NMR and X-ray crystallographic studies of axial and equatorial 2-ethoxy-2-oxo-1,4,2-oxazaphosphinane

Article abstract of DOI:10.1016/S0040-4020(02)01152-3

Condensation of (S)-(N-benzyl)-phenylglycinol with formaldehyde in the presence of diethylphosphite afforded hydroxyaminophosphonate (S)-3, which upon treatment with KH yielded a 97:3 mixture of the interesting, phosphorus-containing 2-ethoxy-2-oxo-1,4,2-

Full text of DOI:10.1016/S0040-4020(02)01152-3

Tetrahedron 58 (2002) 8973–8978
NMR and X-ray crystallographic studies of axial and equatorial
2
-ethoxy-2-oxo-1,4,2-oxazaphosphinane
a,b
Irma Linzaga, Jaime Escalante, Miguel Mu n˜ oz and Eusebio Juaristi
b
b
a,*
a
Departamento de Qu ´ı mica, Centro de Investigaci o´ n y de Estudios Avanzados del Instituto Polit e´ cnico Nacional, Apartado Postal 14-740,
7000 M e´ xico, DF, Mexico
Centro de Investigaciones Qu ´ı micas, Universidad Aut o´ noma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa,
2210 Cuernavaca, Mor., Mexico
0
b
6
Received 10 July 2002; revised 9 September 2002; accepted 12 September 2002
Abstract—Condensation of (S)-(N-benzyl)-phenylglycinol with formaldehyde in the presence of diethylphosphite afforded hydroxy-
aminophosphonate (S)-3, which upon treatment with KH yielded a 97:3 mixture of the interesting, phosphorus-containing 2-ethoxy-2-oxo-
1
permitted unequivocal configurational assignment, as well as examination of the consequences of n
structural properties. q 2002 Elsevier Science Ltd. All rights reserved.
,4,2-oxazaphosphinanes (2S,5S)-1 and (2R,5S)-1. Suitable crystals of both diastereomers were used in X-ray crystallographic studies that
p
O
!sP–O stereoelectronic interactions on
1. Introduction
1
Some years ago, Dellaria, Williams, and co-workers
developed chiral glycine derivatives A and B as convenient
precursors in the enantioselective synthesis of a-substituted
a-amino acids. Inspired by this work, and motivated by the
large range of biological activities presented by the
2
,3
analogous a-phosphonic acids,
Royer et al. recently
4
reported the preparation of oxazaphosphinane derivative C.
Nevertheless, compounds C were obtained as a 4:1
diastereomeric mixture of epimers at phosphorus, that was
not separated into the pure epimers.
In this paper, we describe a highly diastereoselective
synthetic procedure for the preparation of enantiopure
(2S,5S)-4-benzyl-2-ethoxy-2-oxo-5-phenyl-1,4,2-oxaza-
phosphinane [(2S,5S)-1] from (S)-phenylglycinol (Scheme 1).
Scheme 1.
Keywords: phosphorus heterocycles; diastereoselection; NMR; stereoelectronic effects.
*
Corresponding author. Tel.: þ52-55-5747-3722; fax: þ52-55-5747-7113; e-mail: juaristi@relaq.mx
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01152-3

8974
I. Linzaga et al. / Tetrahedron 58 (2002) 8973–8978
9
Figure 1. X-Ray cystallographic structure and solid-state conformation of (2S,5S)-4-benzyl-2-ethoxy-2-oxo-5-phenyl-1,4,2-oxazaphosphinane, (2S,5S)-1.
In addition, isolation of the pure (2R,5S) epimer permitted
2. Results and discussion
1
13
31
comparison of H, C, and P NMR data of both isomers.
Finally, suitable crystals of both (2S,5S)-1 and (2R,5S)-1
were subjected to X-ray crystallographic analysis. This
study not only secured the assignment of configuration
based on infrared and NMR data, but afforded relevant
information on the stereoelectronic interactions that may
account for the increased stability of (2S,5S)-1 (axial
P-ethoxy group).
2.1. Preparation of oxazaphosphinane 2-oxides (2S,5S)-1
and (2R,5S)-1
N-Benzylation of (S)-phenylglycinol was achieved by
condensation with benzaldehyde followed by palladium-
5
catalyzed hydrogenation. N-Benzyl-(S)-phenylglycinol,
(S)-2, was then condensed with formaldehyde (toluene
9
Figure 2. X-Ray crystallographic structure and solid-state conformation of (2R,5S)-4-benzyl-2-ethoxy-2-oxo-5-phenyl-1,4,2-oxazaphosphinane, (2R,5S)-1.

I. Linzaga et al. / Tetrahedron 58 (2002) 8973–8978
8975
solvent) and the resulting imminium salt was immediately
treated with diethyl phosphite to afford Mannich product
6
(
S)-3 in 81% isolated yield.
Treatment of carbinol (S)-3 with KH in THF solution
afforded in good yield and high diastereoselectivity the
cyclization products 1,4,2-oxazaphosphinanes (2S,5S)-1
and (2R,5S)-1, in a 97:3 ratio (Scheme 1). Separation of
these diastereomeric phosphorus-containing heterocycles
was feasible by means of flash column chromatography, and
unequivocal assignment of configuration was achieved by
X-ray diffraction structural determination.
˚
Figure 3. P–O bond lengths A in diastereomeric (a) (2S,5S)-1 and (b)
2R,5S)-1.
(
8
,
isomer presenting the axial P–OR substituent (Scheme 2).
1
2–14
Unexpectedly, all three relevant P–O bond lengths present
in diastereomeric (2S,5S)-1 and (2R,5S)-1 are identical,
within the experimental margin of error (Fig. 3).
That the 97:3 ratio of cyclized derivatives (2S,5S)-1 and
(2R,5S)-1 is the result of kinetic rather than thermodynamic
control is inferred by the fact that treatment of either
diastereomer with KH in THF for two hours and at 2758C
We initially considered the possibility that a dominant
1
3
(i.e. the same conditions employed for the cyclization
reaction) afforded no epimerized product.
exo anomeric interaction
(2R,5S)-1 could be responsible for elongation of the
in (2S,5S)-1 relative to
endocyclic P–O bond in the former, as consequence of
nOEt!s
p
P–O(1)
The crystallographic data of (2S,5S)-1 and (2R,5S)-1 were
also of significant interest with regard the possible
manifestation of stereoelectronic interactions in O–PvO
hyperconjugation (Eq. (1)).
7
,8
and O–P–OEt segments. Furthermore, the availability of
both diastereomeric oxazaphosphinanes in pure form
permitted evaluation of the spectroscopic criteria that are
usually examined for the configurational assignment at
ð1Þ
8
phosphorus.
Nevertheless, examination of the X-ray crystallographic
structures (Figs. 1 and 2) helps discard this hypothesis, since
it is the O–Et bond in (2S,5S)-1 rather than the lone pair at
oxygen that is more closely antiperiplanar to P–O(1):
t¼140.88 (Fig. 4(a)). By contrast, one of the lone electron
pairs at oxygen in the equatorial O–Et isomer (2R,5S)-1 can
2
(
.2. X-Ray crystallographic structural analysis of
2S,5S)-1 and (2R,5S)-1
Figs. 1 and 2 present the solid-state conformations that were
determined by X-ray diffraction analysis of suitable crystals
of (2S,5S)-1 and (2R,5S)-1, respectively.
be located at t¼170.78, i.e. an almost ideal orientation for
p
P–O(1)
the anticipated n !s
OEt
stereoelectronic interaction
(
Fig. 4(b)).
Salient features in the crystallographic structures (Figs. 1
and 2) are the chair conformation of the six-membered
heterocyclic rings and the anchoring effect of the phenyl
It can be appreciated in Fig. 4, that one of the oxygen lone
pairs in (2S,2S)-1 (axial P–OEt) should be nearly
eclipsed with the long P–O(1) endocyclic bond (estimated
dihedral angle between the exocyclic sp -hybridized
lone pair and the endocyclic P–O(1) bond is equal
10,11
substituent at C(5),
equatorial orientation of the PvO phosphoryl group in
2R,5S)-1 and (2S,5S)-1, respectively. Of course, since the
that is reflected in an axial or
3
(
absolute configuration at C(5) is (S), then determination of
the relative configuration at phosphorus establishes the
absolute configuration of this center of chirality as well.
to 20.88). It could be argued that syn-periplanar n
p
P–O(1)
!
OEt
s
hyperconjugation in the nearly syn arrangement
leads to the observed lengthening in the acceptor
1
3
orbital.
(Eq. (2)), counterbalancing the normal
X-Ray crystallography has proved to be a powerful tool to
reveal the effect of substituent orientation on phosphorus in
1
angles about phosphorus. In particular, hyperconjugative
,3,2-dioxaphosphorinanes on critical bond lengths and
1
2
p
stereoelectronic n !s
interaction is expected to be
P–OEt
O
reflected in longer P–OEt bond length when the ethoxy
group is axial, relative to equatorial P–OEt. The double
bond–no bond canonical structure that results from
hyperconjugation (Scheme 2) is also consistent
with the shorter Oring–P bond that is usually observed in the
p
n !s
O
P–OEt
Figure 4. Dihedral angles for the O(1)–P–O–Et segments in epimeric
oxazaphosphinanes (2S,2S)-1 and (2R,2S)-1, as determined from the X-ray
crystallographic structures (Figs. 1 and 2).
Scheme 2.

8976
I. Linzaga et al. / Tetrahedron 58 (2002) 8973–8978
p
P–OEt
4
antiperiplanar nO(1)!s
hyperconjugative interaction.
by Royer and co-workers, perhaps the most distinctive
3
P/H(6ax)
feature for the proton NMR spectra is the smaller J
3
(2.5 vs. 7.2 Hz) and larger J
coupling constants in the major (2S,5S) isomer.
(21.9 vs. 17.4 Hz)
P/H(6eq)
ð2Þ
3
A salient observation from Fig. 5 is that, whereas J for
anti
H(6) in (2S,5S)-1, i.e. axial P–OEt isomer is a normal
11.1 Hz, in the equatorial (2R,5S)-1 compound is only
8.4 Hz. This suggest a possible conformational equilibrium
in the latter, with appreciable amounts of either an inverted
chair (axial P–OEt and axial phenyl group) or a twist-boat
conformation (Eq. (3)).
2
(
.3. Infrared and multinuclear NMR analysis of
2S,5S)-1 and (2R,5S)-1
The most useful criteria for assigning configuration at
phosphorus in individual diastereomers of 1,3,2-dioxa-
phosphorinanes include infrared frequencies for the PvO
3
1
8
stretch and relative P chemical shifts. For the PvO
1
ax
ð3Þ
5
stretch one finds n(PvO ).n(PvO ), and this trend is
eq
2
1
also evident in diastereomeric (2S,5S)-1 with n¼1261 cm
(
1
equatorial phosphoryl), and (2R,5S)-1 with n¼1225 and
256 cm2 (axial phosphoryl).
1
16
1
3
Comparison of the C NMR data for (2S,5S)-1 and (2R,5S)-
1 (Fig. 6) indicates an absence of the g-gauche upfield
3
1
With regard P NMR chemical shifts, an extensive list of
data for 1,3,2-diheterophosphorinanes has been compiled in
Ref. 17, showing that d P(PvO ).d P(PvOeq). This
ax
1
8
shift
at C(3) in the latter isomer. This finding,
3
1
31
17
together with evidence of a deformed chair in the X-ray
crystallographic structure of (2S,5S)-1 (Fig. 2; for
example, the ring torsion angle N(4)–C(3)–P(2)–
O(1)¼52.9(4)8 in (2R,5S)-1 is significantly larger than
trend is also found in epimeric 2-oxo-1,4,2-oxaza-
d
phosphinane (2S,5S)-1 and (2R,5S)-1, where
31
3
1
P(PvO )¼20.3 ppm and d P(PvO )¼19.4 ppm.
ax
eq
t
¼46.8(2)8 for (2S,5S)-1). Thus it is
N(4)–C(3)–P(2)–O(1)
1
13
p
P–OEt
Finally, a remarkable similarity in H and C NMR data for
(
apparent that the absence of the n !s
anomeric
effect in chair-shaped (2R,5S)-1 causes a destabilization,
O(1)
2S,5S)-1 and (2R,5S)-1 is evident. (Figs. 5 and 6). As noted
1
Figure 5. Relevant H NMR chemical shifts (ppm) and coupling contants (Hz) in (2S,5S)-1 and (2R,5S)-1, at 400 MHz.
13
Figure 6. Relevant C NMR chemical shifts (ppm) and coupling contants (Hz) in (2S,5S)-1 and (2R,5S)-1, at 100 MHz.

I. Linzaga et al. / Tetrahedron 58 (2002) 8973–8978
8977
which pushes the ring in the direction of a twist-boat
conformation.
The flask was fitted with a Dean–Stark trap and the reaction
mixture was heated to reflux for 30 min with removal of
water. The flask was allowed to cool to ambient temperature
before the addition of 1.39 g (10 mmol) of diethyl
phosphite, and the reaction mixture was heated to 808C
for 4 h. The solvent was removed in a rotary evaporator and
the residue was purified by flash chromatography (ethyl
acetate–hexane, 8:2!6:4) to give 2.75 g (81% yield) of
3
. Concluding remarks
4
As evidenced by Royer’s observations, the method of
synthesis presented in this report should be applicable when
other aldehydes are employed in place of formaldehyde,
providing ready access to alkylated analogs of phosphonic
acids. Furthermore, given the availability of both isomers of
2
8
aminophosphonate (S)-3 as a colorless liquid: [a]
¼þ66.6
D
(c¼1.42, CHCl
). IR (cm2 ) n 3397, 1663, 1217, 1027. H
1
1
3
NMR (CDCl
Hz), 2.68 (dd, 1H, Jgem¼15.7 Hz, JH/P¼3.3 Hz), 3.26 (dd,
, 400 MHz) d 1.29 and 1.34 (2£t, 6H, Jvic¼7.0
3
2
1
, it should be possible to find conditions to deprotonate and
2
alkylate either isomer to gain access to the analogs noted
above. We are currently pursuing these objectives.
1H, Jgem¼16.1 Hz, JH/P¼17.2 Hz), 3.46 (d, 1H, Jgem¼13.8
4
Hz), 3.65 (dd, 1H, Jgem¼11.0 Hz, JH/P¼18.7 Hz), 4.0 (s,
1
(
H), 4.06 (masked, 1H), ca. 4.1 (masked, 1H), 4.14
1
3
masked, 4H), 7.18–7.44 (m, 10H). C NMR (CDCl ,
3
3
1
4
. Experimental
100 MHz) d 16.5 (d,
1
J
C/P¼5.4 Hz), 45.0 (d,
J
C/P
¼
4
67.6 Hz), 56.7 (d, JC/P¼5.4 Hz), 61.75, 62.2 (d,
4
.1. General
J¼6.9 Hz), 64.3, 127.3, 127.9, 128.5, 128.5, 128.8, 128.9,
3
1
1
35.9, 138.5. P NMR (CDCl , 161.8 MHz) d 27.9. HRMS
3
þ
Flasks, stirring bars, and hypodermic needles used for the
generation and reactions of organolithiums were dried for
about 12 h at 1208C. Anhydrous THF was obtained by
distillation from benzophenone ketyl. The butyllithium
employed was titrated according to the method of Juaristi
calcd for
378.1831.
C
20
H28NO
4
P
(M þ1): 378.1834. Found:
4.1.3. (2R,5S)- and (2S,5S)-4-Benzyl-2-ethoxy-2-oxo-5-
phenyl-1,4,2,-oxazaphos-phinane, (2R,5S)-1 and (2S,5S)-
1. In a 50-mL round-bottom flask fitted with rubber septa
and under nitrogen atmosphere, potassium hydride
(65.7 mg, 1.64 mmol) was suspended in 15 mL of dry
THF. The flask was cooled to 2758C in a dry ice-acetone
bath before the addition of 619 mg (1.64 mmol) of
aminophosphonate (S)-3 in 9 mL of dry THF. The reaction
mixture was allowed to react at 2758C for 2 h before
quenching with 20 mL of brine solution. The organic
product was extracted with three 15-mL portions of ethyl
acetate; dried over anh. sodium sulfate, and evaporated in a
1
9
et al. (4-biphenylmethanol indicator). TLC, F254 silica gel
plates; detection by UV light or iodine vapor. Flash column
chromatography: silica gel (230–400 mesh). All melting
1
points are uncorrected. H NMR spectra: JEOL FX-90Q
(
90 MHz), JEOL GSX-270 (270 MHz), and JEOL Eclipse-
3
1
4
00 (400 MHz) spectrometers. C NMR spectra: JEOL
FX-90Q (22.5 MHz), JEOL GSX-270 (67.8 MHz), and
JEOL Eclipse-400 (100 MHz) spectrometers. Optical
rotations were measured in a Perkin–Elmer Model 241
polarimeter, using the sodium D-line (589 nm). Elemental
analyses were performed by Galbraith Laboratories, Inc.,
TN. The purity of new compounds, for which elemental
analyses are not provided, was judged to be .97%, as
3
1
rotary evaporator. P NMR analysis of the crude product
showed a 97:3 mixture of the expected diastereomeric
products (431 mg, 79% yield), which were separated by
flash chromatography (hexane–ethyl acetate, 75:25).
Recrystallization from hexane–CH Cl (4:1) afforded
1
13
evidenced by H and C NMR spectra.
2
2
4
.1.1. (S)-2-(Benzylamino)-2-phenylethanol, (S)-2. (S)-
crystals suitable for X-ray diffraction analysis.
Phenylglycinol (1.9 g, 13.8 mmol) was placed in a 50-mL
three-neck round-bottom flask fitted with a magnetic stirbar,
a Dean–Stark trap, and a reflux condenser. Toluene (20 mL)
and 1.46 g (13.7 mmol) of benzaldehyde were added to the
flask, and the reaction mixture was heated to reflux for
2
8
(2R,5S)-1: mp 138–1408C; [a]
¼233.9 (c¼1.09, CHCl
IR (cm2 ) n 1256, 1047. H NMR (CDCl
, 400 MHz) d 1.34
(t, 3H, Jvic¼7.0 Hz), 2.54 (dd, 1H, Jgem¼14.1 Hz,
).
D
3
1
1
3
2
2
J
H/P¼12.6 Hz), 3.14 (dd, 1H, Jgem¼14.1 Hz,
J
¼
H/P
3
0 min and then allowed to cool to room temperature. The
15.6 Hz), 3.18 (d, 1H, Jgem¼13.6 Hz), 3.70 (dd, 1H,
resulting imine mixture was immediately treated with 0.31 g
of 10% palladium on charcoal and shaken in a Parr
apparatus during 2.5 h under 60 psi of hydrogen pressure.
After removal of the catalyst by filtration over celite and
evaporation of the solvent, the crude product was recrys-
tallized from methylene chloride–hexane (1:9) to give 2.4 g
J
anti¼8.4 Hz, Jgauche¼3.3 Hz), 3.78 (dd, 1H, Jgem¼13.3 Hz,
4
J
H/P¼6.1 Hz), 4.20 (m, 2H), 4.26 (ddd, 1H, Jgem¼11.9 Hz,
3
J
gauche¼3.2 Hz, JH/P¼17.4 Hz), 4.52 (ddd, 1H, Jgem¼11.7
3
13
Hz, Janti¼8.4 Hz, JH/P¼7.2 Hz), 7.22–7.50 (m, 10H).
C
3
NMR (CDCl
J
, 100 MHz) d 16.6 (d, JC/P¼4.6 Hz), 47.3 (d,
3
1
3
C/P¼144.6 Hz), 60.6 (d,
J
C/P¼16.9 Hz), 62.48 (d,
2
3
2
(
8
[
76% yield) of the desired product as a white solid: mp
4
J
C/P¼6.2 Hz), 65.5 (d,
J
C/P¼3.0 Hz), 71.9 (d,
J
C/P
¼
28
D
4
31
6–878C (lit. mp 888C). [a] ¼þ83.2 (c¼1.6, EtOH) lit.
6.2 Hz), 127.4, 128.5, 128.7, 129.0, 136.7, 137.0; P NMR
(CDCl , 161.8 MHz) d 20.3. X-Ray crystallographic
structure in Fig. 2. Anal. calcd for C H NO P: C,
a] ¼282.5 (c¼1, CHCl ) for the (R) enantiomer.
3
D
3
9
1
8
22
3
4
.1.2. {[Benzyl-(2-hydroxy-1S-phenyl-ethyl)-amino]-
65.24; H, 6.69; N, 4.22. Found: C, 65.58; H, 5.92; N, 3.95.
methyl}-phosphonic acid diethyl ester, (S)-3. N-Benzyl-
ated (S)-phenylglycinol, (S)-2, (2.29 g, 10.0 mmol) was
placed in a 50-mL round-bottom flask and dissolved in
25 mL of toluene before the addition of 0.82 mL of an
aqueous 37% solution of formaldehyde (0.03 g, 10 mmol).
2
8
(2S,5S)-1: mp 92–948C. [a]
¼þ31.0 (c¼1.03, CHCl
(cm ) n 1261, 1039. H NMR (CDCl , 400 MHz) d 1.37 (t,
3H, gem¼14.7 Hz,
vic¼7.1 Hz), 2.50 (dd, 1H,
H/P¼8.8 Hz), 2.93 (d, 1H, Jgem¼13.6 Hz), 3.16 (dd, 1H,
). IR
D
3
2
1
1
3
J
J
2
J

8978
I. Linzaga et al. / Tetrahedron 58 (2002) 8973–8978
2
Jgem¼14.6 Hz, J ¼19.0 Hz), 3.66 (dd, 1H, J ¼10.6
7. Gorenstein, D. G. Chem. Rev. 1987, 1047; and references cited
therein.
H/P
anti
Hz, J
JH/P¼7.5 Hz), 4.07 (ddd, 1H, J ¼11.7 Hz, J
¼2.9 Hz), 3.82 (dd, 1H, J ¼13.4 Hz,
gem
gauche
4
¼3.3
13
8. Bentrude, W. G. Steric and Stereoelectronic Effects in 1,3,2-
Dioxaphosphorinanes. In Conformational Behavior of Six-
Membered Rings. Analysis, Dynamics, and Stereoelectronic
Effects. Juaristi, E., Ed.; VCH: New York, 1995; pp 245–293
Chapter 7.
gem
gauche
3
Hz, J ¼21.9 Hz), 4.13 (m, 2H), 4.27 (ddd, J ø11.1
H/P
gem
3
Hz, Jantiø11.1 Hz, J ¼2.5 Hz), 7.20–7.46 (m, 10H).
C
H/P
3
NMR (CDCl , 100 MHz) d 16.5 (d, J ¼5.3 Hz), 47.5 (d,
3
C/P
1
2
2
3
JC/P¼143.7 Hz), 60.6 (d, JC/P¼18.4 Hz), 61.9 (d,
3
JC/P¼6.2 Hz), 66.7 (d, JC/P¼3.1 Hz), 73.0 (d,
9. Atomic coordinates for all the structures reported in this paper
have been deposited with the Cambridge Crystallographic
Data Centre. The coordinates can be obtained, on request,
from the Director, Cambridge Crystallographic Centre, 12
Union Road, Cambridge CB2 IEZ, UK.
JC/P¼6.9 Hz), 127.5, 128.3, 128.5, 128.7, 128.7, 129.1,
3
1
1
36.9, 137.0. P NMR (CDCl , 161.8 MHz) d 19.4. X-Ray
3
9
crystallographic structure in Fig. 1. Anal. calcd for
C H NO P: C, 65.24; H, 6.69; N, 4.22. Found: C, 65.04;
H, 6.71; N, 4.17.
1
8
22
3
1
0. The conformational free energy difference of a phenyl group
1
1
in cyclohexane (A-value ) amounts to ca. 2.9 kcal/mol. See:
Eliel, E. L.; Manoharan, M. J. Org. Chem. 1981, 46, 1959. See,
also: Bushweller, C. H. Stereodynamics of Cyclohexane and
Substituted Cyclohexanes. Substituent A Values. In Confor-
mational Behavior of Six-Membered Rings. Analysis,
Dynamics, and Stereoelectronic Effects. Juaristi, E., Ed.;
VCH: New York, 1995; pp 25–58 Chapter 2.
Acknowledgements
We are indebted to Conacyt, M e´ xico, for financial support
via grant 33023-E, and to M. L. Kaiser-Carril for technical
assistance. We are also grateful to the referees for many
important suggestions.
1
1. (a) Juaristi, E. Introduction to Stereochemistry and Confor-
mational Analysis. Wiley: New York, 1991. (b) Eliel, E. L.;
Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds. Wiley: New York, 1994.
References
1
2. Van Nuffel, P.; Van Alsenoy, C.; Lenstra, A. T. H.; Geise, H. J.
J. Mol. Struct. 1984, 125, 1.
1
2
. (a) Dellaria, J. F.; Santarsiero, B. D. J. Org. Chem. 1989, 54,
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3
1
3. (a) Juaristi, E.; Cuevas, G. Tetrahedron 1992, 48, 5019. (b) In
The Anomeric Effect and Associated Stereoelectronic Effects.
Thatcher, G. R. J., Ed.; American Chemical Society:
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Stereochem. 1994, 21, 159. (d) Juaristi, E.; Cuevas, G. The
Anomeric Effect. CRC: Boca Raton, FL, 1995.
. For some articles concerning the biological activity of
a-aminophosphonic acid derivatives, see: (a): Huang, J.;
Chen, R. Heteroat. Chem. 2000, 11, 480; and references
therein. (b) Kafarski, P.; Lejczak, B. Phosphorus Sulfur
Silicon Relat. Elem. 1991, 63, 193; and references therein.
. For examples of enantioselective synthesis of a-alkylated
a-aminophosphonic acids, see: (a) Yuan, C.; Li, S.; Wang, G.
Heteroat. Chem. 2000, 11, 528. (b) Sawamura, M.;
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4. Setzer, W. N.; Bentrude, W. G. J. Org. Chem. 1991, 56, 7212.
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3
1
1
6. In a closely related system, 4,5-dimethyl-2-ethoxy-2-oxo-1,2-
oxaphosphorinane, Bergesen and Vikane report
2
559. (c) Gr o¨ ger, H.; Saida, Y.; Sasai, H.; Yamaguchi, K.;
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e) Dhawan, B.; Redmore, D. Phosphorus Sulfur 1987, 32,
2
1
n(PvO )¼1256 cm
eq
and
n(PvO )¼1237
ax
and
2
1
1
250 cm . Bergesen, K.; Vikane, T. Acta Chem. Scand.
972, 26, 1794.
(
1
1
7. Gallagher, M. J. Conformation and Stereochemistry of Cyclic
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Deerfield Beach, FL, 1987; pp 297–330 Chapter 9.
(
1
19. (f) Sch o¨ llkopf, U.; Sch u¨ tze, R. Liebigs Ann. Chem. 1987,
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4
5
6
. Maury, C.; Gharbaoui, T.; Royer, J.; Husson, H. P. J. Org.
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1
8. (a) Grant, D. M.; Cheney, B. V. J. Am. Chem. Soc. 1967, 89,
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. For a general procedure, see: Fields, E. K. J. Am. Chem. Soc.
8, 1.
1
9. Juaristi, E.; Mart ´ı nez-Richa, A.; Garc ´ı a-Rivera, A.; Cruz-
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1952, 74, 1528.