Diastereoselective synthesis of α,α′-disubstituted β-ketophosphonates derivatives as building blocks for automated syntheses

Article abstract of DOI:10.1016/j.jorganchem.2004.10.042

A convenient and efficient synthesis of α,α′- disubstituted β-ketophosphonic derivatives in good to excellent de's and yields has been achieved by α-acylation followed by diastereoselective α-alkylation of chiral 5-membered cyclic phosphonamidates.

Full text of DOI:10.1016/j.jorganchem.2004.10.042

Journal of Organometallic Chemistry 690 (2005) 2626–2637
www.elsevier.com/locate/jorganchem
Diastereoselective synthesis of a,a0-disubstituted
b-ketophosphonates derivatives as building blocks
for automated syntheses
a,
a
a
b
Jean-Luc Pirat *, Xavier Marat , Ludovic Clarion , Arie Van der Lee ,
c
Jean-Pierre Vors , Henri-Jean Cristau
a,
*
a
Laboratoire de Chimie Organique, UMR 5076 – ENSCM, 8, rue de l Ecole Normale, 34296 Montpellier cedex 5, France
b
IEM, UMR 5635, Montpellier, France
c
Bayer Cropscience, Lyon, France
Received 27 July 2004; accepted 25 October 2004
Available online 26 November 2004
Abstract
A convenient and efficient synthesis of a,a0-disubstituted b-ketophosphonic derivatives in good to excellent deÕs and yields has
been achieved by a-acylation followed by diastereoselective a-alkylation of chiral 5-membered cyclic phosphonamidates.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: Diastereoselection; Alkylation; 1,3,2-Oxazaphospholidine; b-Ketophosphonamidate
1. Introduction
in both enantiomeric forms as precursors for heterocy-
clic and peptidic syntheses. Compounds 1a and 1b have
a quaternary chiral carbon center and two heteroatomic
sites (either phosphoryl and hydroxyl groups or phos-
phoryl and amino groups) which can be used in further
chemical manipulations.
The asymmetric synthesis of organophosphorus com-
pounds is a relatively new field. The major factor stimu-
lating the rapid development of the asymmetric
synthesis of P-chiral organophosphorus compounds,
during the past two decades, is their great practical value
as ligands in catalysts for asymmetric organic synthesis.
They are also important as biomolecules (enzyme inhib-
itors, antibiotics, antitumorals, herbicides and fungi-
cides) and also in the study of the stereochemical
course of reactions at stereogenic phosphorus [1]. Our
goal was to find new methods for preparation of novel
libraries of chiral difunctional compounds 1a and 1b
R'O
R'O
R'O
R'O
O
O
P
P
NH2
R1
OH
R1
R2
R2
1b
1a
From the retrosynthetic point of view, the target mol-
ecules (hydroxy 1a and amino 1b) can be obtained by
anionotropic rearrangements (Baeyer–Villiger, Beck-
mann or Schmidt rearrangements) of the corresponding
b-ketophosphonates 2. Both rearrangements are stereo-
specific and are characterised.
*
Corresponding authors. Tel.: 33467144314; fax: 33467144319.
E-mail address: pirat@cit.enscm.fr (J.-L. Pirat).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.10.042

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2627
R1
O
2. Results and discussion
R2
OH
OR'
OR'
1a
Baeyer-Villiger
2.1. Synthesis of 2-tert-butylamino-1,2-diphenyl-ethanol
unlike 6
P
Beckmann
or Schmidt
R1
O
O
R'O
R'O
trans-Stilbene was epoxidised using dimethyldioxi-
rane generated in situ in an oxone/NaHCO3/acetone sys-
tem [2]. Aminolysis with tert-butylamine in acetonitrile
affords a racemic mixture of 2-tert-butylamino-1,2-diph-
enylethanol unlike 6 in 65% yield (Scheme 3).
O
NH2
R2
P
CH3
OR'
OR'
P
R1
R2
2
1b
2.2. Synthesis of phosphorus heterocycles 5
The a,a0-disubstituted b-ketophosphonates 2 can be
obtained from the corresponding b-keto oxazaphosp-
holidines 3, which include the chiral framework neces-
sary for induction of the chirality on the carbon a to
phosphorus. Compound 3 can be prepared by diastereo-
selective C–C bond or C–fluoro bond formation with
asymmetric induction (with asymmetric induction by
chiral phosphorus atom) from a-monosubstituted pre-
cursors 4 (Scheme 1).
The synthesis of cyclic b-ketophosphonamidates 4
could be achieved by direct condensation of 2-tert-
butylamino-1,2-diphenylethanol unlike 6 with various
phosphonic dichlorides, followed by acylation of hetero-
cycles 5 (Scheme 2).
The cyclic phosphonamidates 5 are prepared, on a
large scale, by combining the racemic 2-tert-butyla-
mino-1,2-diphenylethanol unlike 6 with various phos-
phonic
dichlorides.
The
diastereomeric
phosphonamidates, 5 and 50 (Table 1), were separated
chromatographically and their structures were assigned
1
using 31P, 13C and H NMR spectroscopy. In case of
compounds 5a and 50a (R1 = Me) as well as 5b and 50b
(R1 = Ph) the X-ray crystallography confirmed the rela-
tive configuration of phosphorus atom of each diaste-
reoisomer 5 and 50 as the (RSRP/SRSP) and (RSSP/
SRRP) diastereoisomers, respectively. However, the dia-
stereomeric pairs can be more simply described as cis
and trans isomers, respectively, referring to the relative
tBu
Ph
tBu
O
R'O
R'O
O
O
N
O
O
Ph
Ph
O
N
O
P
P
P
CH3
CH3
CH3
O
Ph
R1
R2
R1
R1
R2
4
( + )
(R2 = Alk,F, CF3) ( + )
( + )
3
2
Scheme 1. Retrosynthesis of compounds 2.
tBu
NH
tBu
Ph
tBu
N
Ph
Ph
Ph
N
O
O
O
P
P
OH
CH3
( + ) 4
Ph
O
O
Ph
R1
R1
( + ) 5
( + ) 6
Scheme 2. Retrosynthesis of compounds 4.
tBu
NH
a) Oxone, NaHCO3
Na2EDTA, Acetone
Ph
Ph
Ph
Ph
Tert-Butylamine
CH3CN
Ph
Ph
0˚C (4 h) to r.t. (18 h)
O
OH
( + ) 6
Scheme 3. Synthesis of 2-tert-butylamino-1,2-diphenyl-ethanol unlike 6.

2628
J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
Table 1
Preparation of the phosphonamidates, 5 and 50
CH2R1
tBu
O
P
R1CH2POCl2 1.05 eq.
Et N 2.5 eq.
Ph
Ph
Ph
Ph
P
NH
CH2R1
O
O
THF
O
3
Ph
+
Ph
N
N
OH
48h, 0˚C-20˚C
tBu
tBu
( + ) 5' (RSSP/SRRP)
( + ) 5 (RSRP/SRSP)
( + ) 6
"trans"
"cis"
R1
5/50
Yield (%)
a
b
c
Me
Ph
53/47a
57/43a
54/46
96
65
88
iBu
a
Structures 5 and 50 determined by X-ray diffraction.
position of the two phenyl groups and of phosphoryl on
the 5-membered ring.
phosphonamidate (R1 = Ph) led only to the enolic form
of compound 4b.
2.4. Alkylation of the cis-b-ketophosphonamidates 4
The quaternary chiral carbon center is created by
alkylation of potassium enolates of cis-b-ketophospho-
namidates 4 (Scheme 4).
Denmark and Ambergey [5] have also demonstrated
the importance of the conformation of such phosphorus
heterocycles in controlling the diastereoselectivity of
alkylation: The diastereoselectivity is higher in the cis
series. Therefore, expecting a better diastereoselectivity,
we investigated first the alkylation of the cis isomers of
compounds 4, using as a mixture of diastereoisomers
4l and 4u, since both will afford the same intermediate
enolate (Table 3).
The cis compounds 3 were prepared in excellent yields
(88–98%) (entries 1, 2, 5) and excellent diastereoselectiv-
ities for the new stereogenic center (entries 1, 2, 4, 5).
Concerning entries 3 and 4, the yields decreased with
the competitive formation of the O-alkylation products
7. The structures of all compounds were assigned based
2.3. Synthesis of the b-ketophosphonamidates 4
The preparation of the b-ketophosphonamidates 4 in-
volves acylation of the lithiated heterocycles cis 5, using
ethyl acetate at low temperature (Table 2).
1
on 31P, 13C, H NMR spectroscopy.
Acylation of the lithiated heterocycles cis 5, and
quenching the resulting carbanion with ethyl acetate af-
fords the cis-b-ketophosphonamidates 4 with moderate
yields (38–52% after purification) which was readily
separated from the unreacted starting material by col-
umn chromatography [3]. The diastereoisomers 4l (ma-
jor isomer) and 4u (minor isomer) were separated
chromatographically, and their structures were assigned
based on 31P, 13C and 1H NMR spectroscopy. For
compound 4la (R1 = Me) the structure was confirmed
by X-ray crystallography. The diastereoisomers 4lc
and 4uc (R1 = iBu) were assigned by analogy using
the spectrographic data. The acylation of the benzyl
OR2
O
Ph
P
C
O
CH3
Ph
R1
N
tBu
7
It must be pointed out that in the synthesis of a target
compound 3, with a precise chirality, the introduction
order of the substituents is important: to obtain the best
diastereoselectivity it is necessary to use a b-ketophos-
phonamidate 4, as starting compound with the more

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2629
Table 2
Preparation of the cis-b-ketophosphonamidates 4 [3]
O
P
O
C
O
Ph
Ph
R1
P
O
CH3
O
1) nBuLi/THF/-70˚C
Ph
Ph
R1
tBu
N
N
2) AcOEt/-70˚C
3) NH4Cl
tBu
"cis" ( + ) 5
"cis" ( + ) 4
Product
Product
R1
Yield, %
52
de
4 l*
4 u*
O
O
C
O
O
C
Ph
Ph
P
P
O
O
CH3
CH3
Ph
Ph
a
b
c
Me
0
-
N
N
CH3
tBu
CH3
tBu
O
P
OH
C
Ph
O
CH3
Ph
Ph
38
50
N
Ph
tBu
O
P
O
C
O
P
O
C
Ph
Ph
O
O
CH3
CH3
Ph
Ph
iBu
88
N
N
tBu
tBu
*
l (like) and u (unlike) specify the relative configurations at phosphorus and a carbon atoms [4].
bulky group as R1 substituent [entry 3: 3ac de = 68%
(R1 = Me, R2 = iBu), entry 5: 3ca de > 99% (R1 = iBu,
R2 = Me)].
were easily separated by chromatography from the start-
ing compounds.
For the fluoro compounds de are only 44% and 55%
(entries 6, 7), but a simple chromatography allows to
separate the two diastereoisomers.
2.5. Preparation of fluorinated
cis-b-ketophosphonamidates 3
The structures of all compounds were assigned by
1
31P, 13C, H NMR (and 19F NMR) spectroscopy and
The fluorinated quaternary chiral center is created
by reaction of potassium enolates of various cis-b-
ketophosphonamidates 4 with Selectfluor and Umemoto
reagent (Table 4).
the correct configuration of compounds 3af (R1 = Me,
R2 = F) and 3fa (R1 = F, R2 = Me) were determined
by X-ray crystallography.
For the fluoro and the tri-fluoromethyl derivatives,
obtained, respectively, with Selectfluor (entries 6, 7)
and Umemoto reagent (entry 8) the target compounds
K
O
P
O
C
Ph
O
CH3
Ph
R1
N
tBu
Scheme 4. Potassium enolate of the cis-b-ketophosphonamidates 4.

2630
J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
Table 3
Alkylation of the cis-b-ketophosphonamidates 4
O
P
O
C
O
P
O
C
O
P
O
C
1) KOtBu 1.1 eq.
0˚C THF
Ph
Ph
Ph
O
CH3
O
O
CH3
CH3
Ph
Ph
Ph
2) 10 eq. RX, T˚C
+
R1
R1
tBu
N
R1
tBu
N
R2
R2
tBu
N
"cis" ( + ) 3 (R1,R2)
"cis" ( + ) 3 (R2,R1)
"cis" ( + ) 4
(major isomer)
(minor isomer)
Entry
R1
R2
X
T (ꢁC)
Yield (%)
dea (%)
Isolated compound
1
2
3
4
5
a
a
a
a
b
c
Me
Me
Me
Ph
d
e
c
a
a
Et
I
ꢀ30
ꢀ40
ꢀ40
ꢀ50
ꢀ50
90
98
60
80
88
87
95
3ad
3ae
Bn
iBu
Me
Me
Br
I
68
3ac and 3ca
3ba
3ca
I
>99
>99
iBu
I
Determined by 31P NMR and or 1H NMR.
Table 4
Preparation of fluorinated b-ketophosphonamidates 3
Entry
R1
No. eq. KOtBu
R2
No. eq. R2X
T ꢁC
Yield (%)
dea (%)
Isolated compound
6
7
8
a
a
c
a
Me
iBu
Me
1.1
1.2
2
f
F (Selectfluor)
F (Selectfluor)
CF3(Umemoto reagent) [6]
1.5
1.5
2
ꢀ70
ꢀ70
ꢀ70
91
63
38
55
44
94
3af and 3fab
3cf and 3fc
3ag
f
g
Determined by 19F NMR.
Structures 3af (R1 = Me and R2 = F) and 3fa (R1 = F and R2 = Me) determined by X-ray diffraction.
b
Ph
Ph
O
CH3
CH3
CH3
O
1) KOtBu 1.1 eq.
0˚C THF
O
Ph
Ph
Ph
C
C
P
P
P
C
CH3
O
O
CH3
O
CH3
O
O
O
Ph
Ph
Ph
+
2) BnBr, -78˚C
N
N
N
tBu
tBu
tBu
"trans" ( + ) 3'ha
"trans" ( + ) 4'a
"trans" ( + ) 3'ah
Yield = 85%, de = 76
Scheme 5. Benzylation of the trans b-ketophosphonamidate 4.
2.6. Comparison of the cis and trans series
3. Conclusion
To confirm that the diastereoselection is better in the
cis series than in the trans series, the benzylation of the-
trans b-ketophosphonamidate 40a (R1 = Me) was also
performed (Scheme 5).
The yield was excellent (85%) but the diastereo-
meric excess 76% was less important than for the
alkylation on the cis-b-ketophosphonamidate 4 (yield
98% and de 95%). This result can be explained by
the steric crowding of the enolate faces less hindered
in the transition state of the trans isomer in compari-
son with the cis isomer.
In summary, the alkylation or fluoration of b-keto-
phosphonamidates 4 proceeds with high selectivity and
high yields, and provides access to pure diastereoisomers
of a,a0-disubstituted b-ketophosphonamidates 3. Fur-
ther studies on the deprotection of a,a0-disubstituted
b-ketophosphonamidates 3, and on Baeyer–Villiger,
Beckmann or Schmidt rearrangements of the corre-
sponding a,a0-disubstituted b-ketophosphonates are
currently in progress. Such reactions should lead to gen-
eral and stereospecific syntheses of a,a-dialkylated a-hy-
droxy or a-aminophosphonates.

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2631
4. Experimental
phase was extracted with ammonia. The water was then
extracted with ethyl acetate. The organic phases dried
over MgSO4 and evaporated under vacuum gave 11.8 g
of white solid, yield: 73%; m.p.: 56.7 ꢁC (AcOEt), MS
4.1. General
1H, 13C, 31P and 19F NMR spectra were recorded on a
Bruker AC-200 spectrometer in CDCl3. Chemical shifts
are expressed in parts per million (ppm) and coupling con-
stants inHz downfield from internaltetramethylsilane. All
solvents were distilled prior to use, and commercially
available reagents used without further purification. All
reactions were monitored by TLC (Merk, SIL G/UV254);
Merck silica gel (20–40 lm) was used for flash column
chromatography and Merck silica gel (63–200 lm) for
column chromatography. Melting points were deter-
mined using a Wild Leitz 350 and are given uncorrected.
IR spectra were obtained with a Perkin–Elmer 377 spec-
trometer. Mass spectra were measured with a Jeol JMS
DX-300 spectrometer. High resolution mass spectra were
measured with a Jeol JMS SX-102 spectrometer.
FAB+ (NBA) [M + H]+: 270, H NMR CDCl3: d 7.19–
1
6.96 (m, 10 H, CHar), 4.68 (d, 3J = 5.6, 1 H, HOCHPh),
4.11 (d, 3J = 5.6, 1 H, HNCHPh), 1.00 (s, 9 H, tBu), 13
C
NMR CDCl3: d 142.39 (s, Car), 140.63 (s, CarH),
127.93–126.86 (10 C, CarH), 76.52 (s, C OH), 62.62 (s,
CNH), 51.30 (s, C(CH3)3), 30.2 (s, CH3), yield: 73%.
4.3. Synthesis of the 1,3,2-oxazaphospholidines 5(cis) and
50(trans)
4.3.1. Synthesis of diethyl (3-methylbutyl)phosphonate
[7]
Under N2, are added (0.26 mol, 32 ml) iso-amylbro-
mide and (0.275, 48 ml) triethyl phosphite. The mixture
is stirred 40 h at 140 ꢁC. The diethyl (3-methylbu-
tyl)phosphonate is purified by distillation.
4.2. Synthesis of ( )2-(tert-butylamino)-1,2-
diphenylethanol unlike 6
Boiling point: 100–110 ꢁC (0.5 mmHg), IR (NaCl): m
2990, 2910, 1270, 1040, 31P NMR CDCl3: d 33.90 (s, 1
1
3
3
P), H NMR CDCl3: d 3.96 (qd, JH–P = 8.7, J = 5.7,
4 H, CH2, OCH2CH3), 1.5 (m, 5 H, PCH2, PCH2CH2
4.2.1. Synthesis of 2,3-diphenyloxirane
3
and CH3CHCH3), 1.23 (t, J = 5.7, 6 H, OCH2CH3),
3
0.80 (d, J = 6.4, 6 H, CHCH3), yield: 50%.
To a solution of trans-stilbene (32.22 g, 179 mmol) in
(870 ml) CH3CN and (456 ml) aqueous solution of
EDTA (4 · 10ꢀ4 M), stirred at 0 ꢁC, was added succes-
sively acetone (143 ml) then, every 15 min, by small
scales, an homogenous mixture of Oxoneꢂ (269 g) and
Na2CO3 (120 g) (time of addition: 1.30 h). After 6 h at
0 ꢁC, the mixture was allowed to warm to room temper-
ature during the night. The mixture was filtered, washed
with 50 ml of CH3CN. The filtrate was extracted by 800
ml of water. The water phase was extracted three times
by 500 ml of ether. The organic phases were dried over
MgSO4 and evaporated under vacuum. The yellow vis-
cous oil crystallised, washed with methanol, gave 25 g
(98% yield) of yellow solid stored under nitrogen for
the next synthetic step; m.p.: 68.1–69 ꢁC (methanol),
1H NMR CDCl3: d 7.38–7.42 (m, 10 H, CHar), 3.9 (s,
2 H, CHPh), 13C NMR CDCl3: d 137.12 (s, Car),
125.57 (s, CarH), 128.62 (s, CarH), 128.37 (s, CarH),
62.86 (s, CHPh), IR (CCl4): m 3065, 3031, 2980, 2924,
1499, 1455, 1029, yield: 98%.
4.3.2. Synthesis of phosphonic dichlorides
4.3.2.1. General procedure [8]. In a 1 l one-necked pres-
sure bottle equipped with a magnetic stirring bar were
placed, under N2, (0.12 mol, 26 g) of PCl5, (65 mmol,
6.1 ml) of P(O)Cl3 and (11.2 ml) of diethyl (3-methylbu-
tyl)phosphonate. The pressure bottle was closed with a
robber stopper and the mixture was heated in oil bath
(110 ꢁC) for 14 h. During this period the mixture rapidly
became homogeneous. The mixture was allowed to cool
to ambient temperature, transferred into a distillation
flask and excess of P(O)Cl3 was removed with a rotary
evaporator at 35–40 ꢁC for about 1 h. The crude product
was purified by distillation under gradual heating.
4.3.2.2. (3-Methylbutyl)phosphonic dichloride. Boiling
point: 88–95 ꢁC (0.5 mmHg), 31P NMR CDCl3: d
53.56 (s), 1H NMR CDCl3: d 2.58 (m, 2 H, PCH2),
1.71 [m, 3 H, (CH3)2CHCH2 and (CH3)2CHCH2], 0.90
3
4.2.2. Synthesis of ( )2-(tert-butylamino)-1,2-
diphenylethanol unlike 6
[d, J = 6.3, 6 H, CH3], yield: 86%.
In a 250 ml batch were added (67.8 mmol, 13.3 g) of
2,3-diphenyloxirane, CH3CN (50 ml), lithium perchlo-
rate (14.4 g, 2 eq.) and tert-butyl amine (71.3 ml, 10
eq.). After 24 h at 80 ꢁC, under agitation, the mixture
was allowed to cool to room temperature. The reaction
mixture evaporated under vacuum, gave a yellow oil. This
oil was diluted with 100 ml of dichloromethane and 1 N
aqueous HCl was added until pH 2. The organic phases
were extracted two times with 50 ml of water. The water
4.3.2.3. Benzylphosphonic dichloride. Boiling point:
108–115 ꢁC (0.5 mmHg), 31P NMR CDCl3: d 47.11
1
(s), H NMR CDCl3: d 7.52–7.36 (M, 5 H, Car), 3.91
(d, JH–P = 18, 2 H, CH2), yield: 100%.
2
4.3.3. General procedure for the synthesis of 1,3,2-
oxazaphospholidines 2-oxides 5(cis) and 50(trans)
In a 3-necked round flask (250 ml) equipped with a
magnetic stirring bar were placed, under N2, (5 g 18.6

2632
J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
ml) ( ) 2-(tert-butylamino)-1,2-diphenylethanol unlike
in (40 ml) THF and (5.45 ml, 39.06 mmol, 2.1 eq.) of tri-
ethylamine. The reaction mixture was allowed to cool to
0 ꢁC. Then 1.05 eq. (19.53 mmol) of alkylphosphonic
dichloride were added dropwise in (46 ml) of THF for
45 min. The mixture became rapidly heterogeneous
and after stirring for 1 h at 0 ꢁC, was allowed to return
to ambient temperature for 48 h. The mixture was fil-
tered and the precipitate was washed with 3 · 30 ml of
THF. The organic phases dried over MgSO4 and evap-
orated under vacuum gave orange oil. The crude prod-
uct purified by flash chromatography on silica gel with
CH2Cl2–EtOAc (100/0) as the starting eluent to
CH2Cl2–EtOAc (60/40) gave the two diastereoisomers.
4.3.3.3.
cis-2-Benzyl-3-tert-butyl-4,5-diphenyl-1,3,2-
oxazaphospholidine 2-oxide 5b. Melting point: 266.9–
269.3 ꢁC (CH2Cl2/AcOEt), MS FAB+ (NBA)
[M + H]+: 406, HRMS FAB+ (NBA) (C25H29NO2P).
Found: m/z [M + H]+ 406.1935. Calc.: 406.1936, IR
(CHCl3): m 3088, 3030, 2980, 2917, 1260, 1150, 1051,
754, 31P NMR CDCl3: d 39.85 (s, 1 P), 1H NMR CDCl3:
d 8.03 (bs, 1 H, CHar), 7.32–7.26 (M, 6 H, CHar), 7.06–
6.77 (M, 7 H, CHar), 6.42 (bs, 1 H, CHar), 4.70 (d,
3J = 5.9,
3
H, OCHPh), 4.37 (dd, JH–P = 17.6,
1
3J = 5.9, 1 H, NCHPh), 3.63 (ABX system, dA = 3.74,
dB = 3.57, JP–H = 21.9, JP–H = 17.1, 2J = 15.4, 2 H,
2
2
CH2CH3), 1.34 [s, 9 H, C(CH3)3], 13C NMR CDCl3: d
138.56 (s, Car), 135.22 (d, JC–P = 8.2, Car), 133.01 (d,
3
2JC–P = 9.7, Car), 130.02–125.87 (CHar), 82.31 (s,
2
OCHPh), 65.46 (d, JC–P = 8,2, NCHPh), 53.85 [d,
4.3.3.1. cis-3-tert-Butyl-2-ethyl-4,5-diphenyl-1,3,2-oxaza-
phospholidine 2-oxide (R1 = Me) 5a. Melting point:
167–168 ꢁC (CH2Cl2/AcOEt), Rf: 0.48 (60/40 CH2Cl2/
AcOEt), MS FAB+ (NBA) [M + H]+: 344, HRMS
FAB+ (NBA) (C20H26NO2P). Found: 344.1798. Calc.:
344.1779, IR (CH2Cl2): m 3050, 3010, 2980, 2920, 1650,
1453, 1266, 1213, 1069, 748, 31P NMR (293 K) CDCl3:
2JC–P = 5.6, C(CH3)3], 38.81 (d, JC–P = 119, CH2Ph),
1
3
30.71 [d, JC–P = 2.6, C(CH3)3], yield: 47%.
4.3.3.4.
trans-2-Benzyl-3-tert-butyl-4,5-diphenyl-1,3,2-
oxazaphospholidine 2-oxide 50b. Melting point: 130.8–
131.9 ꢁC (CH2Cl2/AcOEt), MS FAB+ (NBA)
[M + H]+: 406, HRMS FAB+ (NBA) (C25H29NO2P).
Found: m/z [M + H]+406.1951. Calc.: 406.1936, IR
(CHCl3): m 3088, 3030, 2980, 2917, 1260, 1150, 1051,
754, 31P NMR CDCl3: d 42.93 (s, 1 P), 1H NMR CDCl3:
d 7.53–7.36 (M, 5 H, CHar), 7.06–6.86 (M, 8 H, CHar),
6.50–6.47 (M, 2 H, CHar), 5.92 (d, 3J = 6.6, 1 H,
1
d 46.8 (s), H NMR (293 K) CDCl3: d 8.06 (bs, 1 H,
CHar), 7.26 (bs, 1 H, CHar), 7.06–6.94 (M, 6 H, CHar),
6.88 (bs, 1 H, CHar), 6.49 (bs, 1 H, CHar), 5.56 (d,
3
3
3J = 5.9, 1 H, OCHPh), 4.6 (dd, JH–P = 17.1, J = 5.9,
2
1
H, NCHPh), 2.32 (m, JH–P = 16.8, 2J = 15.3,
2
3J = 7.6,
1
H, CH2CH3), 2.07 (m, JH–P = 14.1,
3
2J = 15.3, 3J = 7.6, 1 H, CH2CH3), 1.34 (dt, JH–P
=
OCHPh), 4.77 (t, J = 6.6, 1 H, NCHPh), 3.75 (ABX
2
system, dA = 3.8, dB = 3.7, JP–H = 21.1, JP–H = 19.5,
2J = 15.1, 2 H, CH2Ph), 1.36 [s, 9 H, C(CH3)3], 13C
3
19.7, J = 7.6, 3 H, CH2CH3), 1.27 (s, 9 H, CH3), 13C
NMR (293 K) CDCl3: d 138.9 (s, Car), 135.44 (d,
3JC–P = 8.18, Car), 128.37 (bs, CHar), 127.52–125.84
3
2
3
NMR CDCl3: d 139.33 (d, JC–P = 2.6, Car), 135.45 (d,
2
2
(CHar), 82.11 (s, OCHPh), 65.57 (d, JC–P = 8.2,
2
NCHPh), 53.23 [d, JC–P = 5.6, C(CH3)3], 30.37 [d,
3JC–P = 11.5, Car), 130.37 (d, JC–P = 6.3, Car), 130.43–
2
126.65 (CHar), 81.1 (s, OCHPh), 65.75 (d, JC–P = 5.2,
3JC–P = 2.6, C(CH3)3], 24.37 (d, 1JC–P = 124.3,
NCHPh), 54.52 [d, JC–P = 3.3, C(CH3)3], 37.97 (d,
3
2
2
CH2CH3), 8.14 (d, JC–P = 6.7, CH2CH3), yield: 62%.
1JC–P = 124.6, CH2Ph), 29.8 [d, JC–P = 3.3, C(CH3)3],
yield: 18%.
4.3.3.2.
trans-3-tert-Butyl-2-ethyl-4,5-diphenyl-1,3,2-
oxazaphospholidine 2-oxide (R1 = Me) 50a. Melting
point: 154.9–155.6 ꢁC (CH2Cl2/AcOEt), Rf: 0.3 (60/40
CH2Cl2/AcOEt), MS FAB+ (NBA) [M + H]+: 344,
HRMS FAB+ (NBA) (C20H26NO2P). Found: m/z
[M + H]+ 344.1773. Calc.: 344.1779, IR (CH2Cl2): m
3050, 3010, 2980, 2920, 1650, 1453, 1266, 1213, 1069,
4.3.3.5. cis-3-tert-Butyl-4,5-diphenyl-2-(3-methylbutyl)-
1,3,2-oxazaphospholidine 2-oxide 5c. Melting point:
187.2–189 ꢁC (CH2Cl2/AcOEt), MS FAB+ (NBA)
[M + H]+: 386, HRMS FAB+ (NBA) (C23H33NO2P).
Found: m/z [M + H]+ 386.2248. Calc.: 386.2249, IR
(CHCl3): m 3065, 3033, 2978, 2933, 1219, 1012, 754,
1
1
748, 31P NMR (293 K) CDCl3: d 49.7 (s), H NMR
31P NMR CDCl3: d 46.08 (s, 1 P), H NMR CDCl3: d
(293 K) CDCl3: d 7.01–6.82 (M, 10H, CHar), 5.89 (d,
8.02 (bs, 1 H, CHar), 7.32–7.00 (M, 8 H, CHar), 6.45
3
(bs, 1 H, CHar), 5.55 (d, J = 5.7, 1 H, OCHPh), 4.59
3
3
3J = 6.3, 1 H, OCHPh), 4.78 (dd, JH–P = 7.6, J = 6.3,
3
1 H, NCHPh), 2.34 (m, 2 H, CH2CH3), 1.45 (dt, JH–P
3
=
(dd, JH–P = 17.1, 3J = 5.7, 1 H, NCHPh), 2.40–1.52
3
20, J = 7.6, 3 H, CH2CH3), 1.34 (s, 9 H, CH3), 13C
[M, 5 H, (CH3)2CHCH2, (CH3)2CHCH2 and CH2P],
1.28 [s, 9 H, C(CH3)3], 0.94 [d, 3J = 6.3, 6 H,
(CH3)2CHCH2], 13C NMR CDCl3: d 138.92 (s, Car),
3
NMR (293 K) CDCl3: d 139.6 (d, JC–P = 1.9, Car),
135.52 (d, JC–P = 11.2, Car), 127.70–126.46 (Car),
3
2
80.79 (s, OCHPh), 65.92 (d, JC–P = 5.5, NCHPh),
3
135.5 (d, JC–P = 8.2, Car), 128.67–125.91 (CHar), 82.04
2
(s, OCHPh), 65.68 (d, JC–P = 8.2, NCHPh), 53.34 [d,
2
54.12 [d, JC–P = 3.3, C(CH3)3], 29.74 [d, JC–P = 2.9,
3
1
C(CH3)3], 23.98 (d, JC–P = 130.6, CH2CH3), 8.19 (d,
2JC–P = 5.6, C(CH3)3], 32.59 (d, 2JC–P = 5.4, CH2CH2P),
2JC–P = 6.7, CH2CH3), yield: 26%.
1
30.47 [s, C(CH3)3], 29.46 (d, JC–P = 123, CH2P), 28.98

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2633
3
[d, JC–P = 17.1, (CH3)2CHCH2], 22.11 [s, (CH3)2-
CHCH2], yield: 47%.
3
(O)CCH3], 1.54 [dd, JH–P = 19.5, 3J = 7.2, 3 H,
(O)CCHCH3], 1.33 [s, 9 H, C(CH3)3], 13C NMR CDCl3:
2
2
d 204.20 (d, JC–P = 4.1, C@O), 138.22 (d, JC–P = 0.7,
Car), 135.06 (d, JC–P = 7.8, Car), 128.87–128.33 (bs,
CHar), 127.61–125.92 (CHar), 83.82 (s, OCHPh), 65.78
3
4.3.3.6. trans-3-tert-Butyl-4,5-diphenyl-2-(3-methylbu-
tyl)-1,3,2-oxazaphospholidine 2-oxide 50c. Melting
point: 130.4–131.5 ꢁC (CH2Cl2/AcOEt), MS FAB+
(NBA) [M + H]+: 386, HRMS FAB+ (NBA)
(C23H33NO2P). Found: m/z [M + H]+ 386.2260. Calc.:
386.2249, IR (CHCl3): m 3065, 3033, 2978, 2933, 1219,
1012, 754, 31P NMR CDCl3: d 49.08 (s, 1 P), 1H
NMR CDCl3: d 7.05–6081 (M, 10 H, CHar), 5.90 (d,
2
(d, JC–P = 8.9, NCHPh), 54.19 [d, JC–P = 5.6,
2
1
C(CH3)3], 52.39 [d, JC–P = 108.6, (O)CCHP], 31.11 [s,
3
CHC(O)CH3], 30.42 [d, JC–P = 2.4, C(CH3)3], 12.32
2
[d, JC–P = 4.84, C(O)CHCH3].
4ub. 31P NMR CDCl3: d 38.13 (s, 1 P), H NMR
1
3
CDCl3: d 7.98 (d L, J = 7.7, 1 H, CHar), 7.26 (t L,
3
3
3J = 6.3, 1 H, OCHPh), 4.78 (dd, JH–P = 7.7, J = 6.3,
1 H, NCHPh), 2.35 (m, 2 H, CH2P), 1.75 [M, 3 H,
(CH3)2CHCH2 and (CH3)2CHCH2], 1.35 [s, 9 H,
3J = 7.4, 1 H, CHar), 7.06–6.89 (M, 7 H, CHar), 6.54
(d L, 3J = 7.7, 1 H, CHar), 5.60 (d, 3J = 6, 1 H, OCHPh),
3
3
4.6 (dd, JH–P = 17, J = 6, 1 H, NCHPh), 3.7 [m, 1 H,
(O)CCHCH3], 2.37 [s, 3 H, (O)CCH3], 1.56 [dd,
3
C(CH3)3], 0.99 [d, J = 5.9, 6 H, (CH3)2CHCH2], 13C
3
3
NMR CDCl3: d 139.62 (d, JC–P = 2.2, Car), 135.54 (d,
3JH–P = 18, J = 7.2, 3 H, (O)CCHCH3], 1.23 (s, 9 H,
3JC–P = 11.2, Car), 127.71–126.45 (CHar), 80.86 (s,
C(CH3)3), 13C NMR CDCl3: d 206.06 (d, JC–P = 3.7,
2
2
OCHPh), 65.84 (d, JC–P = 5.5, NCHPh), 54.15 [d,
2
3
C@O), 138.42 (d, JC–P = 0.7, Car), 135.18 (d, JC–P =
2JC–P = 3.3, C(CH3)3], 32.59 (d, 2JC–P = 5.2, CH2CH2P),
8, Car), 128.87–128.33 (bs, CHar), 127.61–125.92 (CHar),
82.47 (s, OCHPh), 65.67 (d, 2JC–P = 8,9, NCHPh), 54.10
[d, 2JC–P = 5, C(CH3)3], 51.77 [d, 1JC–P = 111,
1
29.79 [s, C(CH3)3], 28.87 (d, JC–P = 129, CH2P), 28.89
[d, 3JC–P = 16.1 Hz, (CH3)2CHCH2], 22.27 [s,
(CH3)2CHCH2], 21.94 [s, (CH3)2CHCH2], yield: 41%.
3
(O)CCHP], 30.42 [d, JC–P = 2.4, C(CH3)3], 29.66 [s,
2
CHC(O)CH3], 13.46 (d, JC–P = 5.9, C(O)CHCH3).
4.4. Preparation of the b-ketophosphonamidates 4
4.4.1.2. (1Z)-1-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-
oxazaphosphorinan-2-yl)-1-phenylprop-1-en-2-ol 4b. Melt-
ing point: 117.8–118.5 ꢁC (ether/pentane), MS FAB+
(NBA) [M + H]+: 448, HRMS FAB+ (NBA)
(C27H31NO3P). Found: m/z [M + H]+ 448.2052. Calc.:
448.2355, IR (CHCl3): m 3510, 3080, 3010, 2960, 2930,
1613, 1230, 765, 31P NMR CDCl3: d 39.06 (s, 1 P), ke-
4.4.1. General procedure
In a 4-necked round flask (250 ml) equipped with a
magnetic stirring bar were placed, under N2, (4 g, 10
mmol) of the oxazaphospholidines, 5a and 5b in (50
ml) THF. The reaction mixture was allowed to cool to
ꢀ78 ꢁC before the drop wise addition of (7.25 ml, 1.1
eq.) n-BuLi (1.6 M). Then, after 30 min at ꢀ78 ꢁC, the
reaction mixture was dropwise transferred to a solution
(10 ml, 10 eq.) of AcOEt in (50 ml) THF at ꢀ60 ꢁC. The
mixture was allowed to return to ꢀ40 ꢁC for 30 min.
Then the reaction mixture was allowed to return to
ambient temperature for 15 h. The mixture was washed
three times with 100 ml of ether. The organic phases
dried over MgSO4 and evaporated under vacuum gave
a white solid. The solid, by flash chromatography on sil-
ica gel with CH2Cl2–EtOAc (100/0) as the starting eluent
to CH2Cl2–EtOAc (60/40) gave the diastereoisomers.
1
tone 2 diastereoisomers 33.54 et 33.47 (2s), H NMR
CDCl3: d 12.14 (s, 1 H, OH), 7.99 (bs, 1 H, CHar),
7.64–6.74 (M, 13 H, CHar), 6.37 (bs, 1 H, CHar), 4.62
3
(d, 3J = 5,9, 1 H, OCHPh), 4.31 (dd, JH–P = 17.8,
3J = 6, 1 H, NCHPh), 1.80 (s, 3 H, (HO)CCH3), 1.29
[s, 9 H, C(CH3)3], 13C NMR CDCl3: d 169.93 (d,
2JC–P = 5, (HO)CCH3), 138.53 (s, Car), 135.33 (d, 3JC–P
=
7.8, Car), 135.07 (d, JC–P = 26, Car), 128.92–125.9
3
1
(CHar), 99.45 (d, JC–P = 167, (O)CCHP), 83.15 (s,
2
OCHPh), 64.94 (d, JC–P = 9.7, NCHPh), 54.34 [d,
3
2JC–P = 5.6, C(CH3)3], 30.15 [d, JC–P = 3, C(CH3)3],
3
20.03 (d, JC–P = 13.7, HOC(CH3)).
4.4.1.1.
oxazaphosphorinan-2-yl)butan-2-one
cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-
4a. Melting
4.4.1.3. 3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-5-methylhexan-2-one 4lc. Melting
point: 202.9–204.5 ꢁC (hexane/AcOEt), MS FAB+
(NBA) [M + H]+: 428, HRMS FAB+ (NBA)
(C27H31NO3P). Found: m/z [M + H]+ 428.2351. Calc.:
428.2355, IR (CHCl3): m 3060, 3010, 2940, 2920, 1720,
1238, 31P NMR CDCl3: d 38.26 (s, 1 P), 1H NMR
point: 157.4–161.2 ꢁC (hexane/AcOEt), Rf: 0.3 (60/40
hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 386,
HRMS FAB+ (NBA) (C22H29NO3P). Found: m/z
[M + H]+ 386.1885. Calc.: 386.1885, IR (CHCl3): m
3030, 3010, 2931, 2920, 1712, 1250, 1202, 1068, 765.
4la. 31P NMR CDCl3: d 38.64 (s, 1 P), H NMR
1
3
3
CDCl3: d 7.98 (d L, J = 7.7, 1 H, CHar), 7.26 (t L,
CDCl3: d 7.98 (d L, J = 7.9, 1 H, CHar), 7.26 (t L,
3J = 7.4, 1 H, CHar), 7.06–6.89 (M, 7 H, CHar), 6.54
(d L, 3J = 7.7, 1 H, CHar), 5.73 (d, 3J = 6, 1 H, OCHPh),
3J = 7.6, 1 H, CHar), 7.06–6.96 (M, 6 H, CHar), 6.89 (t
3
L, J = 7.2, 1 H, CHar), 6.55 (d L, J = 6.2, 1 H, CHar),
3
3
4.7 (dd, JH–P = 17.8, J = 6, 1 H, NCHPh), 3.71 [dq,
3
3
5.71 (d, J = 6.1, 1 H, OCHPh), 4.70 (dd, JH–P = 17.7,
3
3
2
2JH–P = 20.3, J = 7.2, 1 H, (O)CCHCH3], 2.57 [s, 3 H,
3J = 6.1, 1 H, NCHPh), 3.73 [ddd, JH–P = 21.7,

2634
J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
1
3J = 2.2, 3J = 12, 1 H, (O)CCHP], 2.54 [s, 3 H,
(O)CCH3], 2.32 (m, 1 H, CHCH2CH), 1.60 (m, 2 H,
CHCH2CH and CH3CHCH3), 1,33 [s, 9 H, C(CH3)3],
40u b. 31P NMR CDCl3: d 41,17 (s, 1 P), H NMR
(250 MHz) CDCl3: d 7.08–6.84 (M, 10 H, CHar), 5.92
(d, 3J = 6.8, 1 H, OCHPh), 4.91 (dd, JH–P = 8.8,
3
0.97 (d, J = 5, 6 H, CH3CHCH3), 13C NMR CDCl3:
3J = 6.8, 1 H, NCHPh), 3.65 (m, 1 H, CHCH3), 2.51
3
2
2
3
3
d 203.8 (d, JC–P = 4.8, C@O), 138.29 (d, JC–P = 0.7,
Car), 135.1 (d, 3JC–P = 7.8, Car), 128.9–128.28 (bs, CHar),
127.60–125.85 (CHar), 83.2 (s, OCHPh), 65.89 (d,
[s, 3 H, C(O)CH3], 1.72 (dd, JH–P = 19, J = 7.1, 3 H,
H11), 1.37 [s, 9 H, C(CH3)3], 13C NMR CDCl3: d
2
204.64 (d, JC–P = 3, C@O), 138.76 (s, Car), 135.08 (d,
2JC–P = 8.9, NCHPh), 56.85 (d, JC–P = 106.4, CHP),
3JC–P = 11.7, Car), 128.08–1226.77 (CHar), 81.26 (s,
1
2
2
2
OCHPh), 65.84 (d, JC–P = 6.3, NCHPh), 55.04 [d,
54.18 [d, JC–P = 5.4, C(CH3)3], 35.91 (d, JC–P = 4.4,
CH2CH(CH3)2), 31.84 [s, (O)CH3], 30.48 [d,
2JC–P = 3.3, C(CH3)3], 52.58 [d, 1JC–P = 114.2,
3JC–P = 2.8, C(CH3)3], 27.17
[d, 3JC–P = 16.1,
CH(CH3)], 29.62 [d, JC–P = 3.3, CH(CH3)], 28.9 [s,
2
(O)CH3], 13,68 [d, JC–P = 5.6, CH(CH3)].
3
CH2CH(CH3)2], 23.68 [s, CH2CH(CH3)2], 21.32 [s,
CH2CH(CH3)2].
4.5. Alkylation of the cis-b-ketophosphonamidates 4(l+u)
4.4.1.4. 3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-5-methylhexan-2-one 4uc. Melting
point: 178–189 ꢁC (hexane/AcOEt), MS FAB+ (NBA)
[M + H]+: 428, IR (CHCl3): m 3060, 3010, 2940, 2920,
1720, 1238, 31P NMR CDCl3: d 36.90 (s, 1 P), 1H
NMR CDCl3: d 7.96 (bs, 1 H, CHar), 7.26 (bs, 1 H,
CHar), 7.07–6.91 (M, 7 H, CHar), 6.49 (bs, 1 H, CHar),
4.5.1. General procedure
In a Schlenk (30 ml) equipped with a magnetic stir-
ring bar were placed, under N2, (0.5 mmol) of the cis-
b-ketophosphonamidates 4 (l, u) in (6 ml) THF. The
reaction mixture was allowed to cool to 0 ꢁC before
the addition of (62 mg, 0.55 mmol) tBuOK. Then, the
reaction mixture was cooled to ꢀ60 ꢁC for 5 min before
the addition in 5 min of the alkylated agent (5 mmol).
The mixture was maintained between ꢀ60 ꢁC and ꢀ40
ꢁC for 2 h. Then the reaction mixture was allowed to re-
turn to 20 ꢁC and stirring for 15 h. The mixture was di-
luted with ether (20 ml), water (10 ml) and sodium
thiosulfate 10% (20 ml). The water phase was extracted
with 2 · 30 ml ether. The organic phases dried over
MgSO4 and evaporated under vacuum gave a solid.
The solid, was purified by flash chromatography on sil-
ica gel with CH2Cl2–EtOAc (100/0) as the starting eluent
to CH2Cl2–EtOAc (80/20).
3
3
5.56 (d, J = 6.1, 1 H, OCHPh), 4.58 (dd, JH–P = 18.2,
2
3
3J = 6, 1 H, NCHPh), 3.4 [ddd, JH–P = 20.6, J = 3.7,
3J = 11.2, 1 H, (O)CCHP], 2.37 [s, 3 H, (O)CCH3],
2.25 (m, 1 H, CHCH2CH), 1.95 (m, 1 H, CHCH2CH),
1.58 (m, 1 H, CH3CHCH3), 1.26 [s, 9 H, C(CH3)3],
3
0.96 [t, J = 6.8, 6 H, CH(CH3)2], 13C NMR CDCl3: d
2
2
205.67 (d, JC–P = 4.3, C@O), 138.46 (d, JC–P = 0.7,
Car), 135.14 (d, JC–P = 8.2, Car), 128.78–128.36 (bs,
CHar), 127.60–125.92 (CHar), 82.46 (s, OCHPh), 65.46
3
2
(d, JC–P = 9.1, NCHPh), 56.64 (d, JC–P = 107.1,
1
2
CHP), 53.91 [d, JC–P = 5.4, C(CH3)3], 37.56 [d,
2JC–P = 5, CH2CH(CH3)2], 30.50 [d, 3JC–P = 2.6,
3
C(CH3)3], 29.95 [s, (O)CH3], 27.11 [d, JC–P = 14.1,
4.5.1.1. cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxa-
zaphosphorinan-2-yl)-3-methylpentan-2-one 3ad. Melt-
ing point: 227.8–228.7 ꢁC (CH2Cl2/AcOEt), Rf: 0.45
(90/10 CH2Cl2/AcOEt), MS FAB+ (NBA) [M + H]+:
414, HRMS FAB+ (NBA) (C24H33NO3P). Found: m/z
[M + H]+ 414.2209. Calc.: 414.2198, IR (CHCl3): m
3030, 3010, 2970, 2920, 1710, 1250, 1068, 760, 31P
NMR CDCl3: d 45.26 (s, 1 P) (other diastereoisomer
CH2CH(CH3)2], 23.32 [s, CH2CH(CH3)2], 21.19 [s,
CH2CH(CH3)2].
4.4.1.5. trans-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-
oxazaphosphorinan-2-yl)butan-2-one
40a. Melting
point: 148.7–150.7 ꢁC, MS FAB+ (NBA) [M + H]+:
386, HRMS FAB+ (NBA) (C22H29NO3P). Found: m/z
[M + H]+ 385.1911. Calc.: 386.1885, IR (CHCl3): m
3040, 3010, 2960, 2920, 1715, 1260, 1075, 760.
1
3
44.70), H NMR CDCl3: d 8 (d L, J = up3J = 7.7, 1
H, CHar), 7.18 (t L, 3J = 6.3, 1 H, CHar), 7.03–6.96
1
3
(M, 6 H, CHar), 6.82 (t L, J = 6.3, 1 H, CHar), 6.45
40l a. 31P NMR CDCl3: d 40.17 (s, 1 P), H NMR
(250 MHz) CDCl3: d 7.08–6.84 (M, 10 H, CHar), 5.94
(d L, 3J = 7.7, 1 H, CHar), 5.66 (d, 3J = 5.6, 1
H, OCHPh), 4.66 (dd, JH–P = 17.5, 3J = 6.1, 1 H,
3
3
(d, 3J = 6.4, 1 H, OCHPh), 4.85 (dd, JH–P = 8.6,
3J = 6.4, 1 H, NCHPh), 3.65 (m, 1 H, CHCH3), 2.42
NCHPh), 2.7 [m, 1 H, CH2 (CH3)], 2.55 [s, 3 H,
C(O)CH3], 2.15 [m, 1 H, CH2(CH3)], 1.50 [d,
3
3
[s, 3 H, C(O)CH3], 1.73 (dd, JH–P = 19.5, J = 7.2, 3
H, CHCH3), 1.38 [s, 9 H, C(CH3)3], 13C NMR CDCl3:
3JH–P = 10.3, 3 H, PC(CH3)], 1.12 [s, 9 H, C(CH3)3],
0.82 [t, J = 7.4, 3 H, CH2(CH3)], 13C NMR CDCl3: d
2
3
d 204.64 (d, JC–P = 3, C@O), 138.74 (s, Car), 135.08
(d, JC–P = 11.7, Car), 128.08–1226.77 (CHar), 81.63 (s,
3
2
2
208.9 (d, JC–P = 3, C@O), 138.74 (d, JC–P = 0.7, Car),
135.34 (d, JC–P = 7.4, Car), 128.83–125.87 (CHar),
2
OCHPh), 66.16 (d, JC–P = 6, NCHPh), 54.75 (d,
3
1
2
83.02 (d, JC–P = 1.5, OCHPh), 66.35 (d, JC–P = 8.2,
2
2JC–P = 3.7, C(CH3)3), 52.17 (d, JC–P = 113.5, CHP),
3
29.96 [d, JC–P = 3.3, C(CH3)3], 28.34 [s, (O)CH3],
1
NCHPh), 60.14 (d, JC–P = 111, PCCH3), 53.7 [d,
2JC–P = 5.2, C(CH3)3], 30.62 [d, JC–P = 2.6, CH(CH3)],
2
3
13.46 [d, JC–P = 5.6, CH(CH3)].

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2635
2
29.51 (d, JC–P = 6, CH2(CH3)), 28.24 [d, JC–P = 1.9,
3
ane/AcOEt), MS FAB+ (NBA) [M + H]+: 442, 31P
2
(O)CCH3], 16.77 (d, JC–P = 1.1, PC(CH3)), 9.02 (d,
1
NMR CDCl3: d 33,38 (s, 1 P), H NMR CDCl3: d 8
(bs, 1 H, CHar), 7.2 (bs, 1 H, CHar), 6.96–6.79 (M, 7
3JC–P = 14.1, CH2CH3).
3
H, CHar), 6.5 (bs, 1 H, CHar), 6.02 (d, J = 6,8, 1 H,
3
4.5.1.2. cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-phenylbutan-2-one 3ae. Melting
point: 209–212 ꢁC (CH2Cl2/AcOEt), Rf = 0.5 (95/10
CH2Cl2/AcOEt), MS FAB+ (NBA) [M + H]+: 476,
HRMS FAB+ (NBA) (C29H34NO3P). Found: m/z
[M + H]+ 476.2344. Calc.: 476.2355, IR (CHCl3): m
3030, 3010, 2980, 2920, 1700, 1250, 1064, 760, 31P
NMR CDCl3: d 44.76 (s, 1 P), 1H NMR CDCl3: d
OCHPh), 4.70 (dd, JH–P = 16.9, 3J = 6.5,
1
H,
NCHPh), 3.79 (s, 3 H, OCH3), 2.55 (m, 1 H, CHCH2),
2.06 (s, 3 H, OCCH3), 2 (m, 2 H, CHH2), 1.18 [s, 9 H,
3
C(CH3)3], 1.02 [d, J = 6.3, 3 H, CH(CH3)2], 0.90 [d,
3J = 6.3, 3 H, CH(CH3)2], 13C NMR CDCl3: d 162.36
(d, JC–P = 1.5, OCCH3), 140.54 (s, Car), 136.93 (d,
2
3JC–P = 8.5, Car), 127.36–126.51 (CHar), 108.87 (d,
1JC–P = 106,
C P), 82.23 (s, OCHPh), 65.80 (d,
4
3
8.09 (d L, J = 7.9, 1 H, CHar), 7.26–7.06 (M, 12 H,
CHar), 6.85 (t L, 3J = 6.5, 1 H, CHar), 6.50 (d L,
3J = 7.5, 1 H, CHar), 5.69 (d, 3J = 6, 1 H, OCHPh),
2JC–P = 10.4, NCHPh), 54.98 (d, JC–P = 0.7, OCH3),
2
2
53.39 [d, JC–P = 6.3, C(CH3)3], 39.39 (d, JC–P = 8.5,
3
CH2CH), 30.23 (d, JC–P = 3, C(CH3)3), 29.73 (s,
CH(CH3)2],), 22.7 [s, CH(CH3)2], 22.15 [s, CH(CH3)2],
3
4.70 (dd, JH–P = 17.3, 3J = 6.1, 1 H, NCHPh), 3.71
3
3
3
15.07 (d, JC–P = 11.7, [s, OC(CH3)]).
(AB system, dA = 4.0, dB = 3.4, JP–HA = 5.4, JP–
HB = 10.7, 2J = 14, 2 H, CH2Ph), 2.62 [s, 3 H,
3
C(O)CH3], 1.47 [d, JH–P = 17.8, 3 H, PC(CH3)], 1.23
4.5.1.5. cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3,5-dimethylhexan-2-one 3ac. Rf:
0.147 (80/20 hexane/AcOEt), MS FAB+ (NBA)
2
[s, 9 H, C(CH3)3], 13C NMR CDCl3: d 207.89 (d, JC–P
=
2
1.1, C@O), 138.68 (d, JC–P = 0.7, Car), 136.28 (d,
3JC–P = 15.2, Car), 135.23 (d, JC–P = 7.8, Car), 130.2–
[M + H]+: 442, 31P NMR CDCl3: d 45,53 (s, 1 P), H
3
1
2
125.9 (CHar), 82.75 (d, JC–P = 1.1, OCHPh), 66.54 (d,
3
NMR CDCl3: d 8.08 (d L, J = 7.9, 1 H, CHar), 7.24 (t
2JC–P = 8.5, NCHPh), 60.56 (d, JC–P = 108, PC), 53.94
L, 3J = 7.4, 1 H, CHar), 7.04–6.79 (M, 7 H, CHar),
1
2
[d, JC–P = 5.2, C(CH3)3], 41.1 (d, JC–P = 3.7, CH2Ph),
2
3
6.45 (d L, J = 7.4, 1 H, CHar), 5.66 (d, J = 6, 1 H,
3
3
30.86 [d, JC–P = 2.6, C(CH3)3], 29.28 (d, JC–P = 6,
3
3
3
OCHPh), 4.65 (dd, JH–P = 17.1, J = 6, 1 H, NCHPh),
2.62 [s, 3 H, C(O)CH3], 2.51 (m, 2 H, CH2CH), 2.1
2
(O)CCH3), 18.6 [d, JC–P = 2.2, PC(CH3)].
3
(m, 1 H, CHCH2), 1.55 [d, JH–P = 10, 3 H, PC(CH3)],
4.5.1.3. cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3,5-dimethylhexan-2-one 3ca. Melt-
ing point: 234.6–235.4 ꢁC (hexane/AcOEt), Rf: 0.15 (80/
20 hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 442,
HRMS FAB+ (NBA) (C26H37NO3P). Found: m/z
[M + H]+ 442.2528. Calc.: 442.2511, IR (CHCl3): m
3030,3010, 2970, 2920, 1710, 1240, 31P NMR CDCl3: d
1.14 [s, 9 H, C(CH3)3], 0.93 [d, 3J = 6.5, 3 H, CH(CH3)2],
3
0.88 [d, J = 6.8, 3 H, CH(CH3)2], 13C NMR CDCl3: d
2
209.55 (d, JC–P = 2.2, C@O), 138.92 (s, Car), 135.44
(d, JC–P = 4, Car), 128.75–125.68 (CHar), 82.85 (s,
3
2
OCHPh), 66.49 (d, JC–P = 8.2, NCHPh), 60.65 (d,
2
1JC–P = 107, CP), 53.74 [d, JC–P = 4.4, C(CH3)3],
2
43.98 (d, JC–P = 6, CH2CH), 30.68 [d, JC–P = 2.6,
3
1
3
3
C(CH3)3], 28.82 [s, (O)CCH3], 25.85 (d, JC–P = 14.1,
CH2CH), 25 [s, CH(CH3)2], 23.96 [s, CH(CH3)2], 17.91
44.66 (s, 1 P), H NMR CDCl3: d 7.91 (d L, J = 7.7,
1 H, CHar), 7.19 (t L, J = 7.6, 1 H, CHar), 6.96–6.79
3
3
(M, 7 H, CHar), 6.5 (d L, J = 7.7, 1 H, CHar), 5.62
(d, 3J = 6, 1 H, OCHPh), 4.63 (dd, JH–P = 16.7,
2
(d, JC–P = 2.2, PCCH3).
3
3J = 6, 1 H, NCHPh), 2.51 [s, 3 H, C(O)CH3], 2.47
(m, 1 H, CH2CH), 1.86 (m, 1 H, CH2CH), 1.63 [d,
3JH–P = 18, 3 H, PC(CH3)], 1.52 (m, 1 H, CH CH2),
1.21 [s, 9 H, C(CH3)3], 0.95 [d, 3J = 6.3, 3 H, CH(CH3)2],
4.5.1.6. cis-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-phenylbutan-2-one 3ba. Melting
point 236.1–237.1 ꢁC (hexane/AcOEt), Rf: 0.4 (90/10
CH2Cl2/AcOEt), MS FAB+ (NBA) [M + H]+: 462,
HRMS FAB+ (NBA) (C28H33NO3P). Found: m/z
[M + H]+ 462.2188. Calc.: 462.2198, IR (CHCl3): m
3080, 3010, 2970, 2920, 1715, 1230, 31P NMR CDCl3:
d 41,90 (s, 1 P), 1H NMR CDCl3: d 7.98 (d L,
3J = 7.4, 1 H, CHar), 7.74–6.73 (M, 13 H, CHar), 6.44
3
0.88 [d, J = 6.6, 3 H, CH(CH3)2], 13C NMR CDCl3: d
3
207.46 (s, C@O), 138.67 (s, Car), 135.33 (d, JC–P = 8,
Car), 128.97–125.67 (CHar), 82.09 (s, OCHPh), 65.87
2
(d, JC–P = 8.5, NCHPh), 59.14 (d, JC–P = 106, CP),
1
2
53.73 [d, JC–P = 5.2, C(CH3)3], 42.86 (d, JC–P = 3.5,
2
3
CH2CH), 30.95 [d, JC–P = 2.6, C(CH3)3], 28.11 [s,
(d L, 3J = 7.4, 1 H, CHar), 4.74 (d, 3J = 6.1, 1 H,
3
(O)CCH3], 25.20 (d, JC–P = 14.1, CH2CH), 25.06 [s,
3
OCHPh), 4.46 (dd, JH–P = 16.9, 3J = 6.1,
1
H,
2
CH(CH3)2], 23,79 [s, CH(CH3)2], 19,74 (d, JC–P = 3,
PCCH3).
3
OCHPh), 2.50 [s, 3 H, C(O)CH3], 2.18 (d, JH–P = 17,
3 H, PCCH3), 1,.13 [s, 9 H, C(CH3)3], 13C NMR
CDCl3:
d
204.86
(s,
C@O),
138.73
(d,
3
4.5.1.4. cis-3-tert-Butyl-4,5-diphenyl-2-[(1Z)-1-(1-meth-
oxyethylidene)-3-methylbutyl]-1,3,2-oxazaphospholidine
2-oxide (O-alkylation product) 7a. Rf: 0.06 (80/20 hex-
3JC–P = 0.7, Car), 136.71 (d, JC–P = 4, Car), 135.4 (d,
3JC–P = 7.8, Car), 129.47–125.81 (CHar), 82.34 (s,
2
OCHPh), 66.28 (d, JC–P = 8.5, NCHPh), 63.8 (d,

2636
J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2
1JC–P = 114, CP), 54.01 [d, JC–P = 5.2, C(CH3)3], 30.8
water (30 ml). The water phase was extracted with
2 · 30 ml ether. The organic phases dried over MgSO4
and evaporated under vacuum gave a solid. The solid,
was purified by flash chromatography on silica gel with
CH2Cl2–EtOAc (100/0) as the starting eluent to
3
[d, JC–P = 2.6, C(CH3)3], 28 [s, (O)CCH3], 20.95 (d,
2JC–P = 4.1, PCCH3).
4.5.1.7.
cis-3-tert-Butyl-4,5-diphenyl-2-[(1Z)-2-meth-
´ ´ ´
CH2Cl2–EtOAc (80/20). Mode operatoire generale.
oxy-1-phenylprop-1-en-1-yl]-1,3,2-oxazaphospholidine 2-
oxide (O-alkylation product) 7b. Rf: 0.1 (90/10 CH2Cl2/
AcOEt), MS FAB+ (NBA) [M + H]+: 442, 31P NMR
CDCl3: d 28.06 (s, 1 P), 1H NMR CDCl3: d 8.3 (bs, 1 H,
CHar), 7.3–6.84 (M, 13 H, CHar), 6.41 (bs, 1 H, CHar),
4.6.1.1. 3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-fluorobutan-2-one 3af. Melting
point: 211.5–212.8 ꢁC (CH2Cl2/AcOEt), Rf: 0.4 (80/20
hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 404,
HRMS FAB+ (NBA) (C22H28FNO3P). Found: m/z
[M + H]+ 404.1768. Calc.: 404.1791, IR (CHCl3): m
3030, 3010, 2970, 2920, 1725, 1260, 1102, 1066, 769,
3
3
5.01 (d, J = 6.1, 1 H, OCHPh), 4.50 (dd, JH–P = 17.7,
3J = 6.1, 1 H, NCHPh), 3.88 (s, 3 H, OCH3), 1.86 (s, 3
H, OCCH3), 1.29 [s, 9 H, C(CH3)3], 13C NMR CDCl3: d
2
165.12 (d, JC–P = 3, OCCH3), 139.8 (s, Car), 137.86 (d,
3
2
2JC–P = 7, Car), 136.41 (d, JC–P = 8.1, Car), 131.76–
31P NMR CDCl3: d 32.45 (d, JP–F = 88.1, 1 P), 19F
1
126.19 (CHar), 111.91 (d, JC–P = 167.8, CP), 82.23 (d,
2
NMR CDCl3: d ꢀ161.35 (d, JF–P = 88.1, 1 F), (dqd,
2JC–P = 1.1, OCHPh), 65.6 (d, JC–P = 10, NCHPh),
2JF–P = 88.1, 3JF–H = 23, 4JF–H = 2.5), 1H NMR CDCl3:
2
4
55.61 (d, JC–P = 1.1, OCH3), 53.78 [d, JC–P = 6,
2
3
d 7.87 (d L, J = 7.5, 1 H, CHar), 7.29–6.92 (M, 8 H,
CHar), 6.43 (d L, 3J = 7.4, 1 H, CHar), 5.79 (d,
2
C(CH3)3], 39.39 [d, JC–P = 8.5, C(CH3)3], 30.47 [d,
3
3JC–P = 3, C(CH3)3], 16.28 (d, 3JC–P = 11.2, OCCH3).
3J = 5.9,
1
H, OCHPh), 4.69 (dd, JH–P = 15.6,
4
3J = 5.9, 1 H, NCHPh), 2.56 (d, JH–F = 2.5, 3 H,
O@CCH3), 1.98 (dd, JH–P = 14.4, JH–F = 23, 3 H,
FCCH3), 1.2 (s, 9 H, C(CH3)3), 13C NMR CDCl3: d
3
3
4.5.1.8. trans-3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-phenylbutan-2-one 30ah. Melting
point: 187.8–189.8 ꢁC (CH2Cl2/AcOEt), MS FAB+
(NBA) [M + H]+: 476, HRMS FAB+ (NBA)
(C29H35NO3P). Found: m/z [M + H]+ 476.2337. Calc.:
462.2355, 31P NMR CDCl3: d 48.1 (s, 1 P), [other diaste-
2
203,3 (d, JC–P = 7.8, C@O), 138.3 (s, Car), 134.76 (d,
3JC–P = 8.5, Car), 128.03–125.87 (CHar), 100.66 (dd,
1JC–F = 200, JC–P = 135.8, FC), 82.71 (d, JC–P = 4,
1
2
2
OCHPh), 66.05 (d, JC–P = 9, NCHPh), 54.22 [d,
1
3
reoisomer: 48.4 (s, 1 P)], H NMR CDCl3: d 7.26–6.93
2JC–P = 5.3, C(CH3)3], 30.45 [d, JC–P = 1.3, C(CH3)3],
2
(M, 15 H, CHar), 6 (d, 3J = 7.1 H, OCHPh), 5 (t, 3J = 7,
1 H, NCHPh), 3.69 (AB system, dA = 4.12, dB = 3.29,
26.85 (s, OCCH3), 22.09 (d, JC–P = 23, FCCH3).
3
2
3JP–HA = 4.4, JP–HB = 13, J = 11.8, 2 H, CH2Ph), 2.46
4.6.1.2. 3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-fluorobutan-2-one 3fa. Melting
point: 213.6–214.4 ꢁC (CH2Cl2/AcOEt), Rf: 0.3 (80/20
hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 404,
HRMS FAB+ (NBA) (C22H28FNO3P). Found: m/z
[M + H]+ 404.1768. Calc.: 404.1791, IR (CHCl3): m
3030, 3010, 2970, 2920, 1725, 1260, 1102, 1066, 769, 31P
3
(s, 3 H, O@CCH3), 1.66 (d, JH–P = 17.7, 3 H, PCCH3),
1.42 [s, 9 H, C(CH3)3], 13C NMR CDCl3: d 207.07 (s,
2
3
C@O), 138.48 (d, JC–P = 2.8, Car), 136.66 (d, JC–P
16, Car), 135.22 (d, JC–P = 11.3, Car), 130.6–126.84
2
(CHar), 81.18 (s, OCHPh), 66.01 (d, JC–P = 4.6,
=
3
1
NCHPh), 58.15 (d, JC–P = 109.6, PCC@O), 55.5 [d,
2
2
2JC–P = 2.6, C(CH3)3], 40.1 (d, JC–P = 2.8, PhCH2),
NMR CDCl3: d 32.14 (d, JP–F = 89, 1 P), 19F NMR
CDCl3: d ꢀ158.91 (d, 2JF–P = 89, 1 F), (dqd, 2JF–P = 89,
3
30.12 [d, JC–P = 3.5, C(CH3)3], 29.58 (s, OCCH3), 19,7
4
1
(d, 2JC–P = 3,9, PCCH3).
3JF–H = 22.5, JF–H = 3.5), H NMR CDCl3: d 7.8 (d L,
3J = 7.4, 1 H, CHar), 7.29-6.83 (M, 8 H, CHar), 6.45 (d
L, 3J = 7.4, 1 H, CHar), 5.82 (d, 3J = 5.9, 1 H, OCHPh),
4.6. Preparation of the fluorinated
b-ketophosphonamidates 3
3
3
4.64 (dd, JH–P = 15.8, J = 5.9, 1 H, NCHPh), 2.56 (d,
3
4JH–F = 3.5, 3 H, O@CCH3), 1.97 (dd, JH–P = 15.1,
4.6.1. General procedure
3JH–F = 22.5, 3 H, FCCH3), 1.26 (s, 9 H, C(CH3)3), 13C
NMR CDCl3: d 203.57 (d, 2JC–P = 4.4, C@O), 138.16 (s,
Car), 134.7 (d, JC–P = 8.9, Car), 128.21–125.84 (CHar),
In a Schlenk (30 ml) equipped with a magnetic stir-
ring bar were placed, under N2, (0.5 mmol) of the cis-
b-ketophosphonamidates 4 (l, u) in (6 ml) THF. The
reaction mixture was allowed to cool to 0 ꢁC before
the addition of (62 mg, 0.55 mmol) tBuOK. Then, the
reaction mixture was cooled to ꢀ60 ꢁC for 5 min before
the addition in 5 min of the fluoro or the tri-fluorom-
ethyl derivatives (between 1.2 and 2 eq). The mixture
was maintained between ꢀ70 ꢁC for 2 h. Then the reac-
tion mixture was allowed to return to 20 ꢁC and stirring
for 15 h. The mixture was diluted with ether (20 ml),
3
1
1
100.23 (dd, JC–F = 201, JC–P = 137.3, FC), 81.88 (d,
2
OCHPh), 65.52 (d, JC–P = 9.3, NCHPh), 54.05 [d,
2JC–P = 5.2, C(CH3)3], 30.68 (d, C(CH3)3), 26.91 (s,
OCCH3), 21.72 (d, 2JC–P = 22.3, FCCH3).
4.6.1.3. 3-(3-tert-butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-fluoro-5-methylhexan-2-one 3fc. Melt-
ing point: 201.5–204.3 ꢁC (hexane/AcOEt), Rf: 0.1 (80/20
hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 446, HRMS

J.-L. Pirat et al. / Journal of Organometallic Chemistry 690 (2005) 2626–2637
2637
3
FAB+ (NBA) (C25H34FNO3P). Found: m/z [M + H]+
446.2245. Calc.: 446.2260, 31P NMR CDCl3: d 32.08 (d,
2JP–F = 91, 1 P), NMR 19F NMR CDCl3: d ꢀ169.61 (d,
CH3CHCH3), 24.12 (s, CH3CHCH3), 23.3 (d, JC–P = 3,5,
OCCH3).
2
3
3
2JF–P = 91, 1 F), (ddd, JF–P = 91, JF–H = 7, JF–H = 44),
4.6.1.5. 3-(3-tert-Butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-4,4,4-trifluoro-3-methylbutan-2-one
3ag. Melting point: 209.7–211.4 ꢁC (CH2Cl2), Rf: 0,28
(100% CH2Cl2), MS FAB+ (NBA) [M + H]+: 454,
HRMS FAB+ (NBA) (C23H28F3NO3P). Found: m/z
[M + H]+ 454.1778. Calc.: 454.1759, IR (CHCl3): m
3050, 3010, 2970, 2920, 1720, 1220, 1170, 1060, 765,
31P NMR CDCl3: d 31.39 (q, JP–F = 7, 1 P), 19F
NMR CDCl3: d ꢀ62.94 (d, JF–P = 7, 3 F), H NMR
CDCl3: d 7.84 (d L, 3J = 7.9, 1 H, CHar), 7.2 (t L,
3J = 6, 1 H, CHar), 7.03–6.88 (M, 7 H, CHar), 6.57 (d
3
1H NMR CDCl3: d 7.84 (d L, J = 7.5, 1 H, CHar), 7.25–
6.85 (M, 8 H, CHar), 6.44 (d L, J = 7.5, 1 H, CHar), 5.77
3
3
(d, J = 6, 1 H, OCHPh), 4.69 (dd, JH–P = 15.6, J = 6, 1
3
3
4
H, NCHPh), 2.6 (m, 1 H, CHCH2), 2.55 (d, JH–F = 2.2, 3
H, O@CCH3), 2.3 (m, 1 H, CHCH2), 1.83 (m, 1 H,
CHCH2), 1.19 [s, 9 H, C(CH3)3], 1 (d, 3J = 7, 3 H,
CH3CHCH3), 0.94 (d, 3J = 7, 3 H, CH3CHCH3), 13C
3
2
3
1
NMR CDCl3: d 203.64 (d, JC–P = 4.3, C@O), 138.48 (s,
Car), 134.9 (d, JC–P = 8.9, Car), 128.2–125.83 (CHar),
3
1
104.62 (dd, JC–F = 203.6, JC–P = 132.6, CF), 82.5 (d,
1
2
3
3
2JC–P = 4, OCHPh), 65.93 (d, JC–P = 9.1, NCHPh), 54.2
L, J = 7.7, 1 H, CHar), 5.8 (d, J = 5.9, 1 H, OCHPh),
2
2
3
4.71 (dd, JH–P = 17.3, J = 5.9, 1 H, NCHPh), 2.67 (s,
3
[d, JC–P = 5, C(CH3)3], 42.68 (d, JC–P = 19.5, CHCH2),
30.46 [s, C(CH3)3], 27.96 (s, CH3CHCH3), 25.45 (d,
3JC–P = 9, CH3CHCH3), 24.32 (s, CH3CHCH3), 23 (d,
3JC–P = 3.5, OCCH3).
3
3 H, OCCH3), 1.78 (d, JH–P = 17, 3 H, PCCH3), 1.16
[s, 9 H, C(CH3)3], 13C NMR CDCl3: d 199.3 (s,
3
C@O), 137.87 (s, Car), 134.59 (d, JC–P = 8.7, Car),
1
128.76–125.61 (CHar), 127 (qd, JC–F = 283, JC–P
2
=
2.6, CF3), 82.1 (s, OCHPh), 66 (d, 2JC–P = 9.8, NCHPh),
1
64.61 (dq, JC–P = 107, JC–F = 24, CCF3), 54.57 [d,
2
4.6.1.4. 3-(3-tert-butyl-4,5-diphenyl-2-oxo-1,3,2-oxaza-
phosphorinan-2-yl)-3-fluoro-5-methylhexan-2-one 3cf. Melt-
ing point: 205.2–206 ꢁC (hexane/AcOEt), Rf: 0.11 (80/20
hexane/AcOEt), MS FAB+ (NBA) [M + H]+: 446, HRMS
FAB+ (NBA) (C25H34FNO3P). Found: m/z [M + H]+
2JC–P = 4.8, C(CH3)3], 30.49 [d, JC–P = 2.6, C(CH3)3],
3
2
29.02 (s, OCCH3), 16.61 (t, JC–P = 2.8, CH3CHCF3).
Acknowledgements
446.2245. Calc.: 446.2260, 31P NMR CDCl3: d 31.84 (d,
2
2JP–F = 92, 1 P), 19F NMR CDCl3: d ꢀ167.1 (d, JF–P
=
Xavier Marat is grateful to Bayer-CropScience and to
CNRS for a scholarship.
92, 1 F), (ddd, JF–P = 92, JF–H = 10, JF–H = 40), 1H
2
3
3
3
NMR CDCl3: d 7.84 (d L, J = 7.5, 1 H, CHar), 7.25–6.85
(M, 8 H, CHar), 6.44 (d L, J = 7.5, 1 H, CHar), 5.75 (d,
3
3J = 5.7, 1 H, OCHPh), 4.69 (dd, JH–P = 15.6, J = 5.7, 1
3
3
References
4
H, NCHPh), 2.41 (m, 1 H, CHCH2), 2.3 (d, JH–F = 2.9,
[1] O.I. Kolodiazhnyi, Tetrahedron: Asymmetry 9 (1998) 1279.
[2] For general epoxidation procedure, see: A. Armstrong, B.R.
Hayter, Tetrahedron 55 (1999) 11119.
3 H, O@CCH3), 2.3 (m, 1 H, CHCH2), 1.83 (m, 1 H,
CHCH2), 1.28 [s, 9 H, C(CH3)3], 1.03 (d, J = 6.8, 3 H,
3
3
CH3CHCH3), 0.98 (d, J = 6.8, 3 H, CH3CHCH3), 13C
[3] V. Roussis, D.J. Wiemer, J. Org. Chem. 54 (1989) 556.
[4] V. Prolog, D. Seebach, Angew. Chem., Int. Ed. Engl. 21 (1982)
654.
2
NMR CDCl3: d 203.21 (d, JC–P = 4.5, C@O), 138.27 (s,
Car), 134.73 (d, JC–P = 8.9, Car), 128.2–125.83 (CHar),
3
1
104.23 (dd, JC–F = 205, JC–P = 132.5, CF), 81.83 (s,
1
[5] S.E. Denmark, J. Ambergey, J. Am. Chem. Soc. 115 (1993) 10386.
[6] T. Umemoto, Chem. Rev. 96 (1996) 1757.
2
OCHPh), 65.46 (d, JC–P = 9.3, NCHPh), 54.12 [d, JC–P
2
=
5, C(CH3)3], 42.68 (d, JC–P = 19.5, CHCH2), 30.79 [s,
[7] A.K. Bhattacharya, G. Thyagarajan, Chem. Rev. 81 (1981) 415.
[8] C. Patois, S. Berte´-Verrando, P. Savignac, Bull. Soc. Chim. Fr. 130
(1993) 485.
2
3
C(CH3)3], 26.98 (s, CH3CHCH3), 25.25 (d, JC–P = 11.5,