an equimolar mixture of the diastereomers anti-2e and syn-2f, the resulting compounds anti-3e and syn-3f, obtained in a 1:1 molar ratio, were separated and characterized by X-ray diffraction. On the basis of the experimental results, we suggest that the migration mechanism is addition-pseudorotation-elimination; this explains the total stereoselectivity observed at the phosphorus atom.

Full text of DOI:10.1002/(SICI)1521-3765(19980615)4:6<1061::AID-CHEM1061>3.0.CO;2-V

FULL PAPER
Totally Stereoselective P ± O to P ± C Migration Rearrangement: Application
to the Synthesis of New Chiral o-Hydroxyaryl Phosphine Oxides
Olivier Legrand, Jean Michel Brunel, Thierry Constantieux, and GeÂrard Buono*
Abstract: The synthesis of a novel class of chiral o-hydroxyaryl phosphine oxides by
the rearrangement of a P ± O to a P ± C bond is described. This reaction proceeds with
excellent yields (75 ± 95%) and total retention of the configuration on the
phosphorus atom. In the case of the treatment of an equimolar mixture of the
diastereomers anti-2e and syn-2 f, the resulting compounds anti-3e and syn-3 f,
obtained in a 1:1 molar ratio, were separated and characterized by X-ray diffraction.
On the basis of the experimental results, we suggest that the migration mechanism is
addition ± pseudorotation ± elimination; this explains the total stereoselectivity
observed at the phosphorus atom.
Keywords: asymmetric synthesis ´
chirality ´ phosphane oxides ´ reac-
tion mechanisms ´ rearrangements
of the amino alcohol under consideration, an epimerization at
the C4 methyl group occurred and an elimination product was
formed. Thus, these results show that a general retention of
the configuration on the phosphorus cannot be unambigu-
ously postulated for the P ± O to P ± C rearrangement. In this
paper, we report a new general procedure for the preparation
of various chiral o-hydroxyaryl diazaphospholidine oxides, o-
hydroxyaryl oxazaphospholidine oxides, or o-hydroxyaryl-
Introduction
In the last 30 years, considerable developments have been
achieved for asymmetric transition metal catalyzed systems[1]
with chiral ligands such as phosphines and, more recently,
phosphorus/nitrogen bidentate donor compounds.[2, 3] In this
area, phosphorus analogues of salicylic aldehyde derivatives,
such as o-hydroxyphenyldialkylphosphine oxides or phos-
phonic acids, may exhibit similar properties.[4] Nevertheless,
few methods for the synthesis of such compounds have been
proposed. In 1981, Melvin reported the synthesis of o-
hydroxyarylphosphonates by the rearrangement of arylphos-
phates induced by a strong base, such as lithium diisopropyl-
amide (LDA) or n-butyllithium.[5] Although the usefulness of
this synthetic method has been extensively developed,[6] few
mechanistic studies have been performed and the rearrange-
ment was considered to take place via an ortho-stabilized
carbanion. The formation of the ortho-lithiated species was
corroborated by Watanabe et al.[7] and Casteel and Peri,[8] who
were able to trap the lithiated intermediate at 1058C. When
the reaction temperature was allowed to rise to 788C, the
rearrangement proceeded rapidly to afford quantitative yields
of the o-hydroxyaryl phosphine oxide compound. Moreover,
only Welch et al. probed the synthesis of such chiral com-
pounds from ( )-ephedrine.[9] Nevertheless, due to the nature
ˆ
phosphonates which feature a basic (P O) and an acid site
(OH) and involve a stereoselective P ± O to P ± C rearrange-
ment. We have investigated the unambiguous stereoselectiv-
ity of this reaction at the phosphorus atom in various cases,
and we propose a mechanistic pathway based on detailed
experiments.
Results and Discussion
Already well-known in the synthesis of organoalkoxysilyl-
phenols, the direct metalation of o-halogenoaryloxy deriva-
tives of tin and phosphorus seems to be a general method for
the preparation of hydroxyaryl tin or phosphorus deriva-
tives.[1, 10, 11] This reaction proceeds via an unstable metalated
intermediate which undergoes a fast 1,3-rearrangement with
formation of an element ± carbon bond. Thus, by the use of a
modified procedure, the synthesis of chiral hydroxyaryl
phosphine oxides 3 may be achieved in a two-step reaction
(Scheme 1).
[*] Prof. G. Buono, Dr. J. M. Brunel, Dr. T. Constantieux, O. Legrand
Â
Á
Â
Â
Â
Ecole Nationale Superieure de Synthese, de Procedes et dꢀIngenierie
Chimiques dꢀAix Marseille
Precursors 2 were readily available from exchange reac-
tions between an aryl phosphorodichloridate and various
chiral substrates, such as amino alcohols, diamines, or diols
with high yields ranging from 76 to 95% (Table 1). Only one
Â
 Ã
UMR CNRS 6516, Faculte de St Jerome
Av. Escadrille Normandie Niemen, 13397 Marseille, Cedex 20 (France)
Fax : (‡ 33)4-91-02-77-76
E-mail: buono@spi.chim.u-3mrs.fr
Chem. Eur. J. 1998, 4, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1061 $ 17.50+.25/0
1061

G. Buono et al.
FULL PAPER
Table 1. Synthesis of precursors 2.
Scheme 1. General procedure for the synthesis of o-hydroxyaryl phos-
phine oxides.
diastereomer is obtained when the chiral auxiliary is of C2
symmetry (entries 5 ± 8). In the other cases, the formation of
the two expected diastereomers was observed in a diastereo-
meric ratio ranging from 75:25 (entry 2) to 50:50 (entry 3),
depending on the nature of the chiral moiety.[12] Moreover, all
attempts to separate the diastereomers failed, except for
entry 2 where diasteromers anti-2c and syn-2d were cleanly
separated by column chromatography and then fully charac-
terized by NMR spectroscopic analysis.[13]
A subsequent P ± O to P ± C rearrangement on treatment of
a mixture of the two diastereomers, anti-2 and syn-2 in a
1:1 molar ratio, with LDA in THF at 788C led to a 50:50
mixture of diastereomers anti-3 and syn-3 (Table 2). In most
cases, these diastereomers were successfully separated by
column chromatography in yields ranging from 80 to 95% for
each diastereomer. Thus, in contrast to the reported proce-
dures, this method allows the synthesis of the two diaster-
eomers anti-3 and syn-3.[15] In the case of entry 4, the
structures of diastereomer anti-3e and syn-3 f have been
clearly established by 1H, 13C, and 31P NMR spectroscopy and
X-ray analysis (Figures 1 and 2).[16]
In order to demonstrate the stereoselectivity of the
mechanism involved in this reaction, a pure sample of
compound anti-3e was prepared by oxidation of the corre-
sponding chiral phosphine 4. Subsequent treatment with LDA
at 788C resulted in the migration of the phosphinyl group
from oxygen to carbon to produce anti-3e stereoselectively in
89% yield (Scheme 2). Thus, the results observed from
diastereomerically pure anti-2c, syn-2d, and anti-2g clearly
[a] Diastereomeric ratio determined by 31P NMR spectroscopy. [b] Isolated
yield after column chromatography. [c] Pure diastereomers separated by
column chromatography (see the Experimental Section). [d] Inseparable
mixture of diastereomers.
show that the rearrangement proceeds by a totally stereo-
selective reaction at the phosphorus atom.[17]
Since it was established that the stereochemistry of the 1,3-
phosphorus migration operates with retention of configura-
tion at the phosphorus atom, a mechanism proceeding via a
trigonal bipyramidal intermediate (TBP) can be postulated
(Scheme 3).[18] This retention of configuration may be ex-
plained by an apical addition followed by an equatorial
elimination (intermediates 6a and 6b) or the opposite
pathway suggesting an equatorial addition followed by an
apical elimination (intermediates 7a and 7b). However,
Mislow et al.[19] suggest that if the bond-making or -breaking
step is rate-determining, then apical addition and elimination
will be more favorable than either equatorial addition and
apical elimination or the opposite pathway. Thus, for associa-
tive processes with strong nucleophiles, it is generally assumed
that the nucleophile approaches a trigonal face of the
tetrahedral phosphorus center to form a pentacoordinate
intermediate with the entering nucleophile in apical position
Á
Abstract in French: La synthese dꢀune nouvelle classe dꢀoxyde
Â
dꢀo-hydroxyaryl phosphines chirales via le rearrangement
dꢀune liaison P ± O en liaison P ± C est decrite. Cette reaction
sꢀeffectue avec dꢀexcellents rendements chimiques (75 a 95%)
et une totale retention de configuration au niveau de lꢀatome de
Â
Â
Á
Â
Â
phosphore. Dans le cas de la transposition dꢀun melange
Â
 Â
Á
equimolaire des deux diastereomeres anti-2e et syn-2 f, les
Â
Â
composes resultants anti-3e et syn-3 f obtenus dans un rapport
molaire 1:1 ont pu etre separes et caracterises par diffraction
des rayons X. Sur la base de nombreux resultats experimen-
taux, le passage par un mecanisme de type addition ± pseudo-
Ã
Â
Â
Â
Â
Â
Â
Â
Â
Ã
Â
rotation ± elimination a pu etre propose et permet ainsi de
 Â
Â
Â
Â
justifier de la totale stereoselectivite observee au niveau de
lꢀatome de phosphore.
1062
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1062 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 6

Stereoselective P±O to P±C Rearrangement
1061±1067
Table 2. Preparation of compounds 3 by a stereoselective P ± O to P ± C
rearrangement of precursors 2.
Figure 1. Structure of anti-3e, showing the labeling scheme. Selected bond
lengths [Š] and angles [8]: P ± O1 1.485(2), P ± N1 1.667(2), P ± N2 1.622(2),
P ± C12 1.790(2), O2 ± C13 1.356(3); O1-P-N1 117.87(9), O1-P-N2 117.64(9),
O1-P-C12 107.89(9), N1-P-N2 94.29(9), N1-P-C12 107.71(9), N2-P-C12
110.7(1), P-N1-C5 114.4(1), P-N1-C6 125.4(1), C5-N1-C6 119.8(2), P-N2-C1
128.4(2), P-N2-C4 115.3(1).
[a] Isolated yield based on the proportion of each diastereomer in the
starting material mixture. [b] See ref. [14]. [c] The rearrangement proceeds
with a totally stereoselective reaction at the phosphorus atom. [d] Re-
arrangement of pure precursor anti-2 led stereoselectively to pure
compound anti-3. [e] A mixture of various nonidentified products was
obtained.
of the TBP (apical attack).[20] Ortho-phenyl anion attack at
one of the adjacent faces of the tetrahedron of 5, in line with
one of the nitrogen atoms of the diazaphospholane ring, leads
to TBP intermediates 6a or 6b in which the four-membered
oxaphosphetane ring and the five-membered diazaphospho-
lane ring adopt an axial ± equatorial position[21±24] and the
electron-donating oxygen anion ligand an equatorial posi-
tion.[25±27] For these TBP intermediates it is possible to
consider a low-energy Berry pseudorotation[28] 6a > 7a and
6b > 7b spanning the more apicophilic oxygen atom of the
oxaphosphetane ring in an apical position. The extracyclic
oxygen anion group tends to remain equatorial throughout
the pseudorotation process by serving as a pivot. These
pseudorotational processes permit overall apical introduction
of the ortho-stabilized carbanion and apical departure of the
Figure 2. Structure of syn-3 f showing the labeling scheme. Selected bond
lengths [Š] and bond angles [8]: P ± O1 1.474(8), P ± C12 1.82(1), P ± N1
1.66(1), P ± N2 1.64(1), O2 ± C13 1.34(2); O1-P-N1 116.9(5), O1-P-N2
115.9(5), O1-P-C12 106.7(5), N1-P-N2 93.3(5), N1-P-C12 111.3(5), N2-P-
C12 112.5(6), P-N1-C5 114.4(8), P-N1-C6 124.1(8), C5-N1-C6 120.(1), P-
N2-C1 127.8(9), P-N2-C4 113.9(9).
leaving group in agreement with the principle of microscopic
reversibility.[20, 29, 30] Moreover, by considering an associative
process, the inversion of the configuration at the phosphorus
atom is energetically unfavorable since it involves the
epimerization of the phosphorus PV atom in the TBP
Chem. Eur. J. 1998, 4, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1063 $ 17.50+.25/0
1063

G. Buono et al.
FULL PAPER
experimentally observed retention of
configuration at the phosphorus atom.
Additional studies concerning the use of
such compounds as catalysts in various
asymmetric catalyzed reactions as well as
potential biological activities are current-
ly under investigation.[33]
Scheme 2. Synthesis of pure anti-3e.
Experimental Section
1
Materials and methods: H NMR, 13C NMR, and
31P NMR spectra were recorded on Bruker AC100
and AC200 spectrometers in CDCl3. The chemical
shifts (ppm) were determined relative to Me4Si
(1H and 13C) and 85% H3PO4 (31P). Toluene,
tetrahydrofuran (THF), and diethyl ether were
distilled from sodium/benzophenone ketyl imme-
diately prior to use. Ethyl acetate and petroleum
ether (35 ± 608C) were purchased from SDS and
used without any further purification. Column
chromatography was performed on Merck silica
gel (70 ± 230 mesh).
General procedure for the preparation of com-
pounds 2a ± l: phenyldichlorophosphate (1.64 mL,
11 mmol) was added dropwise at 08C to a solution
of the corresponding chiral amino alcohol, dia-
mine, or diol (10 mmol) and freshly distilled NEt3
(3.8 mL, 30 mmol) in dry THF (25 mL). The
mixture was stirred under N2 at RT overnight,
then filtered to remove Et3NHCl. The solvent was
evaporated under reduced pressure. The crude
product was purified by flash chromatography on
a silica gel column to give the pure compound.
(2S,4R,5S)-3,4-Dimethyl-2-phenoxy-5-phenyl-1,3-
,2-oxazaphospholidine
2-oxide
(2a)
and
(2R,4R,5S)-3,4-dimethyl-2-phenoxy-5-phenyl-1,3-
,2-oxazaphospholidine 2-oxide (2b): Purification
by column chromatography (silica gel; ethyl
acetate/petroleum ether 90:10) afforded 2a as a
white solid in 57% yield and 2b as a white solid in
12% yield.
Scheme 3. Possible mechanism for the stereoselective P ± O to P ± C migration rearrangement.
2a: M.p. 948C; [a]D25
ˆ
102.0 (c ˆ 1, CH2Cl2); 31P NMR (40.5 MHz,
intermediates. Such an epimerization implies high-energy
CDCl3): d ˆ 13.5; 1H NMR (200 MHz, CDCl3): d ˆ 0.66 (d, J ˆ 6.7 Hz, 3H),
2.88 (d, J ˆ 10.0 Hz, 3H), 3.75 (m, 1H), 5.78 (d, J ˆ 6.2 Hz, 1H), 7.30 (m,
10H); 13C NMR (50 MHz, CDCl3): d ˆ 13.2 (s), 29.5 (d, J ˆ 5.6 Hz), 60.0 (d,
J ˆ 13.6 Hz), 80.9 (d, J ˆ 2.5 Hz), 120.7 (d, J ˆ 4.3 Hz, 2C), 124.9 (s), 125.6
(s, 2C), 128.2 (s), 128.4 (s, 2C), 129.6 (s, 2C), 135.5 (d, J ˆ 8.7 Hz), 151.2 (d,
J ˆ 8.8 Hz); C16H18NO3P (303.29): calcd. C 63.4, H 6.0, N 4.6, P 10.2; found
C 63.7, H 5.9, N 4.8, P 10.5.
intermediates 7 and 8 in which either the oxaphosphetane or
diazaphospholane rings are forced to adopt a constrained
diequatorial position with the oxygen anion group in an apical
position[31, 32] (Scheme 4).
2b: M.p. 1228C; [a]D25
ˆ
34.0 (c ˆ 1, CH2Cl2); 31P NMR (40.5 MHz,
CDCl3): d ˆ 13.5; 1H NMR (200 MHz, CDCl3): d ˆ 0.82 (d, J ˆ 6.5 Hz, 3H),
2.81 (d, J ˆ 10.3 Hz, 3H), 3.60 (m, 1H), 5.38 (dd, J ˆ 6.4 Hz, J ˆ 3.9 Hz,
1H), 7.30 (m, 10H); 13C NMR (50 MHz, CDCl3): d ˆ 14.2 (d, J ˆ 3.6 Hz),
28.6 (d, J ˆ 4.4 Hz), 58.8 (d, J ˆ 12.8 Hz), 81.0 (s), 120.5 (d, J ˆ 4.3 Hz, 2C),
124.8 (s), 125.9 (s, 2C), 128.3 (s, 3C), 129.6 (s, 2C), 135.4 (d, J ˆ 7.2 Hz),
151.1 (d, J ˆ 8.7 Hz); C16H18NO3P (303.29): calcd. C 63.4, H 6.0, N 4.6, P
10.2; found C 63.6, H 6.1, N 4.9, P 10.3.
Scheme 4. High-energy intermediates 7 and 8.
(2S,4S)-4-Isopropyl-2-phenoxy-3-methyl-1,3,2-oxazaphospholidine 2-oxide
(2c) and (2R,4S)-4-isopropyl-2-phenoxy-3-methyl-1,3,2-oxazaphospholi-
dine 2-oxide (2d): Purification by column chromatography (silica gel;
ethyl acetate/petroleum ether 80:20).
Conclusion
2c: Pale yellow syrup; yield: 58%; [a]2D5 ˆ ‡71.4 (c ˆ 1.05, CH2Cl2); 31P
We have described the first synthesis of various new chiral o-
hydroxyaryl phosphine oxides by means of a totally stereo-
selective migration ± rearrangement procedure. A mechanis-
tic rationale involving an addition ± pseudorotation ± elimi-
nation pathway has been proposed in agreement with the
1
NMR (40.5 MHz, CDCl3): d ˆ 16.4; H NMR (200 MHz, CDCl3): d ˆ 0.88
(d, J ˆ 7.0 Hz, 3H), 0.97 (d, J ˆ 6.9 Hz, 3H), 2.07 (m, 1H), 2.74 (d, J ˆ
10.2 Hz, 3H), 3.19 (m, 1H), 4.07 (m, 2H), 7.17 (m, 3H), 7.34 (m, 2H); 13
C
NMR (50 MHz, CDCl3): d ˆ 14.3 (s), 17.6 (s), 27.4 (d, J ˆ 5.6 Hz), 28.9 (d,
J ˆ 5.5 Hz), 62.3 (d, J ˆ 13.6 Hz), 65 (s), 120.3 (d, J ˆ 5.0 Hz, 2C), 124.75 (s),
1064
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1064 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 6

Stereoselective P±O to P±C Rearrangement
1061±1067
129.5 (s, 2C), 150.2 (d, J ˆ 7.5 Hz); C12H18NO3P (255.25): calcd. C 56.5, H
J ˆ 4.4 Hz, 2C), 125.5 (s), 129.8 (s, 2C), 169.7 (s); C13H17O6P (300.24): calcd.
7.1, N 5.5, P 12.1; found C 57.1, H 7.1, N 5.4, P 12.5.
C 52.0, H 5.7, P 10.5; found C 52.6, H 5.8, P 10.1.
2d: Pale yellow syrup, yield: 20%; [a]D25
ˆ
65.5 (c ˆ 1.1, CH2Cl2); 31P
(R,R)-1,1'-Binaphthalene-2,2'-diylphenylphosphate (2l): Purification by
column chromatography (silica gel; ethyl acetate/petroleum ether 20:80)
1
NMR (40.5 MHz, CDCl3): d ˆ 18.7; H NMR (200 MHz, CDCl3): d ˆ 0.63
(d, J ˆ 6.9 Hz, 3H), 0.80 (d, J ˆ 7.0 Hz, 3H), 1.83 (m, 1H), 2.72 (d, J ˆ
10.4 Hz, 3H), 3.35 (m, 1H), 3.80 (m, 1H), 4.22 (m, 1H), 7.14 (m, 3H), 7.34
(m, 2H); 13C NMR (50 MHz, CDCl3): d ˆ 14.5 (s), 17.4 (s), 28.1 (d, J ˆ
6.2 Hz), 30.5 (d, J ˆ 5.5 Hz), 63.4 (d, J ˆ 13.8 Hz), 65.4 (s), 120.7 (d, J ˆ
4.2 Hz, 2C), 124.8 (s), 129.4 (s, 2C), 150.8 (d, J ˆ 8.3 Hz); C12H18NO3P
(255.25): calcd. C 56.5, H 7.1, N 5.5, P 12.1; found C 57.3, H 7.2, N 5.6, P 11.9.
afforded 2l as a white solid in 90% yield. [a]D25
ˆ
276.0 (c ˆ 0.5, CH2Cl2);
31P NMR (40.5 MHz, CDCl3): d ˆ 4.3; H NMR (200 MHz, CDCl3): d ˆ
7.40 (m, 12H), 7.71 (d, J ˆ 8.9 Hz, 1H), 8.04 (m, 4H); 13C NMR (50 MHz,
CDCl3): d ˆ 117.8 (s), 119.9 (s), 120.0 (s), 120.1 (s), 120.6 (d, J ˆ 2.7 Hz),
121.2 (s), 121.6 (s), 123.8 (s), 124.3 (s), 125.6 (s), 125.9 (s, 2C), 126.9 (s, 2C),
127.0 (s), 127.2 (s), 128.6 (d, J ˆ 4.0 Hz), 129.9 (s, 2C), 131.2 (s), 131.7 (s),
132.0 (s), 132.3 (s), 146.0 (d, J ˆ 10.2 Hz), 147.3 (d, J ˆ 12.4 Hz), 150.3 (d,
J ˆ 7.9 Hz); C26H17O4P (424.39): calcd. C 73.6, H 4, P 7.3; found: C 73.4, H
4.2, P 7.2.
1
(2S,5S)-2-Phenoxy-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane 2-
oxide (2e) and (2R,5S)-2-phenoxy-3-phenyl-1,3-diaza-2-phosphabicy-
clo[3.3.0]octane 2-oxide (2 f): Purification by column chromatography
(silica gel; ethyl acetate/petroleum ether 80:20) afforded an equimolar,
inseparable mixture of the two diastereomers 2e and 2 f as a white solid in
91% yield. 31P NMR (40.5 MHz, CDCl3): d ˆ 16.9, 10.9; 1H NMR
(200 MHz, CDCl3): d ˆ 2.05 (m, 4H), 3.50 (m, 5H), 7.20 (m, 10H); 13C
NMR (50 MHz, CDCl3): d ˆ 26 (d, J ˆ 3.7 Hz), 27.1 (d, J ˆ 5.2 Hz), 31.3 (d,
J ˆ 2.8 Hz), 32.3 (d, J ˆ 2.9 Hz), 44.5 (d, J ˆ 2.7 Hz), 46.5 (d, J ˆ 2.7 Hz),
49.7 (d, J ˆ 19.2 Hz), 51.4 (d, J ˆ 16.3 Hz), 56.9 (d, J ˆ 10.6 Hz), 57.7 (d, J ˆ
11.6 Hz), 116.0 (d, J ˆ 3.7 Hz), 117.0 (d, J ˆ 5.2 Hz), 120.8 (d, J ˆ 3.7 Hz),
121.0 (d, J ˆ 5.2 Hz), 121.4 (d, J ˆ 3.7 Hz), 121.8 (d, J ˆ 5.2 Hz), 124.5 (d,
J ˆ 3.7 Hz), 124.7 (d, J ˆ 5.2 Hz), 129.2 (d, J ˆ 4.5 Hz), 129.3 (s), 129.7 (s),
141.4 (s), 141.6 (s), 151.2 (s), 151.9 (s); C17H19N2O2P (314.32): calcd. C 65.0,
H 6.1, N 8.9, P 9.9; found: C 65.6, H 6.2, N 9.0, P 9.8.
General procedure for the preparation of compounds 3b ± k: To a stirred
solution of the corresponding compounds (2a ± k) (2.5 mmol) in dry THF
(25 mL) under N2 was slowly added at 788C a solution of LDA (2m in
THF, 5.5 mmol). The mixture was allowed to warm to RT and was then
quenched by addition of a saturated solution of NH4Cl (20 mL). The
product was extracted with ethyl acetate (2 Â 30 mL). The combined
organic phases were dried over MgSO4, filtered, and evaporated under
reduced pressure. The residue was purified by flash chromatography on a
silica gel column.
(2S,4R,5S)-3,4-Dimethyl-2-(2-hydroxyphenyl)-5-phenyl-1,3,2-oxazaphos-
pholidine 2-oxide (3b): Purification by column chromatography (silica gel;
ethyl acetate/petroleum ether 33:67) afforded 3b as a white solid in 86%
yield. M.p. 1098C; [a]D25
ˆ
4.4 (c ˆ 0.45, CH2Cl2); 31P NMR (40.5 MHz,
(2S,5S)-2-Naphthoxy-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane 2-
oxide (2g) and (2R,5S)-2-naphthoxy-3-phenyl-1,3-diaza-2-phosphabicy-
clo[3.3.0]octane 2-oxide (2h): Purification by column chromatography
(silica gel; ethyl acetate/petroleum ether 75:25) afforded an inseparable
mixture (60:40) of the two diastereomers 2g and 2h as a white solid in 76%
yield. 31P NMR (40.5 MHz, CDCl3): d ˆ 16.7 (major), 11.4 (minor); 1H
NMR (200 MHz, CDCl3): d ˆ 1.85 (m, 4H), 3.50 (m, 5H), 6.90 (m, 1H), 7.15
(m, 8H), 7.50 (m, 1H), 7.80 (m, 2H); 13C NMR (50 MHz, CDCl3): d ˆ 26.0
(d, J ˆ 4 Hz), 27.2 (d, J ˆ 5.3 Hz); 31.4 (d, J ˆ 2.6 Hz), 32.3 (s), 44.8 (d, J ˆ
2.7 Hz), 46.5 (d, J ˆ 2.8 Hz), 49.7 (d, J ˆ 18.6 Hz), 51.7 (d, J ˆ 16.4 Hz), 57.0
(d, J ˆ 10.2 Hz), 58.0 (d, J ˆ 11.5 Hz), 115.5 (d, J ˆ 3.2 Hz), 116.4 (d, J ˆ
4.5 Hz), 117.2 (d, J ˆ 4.5 Hz), 121.4 (s), 121.7 (s), 122 (s), 122.1 (s), 124.3 (s),
124.6 (s), 125.5 (s), 125.9 (s), 126.3 (s), 126.6 (s), 127.2 (s), 127.6 (s), 129.2 (s),
129.4 (s), 134.7 (s), 141.3 (s), 141.6 (s), 147.2 (s), 148 (s); C21H21N2O2P
(364.38): calcd. C 69.2, H 5.8, N 7.7, P 8.5; found C 68.9, H 5.7, N 7.9, P 8.7.
CDCl3): d ˆ 38.6; 1H NMR (200 MHz, CDCl3): d ˆ 0.97 (d, J ˆ 6.5 Hz, 3H),
2.68 (d, J ˆ 10.3 Hz, 3H), 3.90 (m, 1H), 5.76 (dd, J ˆ 6.7 Hz, J ˆ 4.4 Hz,
1H), 7.00 (m, 2H); 7.40 (m, 7H); 10.80 (s, 1H); 13C NMR (50 MHz, CDCl3):
d ˆ 14.8 (s), 28.5 (d, J ˆ 6.1 Hz), 59.4 (d, J ˆ 11.2 Hz), 83.4 (s), 109.2 (d, J ˆ
168.5 Hz), 117.9 (d, J ˆ 11.1 Hz), 119.4 (d, J ˆ 14.4 Hz), 126.1 (s, 2C), 128.4
(d, J ˆ 4.2 Hz, 2C), 131.3 (s), 131.4 (s), 135.2 (s), 135.7 (d, J ˆ 4.6 Hz), 163.4
(d, J ˆ 7.2 Hz); C16H18NO3P (303.29): calcd. C 63.4, H 6.0, N 4.6, P 10.2;
found C 63.5, H 6.1, N 4.7, P 10.1.
(2S,4S)-4-Isopropyl-2-(2-hydroxyphenyl)-3-methyl-1,3,2-oxazaphospholi-
dine 2-oxide (3c): Purification by column chromatography (silica gel; ethyl
acetate/petroleum ether 25:75) afforded 3c as a pale yellow solid in 89%
yield. M.p. 888C; [a]D25 ˆ ‡62.0 (c ˆ 0.55, CH2Cl2); 31P NMR (40.5 MHz,
CDCl3): d ˆ 40.8; 1H NMR (200 MHz, CDCl3): d ˆ 1.01 (d, J ˆ 7.0 Hz, 3H),
1.07 (d, J ˆ 6.8 Hz, 3H), 2.18 (m, 1H), 2.56 (d, J ˆ 9.9 Hz, 3H), 3.58 (m,
1H), 4.35 (m, 2H), 6.92 (m, 2H), 7.17 (m, 1H) ), 7.46 (m, 1H), 10.8 (s, 1H);
13C NMR (50 MHz, CDCl3): d ˆ 14.5 (s), 18.2 (s), 27.6 (d, J ˆ 3.7 Hz), 28.7
(d, J ˆ 8.7 Hz), 64.3 (d, J ˆ 11.5 Hz), 66.8 (s), 109.4 (d, J ˆ 164.5 Hz), 117.9
(d, J ˆ 11.2 Hz), 119.3 (d, J ˆ 14.5 Hz), 130.8 (d, J ˆ 8.7 Hz), 135.0 (s), 163.2
(d, J ˆ 6.7 Hz); C12H18NO3P (255.25): calcd. C 56.5, H 7.1, N 5.5, P 12.1;
found C 56.7, H 7.2, N 5.6, P 12.3.
(1S,6S)-7,9-Dimethyl-8-phenoxy-7,9-diaza-8-phosphabicyclo[4.3.0]nonane
8-oxide (2i): Purification by column chromatography (silica gel; ethyl
acetate/petroleum ether 80:20) afforded 2i as a pale yellow syrup in 85%
yield. [a]2D5
ˆ
56.0 (c ˆ 0.925, CH2Cl2); 31P NMR (40.5 MHz, CDCl3): d ˆ
23.8; 1H NMR (200 MHz, CDCl3): d ˆ 1.25 (m, 4H), 1.80 (m, 2H), 2.05 (m,
2H), 2.60 (m, 2H), 2.60 (d, J ˆ 2.0 Hz, 3H), 2.65 (d, J ˆ 2.1 Hz, 3H), 7.25
(m, 5H); 13C NMR (50 MHz, CDCl3): d ˆ 23.8 (s, 2C), 27.6 (s), 27.8 (s), 28.1
(d, J ˆ 10.6 Hz), 29.7 (d, J ˆ 2.4 Hz), 62.5 (d, J ˆ 10.0 Hz), 64.5 (d, J ˆ
9.9 Hz), 120.7 (d, J ˆ 3.9 Hz, 2C), 124.0 (s), 129.2 (s, 2C), 151.4 (d, J ˆ
9.0 Hz); C14H21N2O2P (280.30): calcd. C 60.0, H 7.5, N 10.0, P 11.0; found C
60.6, H 7.7, N 9.9, P 11.2.
(2R,4S)-4-Isopropyl-2-(2-hydroxyphenyl)-3-methyl-1,3,2-oxazaphospholi-
dine 2-oxide (3d): Purification by column chromatography (silica gel; ethyl
acetate/petroleum ether 25:75) afforded 3d as a pale yellow solid in 92%
yield. M.p. 1068C; [a]D25
ˆ
15.0 (c ˆ 0.6, CH2Cl2); 31P NMR (40.5 MHz,
CDCl3): d ˆ 44.0; 1H NMR (200 MHz, CDCl3): d ˆ 0.98 (d, J ˆ 7.0 Hz, 3H),
1.00 (d, J ˆ 6.9 Hz, 3H), 2.13 (m, 1H), 2.61 (d, J ˆ 11.0 Hz, 3H), 3.55 (m,
1H), 4.15 (m, 1H), 4.45 (m, 1H), 6.90 (m, 2H), 7.30 (m, 2H), 10.8 (s, 1H);
13C NMR (50 MHz, CDCl3): d ˆ 15.1 (s), 18.1 (s), 28.1 (d, J ˆ 7.4 Hz), 29.4
(d, J ˆ 5.7 Hz), 62.7 (d, J ˆ 9.9 Hz), 67.9 (d, J ˆ 2.2 Hz), 109.1 (d, J ˆ
174.5 Hz), 117.9 (d, J ˆ 12.2 Hz), 119.3 (d, J ˆ 14.2 Hz), 132.1 (d, J ˆ
7.2 Hz), 135.3 (d, J ˆ 2.7 Hz), 163.7 (d, J ˆ 4.4 Hz); C12H18NO3P (255.25):
calcd. C 56.5, H 7.1, N 5.5, P 12.1; found C 56.9, H 7.1, N 5.4, P 12.2.
(4S,5S)-1,3-Dimethyl-4,5-diphenyl-2-phenoxy-1,3,2-diazaphospholidine 2-
oxide (2j): Purification by column chromatography (silica gel; ethyl
acetate/petroleum ether 80:20) afforded 2j as a pale yellow syrup in 80%
yield. M.p. 1088C; [a]D25 ˆ ‡22.5 (c ˆ 1, CH2Cl2); 31P NMR (40.5 MHz,
CDCl3): d ˆ 20.3; 1H NMR (200 MHz, CDCl3): d ˆ 2.56 (d, J ˆ 2.5 Hz, 3H),
2.61 (d, J ˆ 6 Hz, 3H), 3.97 (dd, J ˆ 21.3 Hz, J ˆ 8.5 Hz, 2H), 6.90 (m, 2H),
7.30 (m, 13H); 13C NMR (50 MHz, CDCl3): d ˆ 29.8 (d, J ˆ 3.8 Hz), 30.8 (d,
J ˆ 2.4 Hz), 70.3 (d, J ˆ 11.7 Hz), 71.5 (d, J ˆ 12.5 Hz), 121.0 (s), 121.1 (s),
124.5 (s), 127.6 (s, 2C), 127.9 (s), 128.2 (s), 128.5 (d, J ˆ 6.7 Hz, 2C),129.0 (s,
2C), 129.7 (s), 137.0 (d, J ˆ 10.1 Hz), 137.9 (d, J ˆ 7.3 Hz), 152.4 (d, J ˆ
8.6 Hz); C22H23N2O2P (378.41): calcd. C 69.8, H 6.1, N 7.4, P 8.2; found C
70.2, H 6.0, N 7.2, P 8.3.
(2S,5S)-2-(2-hydroxyphenyl)-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]-
octane 2-oxide (3e) and (2R,5S)-2-(2-hydroxyphenyl)-3-phenyl-1,3-diaza-
2-phosphabicyclo[3.3.0]octane 2-oxide (3 f): Purification by column chro-
matography (silica gel; ethyl acetate/petroleum ether 50:50) afforded 3e as
a white solid in 47% yield and 3 f as a white solid in 44% yield.
(1R,7R)-9,9-Dimethyl-4-phenoxy-3,5,8,10-tetraoxa-4-phosphabicyclo-
[5.3.0]decane 4-oxide (2k): Purification by column chromatography (silica
gel; ethyl acetate/petroleum ether 50:50) afforded 2k as a colorless syrup in
25% yield. [a]2D5 ˆ ‡50.9 (c ˆ 1.1, CH2Cl2); 31P NMR (40.5 MHz, CDCl3):
d ˆ 8.1; 1H NMR (200 MHz, CDCl3): d ˆ 1.47 (s, 6H), 4.20 (m, 2H), 4. 50
(m, 4H), 7.30 (m, 5H); 13C NMR (50 MHz, CDCl3): d ˆ 26.6 (s), 26.7 (s),
66.3 (d, J ˆ 5.5 Hz), 67.1 (d, J ˆ 5.8 Hz), 77.6 (s), 78.0 (s), 111.4 (s), 119.9 (d,
3e: M.p. 1588C; [a]D25 ˆ ‡ 51.4 (c ˆ 0.7, CH2Cl2); 31P NMR (40.5 MHz,
1
CDCl3): d ˆ 33.2; H NMR (200 MHz, CDCl3): d ˆ 1.95 (m, 4H), 2.97 (m,
1H), 3.57 (m, 1H), 3.76 (m, 1H), 3.99 (m, 2H), 6.78 (m, 1H), 6.97 (m, 4H),
7.19 (m, 4H), 11.15 (s, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 26.7 (s), 32.3
(s), 44.5 (s), 49.7 (d, J ˆ 14.6 Hz), 60.0 (d, J ˆ 5.9 Hz), 112.8 (d, J ˆ
164.3 Hz), 116.5 (d, J ˆ 5.8 Hz, 2C), 117.6 (d, J ˆ 11.7 Hz), 119.5 (d, J ˆ
13.2 Hz), 121.9 (s), 129.3 (s, 2C), 131.4 (d, J ˆ 7.4 Hz), 134.3 (d, J ˆ 3.0 Hz),
Chem. Eur. J. 1998, 4, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1065 $ 17.50+.25/0
1065

G. Buono et al.
FULL PAPER
141.2 (d, J ˆ 7.0 Hz), 162.9 (d, J ˆ 7.0 Hz); C17H19N2O2P (314.32): calcd. C
(s), 26.8 (s), 64.4 (d, J ˆ 7.3 Hz), 67.4 (d, J ˆ 8.6 Hz), 77.9 (d, J ˆ 2.8 Hz), 78.8
(s), 111.5 (d, J ˆ 151.0 Hz), 112.1 (s), 117.8 (d, J ˆ 12.8 Hz), 119.6 (d, J ˆ
13.6 Hz), 131.7 (d, J ˆ 5.5 Hz), 135.7 (s), 161.2 (s); C13H17O6P (300.24):
calcd. C 52.0, H 5.7, P 10.5; found C 52.4, H 5.9, P 10.2.
65.0, H 6.1, N 8.9, P 9.9; found C 65.6, H 6.0, N 8.7, P 10.0.
3 f: M.p. 1588C; [a]D25 ˆ ‡ 11.4 (c ˆ 0.7, CH2Cl2); 31P NMR (40.5 MHz,
CDCl3): d ˆ 27.9; 1H NMR (200 MHz, CDCl3): d ˆ 1.70 (m, 1H), 2.10 (q,
J ˆ 6.8 Hz, 2H), 2.25 (m, 1H), 3.10 (m, 2H), 3.60 (td, J ˆ 8.7 Hz, J ˆ 1.9 Hz,
1H), 4.10 (m, 1H), 4.30 (m, 1H), 6.90 (m, 4H), 7.30 (m, 5H), 11.40 (s, 1H);
13C NMR (50 MHz, CDCl3): d ˆ 27.4 (d, J ˆ 5.9 Hz), 31.9 (d, J ˆ 4.4 Hz),
44.1 (d, J ˆ 7.2 Hz), 45.4 (d, J ˆ 10.4 Hz), 58.1 (d, J ˆ 10.3 Hz), 108.4 (d, J ˆ
146.8 Hz), 116.1 (d, J ˆ 5.6 Hz, 2C), 118.2 (d, J ˆ 11.3 Hz), 119.5 (d, J ˆ
14.4 Hz), 121.6 (s), 129.3 (s, 2C), 130.5 (d, J ˆ 9.1 Hz), 134.8 (d, J ˆ 2.5 Hz),
141.8 (d, J ˆ 7.4 Hz), 164.8 (d, J ˆ 6.2 Hz); C17H19N2O2P (314.32): calcd. C
65.0, H 6.1, N 8.9, P 9.9; found C 65.7, H 6.2, N 8.8, P 9.7.
Acknowledgments: We thank Dr. Michel Giorgi for his kind assistance
Â
Â
with X-ray analysis of compounds 3e and 3 f and Dr. Frederic Fotiadu for
fruitful discussions. We are grateful to CNRS for its financial support.
Received: November 17, 1997 [F893]
[1] a) I. Ojima, Catalytic Asymmetric Synthesis, VCH, Weinheim, 1993;
b) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1993.
[2] H. Brunner, W. Zeittlmeir, Handbook of Enantioselective Catalysis:
Vol. I, Products and Catalysts, and Vol II, Ligands, References, VCH,
Weinheim, 1993.
[3] a) A. Togni, L. M. Venanzi, Angew. Chem. 1994, 106, 517; Angew.
Chem. Int. Ed. Engl. 1994, 33, 497; b) J. M. J. Williams, Synlett 1996,
705.
[4] These compounds may be regarded as analogues of 1,3-diketone-type
ligands of various transition metals. They may form complexes with
metal ions and have been used in the preparation of ligands capable of
extracting ammonium compounds from aqueous to organic phases.
See: A. H. Alberts, K. Timmer, J. G. Noltes, A. L. Spek, J. Am. Chem.
Soc. 1979, 101, 3375.
(2S,5S)-2-(1-Hydroxy-2-naphthyl)-3-phenyl-1,3-diaza-2-phosphabicy-
clo[3.3.0]octane 2-oxide (3g) and (2R,5S)-2-(1-hydroxy-2-naphthyl)-3-
phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane 2-oxide (3h): Purification
by column chromatography (silica gel; dichloromethane) afforded 3g as a
white solid in 56% yield and 3h as a white solid in 37% yield.
3g: M.p. 2338C; [a]2D5 ˆ ‡161.6 (c ˆ 0.625, CH2Cl2); 31P NMR (40.5 MHz,
1
CDCl3): d ˆ 34.2; H NMR (200 MHz, CDCl3): d ˆ 2.10 (m, 4H), 3.10 (m,
1H), 4.00 (m, 4H), 7.00 (m, 1H), 7.30 (m, 6H), 7.70 (m, 2H), 7.85 (m, 1H),
8.57 (m, 1H), 12.29 (s, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 26.7 (s), 32.3
(s), 44.4 (s), 49.7 (d, J ˆ 14.0 Hz), 60.0 (d, J ˆ 5.3 Hz), 104.4 (d, J ˆ 167 Hz),
116.5 (d, J ˆ 5.3 Hz, 2C), 119.0 (d, J ˆ 14.2 Hz), 121.8 (d, J ˆ 3.2 Hz), 123.5
(d, J ˆ 4.5 Hz), 125.0 (d, J ˆ 4.5 Hz), 125.6 (s, 2C), 125.7 (s), 127.3 (s), 128.7
(s), 129.2 (s), 136.6 (s), 141.1 (s), 161.5 (d, J ˆ 7.7 Hz); C21H21N2O2P
(364.38): calcd. C 69.2, H 5.8, N 7.7, P 8.5; found C 69.1, H 5.7, N 8.1, P 8.6.
3h: M.p. 1978C; [a]D25
ˆ
23.0 (c ˆ 0.4, CH2Cl2); 31P NMR (40.5 MHz,
[5] L. S. Melvin, Tetrahedron Lett. 1981, 22, 3375.
1
[6] a) B. Dhawan, D. Redmore, J. Org. Chem. 1984, 49, 4018; b) B.
Dhawan, D. Redmore, J. Org. Chem. 1986, 51, 179; c) B. Dhawan, D.
Redmore, ibid. 1991, 56, 833; d) B. Dhawan, D. Redmore, Synth.
Commun. 1985, 15, 411; e) B. Dhawan, D. Redmore, ibid. 1987, 17, 465;
f) B. Dhawan, D. Redmore, J. Chem. Res. 1988, 222; g) T. Caloger-
opoulou, G. B. Hammond, D. F. Wiemer, J. Org. Chem. 1987, 52, 4185;
h) S. Li, G. Wang, Phosphorus Sulfur Silicon Relat. Elem. 1991, 61, 119;
i) D. Hellwinkel, R. Lenz, Chem. Ber. 1985, 118, 66 and references
therein.
CDCl3): d ˆ 29.2; H NMR (200 MHz, CDCl3): d ˆ 1.80 (m, 1H), 2.06 (q,
J ˆ 6.8 Hz, 2H), 2.30 (m, 1H), 3.10 (m, 2H), 3.70 (td, J ˆ 2.1 Hz, J ˆ 8.7 Hz,
1H), 4.10 (m, 1H), 4.35 (m, 1H), 6.87 (m, 2H), 7.20 (m, 5H), 7.60 (m, 3H),
8.47 (d, J ˆ 8 Hz, 1H), 12.44 (s, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 27.4
(d, J ˆ 6.6 Hz), 32.0 (d, J ˆ 4.2 Hz), 44.2 (d, J ˆ 7.0 Hz), 54.5 (d, J ˆ
10.2 Hz), 58.1 (d, J ˆ 10.4 Hz), 99.9 (d, J ˆ 149.7 Hz), 116.1 (d, J ˆ 4.5 Hz,
2C), 119.2 (d, J ˆ 14.3 Hz), 121.5 (s), 123.7 (s), 124.7 (d, J ˆ 9.2 Hz), 125.5
(d, J ˆ 10 Hz), 125.9 (s), 127.3 (s), 129.0 (s), 129.3 (s, 2C), 136.8 (s), 141.9 (d,
J ˆ 7.2 Hz), 164.0 (d, J ˆ 7.0 Hz); C21H21N2O2P (364.38): calcd. C 69.2, H 5.8,
N 7.7, P 8.5; found C 69.3, H 5.9, N 7.9, P 8.5.
[7] M. Watanabe, M. Date, K. Kawanishi, T. Hori, S. Furukawa, Chem.
Pharm. Bull. 1990, 38, 2637.
(1S,6S)-7,9-Dimethyl-8-(2-hydroxyphenyl)-7,9-diaza-8-phosphabicy-
clo[4.3.0]nonane 8-oxide (3i): Purification by column chromatography
(silica gel; ethyl acetate/petroleum ether 33:67) afforded 3i as a white solid
in 93% yield. M.p. 1128C; [a]2D5 ˆ ‡ 15.8 (c ˆ 0.95, CH2Cl2); 31P NMR
(40.5 MHz, CDCl3): d ˆ 39.2; 1H NMR (200 MHz, CDCl3): d ˆ 1.19 (m,
4H), 1.97 (m, 4H), 2.27 (d, J ˆ 12.0 Hz, 3H), 2.47 (d, J ˆ 12.0 Hz, 3H), 2.64
(m, 1H), 2.85 (m, 1H), 6.82 (m, 2H), 7.06 (m, 1H), 7.30 (m, 1H), 11.17 (s,
1H); 13C NMR (50 MHz, CDCl3): d ˆ 24.1 (s), 24.2 (s), 28.1 (s, 2C), 28.3 (d,
J ˆ 2.1 Hz), 28.5 (d, J ˆ 6.0 Hz), 63.3 (d, J ˆ 6.0 Hz), 66.0 (d, J ˆ 7.0 Hz),
110.1 (d, J ˆ 149.0 Hz), 117.5 (d, J ˆ 11.0 Hz), 119.0 (d, J ˆ 13.0 Hz), 131.5
(d, J ˆ 8.0 Hz), 134.3 (d, J ˆ 2.0 Hz), 163.7 (d, J ˆ 6.0 Hz); C14H21N2O2P
(280.30): calcd. C 60.0, H 7.5, N 10.0, P 11.0; found C 60.3, H 7.6, N 10.1, P
11.1.
[8] D. A. Casteel, S. P. Peri, Synthesis 1991, 691.
[9] S. C. Welch, J. A. Levine, I. Bernal, J. Cetrullo, J. Org. Chem. 1990, 55,
5991.
[10] a) T. S. Lobana in The Chemistry of Organophosphorus Compounds,
Vol. 2 (Ed.: F. R. Hartley), Wiley, New York, 1992, pp. 409 ± 566;
b) T. S. Lobana, Prog. Inorg. Chem. 1989, 37, 495; c) H. B. Kagan, M.
Sasaki in The Chemistry of Organophosphorus Compounds, (Ed.:
F. R. Hartley), John Wiley, New York, 1990, pp. 51 ± 102.
[11] N. Auner, J. Weis, Organosilicon Chemistry. From Molecules to
Materials, VCH, Weinheim, 1994, pp. 61 ± 63.
[12] The definitions of the syn and anti isomers are according to the
relative positions of substituents C4 and C3 in the five-membered ring
with respect to the extracyclic aryl group. If they are on the same side
of the five-membered phosphorus-containing ring, we call it a syn
isomer, otherwise it is an anti isomer.
[13] The structure of the major diastereomer has been established by
comparison with the results obtained by Inch et al. in the stereo-
specific synthesis of optically active 1,3,2-oxazaphospholidine-2-one
derived from ( )-ephedrine and the fact that these corresponding acid
chlorides undergo substitution with phenoxide anions with retention
of configuration at the phosphorus atom. See: D. B. Cooper, C. R.
Hall, J. M. Harrison, T. D. Inch, J. Chem. Soc. Perkin Trans. I 1977,
1969.
[14] Base-induced rearrangement of diastereomer syn-2b affords a very
labile, nonrearranged eliminative ring-open compound in 60% yield.
Its structure has been clearly established by NMR spectroscopic
analysis; however, the absolute config-
(4S,5S)-1,3-Dimethyl-4,5-diphenyl-2-(2-hydroxyphenyl)-1,3,2-diazaphos-
pholidine 2-oxide (3j): Purification by column chromatography (silica gel;
ethyl acetate/petroleum ether 25:75) afforded 3j as a pale yellow solid in
91% yield. M.p. 1688C; [a]D25
ˆ
49.0 (c ˆ 0.525, CH2Cl2); 31P NMR
(40.5 MHz, CDCl3): d ˆ 38.8; 1H NMR (200 MHz, CDCl3): d ˆ 2.31 (d, J ˆ
10.2 Hz, 3H), 2.50 (d, J ˆ 10.6 Hz, 3H), 4.26 (dd, J ˆ 22.9 Hz, J ˆ 8.7 Hz,
2H), 7.25 (m, 14H), 11.47 (s, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 26.7 (d,
J ˆ 6.5 Hz), 29.8 (d, J ˆ 4.2 Hz), 71.6 (d, J ˆ 7.7 Hz), 73.6 (d, J ˆ 8.7 Hz),
110.2 (d, J ˆ 155.5 Hz), 115.5 (s), 118.0 (d, J ˆ 10.2 Hz), 119.4 (d, J ˆ
14.0 Hz), 120.0 (s), 127.5 (s, 2C), 127.9 (s, 2C), 128.4 (s, 2C), 128.7 (s,
2C), 131.5 (d, J ˆ 7.9 Hz), 134.6 (d, J ˆ 2.3 Hz), 136.9 (d, J ˆ 5.8 Hz), 137.4
(d, J ˆ 8.9 Hz), 164.0 (d, J ˆ 7.2 Hz); C22H23N2O2P (378.41): calcd. C 69.8, H
6.1, N 7.4, P 8.2; found C 70.1, H 6.1, N 7.3, P 8.1.
(1R,7R)-9,9-Dimethyl-4-(2-hydroxyphenyl)-3,5,8,10-tetraoxa-4-phospha-
bicyclo[3.5.0]decane 8-oxide (3k): Purification by column chromatography
(silica gel; ethyl acetate/petroleum ether 25:75) afforded 3k as a white solid
in 95% yield. M.p. 1178C; [a]2D5 ˆ ‡56.0 (c ˆ 0.45, CH2Cl2); 31P NMR
(40.5 MHz, CDCl3): d ˆ 23.7; 1H NMR (200 MHz, CDCl3): d ˆ 1.40 (s, 3H),
1.41 (s, 3H), 4.04 (m, 2H), 4.25 (m, 1H), 4.34 (m, 1H), 4.51 (m, 2H), 6.86
(m, 2H), 7.35 (m, 2H), 9.00 (s, 1H); 13C NMR (50 MHz, CDCl3): d ˆ 26.7
uration at the phosphorus atom has not
been precisely determined. 31P NMR
(40.5 MHz, CDCl3): d ˆ 0.12; 1H NMR
(200 MHz, CDCl3): d ˆ 1.8 (dd, J ˆ
7.4 Hz, J ˆ 2.7 Hz, 3H), 2.6 (dd, J ˆ
12.7 Hz, J ˆ 5.8 Hz, 3H), 3.34 (m, 1H),
1066
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1066 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 6

Stereoselective P±O to P±C Rearrangement
1061±1067
5.89 (dd, J ˆ 7.3 Hz, J ˆ 2.8 Hz, 1H), 6.9 (m, 1H), 7.30 (m, 9H); 13C
NMR (50 MHz, CDCl3): d ˆ 12.9 (s), 27.5 (s), 111.9 (d, J ˆ 4.6 Hz),
115.4 (s), 119.3 (s), 120.1 (d, J ˆ 4.4 Hz), 124.6 (s), 128.0 (d, J ˆ 8.7 Hz,
2C), 128.3 (d, J ˆ 4.8 Hz, 2C), 129.3 (d, J ˆ 14.3 Hz, 2C), 134.1 (d, J ˆ
4.3 Hz), 146.1 (d, J ˆ 9.4 Hz), 150.7 (d, J ˆ 7.1 Hz).
oxaphosphetane ring and the five-membered diazaphospholane ring
in basal positions and the oxygen anion group in an axial position. The
stereochemistry of the migration derives from a cis basal interaction of
the entering/leaving group. See also: G. R. J. Thatcher, R. Kluger in
Mechanism and Catalysis of Nucleophilic Substitution in Phosphate
Esters in Advances in Physical Organic Chemistry, Vol. 25 (Ed.: D.
Betheil), Academic Press, New York, 1989, pp. 99 ± 265.
[15] Hitherto, the only reported method for the preparation of such
compounds consisted of an exchange reaction between bis(dimethyl-
amino)o-anisyl phosphine and a chiral auxiliary, followed by oxidation
with tBuOOH. Subsequent demethylation led exclusively to diaster-
eomer anti-3e with retention of the configuration on the phosphorus.
The syn diastereomer could not be obtained owing to the highly
unstable intermediate compound which totally epimerizes at the
phosphorus atom to produce the thermodynamic anti diastereomer.
See: a) P. Cros, G. Buono, G. Peiffer, D. Denis, A. Mortreux, F. Petit,
New. J. Chem. 1987, 11, 573; b) H. Arzoumanian, G. Buono, MꢀB.
Choukrad, J. F. Petrignani, Organometallics 1988, 7, 59; c) J. M.
Brunel, O. Chiodi, B. Faure, F. Fotiadu, G. Buono, J. Organomet.
Chem. 1997, 529, 285.
[19] K. Mislow, Acc. Chem. Res. 1970, 3, 321.
[20] F. Westheimer, Acc. Chem. Res. 1968, 1, 70.
[21] Such phosphetane intermediates have played an important role in the
elucidation of the factors that influence the stereochemistry of the
Wittig reaction. See: a) B. E. Maryanoff, A. B. Reitz, Chem. Rev. 1989,
89, 863; b) E. Vedejs, C. F. Marth, R. Ruggieri, J. Am. Chem. Soc. 1988,
110, 3940; c) B. E. Maryanoff, A. B. Reitz, Phosphorus Sulfur Relat.
Elem. 1986, 27, 167; d) B. E. Maryanoff, A. B. Reitz, M. S. Mutter,
R. R. Inners, H. R. Almond, Jr., R. R. Whittle, R. A. Olofson, J. Am.
Chem. Soc. 1986, 108, 7664; e) A. B. Reitz, S. O. Nortey, A. D.
Jordan, Jr., M. S. Mutter, B. E. Maryanoff, J. Org. Chem. 1986, 51,
3302; f) H. J. Bestmann, K. Roth, E. Wilhelm, R. Böhme, H. Burzlaff,
Angew. Chem. 1979, 91, 945; Angew. Chem. Int. Ed. Engl. 1979, 18,
876; g) D. Hellwinkel, W. Krapp, ibid. 1974, 86, 524 and 1974, 13, 540.
[22] Recently, the synthesis of isolable 1,2-oxaphosphetanes has been
achieved and X-ray crystallographic analysis have been performed to
determine the structure of such compounds. See: a) T. Kawashima, K.
Kato, R. Okazaki, Angew. Chem. 1993, 105, 941; Angew. Chem. Int.
Ed. Engl. 1993, 32, 869; b) T. Kawashima, K. Kato, R. Okazaki, J. Am.
Chem. Soc. 1992, 114, 4008.
[23] E. Vedejs, T. J. Fleck, J. Am. Chem. Soc. 1989, 111, 5861.
[24] For oxaphosphetane pseudorotation see: E. Vedejs, C. F. Marth, J.
Am. Chem. Soc. 1989, 111, 1519.
[25] R. R. Holmes, Pentacoordinated Phosphorus, Vol. 2, ACS Mono-
graph 176, American Chemical Society, 1980, Washington, D.C.
[26] S. McDowell, A. Streitwieser, J. Am. Chem. Soc. 1985, 107, 5849.
[27] S. J. Tripett, Pure Appl. Chem. 1974, 40, 585.
[28] R. S. Berry, J. Chem. Phys. 1960, 32, 933. Nevertheless, in any case
turnstile rotation must be taken into consideration as a mechanistic
alternative. See: a) P. Gillespie, P. Hoffmann, H. Klusacek, D.
Marquarding, S. Pfohl, F. Ramirez, E. A. Tsolis, I. Ugi, Angew. Chem.
1971, 83, 691; Angew. Chem. Int. Ed. Engl. 1971, 10, 687; b) F. Ramirez,
Bull. Soc. Chim. Fr. 1970, 3491.
[16] a) X-ray analysis of anti-3g: A white plate-like single crystal of
C17H19N2O2P, obtained by recrystallization in toluene, with approx-
imate dimensions 0.4 Â 0.3 Â 0.3 mm, was mounted on a glass capil-
lary. All the measurements were made on a Rigaku diffractometer
with MoKa radiation. Cell constants and the orientation matrix for
data collection were obtained from a least-square refinement with
setting angles of 30 reflections in the range 80 < 2q < 1008, which
corresponded to an orthorhombic cell with dimensions: a ˆ 8.085(3),
b ˆ 10.282(3), c ˆ 19.156(9) Š. For Z ˆ 4 and M ˆ 314.33, 1calcd
ˆ
1.31 gcm 3. The space group was determined to be P212121 from the
systematic absences. A total of 3068 reflections were collected at Tˆ
294 K. The standards were measured after every 120 reflections.
Among the first 200 pairs of reflections, the signs of the corresponding
calculated differences established that the molecule is described with
the correct absolute configuration R. b) X-ray analysis of syn-3 f: A
white plate-like single crystal of C17H19N2O2P, obtained by recrystal-
lization in ethyl acetate, with approximate dimensions 0.7 Â 0.4 Â
0.2 mm, was mounted on a glass capillary. All the measurements
were made on a Rigaku diffractometer with MoKa radiation. Cell
constants and the orientation matrix for data collection were obtained
from a least-square refinement with setting angles of 30 reflections in
the range 80 < 2q < 1008, which corresponded to an orthorhombic cell
with dimensions: a ˆ 9.035(5), b ˆ 10.660(4), c ˆ 32.77(1) Š. For Z ˆ 8
and M ˆ 314.33, 1calcd ˆ 1.32 gcm 3. The space group was determined
to be P212121 from the systemic absences. A total of 3540 reflections
were collected at Tˆ 294 K. The standards were measured after every
120 reflections. Among the first 200 pairs of reflections, the signs of
the corresponding calculated differences established that the molecule
is described with the correct absolute configuration S. Crystallo-
graphic data (excluding structure factors) for the structures reported
in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication no. CCDC-101014.
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-
336-033; e-mail: deposit§ccdc.cam.ac.uk).
[29] K. Mislow, Acc. Chem. Res. 1968, 1, 70.
[30] R. Luckenbach, Dynamic Stereochemistry of Pentacoordinated Phos-
phorus and Related Elements, Thieme, Stuttgart, 1973, pp. 99 ± 107.
[31] Previous investigations have been carried out on the sterochemical
behavior of the four-membered oxyphosphoranes (1,2-oxaphosph-
etanes) which have three P ± C bonds. See: a) F. Ramirez, J. F. Pilot,
O. P. Madan, C. P. Smith, J. Am. Chem. Soc. 1968, 90, 1275; b) F.
Ramirez, C. P. Smith, J. F. Pilot, ibid. 1968, 90, 6726; c) D. B. Denney,
D. Z. Denney, C. D. Hall, K. L. Marsi, ibid. 1972, 94, 245; d) See also
ref. [23] for a recent and pertinent study of the spiro-oxaphosphetane
pseudorotation.
[32] According to Holmesꢀ model for destabilized TBP intermediates 7
and 8, the estimated steric interaction energies between the four-
[17] Such retention of configuration has already been described for
oxirane formation reaction of pentacoordinate 1,2l6-oxathietanes.
See: T. Kawashima, F. Ohno, R. Okazaki, H. Ikeda, S. Inagaki, J. Am.
Chem. Soc. 1996, 118, 12455.
[18] As a result of the stability of some pentacoordinate square pyramidal
(SP) phosphorus species, it is also possible to consider mechanistic
pathways proceeding via SP intermediates with the four-membered
membered oxaphosphetane ring or the five-membered diazaphos-
1
pholane ring and the oxygen anion group are 28 and 26 kcalmol
,
respectively (the relative values of oxaphosphetane ring strain for use
1
in estimating isomer energies in TBP are ax ± eq ˆ 2 kcalmol and
eq ± eq ˆ 26 kcalmol 1). See: a) R. R. Holmes, J. Am. Chem. Soc.
1978, 100, 433; b) ref. [24], Table 1.7 ± 1.9, pp. 35 ± 89.
[33] Recently, analogous chiral compounds, such as phosphoramides[34] as
well as oxazaphospholidine oxides,[35] phosphoramidates, and thio-
phosphinamides[36] have been shown to be efficient chiral catalysts in
various enantioselective reactions.
[34] For recent examples see: a) S. E. Denmark, S. B. D. Winter, X. Su, K.
Wong, J. Am. Chem. Soc. 1996, 118, 7404; b) K. Iseki, Y. Kuroki, M.
Takahashi, Y. Kobayashi, Tetrahedron Lett. 1996, 37, 5149.
[35] O. Chiodi, F. Fotiadu, M. Sylvestre, G. Buono, Tetrahedron Lett. 1996,
37, 39.
[36] a) R. Hulst, H. Heres, N. Peper, R. M. Kellog, Tetrahedron Asym-
metry 1996, 7, 1373; b) K. Soai, Y. Hirose, Y. Ohno, ibid. 1993, 4, 1473;
c) K. Soai, Y. Ohno, Y. Inoue, T. Tsuruoka, T. Hirose, Recl. Trav.
Chim. Pays-Bas 1995, 114, 145.
Chem. Eur. J. 1998, 4, No. 6
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0406-1067 $ 17.50+.25/0
1067