A stereoselective synthetic entry to β-substituted α-[(trans)-vinyl] phosphonamides

Article abstract of DOI:10.1016/j.tet.2009.01.074

α-(trans-Vinyl) phosphonamides with different substituents at the β-position were stereoselectively synthesized in high yields by treatment of β-substituted α-epoxy-α-trimethylsilyl phosphines with oxidizing agents. The corresponding phosphonamides were u

Full text of DOI:10.1016/j.tet.2009.01.074

Tetrahedron 65 (2009) 2451–2454
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journal homepage: www.elsevier.com/locate/tet
A stereoselective synthetic entry to
phosphonamides
b-substituted a-[(trans)-vinyl]
a
a
b
,
,
,c
Ona Illa , Sergio Celis , Aimee El-Kazzi c, Heinz Gornitzka b c, Antoine Baceiredo b
,
´
Vicenç Branchadell a, Rosa M. Ortun˜o a
,
*
a
´
`
Departament de Quımica, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
b Universite´ de Toulouse, UPS, LHFA, 118 route de Narbonne, F-31062 Toulouse, France
c CNRS, LHFA UMR 5069, F-31062 Toulouse, France
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-(trans-Vinyl) phosphonamides with different substituents at the
b
a
-position were stereoselectively
-trimethylsilyl phosphines with
Received 22 December 2008
Received in revised form 14 January 2009
Accepted 16 January 2009
synthesized in high yields by treatment of -substituted -epoxy-
oxidizing agents. The corresponding phosphonamides were unstable in most cases and underwent re-
ductive elimination affording desilylated vinyl derivatives. In turn, -epoxy phosphines resulted from the
[1þ2] addition of [bis(diisopropylamino)phosphino](trimethylsilyl)carbene 2 to aliphatic, aromatic, and
heteroaromatic aldehydes. In this way, a great variety of vinyl compounds have been efficiently prepared
through one-pot procedure.
b
a
a
Available online 23 January 2009
Keywords:
Stable carbene
Epoxy phosphonamides
Vinyl phosphonamides
Reductive elimination
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
In this paper, we describe synthetic routes to
a-vinyl derivatives
6 from the intermediate -epoxy phosphines. When these com-
a
a
-Vinyl phosphonamides are interesting and versatile building
pounds were oxidized by using different oxygen sources instead of
thiolation, the resultant epoxy phosphonamides 5 were unstable
and rearranged in situ to vinyl compounds 6.
blocks in organic synthesis. They have been synthesized by ad-
dition of a
b-vinyl phosphonamide anion to an a,b-unsaturated
ketone,1 and by palladium-catalyzed coupling of diaza-
phospholidines with vinyl halides,2 respectively. The products
obtained have been used, for instance, in the preparation of an-
tibacterial agents3 and as dienophiles in Diels–Alder cycloaddi-
2. Results and discussion
The reaction of carbene 2 with benzaldehyde was carried out
at room temperature, under previously described conditions,8 and
the appearance of a peak in the 31P NMR spectrum at 53 ppm,
attributable to the epoxy phosphine, was observed. After 10 min,
a dichloromethane solution of bis(trimethylsilyl)peroxide was
added and the mixture was stirred for 30 min. The signal at
53 ppm disappeared at the same rate that a new signal at 24 ppm
appeared. This is a typical chemical shift for an oxidized phos-
phorus derivative. Nevertheless, after working-up, the 1H NMR
spectrum of the crude reaction did not show the signal at 4.5 ppm
tions.4 The
a-vinyl phosphonamide unit is also present in the
structure of some nucleoside analogs for antiviral treatment.5
Moreover, in some cases, alcohols and aldehydes have been pre-
pared from
Recently, we reported on the stereoselective synthesis of alkyl,7
aryl,8 and heteroaryl9
-substituted -epoxy thiophosphonamides
a
-vinyl phosphonamides.6
b
a
through the [1þ2] addition of [bis(diisopropylamino)phosphino]-
(trimethylsilyl)carbene 2 to aliphatic, aromatic, and heteroaromatic
aldehydes, respectively. Carbene 2 is a nucleophilic and stable
species, which is photochemically generated from the corre-
attributable to the
a-oxirane proton in the expected epoxy de-
sponding diazo compound 1 (Scheme 1).10 The resultant
a
-epoxy
rivative. Instead, a doublet of doublet at 6.8 ppm was observed
phosphines
3 afforded, under thiolation, the corresponding
2
3
with JP–H¼18.8 Hz and JH–H¼17.2 Hz. The second vinyl proton
could not be differentiated from the absorption of some aromatic
protons at very close chemical shifts. The obtained product was
purified by column chromatography affording a solid in 70% yield
whose structure 6e was unambiguously assigned by an X-ray
diffraction analysis (Scheme 1, Fig. 1). This product was also
a
-epoxy thiophosphonamides 4, which are stable products.
* Corresponding author. Tel.: þ34 93 581 1602; fax: þ34 93 581 1265.
E-mail address: rosa.ortuno@uab.es (R.M. Ortun˜o).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.074

2452
O. Illa et al. / Tetrahedron 65 (2009) 2451–2454
O
iPr2N
iPr2N
iPr2N
iPr2N
R
C
SiMe3
N2
SiMe3
R'2P
Me3Si
H
hν
N2
H
P
C
P C
O
3
R
2
R' = iPr2N
1
S
R'2P
H
S8
Me3Si
O
4
R
Me3SiO-OSiMe3
or Ph2SeO
O
O
R'2P
H
R'2P
H
R
H O
(traces)
2
except for 5a
H
Me3Si
R
O
6b: R = 3-pyridyl
6c: R = 2-thienyl
6d: R = 3-thienyl
6e: R = phenyl
6f: R = 4-MeO-phenyl
6g: R = 4-NO2-phenyl
6h: R = Me
5a: R = 2-pyridyl
5b: R = 3-pyridyl
5c: R = 2-thienyl
5d: R = 3-thienyl
5e: R = phenyl
5f: R = 4-MeO-phenyl
5g: R = 4-NO2-phenyl
5h: R = Me
Scheme 1.
obtained in 74% yield after purification, employing diphenylse-
lenoxide as oxidizing agent.
Table 1
Melting points and isolated yields for epoxide 5a and vinyl derivatives 6b–h
To verify if these results could be extensive to other different
aldehydes, the reaction was carried out with 2- and 3-pyr-
idinecarboxaldehyde, 2- and 3-thiophenecarboxaldehyde,
4-methoxy- and 4-nitrobenzaldehyde, and acetaldehyde, as re-
presentative examples of heteroaromatic, aromatic, and aliphatic
aldehydes. As a result, vinyl phosphonamides 6b–h were, re-
spectively, produced in good yields (Table 1). In the case of
acetaldehyde, the yield was lower due to the competition with
a secondary process that we had been previously observed.7
Interestingly, epoxide 5a, which has been obtained using 2-
pyridincarbaldehyde, could be isolated and fully characterized. This
compound remained unaltered for weeks when stored at the re-
frigerator under nitrogen atmosphere. However, vinyl phosphon-
amide 6a was efficiently produced when 5a was treated with
hydrated tetrabutylammonium fluoride, which is an usual reagent
in desilylation reactions, at room temperature for 4 h (Scheme 2).
Desilylation occurs easily in these type of products in the
presence of humidity or acid traces. Then the resultant species,
probably an oxiranyl anion,11 must evolve to the vinyl derivative
under the reaction conditions. The active role in this process of the
Compound
R
Melting point (ꢁC)
Isolated yield (%)
5a
6b
6c
6d
6e
6f
2-Pyridyl
3-Pyridyl
2-Thienyl
3-Thienyl
60–62a
161–162a
155–157c
161–162a
150–153a
148–150a
230 (dec)a
83–86a
76
95b
63b
85b
70b
90b
52b
12b
Phenyl
4-Methoxyphenyl
4-Nitrophenyl
Methyl
6g
6h
a
From pentane.
Oxidation with bis(trimethylsilyl)peroxide.
From ether.
b
c
phosphoranyl versus thiophosporanyl group is manifested by
considering the stability of epoxide 7, which was prepared by
desilylation of the corresponding parent compound 4e under
similar conditions that in the case of 5a (Scheme 2). The reaction
took place with retention of configuration11 as shown by the
spectroscopic data. Any vinyl product was not observed in this
instance.
Oxygen transfer from phosphoranyl epoxides 5 was manifested
when desilylation of 5a was carried out in the presence of trime-
thylphosphine. The 31P NMR spectrum of the reaction mixture
showed that the signal of the phosphine at ꢀ60 ppm was shifted to
þ30 ppm according to the presence of trimethylphosphine oxide.
In contrast, no change was observed when desilylation of 4e was
01
N2
C3
Bu4NF · H2O
P1
C2
5a
6a: R = 2-pyridyl
4 h
C1
N1
S
S
R'2P
H
R'2P
H
Bu4NF · H2O
4 h
Me3Si
H
O
Ph
O
Ph
4e
7
Figure 1. Structure of vinyl phosphonamide 6e as determined by X-ray structural
analysis.
Scheme 2.

O. Illa et al. / Tetrahedron 65 (2009) 2451–2454
2453
achieved in the presence of trimethylphosphine, even when re-
action went on overnight.
4.2.1. (2RS,3RS)-3-(2-Pyridyl)-2-trimethylsilyl-2-oxiran-2-yl-
N,N,N0,N0-tetraisopropylphosphonodiamide 5a
The reductive formation of vinyl derivatives from epoxides has
also been observed in their reactions with alkyllithium reagents,12
but, as far as we know, there are not precedents on oxygen transfer
from epoxides to yield vinyl derivatives. Active investigation is
carried out in our laboratories to explain the mechanism of this
process.
Crystals, mp 60–62 ꢁC (from pentane). 31P NMR (101.2 MHz,
acetone-d6):
d
23.8. 1H NMR (250 MHz, acetone-d6):
d
ꢀ0.12 (s, 9H,
Si(CH3)3), 0.77 (s, 3H, (CH3)2CHN–), 0.79 (s, 3H, (CH3)2CHN–), 1.23–
1.35 (6s, 18H, (CH3)2CHN–), 3.37 (m, 2H, (CH3)2CHN–), 3.58 (m, 2H,
3
0
(CH3)2CHN–), 5.24 (d, JP–H¼7.0 Hz, 1H, H3), 7.27 (m, 1H, H5 ), 7.70
(ddd, J¼J0¼7.7 Hz, J00¼1.8 Hz, 1H, Harom.), 8.02 (m, 1H, Harom.), 8.48
(m, 1H, Harom.). 13C NMR (62.5 MHz, acetone-d6):
d 0.86 (Si(CH3)3),
2
23.6–24.6 (8 (CH3)2CHN–), 46.4 (d, JP–C¼5.8 Hz, C3), 47.6
3. Concluding remarks
1
0
0
(2(CH3)2CHN), 75.8 (d, JP–C¼134.5 Hz, C2), 124.2 (C3 ), 127.8 (C5 ),
þ
0
0
0
136.8 (C4 ), 148.9 (C6 ), 160.3 (C2 ). MS (m/z): 440.2 (MþH ).
In this work, we offer an efficient one-pot synthetic pathway
for the stereoselective preparation of vinyl phosphonamides
from the reaction between aldehydes and [bis(diisopropylamino)-
phosphino](trimethylsilyl)carbene. This new protocol involves the
oxidation of the resultant epoxy phosphine with bis(trimethylsilyl)-
peroxide or diphenylselenoxide instead of thiolation with elemental
sulfur that affords stable epoxy thiophosphonamides.
4.2.2. (E)-2-(3-Pyridyl)-1-ethenyl-N,N,N0,N0-tetraiso-
propylphosphonodiamide 6b
Crystals, mp 161–162 ꢁC (from pentane). 31P NMR (101.2 MHz,
acetone-d6):
d d 1.22 (s, 6H,
23.1. 1H NMR (250 MHz, acetone-d6):
(CH3)2CHN–), 1.24 (s, 6H, (CH3)2CHN–), 1.30 (s, 6H, (CH3)2CHN–),
1.32 (s, 6H, (CH3)2CHN–), 3.64–3.76 (m, 4H, (CH3)2CHN–), 6.96 (dd,
3
3
2JP–H¼3JH–H¼18.2 Hz, 1H, H1), 7.42 (dd, JP–H¼18.6 Hz, JH–H
¼
4. Experimental section
4.1. General
0
0
0
18.2 Hz,1H, H2), 7.44 (m,1H, H5 ), 8.09 (m,1H, H4 ), 8.57 (m,1H, H6 ),
8.83 (m, 1H, H2 ). 13C NMR (62.5 MHz, acetone-d6):
d
22.1 and
0
0
22.3 ((CH3)2CHN–), 44.8 and 44.9 (2(CH3)2CHN), 123.5 (C5 ), 127.0
(d, 1JP–C¼142.1 Hz, C1), 139.7 (d, 3JP–C¼19.1 Hz, C3 ), 133.2 (C6 ), 139.7
0
0
All manipulations were performed under an inert atmosphere
of nitrogen by using standard Schlenk techniques. Dry, oxygen-
free solvents were employed. Carbene 2 was prepared according
to Ref. 10. All employed aldehydes were distilled before each
reaction. 31P NMR downfield chemical shifts are expressed with
a positive sign, in parts per million, relative to external 85%
H3PO4. Microanalysis of the synthesized compounds used to af-
ford erratic results since combustion of carbon was systematically
incomplete. Purity criterion was assessed from cut-range melting
points and homogeneity of 31P, 1H, and 13C NMR spectra of these
products.
2
0
0
(d, JP–C¼5.7 Hz, C2), 148.7 (C6 ), 149.7 (C2 ). MS (m/z): 352.2
(MþHþ), 374.2 (MþNaþ), 390.1 (MþKþ).
4.2.3. (E)-2-(2-Thienyl)-1-ethenyl-N,N,N0,N0-tetraiso-
propylphosphonodiamide 6c
Crystals, mp 155–157 ꢁC (from ether). 31P NMR (101.2 MHz,
methanol-d4): d d 1.22 (s, 6H,
25.3.1H NMR (250 MHz, methanol-d4):
(CH3)2CHN–), 1.25 (s, 6H, (CH3)2CHN–), 1.30 (s, 6H, (CH3)2CHN–),
1.32 (s, 6H, (CH3)2CHN–), 3.59–3.77 (m, 4H, (CH3)2CHN–), 6.34 (dd,
2JP–H¼19.0 Hz, 3JH–H¼17.0 Hz, 1H, H1), 7.11 (m, 1H, H0), 7.26 (m, 1H,
H0), 7.48 (m, 2H, H2 and H0). 13C NMR (62.5 MHz, methanol-d4):
d
22.1, 23.2, 23.5, and 23.6 ((CH3)2CHN–), 46.6 and 46.7
(2(CH3)2CHN), 123.0 (d, 1JP–C¼148.8 Hz, C1), 128.4, 129.2, and 130.1
4.1.1. Crystal data for 6e
(C3 , C4 , and C5 ), 138.1 (d, JP–C¼5.7 Hz, C2), 143.0 (d, 3JP–C¼21.9 Hz,
C20H35N2OP, M¼350.47, monoclinic, P21/c, a¼12.427(2) Å,
2
0
0
0
b¼11.472(1) Å, c¼15.280(2) Å,
b
¼108.253(2)ꢁ, V¼2068.7(4) Å3,
þ
þ
þ
0
C3 ). MS (m/z): 357.1 (MþH ), 379.2 (MþNa ), 395.1 (MþK ).
Z¼4, T¼193(2) K. 11,847 reflections (4246 independent,
Rint¼0.0407) were collected. Largest electron density residue:
4.2.4. (E)-2-(3-Thienyl)-1-ethenyl-N,N,N0,N0-tetraiso-
propylphosphonodiamide 6d
0.339 e Åꢀ3, R1 (for I>2
s
(I))¼0.0453 and wR2¼0.1201 (all data)
with R1¼
S
jjFojꢀjFcjj/
S
jFoj and wR2¼(
S
Sw(Fo) )
w (Fo2ꢀFc2)2/ 2 2 0.5. All
Crystals, mp 161–162 ꢁC (from pentane). 31P NMR (101.2 MHz,
d d 1.21 (s, 6H,
24.0. 1H NMR (250 MHz, acetone-d6):
data for 6h were collected at low temperatures using an oil-
acetone-d6):
coated shock-cooled crystal on a Bruker-AXS CCD 1000 diffrac-
(CH3)2CHN–), 1.24 (s, 6H, (CH3)2CHN–), 1.29 (s, 6H, (CH3)2CHN–),
1.31 (s, 6H, (CH3)2CHN–), 3.59–3.76 (m, 4H, (CH3)2CHN–), 6.61 (dd,
tometer with Mo K
a
radiation (
l¼0.71073 Å). The structure was
solved by direct methods13 and all non-hydrogen atoms were
refined anisotropically using the least-squares method on F2.14
CCDC 625421 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336033;
e-mail: deposit@ccdc.cam.ac.uk).
3
3
3
2JP–H¼19.2 Hz, JH–H¼17.5 Hz, 1H, H1), 7.46 (dd, JP–H¼19.6 Hz, JH–
¼17.5 Hz, 1H, H2), 7.53 (m, 2H, H2 and H5 ), 7.70 (m, 1H, H4 ). 13C
0
0
0
H
NMR (62.5 MHz, acetone-d6):
d 22.0–22.4 ((CH3)2CHN–), 44.8
1
(2(CH3)2CHN), 124.1 (d, JP–C¼144.0 Hz, C1), 124.9 and 125.1
(C2 and C5 ), 125.5 (C4 ), 137.0 (d, JP–C¼5.7 Hz, C2), 139.8 (d, 3JP–C
¼
2
0
0
0
þ
þ
0
21.1 Hz, C3 ). MS (m/z): 357.2 (MþH ), 379.2 (MþNa ), 395.1
(MþKþ).
4.2. General procedure for the synthesis of epoxide 5a and
vinyl phosphonamides 6b–h
4.2.5. (E)-2-Phenyl-1-ethenyl-N,N,N0,N0-tetraiso-
propylphosphonodiamide 6e
Crystals, mp 150–153 ꢁC (from pentane). 31P NMR (101.2 MHz,
Dried and freshly distilled aldehyde (2 mmol) was added to
a solution of carbene 210 (2 mmol) in THF (2 mL) and the resultant
solution was stirred at room temperature for 10 min under nitrogen
atmosphere. Then bis(trimethylsilyl)peroxide in dichloromethane
(0.93 mL, 3 mmol) or, alternatively, diphenylselenoxide (500 mg,
2.0 mmol) in 3 mL of THF was added. The mixture was stirred for
30 min and solvents were removed. The residue was chromato-
graphed on neutral silica gel (mixtures of hexane–EtOAc as eluents)
to provide the pure product.
acetone-d6): d d 1.18 (s, 6H,
23.8. 1H NMR (250 MHz, acetone-d6):
(CH3)2CHN–), 1.21 (s, 6H, (CH3)2CHN–), 1.26 (s, 6H, (CH3)2CHN–),
1.29 (s, 6H, (CH3)2CHN–), 3.57–3.75 (m, 4H, (CH3)2CHN–), 6.75 (dd,
2
JP–H¼18.8 Hz, 3JH–H¼17.2 Hz, 1H, H1), 7.34–7.41 (m, 4H, H2, H3 , and
0
H4 ), 7.62 (d, JH–H¼6.7 Hz, 2H, H2 ). 13C NMR (62.5 MHz, acetone-
3
0
0
d6):
d 22.9 and 23.5 ((CH3)2CHN–), 45.9 (2(CH3)2CHN), 125.6 (d,
1
0
0
0
JP–C¼144.0 Hz, C1), 127.0, 129.7, and 129.9 (C2 , C3 , and C4 ), 137.6
3
2
0
(d, JP–C¼19.9 Hz, C1 ), 144.1 (d, JP–C¼5.8 Hz, C2). MS (m/z): 351.2
(MþHþ), 372.2 (MþNaþ).

2454
O. Illa et al. / Tetrahedron 65 (2009) 2451–2454
4.2.6. (E)-2-(40-Methoxyphenyl)-1-ethenyl-N,N,N0,N0-
tetraisopropylphosphonodiamide 6f
4.3.1. (E)-2-(2-Pyridyl)-1-ethenyl-N,N,N0,N0-tetraiso-
propylphosphonodiamide 6a
Crystals, mp 148–150 ꢁC (from pentane). 31P NMR (101.2 MHz,
Dense oil. 31P NMR (101.2 MHz, acetone-d6): 24.1. 1H NMR
d
methanol-d4):
d
24.4.1H NMR (250 MHz, methanol-d4):
d
1.20 (s, 6H,
(250 MHz, acetone-d6): d 1.20–1.31 (4s, 24H, (CH3)2CHN–), 3.61 (m,
2
3
(CH3)2CHN–), 1.23 (s, 6H, (CH3)2CHN–), 1.27 (s, 6H, (CH3)2CHN–),
1.30 (s, 6H, (CH3)2CHN–), 3.55–3.76 (m, 4H, (CH3)2CHN–), 3.83 (s,
4H, (CH3)2CHN–), 6.86 (dd, JP–H¼16.1 Hz, JH–H¼7.5 Hz, H1), 7.19
3 3
(dd, JP–H¼7.5 Hz, JH–H¼7.5 Hz, H2), 7.35 (m, 1H, Hheterocycle), 7.80
2
3
3H, –OCH3), 6.46 (dd, JP–H¼20.1 Hz, JH–H¼17.2 Hz, 1H, H1), 6.96
(m,1H, Hheterocycle), 8.07 (m,1H, Hheterocycle), 8.56 (m,1H, Hheterocycle).
3
3
3
(dd, JH–H¼8.7 Hz, 2H, H2 ), 7.28 (dd, JP–H¼20.4 Hz, JH–H¼17.2 Hz,
13C NMR (62.5 MHz, acetone-d6):
d 22.1, 22.3, and 22.9
0
1H, H2), 7.49 (d, 3JH–H¼8.7 Hz, 2H, H3 ). 13C NMR (62.5 MHz, meth-
((CH3)2CHN–), 44.1 and 45.6 ((CH3)2CHN–), 116.9 (d, 1JP–C¼242 Hz,
0
0 0 0 0
C1), 122.4 (C3 ), 123.8 (C5 ), 129.2 (C2), 135.9 (C4 ), 146.6 (C6 ), 156.3
anol-d4):
d
23.2 and 23.6 ((CH3)2CHN–), 46.6 and 46.7 (2(CH3)2CHN),
1
þ
þ
þ
0
0
0
55.8 (CH3O–), 115.4 (C2 ), 121.3 (d, JP–C¼148.8 Hz, C1), 129.8 (C3 ),
(C2 ). MS (m/z): 352.2 (MþH ), 374.2 (MþNa ), 390.1 (MþK ).
3
2
0
0
130.2 (d, JP–C¼21.0 Hz, C4 ), 145.2 (d, JP–C¼5.7 Hz, C2), 162.5 (C1 ).
MS (m/z): 381.2 (MþHþ), 403.2 (MþNaþ).
4.3.2. (2RS,3RS)-3-Phenyl-2-oxiran-2-yl-N,N,N0,N0-
tetraisopropylthiophosphonodiamide 7
4.2.7. (E)-2-(40-Nitrophenyl)-1-ethenyl-N,N,N0,N0-
tetraisopropylphosphonodiamide 6g
Crystals, mp 109 ꢁC (from ethyl acetate). 31P NMR (101.2 MHz,
CDCl3): d d 1.13 (s, 3H, (CH3)2CHN–),
69.4. 1H NMR (250 MHz, CDCl3):
Crystals, mp 230 ꢁC (from pentane). 31P NMR (101.2 MHz,
1.16 (s, 3H, (CH3)2CHN–), 1.24, 1.35, 1.37, 1.38, 1.40, and 1.43 (6s, 18H,
methanol-d4): d d 1.22 (s, 6H,
24.7.1H NMR (250 MHz, methanol-d4):
(CH3)2CHN–), 3.15 (dd, 2JP–H¼27.2 Hz, 3JH–H¼2.3 Hz, 1H, H2), 4.48 (dd,
3
(CH3)2CHN–), 1.24 (s, 6H, (CH3)2CHN–), 1.29 (s, 6H, (CH3)2CHN–),
1.32 (s, 6H, (CH3)2CHN–), 3.61–3.79 (m, 4H, (CH3)2CHN–), 6.92 (dd,
3JP–H¼4.7 Hz, JH–H¼2.3 Hz, 1H, H3), 7.31 (m, 5H, Hphenyl). 13C NMR
2
(62.5 MHz, CDCl3):
d
22.7–23.9 ((CH3)2CHN–), 46.3 (d, JC–P¼4.8 Hz,
3
3
3
2JP–H¼18.9 Hz, JH–H¼17.3 Hz, 1H, H1), 7.44 (dd, JP–H¼20.0 Hz, JH–
(CH3)2CHN), 46.5 (d, 2JC–P¼4.8 Hz, (CH3)2CHN), 60.2 (d,1JC–P¼158.3 Hz,
C2), 61.5 (C3),125.8,128.5,128.6 (CHphenyl),136.0 (Cquaternary). MS (m/z):
405.1 (MþNaþ).
3
0
¼17.3 Hz, 1H, H2), 7.81 (d, JH–H¼8.9 Hz, 2H, H2 ), 8.28 (d,
H
JH–H¼8.9 Hz, 2H, H3 ). 13C NMR (62.5 MHz, methanol-d4):
d 23.2,
3
0
0
23.3, and 23.6 ((CH3)2CHN–), 46.8 (2(CH3)2CHN), 125.2 (C2 ), 129.2
1
(C3 ), 129.5 (d, JP–C¼144.0 Hz, C1), 142.9 (d, 2JP–C¼5.7 Hz, C2), 143.7
0
Acknowledgements
3
þ
0
0
(d, JP–C¼20.0 Hz, C4 ), 149.6 (C1 ). MS (m/z): 396.2 (MþH ), 418.2
(MþNaþ).
´
Financial support from the Ministerio de Educacion y Ciencia
(CTQ2004-01067) and the Generalitat de Catalunya (SGR2005-
00103, LEA-LTPMM) (Spain), and the CNRS (France) (LEA-368) is
gratefully acknowledged.
4.2.8. (E)-1-Propenyl-N,N,N0,N0-tetraisopropylphosphono-
diamide 6h
Crystals, mp 83–86 ꢁC (from pentane). 31P NMR (101.2 MHz,
acetone-d6):
(CH3)2CHN–), 1.17 (s, 6H, (CH3)2CHN–), 1.22 (s, 6H, (CH3)2CHN–),
d d 1.14 (s, 6H,
23.8. 1H NMR (250 MHz, acetone-d6):
References and notes
3
4
1.24 (s, 6H, (CH3)2CHN–), 1.87 (ddd, JH–H¼6.7 Hz, JP–H¼2.2 Hz,
1. Hanessian, S.; Gomtsyan, A.; Malek, N. J. Org. Chem. 2000, 65, 5623.
2. Irao, T.; Masunaga, T.; Yamada, N.; Ohshiro, Y.; Agawa, T. Bull. Chem. Soc. Jpn.
1982, 55, 909.
3. Hanessiam, S.; Griffin, A. M.; Rozema, M. J. Bioorg. Med. Chem. Lett. 1996, 6,
2589.
4. Wyatt, P. W.; Villalonga-Barber, C.; Motevalli, M. Tetrahedron Lett. 1999, 40, 149.
5. Chen, J. M.; Huang, A. X.; Mackman, R. L.; Parrish, J. P.; Perry, J. K.; Saunders,
O. L.; Sperandio, D. WO 2008100447 A2.
4JH–H¼1.7 Hz, 1H, CH3–), 3.48–3.66 (m, 4H, (CH3)2CHN–), 6.04 (ddq,
2JP–H¼21.9 Hz, JH–H¼16.6 Hz, JH–H¼1.7 Hz, 1H, H1), 6.56 (ddq,
3
4
3JP–H¼17.4 Hz, JH–H¼16.6 Hz, JH–H¼6.5 Hz, 1H, H2). 13C NMR
3
3
(62.5 MHz, acetone-d6): d 19.9 (CH3–), 23.0 and 23.4 ((CH3)2CHN–),
1
45.8 (2(CH3)2CHN), 129.6 (d, JP–C¼142.1 Hz, C1), 143.3 (d,
2JP–C¼4.8 Hz, C2). MS (m/z): 289.1 (MþHþ), 311.2 (MþNaþ).
6. Molt, O.; Schrader, T. Synthesis 2002, 2633.
7. Illa, O.; Gornitzka, H.; Branchadell, V.; Baceiredo, A.; Bertrand, G.; Ortun˜o, R. M.
Eur. J. Org. Chem. 2003, 3147.
4.3. Desilylation of 5a and 4e: synthesis of 6a and 7
8. Illa, O.; Gornitzka, H.; Baceiredo, A.; Bertrand, G.; Branchadell, V.; Ortun˜o, R. M.
J. Org. Chem. 2003, 68, 7707.
9. Ferna´ndez, D.; Illa, O.; Avile´s, F. X.; Branchadell, V.; Vendrell, J.; Ortun˜o, R. M.
Bioorg. Med. Chem. 2008, 16, 4823.
10. Igau, A.; Baceiredo, A.; Trinquier, G.; Bertrand, G. Angew. Chem., Int. Ed. Engl.
1989, 28, 621.
11. Chan, T. H.; Lau, P. W. K.; Li, M. P. Tetrahedron Lett. 1976, 17, 2667.
12. (a) Crandall, J. K.; Lin, L.-H. C. J. Am. Chem. Soc. 1967, 89, 4526; (b) Doris, E.;
Dechoux, L.; Mioskowski, C. Synlett 1998, 337.
Preparation of 7 is described. A mixture of epoxide 5h (40 mg,
0.09 mmol) and TBAF$H2O (90 mg, 0.3 mmol) in 2 mL of THF was
stirred at room temperature for 4 h. Solvent was removed at re-
duced pressure and the residue was poured into ether (15 mL). The
resultant solution was successively washed with water (5ꢂ15 mL)
and dried over anhydrous MgSO4, and solvent was evaporated. The
residue was chromatographed on neutral silica gel (EtOAc as elu-
ent) to afford pure 7 (27 mg, 78% yield).
13. SHELXS-97 Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467.
14. Sheldrick, G. M. SHELXL-97, Program for Crystal Structure Refinement; University
of Go¨ttingen: Go¨ttingen, Germany, 1997.