Oxaphospholene and oxaphosphinene heterocycles via RCM using unsymmetrical phosphonates or functional phosphinates

Article abstract of DOI:10.1016/j.tet.2009.11.049

New phosphorus heterocycles were synthesized using RCM reaction. They were prepared from unsymmetrical or polyfunctional insaturated precursor in 50 to 87% yields solving the problem of possible competitive side reactions. In parallel hydroxyphosphinate scaffolds represent a versatile starting material and could be of great interest for the synthesis of phosphosugar libraries.

Full text of DOI:10.1016/j.tet.2009.11.049

Tetrahedron 66 (2010) 758–764
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Oxaphospholene and oxaphosphinene heterocycles via RCM using
unsymmetrical phosphonates or functional phosphinates
Pierre Fourgeaud a, Camille Midrier a, Jean-Pierre Vors b, Jean-Noe¨l Volle a, Jean-Luc Pirat a,
,
David Virieux a
*
a Institut Charles Gerhardt–UMR5253–AM2N–ENSCM, 8, Rue de l’Ecole Normale, F34296 Montpellier Cedex 5, France
b Bayer CropScience, 14-20 rue Pierre Baizet, BP 9163, F69263 Lyon Cedex 09, France
a r t i c l e i n f o
a b s t r a c t
Article history:
New phosphorus heterocycles were synthesized using RCM reaction. They were prepared from un-
symmetrical or polyfunctional insaturated precursor in 50 to 87% yields solving the problem of possible
competitive side reactions. In parallel hydroxyphosphinate scaffolds represent a versatile starting ma-
terial and could be of great interest for the synthesis of phosphosugar libraries.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 7 September 2009
Received in revised form
6 November 2009
Accepted 10 November 2009
Available online 14 November 2009
1. Introduction
unsymmetrical
phosphonates
or
functional
1-hydroxy-
phosphinates with as features the presence of two different func-
tional alkenyl groups directly linked to the phosphorus atom.
Due to their key roles in cells metabolism and their potential to
serve as pharmaceuticals and agricultural agents, phosphorus
molecules are popular targets for the development of new bi-
ologically active compounds.1 General methods to synthesize
phosphorus heterocycles (P–heterocycles) employing functional
group-compatible transition-metal catalyzed processes were a key
achievement of the last few years.2 Among them, the advent of
ring-closing metathesis (RCM)3 as a core synthetic tool has led to
numerous advances in the preparation of small phosphorus mol-
ecules.4 However, synthesis of P-heterocycles by such way is
sometimes clearly impeded by competitive side reactions: So far if
diallyl allylphosphonates mainly furnished the more favored six-
2. Results and discussion
2.1. Preparation of unsaturated functional precursors
Vinyl- or allylphosphonochloridates were the key intermediates
and they constituted a really affordable unsymmetrical phosphorus
reagent.
The synthesis of unsymmetrical allyl vinylphosphonates was
performed according to the Scheme 1. Firstly the reaction of triethyl
phosphite with 1-bromo-2-chloroethane led to diethyl 2-chloro-
ethylphosphonate which was reacted with alcoholic potassium
hydroxide affording diethyl vinylphosphonate 1 in 80% yield. Then,
selective monochlorination using oxalyl chloride gave ethyl
membered
oxaphospholenes,
symmetrical
diallyl
vinyl-
phosphonates led competitively to the formation of both five- and
six-membered P-heterocycles and were consequently not easily
purified.5 Besides in an interesting piece of work, Hanson synthe-
sized phosphonosugars (cyclic phosphonates) utilizing the RCM
reaction. Then, subsequent epoxidation followed by opening of the
epoxide resulted in the formation of the oxaphosphinene con-
taining a hydroxyl group which required two more linear steps
from the ring formation.6
O
a) 140 °C, neat
b) KOH, EtOH, 20 °C, 3h
X
+ P(OEt)3
P(OEt)2
1 (80 %)
4 eq. (COCl)2,
Br
excess
X = Br, Cl
CH2Cl2, 16 h, rt
These findings suggest that the search for novel unsymmetrical
and/or functional unsaturated phosphorus precursors is highly
desirable as illustrated by recently patented anticancer oxaphos-
a program aimed at developing the
construction of diverse phosphorus-containing heterocycles as
potential fungicides, we herein report the RCM reaction of
O
P
O
YH
Cl
phinanes.7 As part of
OEt
P
Et3N, Et2O, 0 °C
OEt
Y
2 (72 %)
3a (Y = O, 67 %)
3b (Y = NHCH2Ph, 50 %)
* Corresponding author. Tel.: þ33 467 144 314; fax: þ33 467 144 319.
E-mail address: david.virieux@enscm.fr (D. Virieux).
Scheme 1. Synthesis of unsymmetrical allyl vinylphosphonates 3a, b.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.049

P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
759
vinylphosphonochloridate 2 in 96% yield. The final step used either
allylic alcohol or N-allyl-N-benzylamine in order to obtain the
precursors 3a, b, respectively in 67% and 50% yields.
Allyl allylphosphonates were obtained using a similar approach.
The Arbuzov reaction of triethyl phosphite with commercial allyl
halides afforded the corresponding allylphosphonates 4a–c in
yields ranging from 58 to 85%. After the quantitative formation of
phosphonochloridate 5a–c, their reactions with allylic alcohols or
N-allyl-N-benzylamine gave precursors 6a–c in 46–67% yields,
Scheme 2.
failed, starting material was recovered after chromatography
showing that no reaction and no degradation occurred.
O
P
O
P
R1
R1
PCy3
Ru
X
X
Cl
Cl
Ph
PCy3
3a-b
8a-b
2-12% Grubbs' catalyst 1st gen.
CH2Cl2, 40 °C, 30 min to 120 h
R2
O
R3
2R3
R
R4
R
O
P
X
R4
R
O
R1
P
X
140 °C, neat
R1
X
+ P(OEt)3
P(OEt)2
4a-c
6a-g
9a-g
4 eq. (COCl)2,
CH2Cl2, 16 h, rt
Scheme 4. RCM reaction of unsymmetrical and functional precursors 3a, b or 6a–g.
R
O
P
O
YH
OEt
Cl
R
P
Y
OEt
Et3N, Et2O, 0 °C
Table 1
5a-c
RCM reaction products from unsymmetrical and hydroxy precursors
Precursor
Product
% Catalyst Time
Yield (%)
64
6a: R = H, Y = O (60%)
6b: R = Cl, Y = O (67%)
O
P
O
6c: R = H, Y = NCH2Ph (46%)
OEt
P
OH
8a
8b
7
2
2 h
O
O
Scheme 2. Synthesis of unsymmetrical allyl allylphosphonates 6a–c.
O
O
Synthesis of functional allyl allylphosphinates 8a–d was per-
formed by another way starting from phenylphosphinic acid. The
esterification of acid took place using a modified Hewitt reaction in
79% yield.8 Then, the Pudovik additions of H–phenylphosphinate to
P
OEt
P
OEt
30 min
80
N
N
Ph
Ph
a
,
b
-unsaturated ketones or aldehydes, using potassium fluoride as
O
P
O
P
a base, led to the functional –hydroxyphosphinates 6d–g in 39–
a
73% yields.9 No diastereoselectivity was observed during those
reactions and the resulting products were obtained with low di-
astereomeric excess. On the other hand, the competitive Michael
addition product was only obtained in 21% yield when methyl-
vinylketone was reacted with 7. However, it was easily removed
after purification by flash chromatography on silica, Scheme 3.
EtO
EtO
EtO
9a
9b
5
2 h 30 min 87
O
O
Cl
O
P
O
P
Cl
EtO
10
48 h
0
O
O
O
O
P
O
P
O
H
H
O
Cl
O
O
Ph
Ph
EtO
Ph
P
N
pyridine, CH2Cl2
OH
EtO
Ph
P
N
9c
2.5
30 min
75
7 (79%)
O
R2
R3
OH
O
R1
OH
OH
KF / Al2O3, neat
O
Ph
P
9d
9e
7.5
2 h
70
0
Ph
P
O
O
R1 OH
O
OH
O
R1, R2 = H, R3 = Me (71%)
R1, R3 = H, R2 = Me (73%)
R1 = H, R2 = Br, R3 = Ph (39%)
R1 = Me, R2, R3 = H (39%)
O
O
R3
Me
P
Ph
P
12
76 h
Ph
P
Ph
R2
O
O
6d-g (39-73%)
Scheme 3. Synthesis of allyl
a
-hydroxyallylphosphinates 6d–g.
OH
Me
O
P
OH
O
Ph
9f
10
12
3 h
50
0
Ph
P
2.2. Ring closure metathesis reactions
O
O
The first generation Grubbs’ catalyst was used in refluxing
dichloromethane to perform the RCM reaction. Scope and limita-
tions were given in Scheme 4 and Table 1. The reaction of alke-
nylphosphonates or phosphinates was sometimes tricky but the
yields were ranging from 50 and up to 87%. When the reaction
O
P
OH
OH
O
Ph
Ph
Br
9g
120 h
Ph
P
O
O
Br

760
P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
Five membered oxaphospholene ester 8a was not stable and
75 mL). The reaction mixture was stirred during one hour then
heated to reflux for 15 min. The solid was filtered off and washed
with ethanol. Ethanol was removed under vacuum and the
remaining oil was distilled under vacuum (Bp 93–97 ꢀC/16 Torr).
Yield: 6.19 g (85%).
was readily hydrolyzed by air moisture into its acid form in 64%
yield as Machida observed with similar structures.10 Surprisingly,
azaphospholene ester 8b was quite stable on fast chromatography
but it was transformed on storage through a phosphorus–nitrogen
bond cleavage.
31P NMR (101.25 MHz, CDCl3):
d
17.9; 1H NMR (250.13 MHz,
3
2
3
Substrates having halogen on double bond did not undergo the
RCM reaction. This was consistent with the fact that only few ex-
amples of ring closure metathesis on vinyl or allyl halide substrates
succeeded using the second generation Grubbs’ catalyst.11
Concerning 3-hydroxyoxaphosphinanes, we were aware that
the Lewis basicity of both phosphoryl group and hydroxy group
may result in catalyst deactivation.12 We were pleased to see that
functional oxaphosphinanes 9d and 9f were obtained, respectively
in 70 and 50% as probably the result of a weak and/or reversible
chelation. However, reactions failed with substituted precursors 6e
and 6g. The course of the RCM reaction was monitored by 31P NMR
to check the difference of behavior between the two dia-
stereoisomers. Unfortunately, the reaction occurred nearly at the
same rate resulting in no possible kinetic resolution. By the way, we
managed to separate the diastereomers of 9d by chromatography.
CDCl3):
d
6.31 (ddd, JHH¼18.7 Hz, JHH¼ꢁ1.9 Hz, JPH¼25.3 Hz, 1H,
3
2
3
]CH2), 6.14 (ddd, JHH¼12.8 Hz, JHH¼ꢁ1.9 Hz, JPH¼51.1 Hz,
3
3
2
1H, ]CH2), 6.07 (ddd, JHH¼12.8 Hz, JHH¼18.7 Hz, JPH¼21.9 Hz,
3
1H, PCH), 4.17–4.02 (m, 4H, 2CH2), 1.29 (t, JHH¼7.6 Hz, 6H, 2CH3);
13C NMR (62.90 MHz, CDCl3):
d
135.0 (d, JPC¼1.9 Hz, CH2), 126.0
2
(d, 1JPC¼184.2 Hz, PCH), 61.7 (d, 2JPC¼5.6 Hz, OCH2), 16.2 (s, CH3).
4.2.2. Ethyl vinylphosphonochloridate (2). Diethylvinylphosphonate
(6.0 g, 36 mmol) in dry CH2Cl2 (100 mL) and oxalyl chloride (18.5 g,
146 mmol, 4.05 equiv) were stirred at room temperature for 24 h and
refluxed for 1 h. Solvent and remaining oxalyl chloride were removed
under vacuum at room temperature. Residue was purified by distill-
ation (Bp 85 ꢀC/15 Torr). Yield: 4.0 g (72%).
31P NMR (101.25 MHz, DMSO-d6):
d
26.9; 13C NMR (62.90 MHz,
1
DMSO-d6):
d
135.6 (s, CH2), 128.5 (d, JPC¼169.3 Hz, CH), 62.9 (d,
2JPC¼7.8 Hz, CH2), 15.1 (d, 3JPC¼7.1 Hz, CH3).
3. Conclusion
4.2.3. Allyl ethyl vinylphosphonate (3a). Ethyl vinylphosphono-
chloridate 2 (1.68 g, 10.9 mmol) in dry Et2O (10 mL) was added
dropwise to a cold mixture of anhydrous allylic alcohol (1.13 g
19.4 mmol, 1.8 equiv) and triethylamine (2.0 g, 19.8 mmol,
1.8 equiv) in dry Et2O (40 mL). The mixture was then stirred for 3 h
at room temperature. The solid was removed by filtration and
washed with Et2O (3ꢂ10 mL). Solvents were removed under vac-
uum and the residue was purified by column chromatography
(AcOEt 100%) Yield: 1.28 g (67%).
In conclusion, we have demonstrated a new way to synthesize
diverse functionalized unsaturated phosphinates and phospho-
nates solving the problem of possible competitive side reactions. In
parallel hydroxyphosphinate scaffolds represent a versatile starting
material and could be of great interest for the synthesis of phos-
phosugar libraries. Perspective work will be devoted to control the
chirality on
a–hydroxyphosphonate or phosphinate precursors
during the RCM13 or from the Pudovik reaction.14 These studies are
underway and will be reported in due course.
31P NMR (81.02 MHz, CDCl3):
d
18.2; 1H NMR (400.13 MHz, CDCl3):
3
2
3
d
6.20 (ddd, JHH¼18.2 Hz, JHH¼ꢁ1.8 Hz, JPH¼25.1 Hz, 1H, ]CH2),
4. Experimental section
4.1. General remarks
6.04 (3JHH¼12.9 Hz, 2JHH¼ꢁ1.8 Hz, 3JPH¼52.7 Hz, 1H, ]CH2), 5.99 (m,
3JHH¼5.8 Hz, 3JHH¼5.6 Hz, 3JHH¼10.4 Hz, 3JHH¼17.2 Hz, 1H, ]CH), 5.98
3
2
(3JHH¼12.9 Hz, JHH¼18.2 Hz, JPH¼20.1 Hz, 1H, PCH), 5.24 (m,
2JHH¼ꢁ1.5 Hz, 4JHH¼1.5 Hz, 4JHH¼1.1 Hz, 3JHH¼17.2 Hz, 1H, CH2), 5.12
(m, 2JHH¼ꢁ1.5 Hz, 4JHH¼1.5 Hz, 4JHH¼1.5 Hz, 3JHH¼10.4 Hz, 1H, CH2),
All reactions were carried under nitrogen atmosphere using
Schlenk techniques. The solvents were dried using standard
methods, distilled and stored under nitrogen. Reactions were
monitored by 31P NMR using DMSO-d6 as internal references. Col-
umn chromatographies were performed on silica gel (Merck 60
3
2
4
4
4.42 (m, JPH¼8.2 Hz, JHH¼ꢁ23.6 Hz, JHH¼1.1 Hz, JHH¼1.5 Hz,
3JHH¼5.8 Hz, 1H, OCH2), 4.38 (m, JPH¼8.0 Hz, JHH¼ꢁ23.6 Hz,
3
2
4JHH¼1.1 Hz, JHH¼1.5 Hz, JHH¼5.6 Hz, 1H, OCH2), 3.99 (qd,
4
3
3JHH¼7.1 Hz, 3JPH¼8.1 Hz, 2H, OCH2),1.22 (t, 3JHH¼7.1 Hz, 3H, CH3); 13
C
AC.C 35–70
mm).
NMR (62.90 MHz, CDCl3):
d
136.0 (s, CH2), 133.0 (d, 3JPC¼6.7 Hz, CH),
31P, 1H and 13C NMR spectra were recorded on a BRUKER
AVANCE 250 and BRUKER AVANCE 400 spectrometers. MS and
HRMS were recorded on a JEOL JMS DX-300 using NBA as matrix in
FABþ ionization mode. IR spectra were measured on a PERKIN-
ELMER spectrum 1000.
126.0 (d, 1JPC¼184.0 Hz, CH), 118.3 (s, CH2), 66.6 (d, 2JPC¼5.3 Hz, CH2),
62.4(d, 2JPC¼5.8 Hz, CH2),16.6(d, 3JPC¼6.2 Hz,CH3); FABMS (NBA, m/z,
I, %): 177 [(MþH)þ, 100%]MS FAB(þ); HRMS m/z (MHþ) 177.0693
(calcd for C7H13O3P: 177.0680); IR (NaCl):
n 3000, 2280, 1400, 1260,
1110, 1070, 1050, 980, 920, 750, 660 cmꢁ1
.
4.2. Synthesis of unsaturated precursors
4.2.4. Ethyl N-allyl-N-benzylvinylphosphonamidate (3b). A solution
of ethyl vinylphosphonochloridate 2 (1.68 g, 10.9 mmol) in dry Et2O
(10 mL) was added dropwise to a cold mixture of anhydrous allyl-
benzylamine (1.6 g 10.9 mmol) and triethylamine (2.0 g,
19.8 mmol) in dry Et2O (40 mL). The mixture was then stirred 44 h
at room temperature. The solid was removed by filtration and
washed with Et2O (3ꢂ10 ml). Solvents were removed under vac-
uum and the residue was purified by column chromatography
(AcOEt 100%). Yield 1.44 g (50%).
4.2.1. Diethyl vinylphosphonate (1). First step: synthesis of diethyl
2-chloroethylphosphonate. Triethyl phosphite (15.0 g, 90 mmol)
and 1-bromo-2-chloroethane (51.8 g, 0.36 mol, 4 equiv) were
heated at 140 ꢀC for 24 h. Remaining starting materials were re-
moved under vacuum. The residue was purified by column chro-
matography (AcOEt 100%) to give a colorless liquid (17.0 g, 94%); 31P
NMR (101.25 MHz, CDCl3):
d
26.7. 1H NMR (250.13 MHz, CDCl3):
d
4.05–3.93 (m, 4H, 2POCH2), 3.78–3.66 (m, 2H, CH2Cl), 2.25–2.15
31P NMR (81.02 MHz, CDCl3):
d
21.3; 1H NMR (400.13 MHz,
3
3
(m, 2H, P-CH2), 1.32 (t, JHH¼7.0 Hz, 6H, 2CH3); 13C NMR
CDCl3):
d
7.42–7.21 (m, 5H, CHAr), 6.18 (m, JHH¼18.6 Hz,
2
3
3
(62.90 MHz, CDCl3):
d
61.5 (d, JPC¼6.5 Hz, OCH2), 34.8 (s, CH2Cl),
2JHH¼ꢁ2.0 Hz, JPH¼23.7 Hz, 1H, ]CH2), 6.14 (m, JHH¼12.7 Hz,
29.9 (d, 1JPC¼140.0 Hz, P-CH2), 15.3 (d, 3JPC¼7.0 Hz, CH3).
3JHH¼18.6 Hz, JPH¼22.3 Hz, 1H, CH), 6.04 (m, JHH¼ꢁ2.0 Hz,
2
2
3
3
Second step: synthesis of diethyl vinylphosphonate (1). Diethyl
2-chloroethylphosphonate (10.0 g, 50.0 mmol) was slowly added to
a cold solution of potassium hydroxide in ethanol (50 mmol,
3JHH¼12.7 Hz, JPH¼48.2 Hz, 1H, ]CH2), 5.72 (tdd, JHH¼6.4 Hz,
3JHH¼10.2 Hz, JHH¼17.1 Hz, 1H, CH), 5.22–5.16 (m, JHH¼ꢁ1.3 Hz,
3
2
2
4
3JHH¼10.2 Hz, 1H, CH2), 5.12 (dddd, JHH¼ꢁ1.3 Hz, JHH¼1.4 Hz,

P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
761
3
2
4JHH¼1.3 Hz, JHH¼17.1 Hz, 1H, CH2), 4.23 (dd, JHH¼ꢁ15.2 Hz,
and oxalyl chloride (23.7 g, 186 mmol) were stirred at room tem-
perature for 10 h and refluxed for 24 h. CH2Cl2 and remaining oxalyl
chloride were removed under vacuum. Product was used without
further purification. Yield: 8.86 g (97%).
2JPH¼9.2 Hz, 1H, NCH2), 4.21 (dd, JHH¼ꢁ15.2 Hz, JPH¼9.2 Hz,
2
2
2
3
3
1H, NCH2), 4.12 (qdd, JHH¼ꢁ10.1 Hz, JHH¼7.2 Hz, JPH¼7.2 Hz, 1H,
2
3
3
OCH2), 3.82 (qdd, JHH¼ꢁ10.1 Hz, JHH¼7.2 Hz, JPH¼7.4 Hz,
2
4
4
1H, OCH2), 3.50 (m, JHH¼ꢁ9.7 Hz, JHH¼1.4 Hz, JHH¼1.3 Hz,
31P NMR (101.25 MHz, DMSO-d6): 33.8; 1H NMR (250.13 MHz,
d
3
2
3JHH¼6.4 Hz, JPH¼10.9 Hz, 1H, CH2), 3.49 (m, JHH¼ꢁ9.7 Hz,
DMSO-d6): d 4.92–5.14 (m, 2H, ]CH2), 3.70–3.91 (m, 2H, OCH2),
4
3
3
3
4JHH¼1.4 Hz, JHH¼1.3 Hz, JHH¼6.4 Hz, JPH¼10.7 Hz, 1H, NCH2),
2.84–2.88 (m, 2H, PCH2), 0.94 (t, JHH¼7.1 Hz, 3H, CH3); 13C NMR
1.32 (t, JHH¼7.2 Hz, 3H, CH3); 13C NMR (100.61 MHz, CDCl3):
(62.90 MHz, DMSO-d6):
d
130.0 (d, JPC¼13.0 Hz, CCl), 118.9 (d,
3
2
2
d
138.2 (d, 3JPC¼2.4 Hz, CHAr), 135.2 (d, 3JPC¼1.8 Hz, ]CH), 135.0 (d,
3JPC¼12.3 Hz, ]CH2), 64.0 (d, JPC¼8.4 Hz, OCH2), 44.0 (d,
2JPC¼1.9 Hz, ]CH2), 128.3 and 128.6 (s, CHAr), 127.3 (s, CH), 126.0 (d,
1JPC¼125.7 Hz, PCH2), 15.8 (d, 3JPC¼6.9 Hz, CH3).
1JPC¼184.0 Hz, PCH]), 118.3 (s, ]CH2), 59.9 (d, 2JPC¼6.7 Hz, OCH2),
2
2
48.1 (d, JPC¼4.3 Hz, NCH2), 47.1 (d, JPC¼4.3 Hz, NCH2), 16.6 (d,
3JPC¼6.7 Hz, CH3); FABMS (NBA, m/z, I, %): 266 [(MþH)þ, 100%];
HRMS m/z (MHþ) 266.1321 (calcd for C14H21NO2P: 266.1310); IR
4.2.9. Allyl ethyl allylphosphonate (6a). A solution of ethyl allyl-
phosphonochloridate (1.84 g, 10.9 mmol) in dry diethylether
(10 mL) was added dropwise to a cold mixture of anhydrous allylic
alcohol (1.13 g, 19.4 mmol) and triethylamine (2.0 g, 19.8 mmol) in
dry diethylether (40 mL). The mixture was then stirred for 3 h at
room temperature. The solid was removed by filtration and washed
with ether (3ꢂ10 ml). Solvents were removed under vacuum and
the residue was purified by column chromatography (AcOEt 100%).
Yield: 1.28 g (67%).
(NaCl):
n 3057, 2977, 2954,1618,1215,1070,1017, 722, 695, 670, 626,
598, 528, 500 cmꢁ1
.
4.2.5. Diethyl allylphosphonate (4a). Triethylphosphite (20 mL,
120 mmol) and allyl bromide (11 mL g, 130 mmol) were heated at
140 ꢀC for 4 h. Remaining allyl bromide was removed under vac-
uum. The product was purified by column chromatography (AcOEt
100%). Yield: 21.38 g (99%).
31P NMR (81.02 MHz, CDCl3):
d
28.0; 1H NMR (250.13 MHz,
CDCl3): 6.02–5.60 (m, 2H, 2 ]CH), 5.41–5.07 (m, 4H, 2 ]CH2),
d
31P NMR (81.02 MHz, CDCl3):
d
27.7; 1H NMR (250.13 MHz,
4.53–4.44 (m, 2H, OCH2), 4.15–3.98 (m, 2H, OCH2), 2.91–2.75 (m,
CDCl3):
d
5.92–5.70 (m, 1H, ]CH), 5.35–5.12 (m, 2H, ]CH2), 4.20–
2JPH¼21.3 Hz, 4JHH¼1.1 Hz, 4JHH¼1.2 Hz, 3JHH¼7.3 Hz, 2H, PCH2), 1.16
4.06 (m, 4H, OCH2), 2.64 (m, 2JPH¼21.9 Hz, 3JHH¼7.4 Hz, 4JHH¼1.2 Hz,
(t, JHH¼7.1 Hz, 3H, CH3); 13C NMR (50.32 MHz, CDCl3):
d 135.4 (d,
3
4JHH¼1.2 Hz, 2H, PCH2), 1.34 (t, JHH¼7.0 Hz, 6H, 2CH3); 13C NMR
3JPC¼6.7 Hz, ]CH), 127.5 (d, JPC¼13.2 Hz, ]CH), 123.2 (d,
3
2
2
2
(50.32 MHz, CDCl3):
d
127.3 (d, JPC¼11.2 Hz, ]CH), 119.5 (d,
3JPC¼16.4 Hz, ]CH2), 118.3 (s, ]CH2), 66.6 (d, JPC¼5.3 Hz, OCH2),
3JPC¼14.5 Hz, ]CH2), 61.7 (d, JPC¼6.7 Hz, OCH2), 31.5 (d,
62.4 (d, JPC¼5.8 Hz, OCH2), 39.2 (d, JPC¼126.6 Hz, PCH2), 16.6 (d,
3JPC¼6.2 Hz, CH3); FABMS (NBA, m/z, I, %): 219 [(MþH)þ, 100%];
HRMS m/z (MHþ) 219.1165 (calcd for C10H20O3P: 219.1150); IR
2
2
1
1JPC¼139.0 Hz, PCH2), 16.2 (d, 3JPC¼6.0 Hz, CH3).
4.2.6. Diethyl 2-chloroallylphosphonate (4b). Triethyl phosphite
(20 mL, 120 mmol), 2-chloroallyl chloride (16.0 g, 140 mmol),
and sodium bromide (14.8 g, 144 mmol) were heated at 140 ꢀC for
18 h. Solid was filtered off and washed with AcOEt (3ꢂ10 mL). The
product was purified by column chromatography (AcOEt/CH2Cl2 1/1).
Yield: 14.9 g (58%).
(NaCl):
n 3330, 3000, 2280, 1690, 1400, 1210, 1110, 1070, 1050, 980,
920, 750, 660 cmꢁ1
.
4.2.10. Allyl ethyl 2-chloroallylphosphonate (6b). A solution of ethyl
2-chloroallylphosphonochloridate (1.13 g, 10.9 mmol) in dry Et2O
(10 mL) was added dropwise to a cold mixture of anhydrous allyl
alcohol (1.13 g 19.4 mmol) and triethylamine (2.0 g, 19.8 mmol) in
dry Et2O (40 mL). The mixture was then stirred for 3 h at room
temperature. The solid was removed by filtration and washed with
Et2O (3ꢂ10 mL). Solvents were removed under vacuum and the
residue was purified by column chromatography (AcOEt 100%).
Yield 1.28 g (67%).
31P NMR (101.25 MHz, CDCl3):
d
23.9; 1H NMR (250.13 MHz,
3
3
CDCl3):
d
5.40–5.37 (m, ]CH2), 4.16 (qd, JHH¼7.1 Hz, JPH¼8.1 Hz,
2
4
4H, OCH2), 2.94 (dd, 2H JPH¼21.4 Hz, JHH¼0.7 Hz, PCH2), 1.35 (t,
3JHH¼7.1 Hz, 6H, CH3); 13C NMR (62.90 MHz, CDCl3):
d 132.0 (d,
2JPC¼11.4 Hz, ]CCl), 117,0 (d, JPC¼10.1 Hz, ]CH2), 62.7 (d,
2JPC¼6.6 Hz, OCH2), 37.5 (d,1JPC¼141.0 Hz, PCH2),16.5 (d, 3JPC¼6.2 Hz,
CH3); FABMS (NBA, m/z, I, %): 213 [(MþH)þ,100%]; HRMS m/z (MHþ)
3
31P NMR (81.02 MHz, CDCl3):
CDCl3): 6.00–5.83 (m,1H ]CH), 5.43–5.21 (m, 4H, ]CH2), 4.59–
d
23.8; 1H NMR (250.13 MHz,
213.0431 (calcd for C7H15ClO3P: 213.0447); IR (NaCl):
n
3680, 3440,
d
3020, 1680, 1400, 1260, 1210, 1100, 750, 660 cmꢁ1
.
4.52 (m, OCH2), 4.20–4.02 (m, OCH2), 2.94 (dd, JPH¼21.4 Hz,
2
4JHH¼0.7 Hz, 2H, PCH2), 1.32 (t, JHH¼7.1 Hz, 3H, CH3); 13C NMR
3
2
4.2.7. Ethyl allylphosphonochloridate (5a). Diethyl allylphospho-
nate (10.0 g, 56.0 mmol) in dry CH2Cl2 (40 mL) and oxalyl chloride
(21.3 g, 168.0 mmol) were stirred at room temperature for 24 h and
refluxed for 1 h. CH2Cl2 and remaining oxalyl chloride were re-
moved under vacuum and the residue was used without further
purification. Yield: 9.21 g (97%).
(62.90 MHz, CDCl3):
d
132.6 (d, JPC¼10.8 Hz, CCl), 131.7 (d,
3JPC¼6.2 Hz, ]CH), 117.8 (s, ]CH2), 116.8 (d, JPC¼10.0 Hz, ]CH2),
3
2
2
66.5 (d, JPC¼5.8 Hz, OCH2), 62.3 (d, JPC¼6.8 Hz, OCH2), 37.1 (d,
1JPC¼141.0 Hz, PCH2), 16.2 (d, 3JPC¼6.2 Hz, CH3); FABMS (NBA, m/z, I,
%): 225 [(MþH)þ, 100%]; HRMS m/z (MHþ) 225.0435 (calcd for
C8H15ClO3P: 225.0447); IR (NaCl):
1260, 1210, 1100 cmꢁ1
n 3680, 3440, 3020, 1680, 1400,
31P NMR (81.02 MHz, DMSO-d6):
d
39.3; 1H NMR (250.13 MHz,
.
3
3
3
DMSO-d6):
d
5.59 (m, JPH¼9.1 Hz, JHH¼12.0 Hz, JHH¼13.3 Hz,
3JHH¼7. 3 Hz, 1H, ]CH), 5.16 (m, JPH¼5.5 Hz, JHH¼ꢁ1.3 Hz,
4.2.11. Ethyl N-allyl-N-benzyl-allylphosphonamidate (6c). A solution
of ethyl allylphosphonochloridate (1.0 g, 5.9 mmol) in dry dieth-
ylether (10 mL) was added dropwise to a cold mixture of anhydrous
allylbenzylamine (0.80 g, 5.45 mmol) and triethylamine (1.0 g,
9.9 mmol) in dry diethylether (40 mL). The mixture was then stir-
red for 48 h at room temperature. The solid was removed by fil-
tration and washed with ether (3ꢂ10 ml). Solvents were removed
under vacuum and the residue was purified by column chroma-
tography (AcOEt 100%). Yield 0.785 g (46%).
4
2
4JHH¼1.2 Hz, JHH¼12.4 Hz, 1H, ]CH2), 5.12 (m, JPH¼4.8 Hz,
3
4
2JHH¼ꢁ1.2 Hz, JHH¼1.1 Hz, JHH¼13.3 Hz, 1H, ]CH2), 4.20–3.96
4
3
2
4
4
(m, 2H, OCH2), 2.92 (m, JPH¼22.4 Hz, JHH¼1.1 Hz, JHH¼1.2 Hz,
3JHH¼7.3 Hz, 1H, PCH2), 2.83 (m, JPH¼21.3 Hz, JHH¼1.1 Hz,
2
4
4JHH¼1.2 Hz, JHH¼7.3 Hz, 1H, PCH2), 1.16 (t, JHH¼7.1 Hz, 3H, CH3);
3
3
13C NMR (50.32 MHz, DMSO-d6):
d
126.3 (d, JPC¼12.9 Hz, ]CH),
2
3
2
121.8 (d, JPC¼16.8 Hz, ]CH2), 63.5 (d, JPC¼8.6 Hz, OCH2), 39.0
(d, 1JPC¼121.9 Hz, PCH2), 16.0 (d, 3JPC¼7.2 Hz, CH3).
31P NMR (81.02 MHz, CDCl3): 27.1; 1H NMR (400.13 MHz, CDCl3):
d
3
3
4.2.8. Ethyl 2-chloroallylphosphonochloridate (5b). Diethyl 2-
chloroallylphosphonate (9.66 g, 45 mmol) in dry CH2Cl2 (80 mL)
d
7.47–7.23 (m, 5H, CHAr), 5.84 (m, JHH¼7.5 Hz, JHH¼7.4 Hz,
3JHH¼9.4 Hz, JHH¼17.7 Hz, JPH¼6.0 Hz, 1H, ]CH), 5.72 (tdd,
3 3

762
P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
3
3JHH¼7.1 Hz, 3JHH¼5.9 Hz, 3JHH¼10.3 Hz, 3JHH¼17.0 Hz,1H, ]CH), 5.20
(m, 1H, CHAr), 7.50–7.46 (m, 2H, CHAr), 5.96 (m, JHH¼7.2 Hz,
2
4
4
3
4
3
3
(m, JHH¼ꢁ1.7 Hz, JHH¼1.3 Hz, JHH¼1.4 Hz, JHH¼9.4 Hz, JPH un-
3JHH¼6.6 Hz, JHH¼10.4 Hz, JHH¼17.2 Hz, 1H, ]CH), 5.75 (m, 1H,
2
4
3
determined, 1H, ]CH2), 5.18 (m, JHH¼ꢁ1.7 Hz, JHH¼1.2 Hz,
]CH–CH3), 5.74 (m, 1H, ]CH–CH3), 5.62 (m, JPH¼4.6 Hz,
4JHH¼1.4 Hz, JHH¼17.7 Hz, JPH undetermined, 1H, ]CH2), 5.17 (m,
3JHH¼16.8 Hz, JHH¼1.5 Hz, JHH¼5.5 Hz, 1H, ]CH), 5.52 (m,
3
4
4
3
2JHH¼ꢁ1.5 Hz, JHH¼1.2 Hz, JHH¼1.2 Hz, JHH¼10.3 Hz, 1H, ]CH2),
3JPH¼4.56 Hz, 3JHH¼15.03 Hz, 4JHH¼1.5 Hz, 3JHH¼4.8 Hz, 1H, ]CH),
4
4
3
2
4
4
3
2
4
4
3
5.12 (m, JHH¼ꢁ1.5 Hz, JHH¼1.4 Hz, JHH¼1.4 Hz, JHH¼17.0 Hz, 1H,
5.36 (m, JHH¼ꢁ2.8 Hz, JHH¼2.4 Hz, JHH¼1.4 Hz, JHH¼17.20 Hz,
2
3
2 4 4
]CH2), 4.25 (dd, JHH¼ꢁ15.0 Hz, JPH¼8.8 Hz, 1H, NCH2Ph), 4.16
(dd, 2JHH¼ꢁ15.0 Hz, 3JPH¼9.4 Hz, 1H, NCH2Ph), 4.12 (qdd,
H, ]CH2), 5.24 (m, JHH¼ꢁ2.8 Hz, JHH¼2.4 Hz, JHH¼1.4 Hz,
2 4
3JHH¼10.4 Hz, 1H, ]CH2), 4.63 (m, JPH¼9.6 Hz, JHH¼13.0 Hz,
2JHH¼ꢁ10.0 Hz, JHH¼7.0 Hz, JPH¼7.0 Hz, 1H, OCH2), 3.88 (qdd,
2JHH¼ꢁ10.0 Hz, 3JHH¼7.2 Hz, 3JPH¼7.2 Hz, 1H, OCH2), 3.50
(m, 2JHH¼ꢁ17.2 Hz, 4JHH¼1.2 Hz, 4JHH¼1.4 Hz, 3JHH¼7.1 Hz,
3JHH¼4.8 Hz, JHH¼1.6 Hz, 1H, CHOH), 4.60 (m, JHH¼ꢁ12.9 Hz,
3
3
5
2
4JHH¼1.3 Hz, JHH¼1.4 Hz, JHH¼6.6 Hz, 1H, OCH2), 4.54 (m,
4
3
3JHH¼0.4 Hz, JHH¼2.4 Hz, JHH¼2.4 Hz, JHH¼7.2 Hz, 1H, CHOH),
4
4
3
2
4
2
2
3
5
3JPH¼10.4 Hz, 1H, NCH2), 3.49 (m, JHH¼ꢁ17.2 Hz, JHH¼1.2 Hz,
4JHH¼1.4 Hz, 3JHH¼5.9 Hz, 3JPH¼10.4 Hz, 1H, NCH2), 2.67
(m, 2JHH¼ꢁ14.9 Hz, 4JHH¼1.4 Hz, 4JHH¼1.4 Hz, 3JHH¼7.4 Hz,
4.47 (m, JPH¼9.6 Hz, JHH¼ꢁ12.9 Hz, JHH¼5.5 Hz, JHH¼1.3 Hz,
5 5 4
1H, OCH2), 1.72 (m, JPH¼5.0 Hz, JHH¼1.6 Hz, JHH¼1.5 Hz,
5
5
3JHH¼6.6 Hz, 3H, CH3), 1.69 (m, JPH¼5.0 Hz, JHH¼1.6 Hz,
2JPH¼21.3 Hz, 1H, PCH2), 2.62 (m, JHH¼ꢁ14.9 Hz, JHH¼1.2 Hz,
4JHH¼1.5 Hz, JHH¼6.58 Hz, 3H, CH3); 13C NMR (100.61 MHz,
2
4
3
4JHH¼1.3 Hz, 3JHH¼7.5 Hz, 2JPH¼20.1 Hz,1H, PCH2),1.28(t, 3JHH¼7.1 Hz,
CDCl3):
d
133.1 (d, 3JPC¼2.4 Hz, ]CH), 133.0 (d, 3JPC¼1.8 Hz, ]CH),
3H, CH3); 13C NMR (100.61 MHz, CDCl3):
d
138.2 (d, 3JPC¼2.4 Hz, CAr),
132.7 (d, JPC¼9.2 Hz, CHAr), 132.6 (d, JPC¼3.1 Hz, CHAr), 132.5 (d,
2
4
3
135.2 (d, JPC¼1.8 Hz, CH]), 128.4 and 128.6 (s, CHAr), 128.4 (d,
2JPC¼9.2 Hz, CHAr), 132.5 (d, 4JPC¼3.7 Hz, CHAr), 128.6
2JPC¼10.4 Hz, ]CH), 127.3 (s, CHAr), 119.6 (d, JPC¼14.1 Hz, ]CH2),
(d, JPC¼120.7 Hz, CAr), 128.1 (d, JPC¼122.6 Hz, CAr), 130.5 (d,
3JPC¼12.2 Hz, ]CH–CH3), 129.6 (d, 3JPC¼12.2 Hz, ]CH–CH3), 128.3
3
1
1
2
2
118.3 (s, ]CH2), 59.9 (d, JPC¼6.7 Hz, OCH2), 48.1 (d, JPC¼4.3 Hz,
NCH2), 47.1 (d, 2JPC¼4.3 Hz, NCH2), 33.5 (d, 1JPC¼128.7 Hz, PCH2), 16.2
3
3
(d, JPC¼12.3 Hz, CHAr), 128.2 (d, JPC¼12.2 Hz, CHAr), 125.4 (d,
(d, JPC¼6.7 Hz, CH3); FABMS (NBA, m/z, I, %): 280 [(MþH)þ, 100%];
2JPC¼1.8 Hz, ]CH), 125.3 (d, JPC¼2.4 Hz, ]CH), 117.7 (s, ]CH2),
3
2
3
HRMS m/z (MHþ) 280.1474 (calcd for C15H23NO2P: 280.1466); IR
117.7 (s, ]CH2), 71.6 (d, 1JPC¼114.6 Hz, PCH), 65.8 (d, JPC¼6.8 Hz,
3
4
(NaCl):
n
3060, 2978, 2960,1600,1222,1076,1025, 723, 690, 671, 540,
.
OCH2), 65.7 (d, JPC¼6.8 Hz, OCH2), 22.9 (d, JPC¼1.8 Hz, CH3), 17.9
(d, 4JPC¼2.4 Hz, CH3); FABMS (NBA, m/z, I, %): 253 [(MþH)þ, 100%];
HRMS m/z (MHþ) 253.0991 (calcd for C13H18O3P: 253.0993); IR
500 cmꢁ1
4.2.12. Allyl phenylphosphinate (7). Pyridine (9.5 g, 120 mmol) was
added dropwise to a mixture of allyl chloroformate (14.5 g,
120 mmol) and phenylphosphinic acid (16.8 g, 120 mmol) in
CH2Cl2 (250 mL). Once gas evolution has stopped, the reaction
mixture was heated to reflux for 15 min, and then cooled to room
temperature and 100 mL of HCl 0.1 N were added and stirred for
30 min. Organic layer was extracted twice with 70 mL of water,
dried with Na2SO4, filtered and solvent was removed under
vacuum. The remaining oil is distilled under vacuum (T¼121 ꢀC,
1 mmHg). Yield 14.12 g (65%).
(NaCl):
n 3266, 2900, 1722, 1649, 1592, 1439, 1424, 1377, 1214,
1121, 1092, 1050, 925, 845, 820, 748, 695, 550 cmꢁ1
.
4.3.2. Allyl 1-hydroxy-2-methylprop-2-enylphenyl-phosphinate (6e).
-unsaturated carbonyl compound: methylacroleine (0.384 g).
Chromatography eluent: AcOEt 100%. Yield 1.00 g (73%).
31P NMR (161.97 MHz, CDCl3): 39.5 (51%), 40.0 (49%); 1H NMR
(400.13 MHz, CDCl3): 7.85–7.75 (m, 2H, CHAr), 7.60–7.55 (m, 1H,
a,b
d
d
3
3
CHAr), 7.50–7.46 (m, 2H, CHAr), 5.95 (m, JHH¼7.1 Hz, JHH¼2.6 Hz,
3JHH¼10.4 Hz, JHH¼17.0 Hz, 1H, ]CH), 5.36 (m, JHH¼ꢁ1.8 Hz,
3
2
4
3
31P NMR (161.97 MHz, CDCl3):
d
25.1; 1H NMR (400.13 MHz,
4JHH¼1.5 Hz, JHH¼1.6 Hz, JHH¼17.0 Hz, H, ]CH2), 5.34 (m,
4
4
3
CDCl3):
d
7.60 (d, 1JPH¼564.9 Hz, 1H, PH), 7.79–7.73 (m, 2H, CHAr),
2JHH¼ꢁ1.8 Hz, JHH¼1.5 Hz, JHH¼1.6 Hz, JHH¼17.0 Hz, H, ]CH2),
5.25 (m, 2JHH¼ꢁ1.8 Hz, 4JHH¼1.5 Hz, 4JHH¼2.6 Hz, 3JHH¼10.4 Hz, 1H,
]CH2), 5.23 (m, 2JHH¼ꢁ1.8 Hz, 4JHH¼1.5 Hz, 4JHH¼2.6 Hz,
7.59–7.55 (m, 1H, CHAr), 7.50–7.47 (m, 2H, CHAr), 5.93 (m,
3JHH¼5.6 Hz, JHH¼5.6 Hz, JHH¼10.3 Hz, JHH¼17.2 Hz, 1H, ]CH),
5.36 (m, 2JHH¼ꢁ1.6 Hz, 4JHH¼1.5 Hz, 4JHH¼1.5 Hz, 3JHH¼17.2 Hz, 1H,
]CH2), 5.24 (m, 2JHH¼ꢁ1.6 Hz, 4JHH¼1.1 Hz, 4JHH¼1.5 Hz,
3
3
3
3JHH¼10.4 Hz, 1H, ]CH2), 4.96 (m, JPH¼5.7 Hz, JHH¼1.2 Hz,
4
4
2JHH¼ꢁ2.9 Hz, JHH¼0.8 Hz, 1H, ]CH2), 4.93 (m, JPH¼4.2 Hz,
4
4
3JHH¼10.3 Hz, 1H, ]CH2), 4.59 (m, JPH¼8.7 Hz, JHH¼ꢁ13.6 Hz,
4JHH¼1.2 Hz, JHH¼ꢁ2.8 Hz, JHH¼1.5 Hz, 1H, ]CH2), 4.92 (m,
3
2
2
4
4JHH¼1.1 Hz, JHH¼1.5 Hz, JHH¼5.6 Hz, H, OCH2), 4.53 (m,
4JPH¼5.7 Hz, JHH¼1.2 Hz, JHH¼ꢁ2.8 Hz, JHH¼0.8 Hz, 1H, ]CH2),
4
3
4
2
4
3JPH¼8.3 Hz, 2JHH¼ꢁ13.6 Hz, 4JHH¼1.1 Hz, 4JHH¼1.5 Hz, 3JHH¼5.6 Hz,
4.90 (m, JPH¼4.2 Hz, JHH¼1.2 Hz, JHH¼ꢁ2.8 Hz, JHH¼1.5 Hz, 1H,
]CH2), 4.63 (m, 2JHH¼ꢁ12.4 Hz, 4JHH¼1.5 Hz, 4JHH¼1.6 Hz,
4
4
2
4
1H, OCH2); 13C NMR (100.61 MHz, CDCl3):
d
133.17 (d, JPC¼3.1 Hz,
4
2
3
CHAr), 132.33 (d, JPC¼6.7 Hz, CHAr), 130.8 (d, JPC¼11.9 Hz, CHAr),
3JHH¼7.1 Hz, 1H,
OCH2),
4.60
(m,
3JPH¼undetermined,
129.6 (d, 1JPC¼132.4 Hz, CAr), 128.7 (d, 3JPC¼14.3 Hz, ]CH), 118.6 (s,
2JHH¼ꢁ12.4 Hz, JHH¼1.5 Hz, JHH¼1.6 Hz, JHH¼7.1 Hz, 1H, OCH2),
4
4
3
2
]CH2), 66.1 (d, JPC¼6.3 Hz, OCH2).
4.48 (m, 3JPH¼undetermined, 2JHH¼ꢁ12.4 Hz, 4JHH¼1.5 Hz,
4JHH¼1.1 Hz, JHH¼2.6 Hz, 1H, OCH2), 4.46 (m, JPH¼undetermined,
3
3
4
4
3
4.3. General procedure for Pudovik reaction compounds 6d–g
2JHH¼ꢁ12.4 Hz, JHH¼1.5 Hz, JHH¼1.1 Hz, JHH¼2.6 Hz, 1H, OCH2),
2
4
4
4.57 (m, JPH¼9.3 Hz, JHH¼1.5 Hz, JHH¼0.8 Hz, 1H, PCH), 1.85 (m,
4JPH¼2.7 Hz, 4JHH¼1.2 Hz, 4JHH¼1.2 Hz, 3H, CH3), 1.76 (m,
In a schlenck tube under N2, potassium fluoride on alumina (5–
10% w/w) was added to a mixture of 1 equiv of allyl phenyl-
4JPH¼2.7 Hz, JHH¼1.2 Hz, JHH¼1.2 Hz, 3H, CH3); 13C NMR
4
4
2
phosphinate and 1 equiv of
a
,b
-unsaturated carbonyl compound
(100.61 MHz, CDCl3):
d
140.6 (d, JPC¼5.1 Hz, ]C), 140.6 (d,
until no liquid phase remained. The mixture was left for 30 min at
room temperature and then extracted with CH2Cl2. The solid phase
was washed with 3ꢂ10 mL of CH2Cl2. Solvent was removed under
reduced pressure and the resulting oil was purified through column
chromatography on silica gel.
2JPC¼5.1 Hz, ]C), 133.0 (d, 3JPC¼6.6 Hz, ]CH), 132.9 (d, 3JPC¼6.6 Hz,
2
4
]CH), 132.7 (d, JPC¼9.5 Hz, CHAr), 132.7 (d, JPC¼2.2 Hz, CHAr),
128.3 (d, 3JPC¼12.4 Hz, CHAr), 128.2 (d, 3JPC¼12.4 Hz, CHAr), 127.7 (d,
1JPC¼122.9 Hz, CAr), 127.5 (d, JPC¼122.9 Hz, CAr), 118.0 (s, ]CH2),
1
114.4 (d, 3JPC¼10.2 Hz, ]CH2), 114.3 (d, 3JPC¼9.5 Hz, ]CH2), 74.6 (d,
1JPC¼109.0 Hz, PCH), 74.5 (d, JPC¼109.8 Hz, PCH), 65.9 (d,
1
4.3.1. Allyl 1-hydroxybut-2-enylphenylphosphinate (6d).
a
,b
-un-
3JPC¼7.3 Hz, OCH2), 65.8 (d, 3JPC¼6.6 Hz, OCH2), 20.1 (d, 3JPC¼2.2 Hz,
3
saturated carbonyl compound: crotonaldehyde (0.384 mg). Chro-
matography eluent: AcOEt 100%. Yield 0.985 g (71%).
CH3), 19.9 (d, JPC¼2.2 Hz, CH3); MS FABþ (NBA) m/z (%): 253
(MþH)þ (100) MS HRþ (NBA) C13H18O3P: 253.0993 found:
31P NMR (161.97 MHz, CDCl3):
d
39.3 (50%), 40.0 (50%); 1H
253.1025; IR (NaCl): n 3280, 3060–2800, 1695, 1592, 1450, 1224,
NMR (400.13 MHz, CDCl3):
d
7.85–7.75 (m, 2H, CHAr), 7.60–7.55
1130, 1050, 925, 760, 682 cmꢁ1
.

P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
763
4.3.3. Allyl 1-hydroxy-1-methylprop-2-enylphenyl-phosphinate (6f).
-unsaturated carbonyl compound: methylvinylketone (0.384 g).
HRMS m/z (MHþ) 393.0260 (calcd for C18H19BrO3P: 393.0255); IR
(NaCl): 3210, 1712, 1594, 1490, 1432, 1220, 1188, 1118, 1095, 1013,
920, 748, 699, 570 cmꢁ1
a
,b
n
Chromatography eluent: AcOEt 100%, Yield 0.510 g (39%).
.
31P NMR (161.97 MHz, CDCl3):
d
41.8 (50%, dia 1), 41.9 (50%, dia
7.92–7.75 (m, 2H, CHAr), 7.64–
2); 1H NMR (400.13 MHz, CDCl3):
d
4.4. General procedure for RCM reactions compounds
8a–b and 9a–g
7.50 (m, 1H, CHAr), 7.53–7.42 (m, 2H, CHAr), 6.10–5.89 (m, 2H, ]CH),
5.40–5.19 (m, 4H, ]CH2), 4.72–4.66 (m, 2H, OCH2), 4.42–4.36 (m,
2H, OCH2), 3.80 (sl, OH), 3.70 (sl, OH),1.56 (d, 3JPH¼14.8 Hz, 3H, CH3),
To a solution of precursor 3a, b or 6a–g in dry CH2Cl2 (0.02 M)
was added Grubb’s first generation catalyst (2% mol). The mixture
was stirred under reflux. The reaction was monitored by 31P NMR. If
after 30 min starting material remained, the reaction was stirred
one more hour. If no evolution occurred, 1% mol of catalyst was
added. After consumption of unsaturated precursor, solvent was
removed under vacuum and the residue was purified by
chromatography.
3
1.49 (d, JPH¼15.0 Hz, 3H, CH3); 13C NMR (100.61 MHz, CDCl3):
d
137.5 (d, 2JPC¼0.9 Hz, ]CH), 138.1 (d, 2JPC¼1.5 Hz, ]CH), 133.0 (d,
JPC¼3.1 Hz, ]CH), 133.1 (d, JPC¼2.4 Hz, ]CH), 132.6 (d, JPC¼9.1 Hz,
3
CHAr), 132.6 (d, JPC¼3.7 Hz, CHAr), 128.2 (d, JPC¼12.3 Hz, CHAr),
128.1 (d, JPC¼11.0 Hz, CHAr), 127.4 (d, 1JPC¼119.5 Hz, CAr), 127.1 (d,
3
1JPC¼120.1 Hz, CAr), 117.8 (s, ]CH2), 117.7 (s, ]CH2), 116.0
3
3
(d, JPC¼9.2 Hz, ]CH2), 115.5 (d, JPC¼9.2 Hz, ]CH2), 74.5 (d,
1JPC¼112.4 Hz, PC), 74.3 (d, 1JPC¼114.6 Hz, PC), 66.1 (d, JPC¼7.1 Hz,
3
3
2
OCH2), 65.9 (d, JPC¼7.4 Hz, OCH2), 22.9 (d, JPC¼2.6 Hz, CH3), 22.6
(d, 2JPC¼2.6 Hz, CH3); FABMS (NBA, m/z, I, %): 253 [(MþH)þ, 100%];
HRMS m/z (MHþ) 253.0997 (calcd for C13H18O3P: 253.0993); IR
4.4.1. 2-Hydroxy-2-oxo-1,2-oxaphosphol-3-ene (8a). Catalyst: 5%,
Eluent: AcOEt/Hexane 8/2 then AcOEt 100%. Yield: 0.215 g (65%).
31P NMR (81.02 MHz, Acetone-D6):
d
42.9; 1H NMR (400.13 MHz,
3
(NaCl):
n
3239, 1590, 1646, 1438, 1364, 1200, 1119, 1020, 855, 832,
Acetone-D6):
d
7.72 (sl, 1H, OH), 7.31 (tdd, JPH¼44.7 Hz,
744, 680, 552 cmꢁ1
.
3JHH¼8.6 Hz, JHH¼1.7 Hz, 1H, ]CH), 6.33 (tdd JPH¼34.6 Hz,
3
2
3JHH¼8.6 Hz, JHH¼2.4 Hz, 1H PCH), 4.82 (ddd, JPH¼6.4 Hz,
4
3
4
4.3.4. Allyl 2-bromo-1-hydroxy-3-phenylprop-2-enylphenylphosphi-
nate (6g). -unsaturated carbonyl compound: 2-bromocinna-
3JHH¼1.7 Hz, JHH¼2.4 Hz, 2H, OCH2); 13C NMR (100.61 MHz, Ace-
2
1
a
,b
tone-D6):
d
148.7 (d, JPC¼17.2 Hz, ]CH), 116.7 (d, JPC¼166.1 Hz,
2
maldehyde (1.16 g). Chromatography eluent: AcOEt/CH2Cl2 4/6.
Yield 0.260 g and 0.280 g (39% for both stereoisomers).
PCH), 70.6 (d, JPC¼14.7 Hz, OCH2); FABMS (NBA, m/z, I, %): 121
[(MþH)þ, 100%]; HRMS m/z (MHþ) 121.0054 (calcd for C3H6O3P:
121.0054); IR (KBr):
n 3425, 3086, 1595, 1322, 1212, 1105, 930, 738,
4.3.4.1. First diastereomer. 31P NMR (161.97 MHz, CDCl3):
1H NMR (400.13 MHz, CDCl3):
7.89–7.83 (m, 2H, CHAr), 7.37–7.28
(m, 5H, CHAr), 7.61–7.56 (m, 1H, CHAr), 7.49–7.44 (m, 2H, CHAr), 6.92
d
39.7;
622 cmꢁ1. Melting point 119 ꢀC (Lit. 110–111 ꢀC).10
d
4.4.2. 1-Benzyl-2-ethoxy-2-oxo-1,2-azaphosphol-3-ene (8b). Catalyst:
4
3
3
(dd, JPH¼4.8 Hz, JHH¼0.4 Hz, 1H, ]CHPh), 6.00 (m, JHH¼5.3 Hz,
2%, Eluent: AcOEt 100%. Yield: 0.250 g (80%).
3JHH¼5.4 Hz, JHH¼10.5 Hz, JHH¼17.1 Hz, 1H, ]CH), 5.45 (m,
31P NMR (81.02 MHz, CDCl3): 38.4; 1H NMR (400.13 MHz,
d
3
3
2JHH¼ꢁ1.4 Hz, JHH¼1.5 Hz, JHH¼1.5 Hz, JHH¼17.1 Hz, 1H, ]CH2),
CDCl3): d 7.48–7.21 (m, 5H, CHAr), 6.90–6.80 (m, 1H, ]CH), 6.12–
4
4
3
5.27 (m, 2JHH¼ꢁ1.4 Hz, 4JHH¼1.4 Hz, 4JHH¼1.4 Hz, 3JHH¼10.5 Hz, 1H,
6.04 (m, 1H, PCH), 4.40–4.35 (m, 2H, NCH2), 4.23 (dd,
2JHH¼ꢁ15.2 Hz, 2JPH¼9.2 Hz, 1H, NCH2Ph), 4.21 (dd, 2JHH¼ꢁ15.2 Hz,
2JPH¼9.2 Hz, 1H, NCH2Ph), 4.20–4.11 (m, 2H, OCH2), 1.35 (t,
2
3
]CH2), 5.02 (dd, JPH¼12.1 Hz, JHH¼1.1 Hz, 1H, CHOH), 4.74 (m,
3JPH¼6.9 Hz, 2JHH¼ꢁ12.9 Hz, 4JHH¼1.5 Hz, 4JHH¼1.4 Hz, 3JHH¼5.3 Hz,
3
2
4
H, OCH2), 4.61 (m, JPH¼7.2 Hz, JHH¼ꢁ12.9 Hz, JHH¼1.5 Hz,
4JHH¼1.4 Hz, 3JHH¼5.3 Hz,1H, OCH2); 13C NMR (100.61 MHz, CDCl3):
3JHH¼7.1 Hz, 3H, CH3); 13C NMR (100.61 MHz, CDCl3):
d 148.7 (d,
3
2JPC¼17.2 Hz, ]CH), 138.2 (d, JPC¼2.4 Hz, CAr), 128.6 and 128.9 (s,
4
4
1
d
135.1 (d, JPC¼3.1 Hz, CHAr), 133.1 (d, JPC¼3.1 Hz, CHAr), 133.0
CHAr), 127 (s, CHAr), 122.9 (d, JPC¼164.2 Hz, PCH), 61.2 (d,
6
3
(d, JPC¼9.8 Hz, CHAr), 132.7 (d, JPC¼6.7 Hz, ]CH), 131.1 (d,
2JPC¼6.7 Hz, OCH2), 53.1 (d, 2JPC¼4.3 Hz, NCH2), 49.1 (d, 2JPC¼4.3 Hz,
2JPC¼9.8 Hz, CHAr), 128.9 (d, 3JPC¼2.4 Hz, ]CH), 128.3
NCH2), 16.3 (d, JPC¼6.7 Hz, CH3); FABMS (NBA, m/z, I, %): 238
3
3
5
(d, JPC¼12.9 Hz, CHAr), 128.0 (d, JPC¼1.8 Hz, CHAr), 128.0 (s, CHAr),
[(MþH)þ, 100%]; HRMS m/z (MHþ) 238.1005 (calcd for C12H17NO2P:
1
126.4 (d, JPC¼127.4 Hz, C), 120.0 (s, CBr), 118.2 (s, ]CH2), 76.4
238.0997); IR (NaCl): n 2977, 1623, 1222, 1074, 1012, 725, 693,
(d, 1JPC¼100.9 Hz, CHOH), 66.5 (d, 2JPC¼7.3 Hz, OCH2); FABMS (NBA,
660 cmꢁ1
.
m/z, I, %): 393 [(MþH)þ, 100%]; HRMS m/z (MHþ) 393.0262 (calcd
for C18H19BrO3P: 393.0255); IR (NaCl):
n
3207, 2826, 1712, 1590,
4.4.3. 4,5-Dehydro-2-ethoxy-2-oxo-1,2-oxaphosphinane (9a). Catalyst:
3.5%, Eluent: AcOEt/Hexane 8/2 then AcOEt 100%. Yield:
0.700 g (87%).
1492, 1439, 1217, 1200, 1122, 1092, 1016, 923, 693, 563 cmꢁ1
.
4.3.4.2. Second diastereomer. 31P NMR (161.97 MHz, CDCl3):
31P NMR (101.25 MHz, CDCl3): 20.8; 1H NMR (250.13 MHz,
d
d
39.9; 1H NMR (400.13 MHz, CDCl3):
7.89–7.83 (m, 2H, CHAr),
7.61–7.56 (m, 1H, CHAr), 7.49–7.44 (m, 2H, CHAr), 7.37–7.28 (m, 5H,
d
CDCl3): d 5.74–5.67 (m, 2H, CH]CH), 4.89–4.71 (m, 2H, OCH2),
4.20–4.11 (m, 2H, CH2), 2.59–2.46 (m, 2H, PCH2),1.35 (t, 3JHH¼7.1 Hz,
4
3
3
CHAr), 6.92 (dd, JPH¼4.8 Hz, JHH¼0.44 Hz, 1H, ]CH), 6.00 (m,
3H, CH3); 13C NMR (62.90 MHz, CDCl3):
d
125.3 (d, JPC¼17.2 Hz,
3JHH¼5.3 Hz, JHH¼5.4 Hz, JHH¼10.5 Hz, JHH¼17.1 Hz, 1H, ]CH),
5.45. (m, 2JHH¼ꢁ1.4 Hz, 4JHH¼1.5 Hz, 4JHH¼1.5 Hz, 3JHH¼17.1 Hz, 1H,
]CH2), 5.27 (m, 2JHH¼ꢁ1.4 Hz, 4JHH¼1.4 Hz, 4JHH¼1.4 Hz,
]CH), 120.7 (d, 2JPC¼9.6 Hz, ]CH), 69.2 (d, 2JPC¼7.7 Hz, OCH2), 61.7
3
3
3
2
1
(d, JPC¼6.6 Hz, OCH2), 22.7 (d, JPC¼133.4 Hz, PCH2), 16.7 (d,
3JPC¼5.7 Hz, CH3); FABMS (NBA, m/z, I, %): 163 [(MþH)þ, 100%];
HRMS m/z (MHþ) 163.0547 (calcd for C6H12O3P: 163.0524); IR
3JHH¼10.5 Hz, 1H, ]CH2), 5.02. (dd, JPH¼12.1 Hz, JHH¼1.1 Hz, 1H,
2
3
CHOH), 4.74 (m, 3JPH¼6.9 Hz, 2JHH¼ꢁ12.9 Hz, 4JHH¼1.5 Hz,
(NaCl):
n .
3512, 3070, 2873, 1452, 1230, 1181, 1063, 954, 840 cmꢁ1
4JHH¼1.4 Hz, JHH¼5.3 Hz, 1H, OCH2), 4.61 (m, JPH¼7.2 Hz,
3
3
2JHH¼ꢁ12.9 Hz, JHH¼1.5 Hz, JHH¼1.4 Hz, JHH¼5.3 Hz, 1H, OCH2);
4.4.4. 1-Benzyl-2-ethoxy-4,5-dehydro-2-oxo-1,2-azaphosphinane
4
4
3
13C NMR (100.61 MHz, CDCl3):
d
135.1(d, JPC¼3.1 Hz, CHAr), 133.1
(9c). Catalyst: 2.5%, Eluent: CH2Cl2/EtOH 97/3. Yield: 0.802 g (88%).
4
4
6
(d, JPC¼3.1 Hz, CHAr), 133.0 (d, JPC¼9.8 Hz, CHAr), 132.7 (d,
31P NMR (101.25 MHz, CDCl3): 25.4; 1H NMR (400.13 MHz,
d
3JPC¼6.7 Hz, ]CH), 131.1 (d, 2JPC¼9.8 Hz, CHAr), 128.9
CDCl3):
d 7.36–7.25. (m, 5H, CHAr), 5.72–5.55 (m, 2H, CH]CH), 4.61
3
3
3
2
(d, JPC¼2.4 Hz, ]CHPh), 128.3 (d, JPC¼12.9 Hz, CHAr), 128.0 (d,
(dd, JPH¼10.6 Hz, JHH¼ꢁ14.7 Hz, 1H, NCH2), 4.08–4.00 (m,
5JPC¼1.8 Hz, CHAr), 128.04 (s, CHAr), 126.4 (d, JPC¼127.4 Hz, PC),
3H,OCH2 and NCH2), 3.47–3.66 (m, 2H, NCH2), 2.69–2.39 (m, 2H,
1
120.0 (s, CBr), 118.2 (s, ]CH2), 76.4 (d, 1JPC¼100.9 Hz, CHOH), 66.5
(d, 2JPC¼7.3 Hz, OCH2); FABMS (NBA, m/z, I, %): 393 [(MþH)þ, 100%];
PCH2), 1.32 (t, JHH¼7.0 Hz, CH3); 13C NMR (62.90 MHz, CDCl3):
3
d
138.2 (d, 3JPC¼5.4 Hz, CAr), 128.8 (s, CHAr), 128.7 (s, CHAr), 126.2 (d,

764
P. Fourgeaud et al. / Tetrahedron 66 (2010) 758–764
4
2
JPC¼15.0 Hz, ]CH), 127.7 (s, CHAr), 120.6 (d, JPC¼10.3 Hz, ]CH), 61.0
1:
d
133.1 (d, JPC¼2.2 Hz, CHAr), 132.4 (d, JPC¼9.5 Hz, CHAr), 129.0
2
3
(d, JPC¼6.5 Hz, OCH2), 50.2 (s, NCH2), 49.5 (s, NCH2), 24.7 (d,
(d, JPC¼12.5 Hz, CHAr), 128.0 (d, JPC¼13.5 Hz, ]CH), 126.9 (d,
1JPC¼126.9 Hz, PCH2), 16.9 (d, 3JPC¼6.1 Hz, CH3); FABMS (NBA, m/z, I,
1JPC¼136.3 Hz, CAr), 126.4 (d, JPC¼2.2 Hz, ]CH), 66.5 (d, 2JPC¼7.4 Hz,
%): 252 [(MþH)þ, 100%]; HRMS m/z (MHþ) 252.1148 (calcd for
OCH2), 63.4 (d, JPC¼112.9 Hz, PCOH), 22.6 (d, JPC¼3.9 Hz, CH3);
1
2
C13H19O2NP: 252.1143); IR (NaCl):
n
3070, 2988, 2960, 1612,
diastereomer 2:
d
134.1 (d, 4JPC¼2.2 Hz, CHAr), 133.2 (d, 2JPC¼10.2 Hz,
1219,1085, 1022, 724, 690 cmꢁ1
.
CHAr), 130.2 (d, JPC¼11.3 Hz, CHAr), 128.5 (d, JPC¼14.2 Hz, ]CH),
3
1
127.2 (d, JPC¼132.5 Hz, CAr), 126.2 (d, JPC¼2.2 Hz, ]CH), 64.2 (d,
1
4.4.5. 4,5-Dehydro-3-hydroxy-2-phenyl-2-oxo-1,2-oxaphosphinane
(9d). Catalyst: 7%, Eluent: CH2Cl2/EtOH 98/2 Yield: two fractions of
diastereomers 0.408 g and 0.320 mg (87%).
2JPC¼7.3 Hz, OCH2), 61.7 (d, JPC¼114.5 Hz, PCOH), 24.2 (d,
2JPC¼4.4 Hz, CH3); FABMS (NBA, m/z, I, %): 225 [(MþH)þ, 100%];
HRMS m/z (MHþ) 225.0701 (calcd for C11H14O3P: 225.0680); IR
(NaCl):
n 3300, 3100, 2900, 1550, 1272, 1225, 1172, 1130, 1099, 1050,
4.4.5.1. First diastereomer. 31P NMR (161.97 MHz, CDCl3):
1H NMR (400.13 MHz, CDCl3):
7.82–7.77 (m, 2H, CHAr), 7.55–7.51 (m,
d
29.3;
954, 743, 696 cmꢁ1
.
d
3
1H, CHAr), 7.45–7.40 (m, 2H, CHAr), 5.88 (m, JPH¼19.0 Hz,
Acknowledgements
3JHH¼11.2 Hz, 3JHH¼2.5 Hz, 4JHH¼2.4 Hz, 4JHH¼2.4 Hz, 1H, ]CH), 5.75
(m,
4JPH¼3.0 Hz,
3JHH¼11.2 Hz,
4JHH¼2.6 Hz,
3JHH¼2.4 Hz,
2
This research was supported by Bayer CropScience SA and the
3
3JHH¼2.6 Hz, 1H, ]CH), 4.89 (m, JPH¼3.1 Hz, JHH¼ꢁ16.7 Hz,
´
Region Languedoc-Roussillon.
3JHH¼2.6 Hz, JHH¼2.4 Hz, JHH¼2.7 Hz, 1H, OCH2), 4.63 (m,
4
5
3JPH¼15.4 Hz, 2JHH¼ꢁ16.7 Hz, 3JHH¼2.4 Hz, 4JHH¼2.4 Hz, 5JHH¼2.6 Hz,
References and notes
2
4
3
1H, OCH2), 4.45 (m, JPH¼3.1 Hz, JHH¼2.6 Hz, JHH¼2.5 Hz,
5JHH¼2.6 Hz, 5JHH¼2.7 Hz, 1H, CHOH); 13C NMR (100.61 MHz, CDCl3):
1. (a) Westheimer, F. H. Science 1987, 235, 1173; (b) Seto, H.; Kuzuyama, T. Nat.
Prod. Rep. 1999, 16, 589; For more representative examples of phosphorus-
containing pharmaceutical agents, see: (c) Kafarski, P.; Lejczak, B. Phosphorus
Sulfur Silicon Relat. Elem. 1991, 63, 193; (d) Colvin, O. M. Curr. Pharm. Des. 1999, 5,
555; (e) Zon, G. Prog. Med. Chem. 1982, 19, 205; (f) Fields, S. C. Tetrahedron 1999,
55, 12237; (g) Kafarski, P.; Lejczak, B. Curr. Med. Chem. 2001, 1, 301; (h) Mu-
kherjee, S.; Huang, C.; Guerra, F.; Wang, K.; Oldfield, E. J. Am. Chem. Soc. 2009,
131, 8374.
2. Fourgeaud, P.; Vors, J. P.; Virieux, D. Targets in Heterocycl. Systems 2005, 9, 254.
3. For reviews of RCM see: (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18; (b) Furstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012; (c) Grubbs, R. H.
Handbook of Metathesis; Wiley-VCH: Weinheim, 2003.
4. For review of RCM in heterocyclic phosphorus compound synthesis see: (a)
McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104, 2239;
(b) Sieck, S. R.; McReynolds, M. D.; Schroeder, C. E.; Hanson, P. R. J. Organomet.
Chem. 2006, 691, 5307.
5. (a) Ahmed, M.; Atkinson, C. E.; Barrett, A. G. M.; Malagu, K.; Procopiou, P. A. Org.
Lett. 2003, 5, 669; (b) Hetherington, L.; Greedy, B.; Gouverneur, V. Tetrahedron
2000, 56, 2053; (c) Hanson, P. R.; Stoianova, D. S. Tetrahedron Lett. 1998, 39,
3939.
d
133.1 (d, 4JPC¼2.9 Hz, CHAr), 131.7 (d, 3JPC¼10.2 Hz, CHAr), 128.7 (d,
3JPC¼13.9 Hz, CHAr),128.5(d,1JPC¼134.7 Hz, CAr),128.0 (d, 2JPC¼2.9 Hz,
]CH), 125.4 (d, 2JPC¼11.7 Hz, ]CH), 65.6 (d, 2JPC¼7.3 Hz, OCH2), 62.5
(d,1JPC¼102.4 Hz, CHOH);FABMS(NBA, m/z, I, %): 211 [(MþH)þ,100%],
193 [(M-OH)þ, 25%]; HRMS m/z (MHþ) 211.0527 (calcd for C10H12O3P:
211.0524); IR (NaCl):
n 3252, 3063, 2880, 1443, 1272,1234,1175, 1119,
1099, 1063, 954, 743, 696 cmꢁ1
.
4.4.5.2. Second diastereomer. 31P NMR (161.97 MHz, CDCl3):
34.5; 1H NMR (400.13 MHz, CDCl3):
7.81–7.76 (m, 2H, CHAr),
d
d
7.50–7.45 (m, 1H, CHAr), 7.37–7.33 (m, 2H, CHAr), 5.96–5.86 (m, 1H,
]CH), 5.79–5.75 (m, 1H, ]CH), 4.83–4.76 (m, 1H, OCH2), 4.62–4.57
(m, 1H, OCH2), 4.32–4.21 (m, 1H, CHOH); 13C NMR (100.61 MHz,
4
2
CDCl3):
d
133.0 (d, JPC¼2.2 Hz, CHAr), 132.5 (d, JPC¼9.5 Hz, CHAr),
128.4 (d, 3JPC¼12.4 Hz, CHAr), 127.9 (d, JPC¼13.5 Hz, ]CH), 126.9 (d,
1JPC¼133.9 Hz, CAr), 126.4 (d, JPC¼2.2 Hz, ]CH), 66.5 (d, 2JPC¼7.3 Hz,
OCH2), 61.7 (d, 1JPC¼106.1 Hz, CHOH); FABMS (NBA, m/z, I, %): 211
[(MþH)þ, 100%]; HRMS m/z (MHþ) 211.0527 (calcd for C10H12O3P:
6. (a) Stoianova, D. S.; Whitehead, A.; Hanson, P. R. J. Org. Chem. 2005, 70, 5880;
(b) Stoianova, D. S.; Hanson, P. R. Org. Lett. 2001, 3, 3285 Other groups where
interested by such intermediates: (c) Zhang, H.; Tsukuhara, R.; Tigyi, G.; Pre-
stwich, G. D. J. Org. Chem. 2006, 71, 6061.
7. Pirat, J.-L.; Virieux, D.; Clarion, L.; Volle, J.-N.; Bakalara, N.; Mersel, M.; Mon-
tbrun, J.; Cristau, H.-J. PCT Int. Appl. WO09004096, 2009.
211.0524); IR (NaCl): n 3300, 1523, 1225, 1163, 1121, 1084, 1063, 922,
726 cmꢁ1; Melting point 158 ꢀC.
8. Afarinka, K.; Yu, H. Tetrahedron Lett. 2003, 44, 781.
9. Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 165.
10. Machida, Y.; Saito, I. J. Org. Chem. 1979, 44, 865.
11. Weinreb, S. M.; Chao, W. Org. Lett. 2003, 5, 2505.
4.4.6. 4,5-Dehydro-3-hydroxy-3-methyl-2-phenyl-2-oxo-1,2-ox-
aphosphinane (9f). Catalyst: 10%, Eluent: CH2Cl2/EtOH 98/2. Yield:
0.444 g (50%).
12. Fox, H. H.; Lee, J. K.; Park, L. Y.; Schrock, R. R. Organometallics 1993, 12, 759.
13. (a) Harvey, J. S.; Malcolmson, S. J.; Dunne, K. S.; Meek, S. J.; Thompson, A. L.;
Schrock, R. R.; Hoveyda, A. H.; Gouverneur, V. Angew. Chem. 2009, 48, 762; (b)
Vinokurov, N.; Michrowska, A.; Szmigielska, A.; Drzazga, Z.; Wojciuk, G.;
Demchuk, O. M.; Grela, K.; Pietrusiewicz, K. M.; Butenscho¨n, H. Adv. Synth. Catal.
2006, 348, 931.
14. (a) Davies, S. R.; Mitchell, M. C.; Cain, C. P.; Devitt, P. G.; Taylor, R. J.; Kee, T. P.
J. Organomet. Chem. 1998, 550, 29; (b) Merino, P.;Marques-Lopez, E.;Herrera, R. P.
Angew. Chem. 2008, 47, 5646.
31P NMR (CDCl3. 161.97 MHz):
d
38.5 (55% dia. 1), 32.1 (45% dia.
2); 1H NMR (CDCl3. 400.13 MHz):
d 7.81–7.76 (m, 2H, CHAr), 7.50–
7.45 (m, 1H, CHAr), 7.37–7.33 (m, 2H, CHAr), 5.96–5.86 (m, 2H,
CH]CH), 5.10–5.02 (m, 1H, OCH2), 4.90–4.76 (m, 1H, OCH2), 1.56 (d,
3JPH¼14.8 Hz, 3H, CH3); 13C NMR (CDCl3. 100.61 MHz): diastereomer