Epoxysilanes as substrates in regio- and stereo-specific synthesis of silylated γ-hydroxyphosphane oxides, precursors of stereodefined allylphosphane oxides

Article abstract of DOI:10.1016/j.tet.2013.06.039

Epoxysilanes experienced trans stereospecific α- or β-cleavage by the lithium derivative of methyldiphenylphosphane oxide leading to different compounds. The behaviour of the epoxysilanes towards this nucleophilic reagent depends on the nature of the sily

Full text of DOI:10.1016/j.tet.2013.06.039

Tetrahedron 69 (2013) 8080e8087
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Epoxysilanes as substrates in regio- and stereo-specific synthesis of
silylated g-hydroxyphosphane oxides, precursors of stereodefined
allylphosphane oxides
*
ꢀ
ꢀ
Ana M. Gonzalez-Nogal , Purificacion Cuadrado
ꢀ
ꢀ
Departamento de Química Organica, Facultad de Ciencias and Centro de Innovacion en Química y Materiales Avanzados (CINQUIMA), Universidad de
Valladolid, Dr. Mergelina s/n, 47011 Valladolid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Epoxysilanes experienced trans stereospecific
diphenylphosphane oxide leading to different compounds. The behaviour of the epoxysilanes towards
this nucleophilic reagent depends on the nature of the silyl group, the position of the substituents and
a- or b-cleavage by the lithium derivative of methyl-
Received 15 February 2013
Received in revised form 7 June 2013
Accepted 12 June 2013
the configuration of the epoxysilane. Unsubstituted and cis
b-substituted dimethylphenylsilylepoxides
Available online 18 June 2013
underwent -nucleophilic attack of lithium methyldiphenylphosphane oxide giving stereodefined
a
g-
phosphanyl-
b
-silylalcohols 2. Nevertheless, in the same conditions the intermediate
b-hydroxysilane,
Keywords:
Epoxysilanes
Cleavage reactions
Silylated g-hydroxyphosphane oxides
Allylphosphane oxides
formed by
a
-opening from trans -substituted dimethylphenylsilylepoxides, experienced Peterson
b
elimination to give stereodefined allylphosphane oxides 3. The steric requirements for the nucleophilic
attack determined the regiochemistry of the reaction. -Substituted phenyldimethylsilyl and tert-bu-
tyldiphenylsilylepoxides were exclusively attacked at the -position affording -hydroxy- -silylphos-
phane oxides 4 and -phosphanyl silyl ethers 5, resulting from Brook rearrangement.
On the other hand, the allylphosphane oxides 3 resulting from syn- or anti-eliminacion of
phenylsilyl- -hydroxyphosphane oxides 2, are of interest in the synthesis of phosphorylated and func-
tionalised building blocks.
a
b
g
g
g
ꢀ
b
-dimethyl-
g
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
lithium diphenylphosphide. The anti stereospecific nucleophilic
opening from silyl and disilylepoxides6 took place regioselectively
Organophosphorus compounds are of great chemical and bi-
ological interest1. They have also found much utility as ligands in
asymmetric catalysis2. These hemilabile ligands have also en-
countered success with applications in small-molecule activation,
small-molecule sensing and stabilization of transition complexes 3.
Owing to the multiple ways in which they can be employed, the
synthesis of small molecules containing phosphorus has garnered
significant attention4. More importantly, the ability to generate
phosphorus compounds with chiral centres at or near phosphorus
in an asymmetric fashion is particularly attractive. Furthermore, it
is known that phosphorus substituents regulate important bi-
ological functions5, and that the introduction of organophosphorus
functionalities in simple synthons may afford useful substrates for
the preparation of biologically active compounds.
in
or
a
a
or
- and
b
depending of the substrate structure. Using unsubstituted
-C-substituted silylepoxides, we have synthesised
-opening
-opening.
-disilylepoxides afforded -silyl
-silylated silyl enol ethers by - and
b
vinylphosphonium iodides or vinylphosphane oxides by
and silyl enol ethers, vinylsilanes or -hydroxysilanes by
On the other hand, - or
vinylphosphane oxides or
cleavage, respectively. In view of the different behaviour of silyl-
and stannyloxiranes towards the nucleophilic attack and with the
aim of increasing the synthetic possibilities of the cleavage of
metallated epoxides by lithium diphenylphosphide, we extended
this methodology to stannylated epoxides7. Unsubstituted or C-
substituted stannyloxiranes reacted stereospecifically with lithium
a
b
a
a
,b
a,
a
b
a
a
b-
diphenylphosphide to give either
resulting from -opening or -phosphanyl ketones by
Furthermore, the reactivities of distannyloxiranes depend on their
configurations. The cis isomers afforded the corresponding a,b-
b
-hydroxyphosphane oxides
a
b
b-opening.
Previously, we have synthesised various organophosphorus
compounds from silyl and stannylepoxides by cleavage with
diphosphanyl alcohols, while the trans isomers were shown to be
unreactive. On the other hand, the regiochemistry of the ring-
opening from
b-silylated stannyloxiranes is controlled by the tin
* Corresponding author. Tel.: þ34 983 423213; fax: þ34 983 423013; e-mail
ꢀ
group and, depending on the nature of the silyl group, led either to
address: agn@qo.uva.es (A.M. Gonzalez-Nogal).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.039

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8081
stereodefined
enol ethers. Finally, the gem-silyl-stannyloxiranes underwent
opening to give mixtures of -phosphanyl acylsilanes and silyl enol
b
-silyl vinylphosphane oxides or to
b
-stannyl silyl
Nevertheless, in the same conditions the
a-opening of trans b-
b
-
phenyl- 1c and -silyl dimethylphenylsilylepoxide 1d was followed
b
b
by Peterson-elimination affording the trans allylphosphane oxides
3a and 3b, respectively (Scheme 3).
ethers. All compounds are interesting synthons of great versatility
in organic chemistry.
Recently we have reported8 some synthetic applications of the
vinylphosphane oxides as Michael acceptors, 1,3-dipolarophiles
and precursors in the synthesis of allenes.
O
R
R
1. LiCH2PPh2,THF, 0 ºC r.t.
O
2. H2O + NH4Cl
SiMe2Ph
PPh2
O
Following on with our current research in the synthesis of or-
ganophosphorus compounds from silylepoxides, in this occasion
we have studied the regio- and stereo-specific cleavage of epox-
ysilanes with the lithium derivative of the methyl-
diphenylphosphane oxide with the aim of synthesising
stereodefined allylphosphane oxides. Allylic phosphorous com-
pounds are attractive electrophiles in organic synthesis, because an
allylic fragment in the molecule provides possibilities for further
functionalisation.
3a (68%); R = Ph
3b (61%); R = SiMe2Ph
1c; R = Ph
1d; R= SiMe2Ph
Scheme 3.
Probably in this case, the Peterson elimination took place be-
cause the stability of the necessary conformation for the OeP in-
teractions in the corresponding intermediate B is minor than the
intermediate A. In the intermediate B the R group (phenyl or
dimethylphenylsilyl) should be eclipsed with the dimethylphe-
nylsilyl group (Scheme 4), whereas in the intermediate A the
methyl and silicon group are staggered (Scheme 2).
2. Results and discussion
2.1. Cleavage of silylepoxides with lithium methyl-
diphenylphosphane oxide
OLi
O
Ph
Ph
The behaviour of silylepoxides towards the lithium derivative of
the methyldiphenylphosphane oxide depends on the nature of the
silyl group, the position of the substituents and configuration of the
CH2PPh2
Li
P
R
PPh2
R
O
SiMe2Ph
LiO
SiMe2Ph
O
R
SiMe2Ph
epoxysilane. Unsubstituted 1a and cis
b-methyl dimethylphenylsi-
B
lylepoxide 1b underwent -nucleophilic attack of lithium methyl-
a
O
diphenylphosphane oxide giving stereodefined
phosphane oxides 2a,b (Scheme 1).
g
-hydroxy-b-silyl
R
PPh2
R
-LiOSiMe2Ph
O
LiO
SiMe2Ph
PPh2
R = Ph, SiMe2Ph
O
O
HO
R
PPh2
1. LiCH2PPh2,THF, 0 ºC r.t.
2. H2O + NH4Cl
Scheme 4.
SiMe2Ph
R
O
SiMe2Ph
On the other hand, the bulky tert-butyldiphenylsilyl group
changes the regioselectivity and supplies useful differences in the
chemistry of silylepoxides. Unsubstituted tert-butyldiphenylsily-
1a; R = H
2a (94%); R = H
anti-2b (73%); R = Me
1b; R= Me
lepoxide 1e was exclusively attacked by nucleophile at the
sition to give a mixture of the -hydroxy- -silylphosphane oxide 4a
and the -phosphanyl silyl ether 5a, in which the latter was the
b-po-
Scheme 1.
g
g
g
major product (Scheme 5).
The outcome is different to the observed by us in the
cleavage of silylepoxides towards other nucleophiles, such as:
lithium diphenylphosphide6, or lithium phenylsulfide9. In this
O
O
O
Ph2P
SiPh2But
Ph2P
1. LiCH2PPh2,THF reflux
2. H2O + NH4Cl
case the
resulting from the
g
-alkoxy-
b
a
-silyl phosphane oxide intermediate A,
-opening, does not experience Peterson
SiPh2But
OH
OSiPh2But
O
1e
4a (15%)
Scheme 5.
5a (35%)
elimination due to its stabilisation by coordination of the
alkoxyl group with the phosphorus leading to regio- and stereo-
specific
g
-hydroxy-
b
-silyl phosphane oxides 2 in the final hy-
drolysis (Scheme 2).
The formation of 4a and 5a should occur by hydrolysis of the
intermediate C formed from -opening (4a) and the intermediate
b
D, resulting Brook rearrangement (5a). This latter is the major
product due to the high migratory aptitude of the tert-butyldi-
phenylsilyl group[6b] (Scheme 6).
OLi
O
Ph
Ph
CH2PPh2
Li
P
Me
PPh2
O
O
Li
SiMe2Ph
Me
LiO
SiMe2Ph
O
O
CH2PPh2
Me
SiMe2Ph
A
Ph2P
H
r-Brook
Ph
1b (cis)
O
C
SiR3
O
P
O
O
SiR3
1e;R3 = Ph2But
O
R3Si
H
HO
PPh2
Ph
H2O + NH4Cl
D
Me
anti-2b
SiMe2Ph
4a
5a
Scheme 6.
Scheme 2.

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8082
When the
did not take place.
1f,g were recovered even after prolonged heating with lithium
methyldiphenylphosphane oxide in THF at reflux (Scheme 7).
b
-position bears an alkyl or phenyl group the reaction
-Substituted tert-butyldiphenylsilylepoxides
interesting precursors of chiral 1,3-hydroxyphosphines, a class of
b
versatile mixed bidentate 1,3-donor ligands for transition-metal-
catalysed asymmetric synthesis11. Moreover, silylated hydrox-
yphosphane oxides 2 or 4 can undergo a wide range of reactions. It
includes transformations of the hydroxyl group or those of the
phosphanyl functionality or both. We have used the
silyl phosphane oxides 2 in the synthesis of allyl phosphane oxides
and -phosphanyl- -silylketones.
g-hydroxy-b-
O
R
1. LiCH2PPh2,THF reflux
2. H2O + NH4Cl
b
a
SiPh2But
O
2.2. Synthesis of allylphosphane oxides
1f; R = Me (cis)
1g; R = Ph (trans)
2-Dimethylphenylsilyl-3-hydroxyphosphane oxides
2 have
proven to be of great utility in the synthesis of stereodefined allyl
phosphane oxides. They experience acid-catalysed anti-elimination
of HOSiMe2Ph affording allylphosphane oxides, which are stereo-
isomers of those we have obtained by thermal syn-elimination
(Scheme 10).
Scheme 7.
The steric requirements for the nucleophilic attack determined
the regiochemistry of the reaction. If the -position is substituted,
even starting from dimethylphenylsilylepoxides, only -cleavage
took place. The 1-methyl-1-dimethyl phenylsilylepoxide 1h and
a
b
R
HClO4
O
the 1-methyl-1-tert-butyl diphenylepoxide 1i underwent
ing affording the -hydroxy-
b
-open-
H2O + EtOH
PPh2
g
g-silyl phosphane oxide 4b and the
g-
O
phosphanyl silyl ether 5b, respectively (Scheme 8).
HO
R
PPh2
3c (86%); R = H
E-3d (96%); R = Me
SiMe2Ph
O
Ph2P
O
SiMe2Ph
Me
Me
SiMe2Ph
1. LiCH2PPh2,THF reflux
2. H2O + NH4Cl
2a; R = H
anti-2b; R = Me
reflux of xylene
O
O
OH
R
PPh2
1h
4b (76%)
O
O
3c (73%); R = H
Ph2P
Me
Me
1. LiCH2PPh2,THF reflux
Z-3d(80%); R = Me
2. H2O + NH4Cl
SiPh2But
OSiPh2But
O
Scheme 10.
1i
5b (68%)
Scheme 8.
2.3. Synthesis of b-phosphanyl-a-silylketones
Oxidation of 2-dimethylphenylsilyl-3-hydroxyphosphane oxide
2b with PCC/Py in methylene chloride at room temperature led to
Again the higher migratory aptitude of the tert-butyldiphe-
nylsilyl than the dimethylphenylsilyl group was made plain (phenyl
groups on silicon have been shown to accelerate the Brook
the desilylated ketone. Fortunately, the
b-phosphanyl-a-silylketone
rearrangement)10
.
6 was isolated using DesseMartin oxidation (Scheme 11).
It is known that alkyl-substitution at the carbon atom on which
a carbanion is generated slows down the rate of a Brook rear-
O
O
rangement. Nevertheless,
a-methylepoxysilane 1i produced solely
HO
Me
PPh2
O
PPh2
Brook-rearrangement product 5b, in contrast to the result with
a
-
Dess-Martin periodinane
CH2Cl2, r.t.
unsubstituted 1e in which a mixture of unrearranged product 4a
and rearranged product 5a was formed. The absence of unrear-
ranged product starting from 1i could be explained considering the
SiMe2Ph
Me
SiMe2Ph
anti-2b
6 (76 %)
high instability of initial intermediate C, resulting from b-opening,
Scheme 11.
due to the steric interaction between the methyl and phenyl group
in the more favourable folded conformation. In this case, the re-
action evolved exclusively through the rearranged intermediate D
leading to the
g-phosphanyl silyl ether 5b (Scheme 9).
2.4. Synthetic applications of allylphosphane oxides
Li
O
CH2PPh2
Me
O
Allylphosphane oxides are attractive reagents in organic syn-
thesis. They can be of great interest as substrates in carbanion-
stabilised reactions12. Likewise, as occur with allylic phosphates
and allylic phosphinates13, they could be used as electrophiles for
the introduction of an allylic fragment in the molecule through
copper-mediated coupling reaction with organometallic reagents.
We have used allylphosphane oxides as stabilised carbanions
in addition and substitution process with the aim of synthesising
versatile functionalised synthons. Now we described some
initial results starting from the unsubstituted allylphosphane
oxide 3c.
Ph
Ph2P
Me
O
O
SiR3
Me
r-Brook
P
5b
O
O
SiR3
Ph
R3Si
C
D
1i;R3 = Ph2But
Scheme 9.
2-Silyl-3-hydroxyphosphane oxides 2 resulting from
and 3-silyl-3-hydroxy phosphane oxides 4 formed by
a
-opening
b-opening are

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8083
The allylic phosphane oxide 3c when treated with n-butyl-
lithium delivers an allylphosphanyl anion. This phosphorus-
stabilised allyl anion is an ambident nucleophile capable to re-
OH
R
O
H
R
H
H
PPh2
O
φ = 180º
JH/H= 9.2 Hz
R
Ph2P
Ph2P
O
O
PPh2
act with a variety of electrophiles at two sites (a- or g-position)
O
O
O
syn
to give versatile allyl or vinylphosphane oxides, respectively.
Although a number of factors have been identified as important
influences on site selectivity, there is as yet no comprehensive
basis for predicting the observed regiochemistry. We have proved
H
OH
R
O
H
H
H
R
PPh2
O
φ = 60º
H/H= 2.1 Hz
R
J
PPh2
total
g-regioselectivity in the reaction with chlorodimethyl
anti
O
phenylsilane, in agreement with earlier reports using
chlorotrimethylsilane as an electrophile14. Nevertheless, the sta-
bilised carbanion derivated from 3c reacted with some aldehydes,
such as isobutyraldehyde, benzaldehyde and thiazole-2-
H
Fig. 1. Newman projections of syn and anti isomers.
observed regioselectivity will be published by us as soon as
possible.
On the other hand, the double bond of allyl phosphane oxides
provides possibilities for further functionalisation (hydroxylation
16, epoxidation, halogenation, etc.).
carbaldehyde giving predominantly or exclusively the g-product,
in contrast to the
a-regioselectivity observed by other
authors[14b,15] (Scheme 12).
O
We have proved the easy epoxidation of allylphosphane oxides
3 and subsequent cleavage by different nucleophiles. Thus, the
unsubstituted allylphosphane oxide 3c was converted with ex-
Ph2P
SiMe2Ph
cellent yield into the b-phosphanyl epoxide 10, which was cleav-
7 (98%)
age by heteroatomic nucleophiles (silyl- and stannyl-cuprates,
lithium phenylsulfide, lithium diphenylphosphide and lithium
diisopropylamide) giving versatile trifunctionalised synthons
(Scheme 13).
ClSiMe2Ph
–78 ºC
O
O
Ph2P
O
BuLi
Ph2P
Ph2P
–78 ºC
3c
O
Ph2P
RCHO
–78 0 ºC
O
Ph2P
MCPBA, CH2Cl2
HCO3Na
O
OH
O
Ph2P
3c
11 (80%)
R
R
O
PPh2
OH
8
9
O
O
O
Ph2P
R = Pri
anti-8a (22%)
9a (56%)
9b (78%)
Ph2P
Ph2P
Nu
Nu, THF
– 78 0 ºC
R = Ph
syn-8b (3%) + anti-8b (5%)
Nu
OH
HO
O
____
11
9c (75%)
R = 2- Thiazolyl
Scheme 12.
12a (52%); Nu = SiMe2Ph
13a (14%); Nu = SiMe2Ph
13b (64%); Nu = SnBu3
Nu = Bu(SiMe2Ph)CuLi
Nu = Bu(SnBu3)CuLi
12b (21%); Nu = SnBu3
12c (12%); Nu = SPh
13c (62%); Nu = SPh
Nu = PhSLi
From the stereochemical viewpoint, the reaction took place with
high diastereoselectivity. In all cases, the formation of -adducts
proceeds with total E stereoselectivity. On the other hand, in the
____
Nu = Ph2P(O)Li
12d (75%); Nu = P(O)Ph2
g
a
-
O
O
adduct two chiral carbons are created and, consequently, two di-
astereoisomers could be obtained. The reactions with iso-
butyraldehyde took place with total diastereoselectivity to give
anti-8a as sole isomer. However, with benzaldehyde a mixture of
syn-8b and anti-8b was isolated, in which the anti is the major
diastereoisomer.
Ph2P
Ph2P
iPrNLi
THF, –78 ºC
O
OH
14 (83%)
11
Scheme 13.
The configurational assignation of the syn and anti isomers was
possible by IR and 1H NMR spectroscopy. Intramolecular hydrogen
bond between the hydroxy and phosphanyl groups was confirmed
by comparative IR spectroscopy of the compounds in film and at
Except for the phosphorus nucleophile, the reaction was not
regioselective leading to a mixture of regioisomers 12 and 13.
Probably the initial complexation of the metal species to the
different dilutions in CH2Cl2. The frequency and shape of the
n
OH
phosphanyl group favours the nucleophilic attack at the b-position
band did not change. Starting from this fact, the coupling constants
between vic-protons are those expected according to the dihedral
giving the chelation-controlled product 12 via the intermediate E
stabilized by PeO coordination (pathway a). Soft and bulky stannyl
and sulfur nucleophiles preferred the attack at the unsubstituted
carbon atom to give the stereo-controlled product 13 across the
less hindered intermediate F (pathway b). On the other hand, LDA
angle,
f
¼180ꢀ in the syn isomer and
f
¼60ꢀ in the anti isomer. Thus,
the syn-8b, which in the chelated conformation has a
f
¼180ꢀ
showed a JH/H¼9.6 Hz, while the anti-8a or anti-8b, with
f
¼60ꢀ has
a JH/H¼2.1 Hz (Fig. 1).
behaves as
a base, extracting a proton from the adjacent
The scope of this methodology is being object of research by
our group using Z or E differently substituted allylphosphane ox-
ides. The experimental results and theoretical study to explain the
methylene to the phosphanyl group. The resulting phosphorus-
stabilised carbanion led to the allylic alcohol 14 by ring cleavage
(Scheme 14).

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8084
bis-stannylcuprates because they cheapen the synthesis and sim-
plify the isolation process. The DesseMartin periodinane was
bought (Aldrich).
O Li
PPh2
O
O
Ph2P
Li
a
O
Nu
b
a
a
Nu
OH
Nu
Ph2P
12
E
4.2. Cleavage of epoxysilanes with lithium methyldiphenyl
phosphane oxide. Typical procedure
Nu
O
a
b
O
O
b
11
Ph2P
Nu
Ph2P
Li
To a stirred THF solution of lithium methyldiphenyl phosphane
oxide [prepared from methyldiphenylphosphane oxide (1 mmol)
and butyllithium (0.625 mL, 1.6 M solution in hexane, 1 mmol) in
THF (5 mL) at 0 ꢀC under an N2 atmosphere for 30 m] was added
dropwise a solution of the silyloxirane 1aei (1 mmol) in THF (5 mL).
Depending on the reactivity of the silylepoxide, the resulting so-
lution was allowed to warm up to room temperature for 1aed, or
heated at reflux for 1eei. The reaction mixture was stirred at this
temperature until TLC indicated complete reaction. Ammonium
chloride aqueous solution was added and the mixture was extrac-
ted with ether and dried (MgSO4). The ethereal solvents were
evaporated and the residue chromatographed to give the following
compounds.
F
Li
O
HO
13
O
NPri
O
H
Ph2P
Ph2P
OH
11
14
O
Scheme 14.
With the aim of knowing and explaining the regiochemistry
and diastereoselectivity of this opening we are studying the re-
action of Z or E substituted
b-phosphanylepoxides towards the
same heteronucleophiles. The results will be published as soon as
possible.
4.2.1. 2-(Dimethylphenylsilyl)-3-(diphenylphosphanyl) propan-1-ol
(2a). Yield 370 mg (94%); Rf (AcOEt) 0.38; IR (CHCl3) 3296, 1437,
1254,1158,1110 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.28 (s, 3H), 0.29
3. Conclusions
(s, 3H), 1.37 (m, 1H), 2.19 (dt, J¼11.6, 15.4 Hz, 1H), 2.45 (dd, J¼5.6,
15.4 Hz, 1H), 3.64 (dt, J¼2.1, 9.9 Hz, 1H), 3.91 (dt, J¼2.1, 9.9 Hz, 1H),
5.75 (dd, J¼2.1, 9.9 Hz, 1H), 7.35e7.64 (m, 15H); 13C NMR (75 MHz,
We have developed an efficient stereoselective synthesis of 2-
and 3-silylated 3-hydroxyphosphane oxides 2 and 4 by
a- or b-
CDCl3)
d
ꢁ6.0, ꢁ4.2, 25.3, 30.5 (d, J¼65.6 Hz), 64.0, 128.3, 128.7,
opening of silylepoxides with the lithium derivative of the meth-
129.5, 130.0 (d, J¼98.6 Hz), 130.4 (d, J¼9.4 Hz), 131.8, 133.8, 136.2;
yldiphenylphosphane oxide. Moreover, we have proved that
phosphanyl-
mild condition by the use of the DesseMartin reagent, to give
phosphanyl -silylketones.
serve not only for the stereoselective synthesis of biologically im-
portant primary or secondary -vinylcarbonyl compounds but also
g-
31P NMR (121 MHz, CDCl3)
d
37.29; [Found: C, 70.39; H, 6.73.
b
-silyl alcohols 2 can be oxidized, under extremely
C33H37O2PSi (394.15) requires C, 70.02; H, 6.90%].
b
-
a
a
-Silyl aldehydes17 or ketones18 can
4.2.2. (2SR,3SR)-3-(Dimethylphenylsilyl)-4-(diphenylphosphanyl)bu-
tan-2-ol (anti-2b). Yield 297 mg (73%); Rf (AcOEt) 0.40; IR (CHCl3)
a
3297, 1437, 1250, 1158, 1110 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.28
for the preparation of synthetic intermediates, e.g., substrates for
Cope and Claisen rearrangements. Moreover, the presence in all
compounds of a phosphanyl group increases their biological and
synthetic interest.
Finally, we have shown some synthetic applications of the
allylphosphane oxides, resulting from a-opening from epoxysilanes
(s, 3H), 0.29 (s, 3H), 1.23 (d, J¼6.2 Hz, 3H), 1.25 (m, 1H), 2.27 (ddd,
J¼1.1, 6.1, 15.4 Hz, 1H), 2.46 (dt, J¼10.6, 15.4 Hz, 1H), 3.84 (dq, J¼8.1,
6.2 Hz, 1H), 7.33e7.62 (m, 15H); 13C NMR (75 MHz, CDCl3)
d
ꢁ5.3,
ꢁ2.7, 25.9, 27.8 (d, J¼66.2 Hz), 28.5 (d, J¼6.2 Hz), 67.9, 128.0,
128.6 (d, J¼11.6 Hz), 129.3, 130.5 (d, J¼9.2 Hz), 131.8, 133.3 (d,
J¼97.7 Hz), 133.8, 137.4; 31P NMR (121 MHz, CDCl3)
d 37.49; [Found:
or subsequent syn or anti elimination.
C, 70.79; H, 6.98. C24H29O2PSi (408.17) requires C, 70.56; H, 7.15%].
4. Experimental section
4.1. General
4.2.3. (E)-3-(Diphenylphosphanyl)-1-phenylprop-1-ene (3a). Yield
216 mg (68%); Rf (AcOEt) 0.42; IR (CHCl3) 1641, 1437, 1184,
896 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
3.30 (ddd, J¼0.6, 7,5,15.0 Hz,
2H), 6.18 (ddt, J¼13.5, 15.8, 7.5 Hz, 1H), 6.43 (ddt, J¼4.4, 15.8, 0.6 Hz,
1H), 7.17e7.80 (m, 15H); 13C NMR (75 MHz, CDCl3)
35.6 (d,
THF was distilled from sodium benzophenone ketyl in a recy-
cling still. All chromatographic and work-up solvents were dis-
tilled prior to use. All reactions involving organometallic reagents
were carried out under nitrogen atmosphere. 1H and 13C NMR
spectra were recorded at 300 and 75 MHz, respectively, in CDCl3 as
an internal standard. Carbon multiplicities were assigned by DEPT
experiments. Reactions were monitored by TLC on pre-coated
plates (Silicagel 60, nano-SIL-20, MachereyeNagel). Flash chro-
matography was performed on silica gel 60 (230e400 mesh,
MeN). Silylepoxides 1aec, 1eei were prepared by epoxidation
d
J¼68.7 Hz), 118.3 (d, J¼9.7 Hz), 126.2, 127.5, 128.4, 128.6 (d,
J¼11.5 Hz), 131.0 (d, J¼9.0 Hz), 131.9, 132.3 (d, J¼98.7 Hz), 135.6 (d,
J¼12.1 Hz), 137.0; 31P NMR (121 MHz, CDCl3)
d 30.86; [Found: C,
79.59; H, 5.88. C21H19OP (318.12) requires C, 79.23; H, 6.02%].
4.2.4. (E)-1-(Dimethylphenylsilyl)-3-(diphenylphosphanyl)prop-1-
ene (3b). Yield 229 mg (61%); Rf (AcOEt) 0.41; IR (CHCl3) 1590,
1443, 1250, 1187, 1112, 990 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.42
(s, 6H), 3.15 (ddd, J¼1.1, 6.5, 15.2 Hz, 2H), 5.76 (ddt, J¼4.5, 19.8,
[19,20]
of the corresponding vinylsilanes obtained by reaction with
1.1 Hz,1H), 6.28 (ddt, J¼19.8, 6.5,1.1 Hz,1H), 7.26e7.78 (m,15H); 13C
electrophiles of the intermediates from dimethylphenylsilyl- or
tert-butyldiphenylsilyl cupration of alkynes
NMR (75 MHz, CDCl3)
d
ꢁ2.7, 34.9 (d, J¼66.3 Hz), 122.3 (d,
[20,21]
(1aec, 1eeg) or
J¼10.3 Hz), 127.8, 128.6, 129.0, 131.2 (d, J¼9.3 Hz), 132.6, 133.9, 134.6
allene [22,23] (1h and 1i). The synthesis of the 1,2-disilylepoxide 1d
was previously described by us[6b]. In the reactions with silyl or
stannylcuprates we have used mixed higher order cuprates of
carbon and silicon or tinelithium butylsilyl or butyl-
stannylcuprates, which selectively transfer the silyl or stannyl
group but they are more advantageous than lithium bis-silyl or
(d, J¼96.8 Hz), 138.7; 31P NMR (121 MHz, CDCl3)
d 30.73; [Found: C,
72.98; H, 6.93. C23H25OPSi (376.14) requires C, 73.37; H, 6.69%].
4.2.5. 1-(tert-Butyldiphenylsilyl)-3-(diphenylphosphanyl)propan-1-
ol (4a). Yield 75 mg (15%); Rf (AcOEt) 0.35; IR (CHCl3) 3395, 1437,
1184, 1110 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 1.09 (s, 9H), 1.88 (m,

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8085
2H), 2.49 (m, 2H), 3.84 (dd, J¼4.1, 9.5 Hz, 1H), 7.27e7.74 (m, 20H);
13C NMR (75 MHz, CDCl3)
18.4, 26.9, 28.2, 28.8 (d, J¼72.9 Hz), 63.5,
consumption of starting material was observed by TLC (reaction
time: 5 h). The solvent was evaporated and the residue was chro-
matographed to give the following compounds.
d
127.5, 128.6 (d, J¼11.3 Hz), 129.1, 130.7 (d, J¼9.4 Hz), 131.7, 133.0,
133.5 (d, J¼92.8 Hz), 136.0; 31P NMR (121 MHz, CDCl3)
d 35.87;
[Found: C, 74.39; H, 6.94. C31H35O2PSi (498.21) requires C, 74.67; H,
7.07%].
4.3.3. 3-(Diphenylphosphanyl)prop-1-ene (3c). Yield: 176 mg (73%).
4.3.4. (Z)-4-(Diphenylphosphanyl)but-2-ene (Z-3d). Yield 204 mg
4.2.6. 2-(Dimethylphenylsilyl)-4-(diphenylphosphanyl)butan-2-ol
(80%); Rf (AcOEt) 0.41; IR (CHCl3) 1612, 1437, 1184, 701 cmꢁ1 1H
;
(4b). Yield 310 mg (76%); Rf (AcOEt) 0.24; IR (film) 3344, 1437, 1173,
NMR (300 MHz, CDCl3)
14.8 Hz, 2H), 5.48 (m, 1H), 5.67 (m, 1H), 7.43e7.78 (m, 10H); 13C
NMR (75 MHz, CDCl3)
13.0, 29.7 (d, J¼70.3 Hz), 118.3 (d, J¼8.6 Hz),
d
1.48 (dd, J¼2.2, 4.3 Hz, 3H), 3.15 (dd, J¼7.4,
1248, 1119 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
0.31 (s, 3H), 0.32 (s,
3H), 1.19 (s, 3H), 1.81 (m, 2H), 2.35 (m, 2H), 7.29e7.75 (m, 15H); 13C
NMR (75 MHz, CDCl3)
d
d
ꢁ5.9, 18.4, 22.8 (d, J¼72.4 Hz), 23.4, 30.4,
128.5 (d, J¼11.7 Hz), 129.5 (d, J¼11.7 Hz), 131.0 (d, J¼9.2 Hz), 131.7,
64.6 (d, J¼9.8 Hz), 127.8, 128.6 (d, J¼10.9 Hz), 129.2, 130.8 (d,
132.6 (d, J¼98.6 Hz); 31P NMR (121 MHz, CDCl3)
d 31.24; [Found: C,
J¼9.8 Hz), 131.7, 132.5 (d, J¼98.7 Hz), 134.4, 136.3; 31P NMR
74.73; H, 6.81. C16H17OP (256.10) requires C, 74.99; H, 6.69%].
(121 MHz, CDCl3)
d 35.81; [Found: C, 70.39; H, 6.95. C24H29O2PSi
(408.12) requires C, 70.56; H, 7.15%].
4.4. Oxidation of 2-dimethylphenylsilyl-3-hydroxy phos-
phane oxide 2b. Synthesis of the b-phosphanyl-a-silylketone 6
4.2.7. Diphenyl-[3-(tert-butyldiphenylsilyloxy)propyl]phosphane ox-
ide (5a). Yield 174 mg (35%); Rf (AcOEt) 0.38; IR (CHCl3) 1434, 1106,
To a solution of 2b (0.40 g, 1 mmol) in methylene chloride
(10 mL) was added DesseMartin periodinane (0.51 g, 1.2 mmol)
under a nitrogen atmosphere at room temperature. The reaction
mixture was stirred at the same temperature until starting alcohol
was consumed, as determined by TLC analysis. Et2O (20 mL) and aq
1% Na2S2O3 solution (5 mL) were added followed by satd
aq NaHCO3 (5 mL) and the resulting mixture was stirred for 15 min.
The organic phase was separated, dried (MgSO4), and concentrated.
1100 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
1.05 (s, 9H), 1.85 (m, 2H),
2.42 (dt, J¼4.7, 11.6 Hz, 2H), 3.71 (t, J¼5.8 Hz, 2H), 7.27e7.76 (m,
20H); 13C NMR (75 MHz, CDCl3)
d
19.2, 26.1 (d, J¼63.5 Hz), 26.9,
29.7, 63.8 (d, J¼16.0 Hz), 127.7, 128.7 (d, J¼11.4 Hz), 129.7, 130.8 (d,
J¼9.2 Hz), 131.7, 132.9 (d, J¼96.6 Hz), 133.5, 135.5; 31P NMR
(121 MHz, CDCl3)
d 33.81; [Found: C, 74. 91; H, 7.19. C31H35O2PSi
(498.21) requires C, 74.67; H, 7.07%].
Purification by chromatography provided the
(308 mg, 76%) as a colourless oil; Rf (hexane/AcOEt¼10:1) 0.36; IR
(CH2Cl2) 1712, 1438, 1252, 1195, 1100 cmꢁ1 1H NMR (300 MHz,
CDCl3) 0.14 (s, 3H), 0.20 (s, 3H), 2.13 (s, 3H), 2.57 (m, 2H), 2.78 (m,
1H), 7.35e7.78 (m,15H); 13C NMR (75 MHz, CDCl3)
a-silylketone 6
4.2.8. Diphenyl-[3-(tert-butyldiphenylsilyloxy)butyl]phosphane ox-
ide (5b). Yield 348 mg (68%); Rf (AcOEt) 0.40; IR (CHCl3) 1437, 1188,
;
1111 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
0.95 (s, 9H),1.07 (d, J¼6.2 Hz,
3H), 1.72 (m, 2H) 2.15 (m, 1H), 2.41 (m, 1H), 3.95 (m, 1H), 7.30e7.72
(m, 20H); 13C NMR (75 MHz, CDCl3)
d
d
ꢁ3.9, ꢁ2.1, 23.2
d
19.2, 22.8, 25.1 (d, J¼73.3 Hz),
(d, J¼66.7 Hz), 29.7, 32.2, 127.3, 128.7 (d, J¼11.9 Hz), 129.6, 130.7 (d,
27.0, 29.6, 69.3 (d, J¼16.1 Hz),127.4,127.5,128.5 (d, J¼10.5 Hz),129.6,
J¼9.5 Hz), 131.9, 134.2 (d, J¼98.7 Hz), 133.0, 136.8, 201.3; 31P NMR
130.7 (d, J¼9.1 Hz), 131.5, 133.0 (d, J¼98.4 Hz), 134.0, 134.2, 135.7,
(121 MHz, CDCl3)
d 32.89; [Found: C, 71.16; H, 6.81. C24H27O2PSi
135.8; 31P NMR (121 MHz, CDCl3)
d
34.00; [Found: C, 75. 11; H, 7.41.
(406.15) requires C, 70.91; H, 6.69%].
C32H37O2PSi (512.23) requires C, 74.97; H, 7.27%].
4.5. Reaction of lithiated allylphosphane oxides with elec-
trophiles. Typical procedure
4.3. Elimination of -hydroxysilanes. Stereospecific synthesis
b
of allylphosphane oxides
To a solution of the allyldiphenylphosphane oxide 3c (1.5 mmol)
in dry THF (3 mL) was added a solution of BuLi (0.94 mL, 1.6 M
solution in hexane, 1.5 mmol) in dry THF (3 mL) at ꢁ78 ꢀC under N2.
The resulting mixture was stirred at this temperature for 10 min
and then was added the chlorodimethylphenylsilane (3 mmol),
isobutyraldehyde (4.5 mmol), benzaldehyde (2.2 mmol) or thia-
zole-2-carbaldehyde (2.5 mmol). For the silylation the system was
stirred at ꢁ78 ꢀC and for the reaction with aldehydes the mixture
was allowed to warm at 0 ꢀC until TLC indicated complete reaction
(reaction time¼1e2 h). The mixture was hydrolysed with methanol
(silylation) or with a satd aq NH4Cl soln and extracted with diethyl
ether, and the organic layer was dried (MgSO4). The residue ob-
tained after evaporation of solvents was purified by flash chroma-
tography on silica gel using AcOEt as eluent to give the compounds
characterized below.
Method A. To a solution of the b-hydroxysilane 2a or 2b (1 mmol)
in MeOH/H2O¼20:1 (10 mL) was added perchloric acid (1 mL). The
mixture was stirred at room temperature for 3 h. Quenching with
ice/H2O, aqueous work-up with diethyl ether, drying (MgSO4) and
flash chromatography gave the following products.
4.3.1. 3-(Diphenylphosphanyl)prop-1-ene (3c). Yield 208 mg (86%);
Rf (AcOEt) 0.48; IR (CHCl3) 1636, 1437, 1178, 997, 924 cmꢁ1; 1H NMR
(300 MHz, CDCl3)
d
3.15 (dd, J¼7.5, 15.6 Hz, 2H), 5.15 (m, 2H), 5.67
(m, 1H), 7.40e7.78 (m, 10H); 13C NMR (75 MHz, CDCl3)
d
36.0 (d,
J¼68.7 Hz), 121.0 (d, J¼11.8 Hz), 127.5 (d, J¼9.3 Hz), 128.3 (d,
J¼11.7 Hz), 131.0 (d, J¼9.1 Hz), 131.8, 132.2 (d, J¼99.1 Hz); 31P NMR
(121 MHz, CDCl3)
d 30.69; [Found: C, 74.52; H, 6.08. C15H15OP
(242.09) requires C, 74.37; H, 6.24%].
4.3.2. (E)-4-(Diphenylphosphanyl)but-2-ene (E-3d). Yield 245 mg
4.5.1. (E)-3-(Dimethylphenylsilyl)-1-(diphenylphosphanyl)prop-1-
(96%); Rf (AcOEt) 0.43; IR (CHCl3) 1652, 1436, 1182, 972 cmꢁ1
;
1H
ene (7). Yield 368 mg (98%); Rf (AcOEt) 0.62; IR (CHCl3) 1606, 1437,
NMR (300 MHz, CDCl3)
J¼0.9, 7.1, 14.0 Hz, 2H), 5.43 (dq, J¼15.0, 6.4 Hz, 1H), 5.51 (dt, J¼15.0,
7.1 Hz, 1H), 7.30e7.78 (m, 10H); 13C NMR (75 MHz, CDCl3)
18.1,
d
1.62 (dd, J¼1.6, 6.4 Hz, 3H), 3.09 (ddd,
1257, 1112, 970 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.45 (s, 3H), 2.05
(dd, J¼7.8, 2.1 Hz, 2H), 5.95 (ddt, J¼22.8, 15.6, 2.1 Hz, 1H), 6.71 (ddt,
d
J¼19.2, 15.6, 7.8 Hz, 1H), 7.40e7.70 (m, 15H); 31P NMR (121 MHz,
34.7 (d, J¼69.8 Hz), 118.9 (d, J¼9.4 Hz), 128.5 (d, J¼11.7 Hz), 131.0 (d,
CDCl3) d 24.96; [Found: C, 73.15; H, 6.51. C23H25OPSi (376.14) re-
J¼8.9 Hz), 131.7, 131.9 (d, J¼11.8 Hz), 132.7 (d, J¼97.5 Hz); 31P NMR
quires C, 73.37; H, 6.69%].
(121 MHz, CDCl3)
d 30.97; [Found: C, 75.21; H, 6.52. C16H17OP
(256.10) requires C, 74.99; H, 6.69%].
Method B. A solution of the -hydroxysilane 2a or 2b (1 mmol) in
xylene (5 mL) was heated to reflux of xylene until the full
4.5.2. (3RS,4SR)-2-Methyl-4-(diphenylphosphanyl)hex-5-en-3-ol
b
(anti-8a). Yield 69 mg (22%); Rf (AcOEt) 0.40; IR (film) 3300, 1440,
1150, 997, 924 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
0.81 (d, J¼5.1 Hz,

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8086
3H), 0.95 (d, J¼5.1 Hz, 3H), 1.82 (m, 1H), 3.25 (dt, J¼2.1, 7.2 Hz, 1H),
3.62 (dt, J¼2.1, 7.5 Hz, 1H), 5.05 (dd, J¼16.3, 2.1 Hz, 1H), 5.23 (dd,
J¼10.4, 3.0 Hz, 1H), 6.10 (ddt, J¼16.3, 10.4, 7.5 Hz, 1H), 7.30e7.92 (m,
The mixture was washed several times with an aqueous solution of
NaHSO3, NaHCO3, and NaCl. The organic layer was dried (MgSO4),
the solvent removed and the residue was purified by chromatog-
10H); 13C NMR (75 MHz, CDCl3)
d
18.5,19.5, 32.2, 47.5 (d, J¼67.0 Hz),
raphy (Silicagel, AcOEt) to give the
(413 mg, 80%) as a colourless oil; Rf (AcOEt) 0.23; 1H NMR
(300 MHz, CDCl3)
2.33 (dt, J¼6.7, 12.2 Hz, 1H), 2.50 (dd, J¼4.5,
2.6 Hz,1H), 2.75 (t, J¼4.5 Hz,1H), 2.81 (ddd, J¼5.4,10.6,12.2 Hz,1H),
3.25 (m, 1H), 7.45e7.81 (m, 10H); 13C NMR (75 MHz, CDCl3)
34.1
b-phosphanylepoxide 11
75.1, 122.1 (d, J¼12.1 Hz), 128.5 (d, J¼16.2 Hz), 129.4 (d, J¼9.5 Hz),
130.1 (d, J¼98 Hz), 131.5 (d, J¼8.2 Hz), 132.7, 143.7; 31P NMR
d
(121 MHz, CDCl3)
d 38.45; [Found: C, 72.81; H, 7.18. C19H23O2P
(314.14) requires C, 72.59; H, 7. 37%].
d
(d, J¼68.5 Hz), 46.6, 47.4 (d, J¼5.1 Hz), 128.7 (d, J¼11.9 Hz), 130.6 (d,
4.5.3. (E)-2-Methyl-6-(diphenylphosphanyl)hex-5-en-3-ol (9a). Yield
J¼10.1 Hz), 132.0, 133.2 (d, J¼88.9 Hz); 31P NMR (121 MHz, CDCl3)
176 mg (56%); Rf (AcOEt) 0.22; IR (film) 3250, 1443, 1125, 920 cmꢁ1
;
d 29.75; [Found: C, 69.58; H, 6.01. C15H15O2P (258.08) requires C,
69.76; H, 5.85%].
1H NMR (300 MHz, CDCl3)
(m,1H), 2.53 (m,1H), 3.55 (m,1H), 6.35 (dd, J¼18.2, 24.0 Hz,1H), 6.82
(m, 1H), 7.43e7.82 (m, 10H); 13C NMR (75 MHz, CDCl3)
17.3, 19.6,
d
0.95 (d, J¼6.1 Hz, 6H), 1.72 (m, 1H), 2.43
d
4.7. Cleavage of the b-phosphanylepoxide 11 with heteronucl
34.2, 39.3 (d, J¼8.2 Hz), 74.1, 124.4 (d, J¼73.2 Hz), 129.5, 130.7, 131.7,
eophiles. General procedure
132.5, 133.7 (d, J¼90.2 Hz), 151; 31P NMR (121 MHz, CDCl3)
d 24.22;
[Found: C, 72.98; H, 7.51C19H23O2P (314.14) requires C, 72.59; H, 7.
37%].
A solution of 11 (1 mmol) in dry THF (5 mL) was added dropwise
to a stirred THF solution of nucleophile (1.5 mol) in THF (5 mL) at
ꢁ78 ꢀC under N2. As nucleophiles were used: lithium butyl(dime-
4.5.4. (1RS,2RS)-1-phenyl-2-(diphenylphosphanyl)but-3-en-1-ol (syn-
8b). Yield 10.5 mg (3%); Rf (AcOEt) 0.45; IR (film) 3300, 1445, 1147,
thylphenylsilyl)cuprate24, lithium butyl (tributylstannyl)cuprate25
,
lithium phenylsulfide [prepared from benzenethiol (0.15 mL,
1.5 mmol) and butyllithium (0.936 mL, 1.6 M solution in hexane,
1.5 mmol) in THF (5 mL) at ꢁ78 ꢀC under N2 for 10 min], lithium
diphenylphosphide [prepared from diphenylphosphine (0.258 mL,
1.5 mmol) and BuLi (0.936 mL, 1.6 M solution in hexane, 1.5 mmol)
in THF (5 mL) at 0 ꢀC under N2 for 30 min] or lithium diisopropy-
lamide [prepared from diisopropyl amine (0.21 mL, 1.5 mmol) and
BuLi (0.936 mL, 1.6 M solution in hexane, 1.5 mmol) in dry THF
(5 mL) at ꢁ20 ꢀC under N2 for 15 min]. The mixture was slowly
allowed to warm to 0 ꢀC and stirred at this temperature, except for
the reaction with LDA (ꢁ78 ꢀC) until TLC indicated complete re-
action (30e60 min). When the reaction was carried out at 0 ꢀC, the
mixture was quenched with aqueous NH4Cl, and with methanol in
the reactions at ꢁ78 ꢀC. The organic layer was extracted with Et2O
and dried with MgSO4, the ethereal solvents were removed under
reduced pressure and the residue chromatographed to give the
following compounds.
990, 930 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
3.55 (ddd, J¼21.8, 9.6,
2.5 Hz, 1H), 4.75 (dd, J¼17.1, 2.3 Hz, 1H), 4.90 (dd, J¼10.2, 2.3 Hz, 1H),
5.05 (t, J¼9.6 Hz,1H), 5.22 (dtd, J¼17.1,10.2, 2.5 Hz,1H), 7.20e7.95 (m,
15H); 13C NMR (75 MHz, CDCl3)
d
53.5 (d, J¼100 Hz), 72.2, 121.6 (d,
J¼9.1 Hz), 126.4, 127.5 (d, J¼10.2 Hz), 128.2, 129.1, 129.6, 131.7 (d,
J¼10.1 Hz), 133.1 (d, J¼90 Hz),142.1 (d, J¼8.3 Hz); 31P NMR (121 MHz,
CDCl3) d 37.33; [Found: C, 75.61; H, 5.91. C22H21O2P (348.13) requires
C, 75.85; H, 6. 08%].
4.5.5. (1RS,2SR)-1-phenyl-2-(diphenylphosphanyl)but-3-en-1-ol
(anti-8b). Yield 17.5 mg (5%); Rf (AcOEt) 0.33; IR (film) 3300, 1445,
1147, 990, 930 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
3.25 (dt, J¼2.1,
6.2 Hz, 1H), 4.71 (dd, J¼8.7, 2.1 Hz, 1H), 5.12 (dd, J¼10.9, 3.5 Hz, 1H),
5.42 (dd, J¼9.6 Hz, 1H), 6.12 (dtd, J¼17.2, 10.9, 6.0 Hz, 1H), 7.20e7.95
(m, 15H); 13C NMR (75 MHz, CDCl3)
d
53.2 (d, J¼66.2 Hz), 71.6, 122.7
(d, J¼11.7 Hz), 126.2, 127.1, 128.5, 129.6 (d, J¼9.5 Hz), 130.9 (d,
J¼97.2 Hz), 131.5 (d, J¼8.3 Hz), 132.0, 133.4, 141.6 (d, J¼8.3 Hz); 31P
NMR (121 MHz, CDCl3)
d
37.55; [Found: C, 76.03; H, 6.2.0.
4.7.1. 2-(Dimethylphenylsilyl)-3-(diphenylphosphanyl)propan-1-ol
C22H21O2P (348.13) requires C, 75.85; H, 6. 08%].
(12a)¼(2a). Yield 205 mg (52%).
4.5.6. (E)-1-phenyl-4-(diphenylphosphanyl)but-3-en-1-ol
4.7.2. 1-(Dimethylphenylsilyl)-3-(diphenylphosphanyl)propan-2-ol
(9b). Yield 272 mg (78%); Rf (AcOEt) 0.18; IR (film) 3250,1445, 1120,
(13a). Yield 55 mg (14%); Rf (AcOEt) 0.39; IR (film) 3200, 1445,
925 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
2.65 (m, 2H), 4.76 (t,
J¼6.2 Hz, 1H), 6.05 (dd, J¼17.3, 24.1 Hz, 1H), 6.65 (m, 1H), 7.24e7.52
(m, 15H); 13C NMR (75 MHz, CDCl3)
1252, 1185, 1110 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.31 (s, 6H), 1.25
(m, 2H), 2.45 (ddd, J¼15.2, 12.4, 1.5 Hz, 1H), 2.55 (ddd, J¼5.4, 15.2,
d
44.3 (d, J¼17.1 Hz), 72.3, 125.2
12.4 Hz, 1H), 4.41 (m, 1H), 7.40e7.70 (m, 15H); 13C NMR (75 MHz,
(d, J¼92.2 Hz), 126.4, 127.6, 128.8, 129.6 (d, J¼9.5 Hz), 130.9 (d,
CDCl3)
J¼11.8 Hz), 129.6, 131.3 (d, J¼8.8 Hz), 131.7, 132.9 (d, J¼94.1 Hz),
142.4; 31P NMR (121 MHz, CDCl3)
35.20; [Found: C, 70.22; H,
d
ꢁ3.6, 18.9, 44.8 (d, J¼65.7 Hz), 71.5, 126.4, 127.2, 128.5 (d,
J¼8.6 Hz), 132.3, 133.1 (d, J¼100 Hz), 143.9, 148.7; 31P NMR
(121 MHz, CDCl3)
d
24.54; [Found: C, 75.68; H, 5.97 C22H21O2P
d
(348.13) requires C, 75.85; H, 7. 08%].
6.78C23H27O2PSi (394.15) requires C, 70.02; H, 6.90%].
4.5.7. (E)-4-(Diphenylphosphanyl)-1-(2-thiazolyl)but-3-en-1-ol
4.7.3. 2-(Tributylstannyl)-3-(diphenylphosphanyl)propan-1-ol
(9c). Yield 266 mg (75%); Rf (AcOEt) 0.12; IR (film) 3250, 1445, 1120,
(12b). Yield 115 mg (21%); Rf (AcOEt) 0.42; IR (film) 3250, 1445,
925 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
2.85 (m, 1H), 3.04 (m, 1H),
1185 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 0.90 (m, 15H), 1.30 (m, 6H),
5.20 (dd, J¼6.2, 5.6 Hz, 1H), 6.38 (dd, J¼18.6, 16.9 Hz, 1H), 6.84 (tt,
1.37 (m, 1H), 1.50 (m, 6H), 2.45 (dt, J¼5.6, 15.4 Hz, 1H), 2.54 (dt,
J¼16.9, 6.2 Hz, 1H), 7.30e7.70 (m, 12H); 13C NMR (75 MHz, CDCl3)
J¼2.2, 5.4 Hz, 1H), 3.75 (m, 2H), 5.65 (sbr, 1H), 7.40e7.54 (m, 10H);
d
42.5 (d, J¼12.1 Hz), 61.5, 119.3, 124.2 (d, J¼89.1 Hz), 125.6 (d,
13C NMR (75 MHz, CDCl3)
d
8.7, 13.5, 18.6, 27.3 (d, JC,Sn¼52.8 Hz),
J¼100 Hz),128.5 (d, J¼11.3 Hz),132.5 (d, J¼8.6 Hz),133.3,142.9,148.5,
29.2 (d, JC,Sn¼19.8 Hz), 30.5 (d, JC,P¼94.6 Hz), 66.0, 128.5 (d,
176.6; 31P NMR (121 MHz, CDCl3)
d
25.62; [Found: C, 64.42; H, 5.27
JC,P¼11.3 Hz),130.5 (d, JC,P¼9.0 Hz), 131.4, 133.6 (d, JC,P¼95.4 Hz); 31
P
C19H18NO2PS (348.13) requires C, 64.21; H, 5.11%].
NMR (121 MHz, CDCl3)
d
36.43 (J P,Sn¼198.0 Hz); [Found: C, 59.32;
H, 8.08. C27H43O2PSn (550.20) requires C, 59.04; H, 7.89%].
4.6. Epoxidation of allylphosphane oxide 3c
4.7.4. 1-(Tributylstannyl)-3-(diphenylphosphanyl)propan-2-ol
MCPBA (3 mmol) and NaHCO3 (4 mmol) were added to a solu-
tion of 3c (2 mmol) in CH2Cl2 (6 mL). The reaction mixture was
stirred at room temperature until TLC indicated complete reaction.
(13b). Yield 352 mg (64%); Rf (AcOEt) 0.44; IR (film) 3350, 1445,
1185 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
0.90 (m, 15H), 1.25 (m, 6H),
1.53 (m, 6H), 1.90 (m, 1H), 2.05 (m, 1H), 2.45 (dt, J¼1.6, 12.4 Hz, 1H),

ꢀ
A.M. Gonzalez-Nogal, P. Cuadrado / Tetrahedron 69 (2013) 8080e8087
8087
2.54 (dt, J¼5.4,12.4 Hz,1H), 4,4 (m,1H), 5.50 (sbr,1H), 7.35e7.64 (m,
10H); 13C NMR (75 MHz, CDCl3)
8.4, 11.2, 13.7, 27.5 (d,
References and notes
d
1. (a) Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley-Interscience: New
York, NY; (b) Engel, R. Handbook of Organophosphorus Chemistry; M. Dekker:
New York, NY; (c) Kafarski, P.; Lejezak, B. Phosphorus Sulfur Relat. Elem. 1991, 63,
193e215; (d) Toy, A. D. F.; Walsh, E. N. Phosphorus Chemistry in Everyday Living;
American Chemical Society: Washington, DC333; (e) Hoagland, R. E. In Bi-
ologically Active Natural Products; Culter, H. G., Ed.; ACS Symposium Series;
American Chemical Society: Washington, DC, 1988; vol. 380, p 182; (f) Hwang,
J. T.; Choi, J. R. Drugs Future 2004, 29, 163e177.
JC,Sn¼53.4 Hz), 29.2 (d, JC,Sn¼19.3 Hz), 34.2 (d, JC,P¼110 Hz), 69.4,
128.7 (d, JC,P¼11.6 Hz), 130.5 (d, JC,P¼98.6 Hz), 132.4 (d, JC,P¼9.4 Hz),
132.6; 31P NMR (121 MHz, CDCl3)
C, 58.71; H, 7.63. C27H43O2PSn (550.20) requires C, 59.04; H, 7.89%].
d
34.23 (JP,Sn¼177.0 Hz); [Found:
4.7.5. 3-(Diphenylphosphanyl)-2-(phenylthio)propan-1-ol
2. See for example: (a) Brown, J. M.; Chaloner, P. A. In Homogeneous Catalysis with
Metal Phosphane Complexes; Fackler, J. P., Jr., Ed.; Plenum: New York, NY, 1983;
pp 137e165; (b) Tang, W. J.; Zhang, X. M. Chem. Rev. 2003, 103, 3029e3069; (c)
Chan, A. C. S.; Au-Yeung, T. T. Coord. Chem. Rev. 2004, 248, 2151e2164; (d) Zhou,
Y. G. Acc. Chem. Res. 2007, 40, 1357e1366.
(12c). Yield 44 mg (12%); Rf (AcOEt) 0.31; IR (CHCl3) 3300, 1440,
1180 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
3.15 (m, 2H), 3.95 (m,1H), 4.25
(dd, J¼2.5, 9.9 Hz, 1H), 4.34 (dd, J¼5.5, 9.9 Hz, 1H), 5.3 (s br, 1H),
7.25e7.82 (m, 15H); 13C NMR (75 MHz, CDCl3)
30.3 (d, J¼65.6 Hz),
d
3. Angell, S. E.; Rogers, C. W.; Zhang, Y.; Wolf, M. O.; Jones, W. E., Jr. Coord. Chem.
Rev. 2006, 250, 1829e1841.
68.8, 69.1,126.0, 128.7 (d, J¼11.6 Hz), 129.5, 130.0 (d, J¼98.6 Hz),130.4
(d, J¼9.4 Hz), 131.9, 133.8, 135.2; 31P NMR (121 MHz, CDCl3)
d 36.62;
4. (a) Mader, M. M.; Bartlett, P. A. Chem. Rev. 1997, 97, 1281e1301; (b) Hanessian,
S.; Rogel, O. J. Org. Chem. 2000, 65, 2667e2674; (c) Bricklebank, N. Organo-
phosphorus Chem. 2003, 33, 289e301; (d) McReynolds, M. D.; Dougherty, J. M.;
Hanson, P. R. Chem. Rev. 2004, 104, 2239e2258; (e) Montchamp, J. L. J. Orga-
nomet. Chem. 2005, 690, 2388e2406; (f) Baumgartner, T.; Reau, R. Chem. Rev.
2006, 106, 4681e4727.
5. For reviews, see: (a) Kafarski, P.; Lejezak, B. Phosphorus Sulfur 1991, 63,
193e215; (b) Hoagland, R. E. In Biologically Active Natural Products; Culter, H. G.,
Ed.; ACS Symposium Series; American Chemical Society: Washington, DC, 1988;
vol. 380, p 182.
[Found: C, 68.66; H, 5. 53. C21H21O2PS (368.10) requires C, 68.46; H,
5.75%].
4.7.6. 1-(Diphenylphosphanyl)-3-(phenylthio)propan-2-ol
(13c). Yield 228 mg (62%); Rf (AcOEt) 0.33; IR (film) 3350, 1440,
1180 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 2.51 (m, 1H), 2.83 (m, 1H),
3.00 (dd, J¼6.0, 14.5 Hz 1H), 3.25 (dd, J¼6.0, 14.5 Hz, 1H), 4.15 (m,
1H), 4.78 (s br, 1H), 7.35e7.80 (m, 15H); 13C NMR (75 MHz, CDCl3)
6. (a) Cuadrado, P.; Gonzalez-Nogal, A. M. Tetrahedron Lett. 1997, 38, 8117e8120;
(b) Cuadrado, P.; Gonzalez-Nogal, A. M.; Sarmentero, M. A. Chem.dEur. J. 2004,
10, 4491e4497.
d
35.5 (d, J¼71.3 Hz), 41.5, 66.5, 69.1, 126.0 (d, J¼14.1 Hz), 128.9 (d,
J¼11.6 Hz), 129.5, 1310 (d, J¼96.1 Hz), 132.4 (d, J¼11.4 Hz), 132.9,
133.6, 137.6; 31P NMR (121 MHz, CDCl3)
35.37; [Found: C, 68.26;
ꢀ
7. Gonzalez-Nogal, A. M.; Cuadrado, P.; Sarmentero, M. A. Eur. J. Org. Chem. 2009,
850e859.
d
8. Gonzalez-Nogal, A. M.; Cuadrado, P. Tetrahedron 2010, 66, 9610e9619.
H, 5. 98. C21H21O2PS (368.10) requires C, 68.46; H, 5.75%].
ꢀ
9. Cuadrado, P.; Gonzalez-Nogal, A. M. Tetrahedron Lett. 2000, 41, 1111e1114.
10. Brook, A. G.; LeGrow, G. E.; MacRae, D. M. Can. J. Chem. 1967, 45, 239e245.
€
11. (a) Holz, J.; Quirmbach, M.; Borner, A. Synthesis 1997, 983e1006; (b) Tannert, R.;
4.7.7. 2,3-Bis(diphenylphosphanyl)propan-1-ol (12d). Yield 345 mg
Pfaltz, A. In Phosphorus (III) Ligands in Homogeneous Catalysis: Design and Syn-
thesis; Kamer, P. C. J., VanLeeuwe, P. W. N. M., Eds.; Wiley: Chichester, UK, 2012;
pp 250e252; (Chapter 6).
(75%); Rf (AcOEt) 0.13; IR (film) 3300, 1445, 1188 cmꢁ1 1H NMR
;
(300 MHz, CDCl3)
d
2.65 (m, 1H), 2.73 (m, 1H), 3.15 (m, 2H), 3.55
27.1 (d,
(m, 1H), 7.36e7.87 (m, 20H); 13C NMR (75 MHz, CDCl3)
d
12. (a) Binns, M. R.; Haynes, R. K.; Katsifis, A. G.; Schober, P. A.; Vonwiller, S. C. J. Am.
Chem. Soc. 1988, 110, 5411e5423; (b) Haynes, R. K.; Katsifis, A. G.; Vonwiller, S.
C.; Hamhley, T. W. J. Am. Chem. Soc. 1988, 110, 5423e5433; (c) Haynes, R. K.;
Voniviller, S. C. J. Chem. Soc., Chem. Commun. 1987, 92e95; (d) Binns, M. R.;
Haynes, R. K.; Katsifis, A. G.; Schoher, P. I.; Vonwiller, S. C. Tetrahedron Lett. 1985,
26, 1565e1568; (e) Haynes, R. K.; Vonwiller, S. C.; Hamhley, T. W. J. Org. Chem.
1989, 54, 5162e5170; (f) Haynes, R. K.; Loughlin, W. A.; Hamhley, T. W. J. Org.
Chem. 1991, 56, 5785e5790; (g) Denmark, S. E.; Kim, J. _H. J. Org. Chem. 1995, 60,
7535e7547; (h) Ruan, W. J.; Hassner, A. Eur. J. Org. Chem. 2001, 7, 1259e1266.
J¼22.3 Hz), 28.3 (d, J¼26.1 Hz), 61.1, 128.7 (d, J¼11.6 Hz), 130.0
(d, J¼98.6 Hz), 131.4 (d, J¼9.4 Hz), 133.7; 31P NMR (121 MHz,
CDCl3)
d
31.64 (d, JP,P¼49.8 Hz), 36.19 (d, JP,P¼49.8 Hz); [Found:
C, 70.26; H, 5.45. C27H26O3P2 (460.14) requires C, 70.43; H,
5.69%].
€
13. Liepins, V.; Karlstrom, A. S. E.; Backvall, J.-E. J. Org. Chem. 2002, 67,
4.7.8. (E)-3-(Diphenylphosphanyl)prop-2-en-1-ol
(14). Yield
2136e2143.
214 mg (83%); Rf (AcOEt) 0.25; IR (film) 3300, 1445, 1188 cmꢁ1; 1H
14. (a) Grayson, J. I.; Warren, S.; Zaslona, A. T. J. Chem. Soc., Perkin Trans. 1 1987,
967e976; (b) Katritzky, A. R.; Piffl, M.; Lang, H.; Anders, E. Chem. Rev. 1999, 99,
665e722.
NMR (300 MHz, CDCl3)
d
4.45 (m, 2H), 6.65 (ddd, J¼26.3, 15.7,
4.1 Hz), 6.92 (dt, J¼15.7, 2.2 Hz), 7.44e7.75 (m, 10H); 13C NMR
15. Ikeda, Y.; Ukai, J.; Ikeda, N.; Yamamoto, H. Tetrahedron 1987, 43, 723e730.
16. Nelson, A.; O’Brien, P.; Warren, S. Tetrahedron Lett. 1995, 36, 2685e2688.
17. Hudrlik, P. F.; Kulkarni, A. K. J. Am. Chem. Soc. 1981, 103, 6251e6253.
18. (a) Hudrlik, P. F.; Peterson, D. Tetrahedron Lett. 1972, 1785e1787; (b) Hudrlik, P.
F.; Peterson, D. Tetrahedron Lett. 1974, 1133e1136; (c) Hudrlik, P. F.; Peterson, D.
J. Am. Chem. Soc. 1975, 97, 1464e1468; (d) Ruden, R. A.; Gaffney, B. L. Synth.
Commun. 1975, 5, 15e19; (e) Utimoto, K.; Obayashi, M.; Nozaki, H. J. Org. Chem.
1976, 41, 2940e2941; (f) Obayashi, M.; Utimoto, K.; Nozaki, H. Tetrahedron Lett.
1977, 4513e4516.
19. Fleming, I.; Newton, T. W. J. Chem. Soc., Perkin Trans. 1 1984, 119e123.
20. Barbero, A.; Cuadrado, P.; Fleming, I.; Gonzalez-Nogal, A. M.; Pulido, F. J.;
Sanchez, A. J. Chem. Soc., Perkin Trans. 1 1995, 1525e1532.
21. Fleming, I.; Newton, T. W.; Roessler, F. J. Chem. Soc., Perkin Trans. 1 1981,
2527e2532.
(75 MHz, CDCl3)
d
62.2 (d, J¼17.1 Hz), 119.7 (d, J¼105.1 Hz), 128.7 (d,
J¼12.2 Hz), 130.9 (d, J¼9.9 Hz), 131.8, 132.3 (d, J¼106.8 Hz), 152.5;
31P NMR (121 MHz, CDCl3)
d
24.54; [Found: C, 69.16; H, 5.64.
C15H15O3P (258.08) requires C, 69.76; H, 5.85%].
Acknowledgements
ꢀ
ꢀ
We thank the Spanish Ministerio de Ciencia y Tecnologia
(MCYT) for supporting this work.
ꢀ
22. Fleming, I.; Rowly, M.; Cuadrado, P.; Fleming, I.; Gonzalez-Nogal, A. M.; Pulido,
F. J. Tetrahedron 1989, 45, 413e424.
23. Barbero, A.; Cuadrado, P.; Fleming, I.; Gonzalez-Nogal, A. M.; Pulido, F. J. J. Chem.
ꢀ
Supplementary data
Soc., Perkin Trans. 1 1991, 2811e2816.
24. Gonzalez-Nogal, A. M.; Calle, M.; Cuadrado, P. Eur. J. Org. Chem. 2007,
ꢀ
6089e6096.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.06.039.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
ꢀ
25. (a) Barbero, A.; Cuadrado, P.; Fleming, I.; Gonzalez-Nogal, A. M.; Pulido, F. J. J.
Chem. Soc., Chem. Commun. 1992, 351e353; (b) Barbero, A.; Cuadrado, P.;
Fleming, I.; Gonzalez-Nogal, A. M.; Pulido, F. J. J. Chem. Soc., Perkin Trans. 1 1993,
1657e1662.
ꢀ