Remarkable tolerance of ethynyl steroids to air and water in microwave-assisted hydrophosphinylation: Reaction scope and limitations

Article abstract of DOI:10.1016/j.jorganchem.2006.06.007

The microwave-assisted hydrophosphinylation of propargyl alcohols has been investigated using group 9 catalysts under solvent-free conditions as well as with pure water, ethyl lactate, or THF as the solvent. Reactions involving simple propargyl alcohols g

Full text of DOI:10.1016/j.jorganchem.2006.06.007

Journal of Organometallic Chemistry 691 (2006) 4042–4053
www.elsevier.com/locate/jorganchem
Remarkable tolerance of ethynyl steroids to air
and water in microwave-assisted hydrophosphinylation:
Reaction scope and limitations
a,
a
a
a
Robert A. Stockland Jr. *, Adam J. Lipman , John A. Bawiec III , Peter E. Morrison ,
b
a
a
Ilia A. Guzei , Peter M. Findeis , John F. Tamblin
a
Department of Chemistry, Bucknell University, 312 Rooke Chemistry, Lewisburg, PA 17837, United States
Molecular Structure Laboratory, Department of Chemistry, University of Wisconsin, Madison, WI 53706, United States
b
Received 18 April 2006; received in revised form 3 June 2006; accepted 3 June 2006
Available online 15 June 2006
Abstract
The microwave-assisted hydrophosphinylation of propargyl alcohols has been investigated using group 9 catalysts under solvent-free
conditions as well as with pure water, ethyl lactate, or THF as the solvent. Reactions involving simple propargyl alcohols gave mixtures
containing significant amounts of elimination products. In contrast, analogous reactions involving ethynyl steroids afforded a single spe-
cies with only trace amounts of elimination products. The molecular structures of several derivatives have been determined and are
discussed.
Ó 2006 Elsevier B.V. All rights reserved.
Keywords: Hydrophosphinylation; Rhodium; Microwave-assisted; Aqueous
1. Introduction
that has been devoted to this chemistry, a number of chal-
lenges still remain. For example, propargyl alcohols are a
particularly problematic class of compounds for metal
catalyzed hydrophosphinylation reactions due to the gener-
ation of a wide range of products. This product distribu-
tion often depends upon the metal catalyst and additives
(Fig. 1). Recently, Uemura et al. found that dinuclear
ruthenium catalysts promoted the conversion of propargyl
alcohols to ethynyl phosphine oxides in 1,2-dichloroethane
[12]. Han et al. recently reported that a nickel catalyst gen-
erated mixtures of phosphinoyl 1,3-butadienes and alkenyl
phosphine oxides in THF [13]. Tanaka et al. has shown
that Wilkinson’s catalyst promoted the addition of a pina-
col derived hydrogen phosphonate to 2-methyl-3-butyn-2-
ol in THF [14].
The development of organometallic reactions that pro-
ceed in water as well as other ‘‘green’’ solvents is a current
and challenging goal [1,2]. Recent developments include
the synthesis of small molecules and polymeric materials
through Suzuki-type coupling reactions [3,4], the aqueous
phase reduction of ketones and aldehydes [5], and the use
of a sulfonated XANTPHOS ligand for a regioselective
hydroformylation reaction in water [6]. Additionally, water
is an attractive solvent for microwave-assisted chemistry
due to its high absorption of microwave radiation.
The transition metal catalyzed addition of P(O)–H
bonds to alkenes and alkynes is a powerful way to generate
P–C bonds [7–11]. Despite the intense amount of research
Ethynyl steroids are a particularly attractive class of
propargyl alcohols. The development of methodology for
the functionalization of ethynyl steroids is an important
*
Corresponding author. Tel.: +1 570 577 1665; fax: +1 570 577 1739.
E-mail address: rstockla@bucknell.edu (R.A. Stockland Jr.).
0022-328X/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.06.007

R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
4043
O
PPh2
dinuclear
Ru-catalysts
OH
O
O
Ni(PMe2Ph)4
PPh2
PPh2
+
Ph2P(O)(OH)
THF
H
O
mononuclear
Rh-based
catalyst
Ph2P
OH
E/Z = 75:25
Fig. 1. Addition of diphenylphosphine oxide to 2-methyl-3-butyn-2-ol with different catalysts and additives.
area of research since steroid derivatives often exhibit a
high degree of biological activity [15,16]. For example,
sulfonylpyrazole and related derivatives of ethisterone are
anti-androgenic agents [17,18] and arylated ethisterone spe-
cies are modulators of ion channels in the mammalian
brain (c-aminobutyric acid receptors) [19]. Recent reports
on ethynyl steroid functionalization have focused on the
reactivity of the acetylenic hydrogen and include the Sono-
gashira coupling of ethynyl steroids with aryl halides [20],
the palladium catalyzed amination of estrone [21], and
the synthesis of estradiol-based pincer compounds [22].
The latter are attractive agents for the targeted cellular
delivery of platinum to cancerous tissues that are rich in
estrogen receptors. As part of our continuing studies on
the development of microwave-assisted approaches for
the formation of carbon-heteroelement bonds [23], we have
investigated the addition of P(O)–H bonds to simple prop-
argyl alcohols as well as ethynyl steroids under solvent-free
conditions and with water, THF, or ethyl lactate as the
solvent.
3-butyn-2-ol gave mixtures of addition and elimination
products when common homogenous catalysts such as
[Rh(cod)Cl]2 and (Ph3P)3RhCl were used. Similar results
were
obtained
when
the
Rh(III)
precatalyst
(Me2PhP)3RhMe3 [24] was employed. Extensive manipula-
tion of the catalyst loading, reaction temperature, and the
presence or absence of solvent only changed the ratio of
the products. Propargyl alcohol does not have the problem
of elimination, however, analogous reactions using this
substrate afforded a reaction mixture with 12 resonances
in the 31P{1H} NMR spectrum with less than 40% conver-
sion into the desired phosphine oxide. In contrast to the
problematic addition/elimination chemistry exhibited by
simple propargyl alcohols, an ethynyl steroid (ethisterone)
was cleanly hydrophosphinylated using (Me2PhP)3-
RhMe3 as the precatalyst. While the precise rationale for
this observation is unknown, the conformational restric-
tion of the steroid ring system as well as the syn-methyl
group is likely to play a role. Remarkably, the reactions
could be carried out under an atmosphere of air with no
precautions for the removal of oxygen. High yielding sol-
vent-free reactions were also carried out using the model
system of ethisterone and HP(O)Ph2. Similar to the aque-
ous reactions, the solvent-free processes could be carried
out under an atmosphere of air without significant
decreases in yield. Analysis of the crude reaction mixture
by 31P NMR spectroscopy revealed only small amounts
of rearrangement, dehydration, or elimination products
(totaling less than 5%). For comparison, the addition reac-
tion was carried out using conventional heating in water as
well as THF. After dunking the reaction mixtures into a
preheated oil bath at 150 °C and stirring for 10 min, anal-
ysis of the crude reaction mixtures revealed the desired
alkenyl phosphine oxide (water, 64%; THF, 72%). As part
of the preliminary investigation, analogous reactions were
carried out using (Ph3P)3RhBr according to Tanakas
2. Results and discussion
To determine an effective catalyst system for the micro-
wave-assisted addition of P(O)–H bonds to propargyl alco-
hols using water as the solvent, a number of group 9
catalysts were screened for activity. Palladium, nickel,
and dinuclear ruthenium catalysts were not selected for
the microwave-assisted reactions since significant amounts
of competing elimination, dehydration, and rearrangement
reactions were observed in conventionally heated reactions
(Fig. 1) using these catalysts. Cyclic and acyclic propargyl
alcohols as well as secondary systems were investigated
using HP(O)Ph2 as the source of the R2P(O)–H unit (Table
1). Using microwave heating, reactions involving simple
substrates such as 1-ethynyl-1-cyclohexanol and 2-methyl-

4044
R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
protocol.8 After stirring ethisterone with HP(O)Ph2 using
(Ph3P)3RhBr as the catalyst in toluene for 1 h, analysis of
the reaction mixture revealed only a 5% conversion into
the desired alkenyl phosphonate. This lack of reactivity
could be due to the limited solubility of the ethynyl steroid
in toluene. Control reactions revealed no consumption of
HP(O)Ph2 in reactions without a metal catalyst.
Since the hydrophosphinylation reactions were selective
and high yielding with ethisterone, these atom-efficient
transformations were extended to mestranol and ethynyl
estradiol as well as 6H-dibenz[c,e][1,2]oxaphosphorin,6-
oxide (DOPO) and ethyl phenylphosphinate (Table 2).
Similar to reactions with HP(O)Ph2, the microwave-
assisted additions of DOPO to ethynyl steroids were rapid
and moderate yields of the desired alkenyl phosphinates
were obtained. For comparison, reactions were carried
out under solvent-free conditions as well as with THF or
(À)-ethyl L-lactate as the solvent. (À)-Ethyl L-lactate is a
biodegradable solvent with an attractive temperature range
(boiling point = 154 °C) that has replaced a number of sol-
vents such as methyl ethyl ketone and methyl isobutyl
ketone in organic transformations [25]. The addition reac-
tions were rapid and high yielding with diphenylphosphine
oxide and DOPO using (Me2PhP)3RhMe3 as the precata-
lyst with microwave heating. Similar to reactions carried
out in water, the reactions were insensitive to air and mod-
erate to high yields of the alkenyl phosphine oxides and
phosphinates were obtained. The solvent-free reactions
were successful using (Ph3P)3RhCl as the catalyst. A simple
trituration was the only purification step that was needed
to isolate the desired addition product. Analogous reac-
tions using ethyl phenylphosphinate were challenging,
and after an extensive number of catalysts and solvents
were screened, moderate yields of the addition products
were observed when THF was used as the solvent with
[Rh(cod)Cl]2 as the catalyst. However, lower yields were
obtained in pure water or under solvent-free conditions.
The resulting functionalized steroids were isolated as
successful white solids. The retention of the 17a-OH was
the most important factor when catalyst systems were
screened since previous studies demonstrated that this
group was critical to the binding of the steroid to the estro-
gen receptor hormone binding domain [26]. The 17-OH
group remained intact in these reactions and was observed
Table 1
a
Microwave-assisted reaction of propargyl alcohols with HP(O)Ph2
P(O)Ph2
OH
OH
R
Rh catalyst
R
+
P(O)Ph2
water
HP(O)Ph2
MW
R
R
R
A
B
#
1
Propargyl alcohol
Catalystb
Product Ac
Product Bc
(Ph3P)3RhCl
[Rh(cod)Cl]2
(Me2PhP)3RhMe3
40
31
26
25
22
30
OH
Me
Me
2
(Ph3P)3RhCl
[Rh(cod)Cl]2
(Me2PhP)3RhMe3
48
25
31
32
19
25
OH
3
4
(Ph3P)3RhCl
[Rh(cod)Cl]2
(Me2PhP)3RhMe3
58
41
55
20
30
21
OH
Me
H
(Ph3P)3RhCl
[Rh(cod)Cl]2
(Me2PhP)3RhMe3
35
39
86
10
5
1
Me OH
Me
O
Reactions carried out in pure water (1.5 mL) using 0.32 mmol of propargyl alcohol and HP(O)Ph2.
a
b
c
3 mol% (stable Rh). The reactions were irradiated for 15 min at 150 °C using 70–100 W of microwave power.
The listed yields of the products in these screening reactions were determined by integration of the appropriate resonances in the 1H and 31P NMR
spectra using hexamethylbenzene and triphenylphosphine oxide as internal standards.

R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
4045
Table 2
Microwave-assisted functionalization of ethynyl steroids
O
P
R
OH
O
P
Ph
OH
Me
Me
H
R
H
Ph
Rh catalyst
MW
H
#
1
Steroid
Product
Solvent-freea,f
80
Waterb,f
79
THFc,f
86
Ethyl lactated,f
80
Ethisterone
1
Me OH
O
PPh2
Me
O
2
Ethynyl estradiol
2
83
75
85
71
OH
Me
O
PPh
2
HO
3
Mestranol
3
85
81
80
73
O
PPh2
OH
Me
MeO
4
Ethisterone
4
21e (1:1.1)
11e (1:1.1)
55g (1:1.2)
25e (1:1.1)
OH
Me
O
P
O
Me
O
5
6
Ethynyl estradiol
5
17e (1:1.3)
12e (1:1.1)
41g (1:1)
21e (1:1.2)
O
P
OH
Me
O
HO
Mestranol
6
35e (1:1.2)
25e (1:1.1)
58g (1:1.5)
34e (1:1.1)
OH
Me
O
O
P
MeO
7
8
Ethisterone
7
35 (1:1.5)
42 (1:1.4)
53 (1:1.3)
50 (1:1.5)
Me OH
O
P
O
Me
O
Ethynyl estradiol
8
41 (1:1.2)
57 (1:1.3)
65 (1:1)
49 (1:1.5)
O
P
OH
Me
O
HO
(continued on next page)

4046
R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
Table 2 (continued)
#
9
Steroid
Product
Solvent-freea,f
45 (1:1.3)
Waterb,f
THFc,f
Ethyl lactated,f
45 (1:1.2)
Mestranol
9
50 (1:1.7)
60 (1:1.2)
MeOH
O
P
O
MeO
Equimolar ratios of phosphine oxide and ethynyl steroid were used in all experiments.
a
Neat reagents (60 min, 125 °C), (Ph3P)3RhCl (1.7 mol%).
1.5 mL of water as the solvent (10–15 min, 150 °C), (Me2PhP)3RhMe3 (3.1 mol %).
1.0–3.0 mL of THF as the solvent (10–15 min, 150 °C), (Ph3P)3RhCl (1.7 mol%).
0.4–1.0 mL of (À)-ethyl L-lactate as the solvent (20 min, 120–150 °C), (Me2PhP)3RhMe3 (3.1 mol%).
Determined by 1H or 31P{1H} NMR spectroscopy using appropriate internal standards.
Yields are based upon isolated material.
b
c
d
e
f
g
[Rh(cod)Cl]2 (1.3 mol%) was used as the catalyst in these reactions. The numbers in parenthesis refer to the ratio of diastereomers as determined by
quantitative 31P{1H} NMR spectroscopy. The microwave power levels needed to maintain the desired temperatures were: solvent-free (70–90 W), water
(70–80 W), THF (210–280 W), ethyl lactate (20–75 W).
1
˚
as a singlet in the H NMR spectrum (5.04 ppm for 1;
DMSO-d6). Compounds 1–9 gave strong M + H+ peaks
for the title compounds in electrospray ionization mass
tance (1.314(5) A) is lengthened relative to free
˚
˚
ethisterone (1.171 A) [29] and mestranol (1.176 A) [30].
An analysis of the packing revealed that 1 crystallized as
1
spectrometric (ESI-MS) studies. Analysis of the H NMR
spectra revealed that only the (E)-1,2 substituted com-
pounds were formed [27,28]. No dehydrated, vinylidene,
or Z-isomers were isolated from these experiments. Due
to the chiral phosphorus centers in 4–9, diastereomers
resulted from the addition reaction. The diastereomeric
ratio was readily determined from the 31P{1H} NMR spec-
trum. Although the resolved (À)-ethyl L-lactate was used as
the solvent in several reactions, the addition process was
not diastereoselective.
3. Molecular structures of hydrophosphinylated steroids
Long needles of 1 and 2 were obtained by slow diffusion
of pentane into solutions containing 1 and 2. Compound 1
crystallizes in the chiral space group P21 with one molecule
of crystallization solvent (C6H6) per 1. The molecular
structures of 1 and 2 are shown in Fig. 2, and the extended
structures are displayed in Figs. 3 and 4. The crystallo-
graphic parameters are listed in Table 3. For 1, the E
stereochemistry and regioselectivity about the alkene frag-
ment are evident from the diagrams, and the –C@C– dis-
Fig. 3. The polymeric structure of 1 showing the hydrogen bonding
between the phosphoryl oxygen and the 17-OH. Thermal ellipsoids are
shown at 50% probability.
Fig. 2. Molecular structures of 1 and 2. Thermal ellipsoids are shown at 50% probability.

R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
4047
Fig. 4. The repeat unit from the polymeric framework of 2. Thermal ellipsoids are shown at 50% probability.
a 1-dimensional polymer linked by hydrogen bonds
between the phosphoryl oxygen and the 17-OH of an
adjacent molecule. Compound 2 crystallizes in the non-
centrosymmetric space group P212121 with no solvent of
crystallization. In contrast to the packing found in 1, com-
pound 2 exists as a 3-dimensional framework with each
repeat unit comprised of three molecules of 2. The individ-
ual units are held together by a bifurcated hydrogen bond
between the phosphoryl oxygen, the 17-OH, and the 3-OH
of the 3 adjacent molecules of 2 [31].
In summary, although simple propargyl alcohols gener-
ated mixtures of products in microwave-assisted hydropho-
sphinylation reactions, analogous reactions involving
ethynyl steroids cleanly generated a single product under
a variety of conditions. The aqueous catalytic reactions
involving ethynyl steroids were also remarkably tolerant
to oxygen and could be carried out under an atmosphere
of air with no precaution for the removal of oxygen.
4. Experimental
General considerations. Coupling reactions were carried
out under an atmosphere of air. Diethyl ether, dichloro-
methane, and hexane were dried using a Grubbs-style sol-
vent purification system. THF was dried by distillation
from Na/benzophenone. Mestranol, ethynyl estradiol,
ethisterone, diphenylphosphine oxide, DOPO, and ethyl
phenylphosphinate were obtained from Aldrich and used
as received. All yields are based upon isolated material
unless specified. Electrospray ionization mass spectromet-
ric (ESI-MS) data were recorded on a SCIEX Model API
III+ operating in positive ion mode using acetonitrile as
the solvent. Elemental analyses were performed by Mid-
west Microlabs. 1H and 13C{1H} chemical shifts were
determined by reference to residual protonated solvent res-
onances. All coupling constants are given in Hertz.
31P{1H} NMR spectra were referenced to external H3PO4
(0 ppm). Quantitative 31P{1H} NMR spectra were col-
lected using an inverse-gated decoupling sequence with a
recycle delay of 30 s. Ionizable hydrogens were identified
using acetone-d6 or DMSO-d6 as the solvent. Microwave
catalyzed reactions were carried out in 10 mL pressure
tubes using a CEM Discover microwave reactor.
Table 3
Crystal data and structure refinement for 1 and 2
Compound
1
2
Formula
C
39H45O3P
C32H35O3P
498.57
Orthorhombic
P212121
9.1595(11)
13.2685(16)
22.093(3)
90
Formula weight
Crystal system
Space group
592.72
Monoclinic
P21
6.1340(13)
24.554(5)
10.957(2)
90
˚
a (A)
˚
b (A)
˚
c (A)
a (°)
4.1. Preparation of 1 (solvent-free)
b (°)
c (°)
104.523(3)
90
90
90
A microwave reactor vial was charged with ethisterone
(0.10 g, 0.32 mmol), (Ph3P)3RhCl (0.005 g, 5.4 lmol), a
magnetic stirring bar, and HP(O)Ph2 (0.065 g, 0.32 mmol).
The vial was sealed, placed in the reactor, and irradiated.
The microwave power was maintained between 70 and
75 W for the duration of the experiment. The desired tem-
perature (125 °C) was reached after 5.0 min. After a total
of 60 min irradiation, the vial was cooled to ambient tem-
perature and triturated twice with diethyl ether (6 mL)
Temperature (K)
V (A )
Z
100(2)
1597.6(6)
2
26.43
1.232
18220
6411
0.0644
À0.01(13)
0.996
100(2)
2685.1(6)
4
26.41
1.233
14767
5476
0.0381
À0.04(8)
1.030
3
˚
hmax (°)
D(calcd) (Mg mÀ3
)
No. of reflections collected
No. of independent reflections
R (I > 2r(I))
Absolute structure parameters
GOF

4048
R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
containing 9 drops of CH2Cl2. The solid was collected and
dried under vacuum to afford 0.13 g (80%) of the title com-
pound. Anal. Calc. for C33H39O3P: C, 77.02; H, 7.64.
Found: C, 76.70; H, 7.46. ESI-MS: m/z = 515 (M + H+).
1H NMR (CDCl3, 25 °C): d 7.70–7.64 (m, 4H, Ar-H),
7.52–7.41 (m, 6H, Ar-H), 7.05 (dd, 1H, J = 20.2, 16.4,
@CH–), 6.51 (dd, 1H, J = 27.0, 16.3, @CH–), 5.72 (s,
1H, @CH–), 2.37–2.29 (m, 6H, –CH– or –CH2–), 2.00–
1.33 (m, 11H, –CH– or –CH2–), 1.17 (m, 3H, –CH3),
0.98 (s, 3H, –CH3), 0.98–0.80 (m, 2H, –CH– or –CH2–).
1H NMR (acetone-d6, 25 °C, only alcohols listed): d 5.04
(br s, –OH). 13C{1H} NMR (CDCl3, 25 °C): d 199.5 (s,
C@O), 170.9 (s, quat), 155.6 (d, J = 2.4, –C@CP(O)–),
133.2 (d, J = 105.3, ipso–C6H5), 133.18 (d, J = 105.3,
ipso–C6H5), 131.8 (d, J = 3.1, Ar-C), 131.7 (d, J = 3.1,
Ar-C), 131.2 (d, J = 5.4, Ar-C), 131.1 (d, J = 5.2, Ar-C),
128.5 (d, J = 11.5, Ar-C), 123.9 (s, @CH–), 117.9 (d,
J = 101.9, –C@CP(O)–), 84.8 (d, J = 14.5, quat), 53.1 (s,
–CH–), 50.0 (s, –CH–), 47.3 (d, J = 1.0, quat), 38.5 (s,
–CH2–), 37.3 (s, quat), 36.3 (s, –CH–), 35.6 (s, –CH2–),
33.9 (s, –CH2–), 32.7 (s, –CH2–), 32.3 (s, –CH2–), 31.5 (s,
–CH2–), 23.8 (s, –CH2–), 20.6 (s, –CH2–), 17.4 (s, –CH3),
14.2 (s, –CH3). 31P{1H} NMR (CDCl3, 25 °C): d 22.9 (s).
125.6 (s, Ar-C), 116.1 (d, J = 102.6, –C@CP–), 115.3 (s,
Ar-C), 112.4 (s, Ar-C), 85.3 (d, J = 14.3, quat), 49.5 (s,
–CH–), 47.6 (s, quat), 41.8 (s, –CH–), 38.8 (s, –CH–),
38.1 (s, –CH2–), 32.3 (s, –CH2–), 29.6 (s, –CH2–), 27.1 (s,
–CH2–), 25.7 (s, –CH2–), 23.5 (s, –CH2–), 14.1 (s, –CH3).
31P{1H} NMR (CDCl3, 25 °C): d 24.2 (s).
4.3. Preparation of 3 (in water)
A microwave reactor vial was charged with mestranol
(0.10 g, 0.32 mmol), (Me2PhP)3RhMe3 (0.006 g, 10 lmol),
a magnetic stirring bar, HP(O)Ph2 (0.064 g, 0.32 mmol),
and water (1.5 mL). The reactor vial was sealed, placed
in the reactor, and irradiated. The microwave power
was held at 150 W until the desired temperature
(150 °C) was reached (2.2 min). The microwave power
was reduced to 70–80 W for the remainder of the experi-
ment in order to maintain the temperature. After a total
irradiation time of 10 min, the reaction mixture was
cooled to ambient temperature and extracted with
CH2Cl2. After drying the organic layer with MgSO4, the
volatiles were removed under vacuum, and the residue
was triturated twice with diethyl ether (6 mL) containing
9 drops of CH2Cl2. The solid was collected and dried
under vacuum to afford 0.134 g (81%) of the title com-
pound. Anal. Calc. for C33H37O3P: C, 77.32; H, 7.28.
Found: C, 77.08; H, 7.15. ESI-MS: m/z = 513
(M + H+). 1H NMR (CDCl3, 25 °C): d 7.74–7.67 (m,
4H, Ar-H), 7.54–7.43 (m, 6H, Ar-H), 7.17 (d, 1H,
J = 9.0, Ar-H), 7.13 (dd, 1H, J = 19.8, 16.7,
–HC@CHP(O)–), 6.70 (dd, 1H, J = 8.5, 2.7, Ar-H), 6.63
(d, 1H, J = 2.7, Ar-H), 6.54 (dd, 1H, J = 27.2, 16.8,
–HC@CHP(O)–), 3.78 (s, 3H, –OMe), 2.84 (m, 2H,
–CH2–), 2.27–1.21 (m, 13H, –CH2–, –CH–), 0.97 (s, 3H,
4.2. Preparation of 2 (in water)
A microwave reactor vial was charged with ethynyl
estradiol (0.10 g, 0.34 mmol), (Me2PhP)3RhMe3 (0.006 g,
10 lmol), a magnetic stirring bar, HP(O)Ph2 (0.068 g,
0.34 mmol), and water (1.5 mL). The vial was sealed,
placed in the reactor, and irradiated. The microwave power
was held at 150 W until the desired temperature (150 °C)
was reached (2.0 min). The microwave power was
decreased to 70–85 W for the remainder of the experiment
in order to maintain the temperature. After a total irradia-
tion time of 10 min, the reaction mixture was cooled and
extracted with CH2Cl2. After drying the organic layer with
MgSO4, the volatiles were removed under vacuum, and the
residue was triturated twice with diethyl ether (6 mL) con-
taining 9 drops of CH2Cl2. The solid was collected and
dried under vacuum to afford 0.126 g (75%) of the title
compound. Anal. Calc. for C32H35O3P: C, 77.09; H, 7.08.
Found: C, 77.15; H, 7.09. ESI-MS: m/z = 499 (M + H+).
1H NMR (CDCl3, 25 °C): d 7.78–7.70 (m, 4H, Ar-H),
7.57–7.47 (m, 6H, Ar-H), 7.31 (dd, 1H, J = 20.3, 16.8,
@CH–), 6.84 (d, 1H, J = 8.4, Ar-H), 6.70 (dd, 1H, J =
8.4, 2.4, Ar-H), 6.60 (m, 1H, Ar-H), 6.59 (dd, 1H,
J = 30.3, 16.8, @CH–), 2.80–2.62 (m, 2H, –CH– or
–CH2–), 2.09–1.64 (m, 5H, –CH– or –CH2–), 1.44–1.20
(m, 6H, –CH– or –CH2–), 0.99 (m, 2H, –CH– or –CH2–),
0.87 (s, 3H, –CH3). 1H NMR (acetone-d6, 25 °C, only
–OH groups): d 8.87 (br s, –OH), 4.17 (s, –OH). 13C{1H}
NMR (CDCl3, 25 °C): d 156.5 (d, J = 2.5, C@CP–),
155.3 (s, quat), 137.5 (s, quat), 132.9 (d, J = 110.2, Ar-C),
132.8 (d, J = 110.1, Ar-C), 132.0 (d, J = 2.9, Ar-C), 131.9
(d, J = 3.1, Ar-C), 131.2 (d, J = 10.1, Ar-C), 131.0 (s,
quat), 128.8 (d, J = 7.5, Ar-C), 128.6 (d, J = 7.5, Ar-C),
1
–CH3). H NMR (acetone-d6, 25 °C, only –OH groups):
d 3.90 (br s, –OH). 13C{1H} NMR (CDCl3, 25 °C): d
157.4 (s, quat), 155.9 (d, J = 2.6, –C@CHP(O)–), 137.9
(s, quat), 133.3 (d, J = 105.1, ipso-C6H5), 133.27 (d,
J = 105.1, ipso-C6H5), 132.4 (s, quat), 131.8 (d, J = 3.0,
Ar-C), 131.6 (d, J = 3.0, Ar-C), 131.3 (d, J = 6.9, Ar-C),
131.2 (d, J = 6.6, Ar-C), 128.6 (d, J = 12.2, Ar-C), 126.3
(s, Ar-C), 118.0 (d, J = 102.1, =CHP(O)–), 113.8 (s, Ar-
C), 111.5 (s, Ar-C) 85.1 (d. J = 14.5, –COH), 55.2 (s,
–OMe), 49.6 (s, –CH–), 47.7 (s, quat), 43.4 (s, –CH–),
39.4 (s, –CH–), 37.5 (s, –CH2–), 32.7 (s, –CH2–), 29.7
(s, –CH2–), 27.4 (s, –CH2–), 26.2, (s, –CH2–), 23.5 (s,
–CH2–), 14.2 (s, –CH3). 31P{1H} NMR (CDCl3, 25 °C):
d 23.2 (s).
4.4. Preparation of 4 (in THF)
A microwave reactor vial was charged with ethisterone
(0.10 g, 0.32 mmol), [Rh(cod)Cl]2 (0.002 g, 4.1 lmol),
HP(O)(OEt)Ph (48.3 lL, 0.32 mmol), a magnetic stirring
bar, and THF (3.0 mL). The vial was sealed, placed in
the reactor, and irradiated for a total of 10 min. The micro-
wave power was held at 220 W (3.0 min) until the desired

R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
4049
temperature was reached (150 °C). The microwave power
decreased to 200–210 W for the remainder of the run to
maintain the temperature. The vial was cooled to ambient
temperature and the volatiles were removed under vacuum.
The title compound was isolated as a colorless solid
(0.085 g, 55%; 1:1.2 ratio of diastereomers) after purifica-
tion of the reaction residue by column chromatography
(silica gel, 30% THF in Et2O). Anal. Calc. for
C29H39O4P: C, 72.18; H, 8.15. Found: C, 71.90; H, 8.14.
6.84–6.55 (m, 3H, Ar-H), 4.18–3.99 (m, 2H, –OCH2–),
2.80–2.62 (m, 2H, –CH– or –CH2–), 2.09–1.64 (m, 5H,
–CH– or –CH2–), 1.44–0.99 (m, 13H, –CH– or –CH2–),
0.87 (s, 3H, –CH3). 1H NMR (acetone-d6, 25 °C, only
–OH groups): d 9.00 (br s, –OH), 4.20 (s, –OH). 13C{1H}
NMR (both diastereomers, CDCl3, 25 °C): d 157.7 (d,
J = 5.4, @CH), 157.5 (d, J = 5.4, @CH), 154.70 (s, quat),
154.67 (s, quat), 142.8 (s, quat), 137.6 (s, quat), 132.8 (d,
J = 66.8, quat), 132.7 (d, J = 66.7, quat), 132.4 (d, J =
2.8, Ar-H), 132.3 (d, J = 3.7, Ar-H), 131.18 (d, J = 10.3,
Ar-H), 131.13 (d, J = 10.4, Ar-H), 128.69 (d, J = 18.5,
Ar-H), 128.5 (d, J = 18.9, Ar-H), 125.8 (s, Ar-H), 115.4
(d, J = 136.9, @CH), 115.3 (s, Ar-H), 115.2 (d, J = 136.9,
@CH), 112.4 (s, Ar-H), 84.1 (d, J = 4.9, quat), 84.9 (d,
J = 4.8, quat), 61.33 (d, J = 5.8, –OCH2–), 61.25 (d, J =
5.8, –OCH2–), 49.5 (s, –CH–), 47.6 (s, quat), 47.5 (s, quat),
42.1 (s, –CH–), 42.0 (s, –CH–), 38.9 (s, –CH–), 38.1 (s,
–CH2–), 37.9 (s, –CH2–), 32.4 (s, –CH2–), 32.2 (s,
–CH2–), 29.9 (s, –CH2–), 27.1 (s, –CH2–), 25.8
(s, –CH2–), 25.7 (s, –CH2–), 23.4 (s, –CH2–), 16.43 (d,
J = 6.7, –CH3), 16.39 (d, J = 6.7, –CH3), 14.1 (s, –CH3).
31P{1H} NMR (both diastereomers, CDCl3, 25 °C): d
32.8 (s, one diastereomer), 31.9 (s, second diastereomer).
1
ESI-MS: m/z = 484 (M + H+). H NMR (both diastereo-
mers, CDCl3, 23 °C): d 7.80 (m, 2H, Ar-H), 7.49 (m, 3H,
Ar-H), 6.99 (dd, 1H, J = 20.8, 17.0, @CH–), 6.16 (dd,
J = 17.0, 23.5, @CH–), 6.14 (dd, J = 17.0, 24.0, @CH–),
5.74 (s, 1H, @CH–), 4.05 (m, 2H, –OCH2CH3), 2.37 (m,
4H, –CH2–, –CH–), 2.10–0.85 (m, 15H, –CH2–, –CH–),
1.32 (t, 3H, J = 7.0, –OCH2CH3), 1.19 (s, –CH3), 1.17 (s,
–CH3), 0.97 (s, –CH3), 0.95 (s, –CH3). 1H NMR (ace-
tone-d6, 25 °C, only alcohols listed): d 4.11 (br s, –OH,
one diastereomer), 3.79 (br s, –OH, second diastereomer).
13C{1H} NMR (both diastereomers, CDCl3, 25 °C): d
199.4 (s, –C@O), 170.7 (s, quat), 155.9 (d, J = 4.9, –C@
CP(O)), 155.8 (d, J = 4.7, –C@CP(O)), 132.1 (d, J = 2.6,
Ar-C), 131.54 (d, J = 136.4, quat), 131.51 (d, J = 136.7,
quat), 131.3 (d, J = 10.2, Ar-C), 131.2 (d, J = 10.2, Ar-
C), 128.5 (d, J = 13.2, Ar-C), 123.9 (s, Ar-C), 117.3 (d,
J = 136.3, –C@CP(O)), 84.6 (d, J = 16.1, quat), 84.5 (d,
J = 16.4, Ar-C), 60.7 (d, J = 5.9, –OCH2CH3), 53.2 (s,
–CH–), 53.1 (s, –CH–), 50.0 (s, –CH–), 47.2 (s, quat),
47.1 (s, quat), 38.5 (s, quat), 37.2 (m, –CH2–), 36.3 (s,
–CH–), 35.6 (s, –CH2–), 33.9 (s, –CH2–), 32.7 (s, –CH2–),
32.3 (s, –CH2–), 32.2 (s, –CH2–), 31.5 (s, –CH2–), 23.7 (s,
–CH2–), 20.6 (s, –CH2–), 20.5 (s, –CH2–), 17.3 (s, –CH3),
16.51 (d, J = 7.7, –CH2CH3), 16.48 (d, J = 6.7, –CH2CH3),
14.2 (s, –CH3). 31P{1H} NMR (both diastereomers,
CDCl3, 25 °C): d 30.14 (s, one diastereomer), 30.10 (s, sec-
ond diastereomer).
4.6. Preparation of 6 (in THF)
A microwave reactor vial was charged with mestranol
(0.10 g, 0.32 mmol), [Rh(cod)Cl]2 (0.002 g, 4.1 lmol),
HP(O)(OEt)Ph (48.3 lL, 0.32 mmol), a magnetic stirring
bar, and THF (3.0 mL). The vial was sealed, placed in
the reactor, and irradiated for a total of 10 min. The micro-
wave power was held at 220 W (3.0 min) until the desired
temperature was reached (150 °C). The microwave power
was decreased to 210 W for the remainder of the run to
maintain the temperature. The vial was cooled to ambient
temperature and the volatiles were removed under vacuum.
The title compound was isolated as a colorless solid
(0.090 g, 58%; 1:1.5 ratio of diastereomers) after purifica-
tion of the reaction residue by column chromatography
(silica gel, THF/Et2O 3:10). Anal. Calc. for C29H37O4P:
C, 72.48; H, 7.76. Found: C, 72.26; H, 8.04. ESI-MS:
m/z = 482 (M + H+). 1H NMR (both diastereomers,
CDCl3, 25 °C): d 7.80 (m, 2H, Ar-H), 7.47 (m, 3H, Ar-
H), 7.18 (m, 1H, Ar-H), 7.08 (dd, 1H, J = 20.4, 16.2,
@CH–), 6.70 (m, 1H, Ar-H), 6.64 (m, 1H, Ar-H), 6.193
(dd, J = 23.5, 16.9, @CH–), 6.190 (dd, J = 24.3, 16.8,
@CH–), 4.03 (m, 2H, –OCH2CH3), 3.78 (s, –OCH3), 3.77
(s, –OCH3), 2.85 (m, 2H, –CH– or –CH2–), 2.17–1.26 (m,
13 H, –CH–, –CH2–), 1.34 (t, J = 7.0, –OCH2CH3), 1.33
(t, J = 7.0, –OCH2CH3), 0.96 (s, –CH3), 0.94 (s, –CH3).
1H NMR (both diastereomers, acetone-d6, 25 °C, only
–OH groups): d 4.40 (br s, –OH). 13C{1H} NMR (both
diastereomers, CDCl3, 25 °C): d 157.4 (s, quat), 156.4 (d,
J = 4.7, –C@CP(O)), 156.3 (d, J = 4.6, –C@CP(O)), 137.9
(s, quat), 132.4 (s, quat), 132.3 (s, quat), 132.1 (d, J =
2.8, Ar-C), 131.61 (d, J = 136.9, quat), 131.59 (d,
J = 137.2, quat), 131.26 (d, J = 9.9, Ar-C), 131.24 (d,
4.5. Preparation of 5 (in THF)
A microwave reactor vial was charged with ethynyl
estradiol (0.10 g, 0.34 mmol), [Rh(cod)Cl]2 (0.002 g,
4.1 lmol), HP(O)(OEt)Ph (50.1 lL, 0.34 mmol), a mag-
netic stirring bar, and THF (3.0 mL). The vial was sealed,
placed in the reactor, and irradiated for a total of 10 min.
The microwave power was held at 220 W (3.0 min) until
the desired temperature was reached (150 °C). The micro-
wave power decreased to 200–210 W for the remainder of
the run to maintain the temperature. The vial was cooled
to ambient temperature and the volatiles were removed
under vacuum. The title compound was isolated as a color-
less solid (0.065 g, 41%; 1:1 ratio of diastereomers) after
purification of the reaction residue by column chromatog-
raphy (silica gel, 30% THF in Et2O). Anal. Calc. for
C28H35O4P: C, 72.08; H, 7.56. Found: C, 71.90; H, 8.14.
1
ESI-MS: m/z = 467 (M + H+). H NMR (both diastereo-
mers, CDCl3, 23 °C): d 7.90–7.65 (m, 2H, Ar-H), 7.57–
7.47 (m, 3H, Ar-H), 7.25–7.08 (m, 2H, @CH– and Ar-H),

4050
R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
J = 10.4, Ar-C), 128.5 (d, J = 12.9, Ar-C), 126.2 (s, Ar-C),
117.14 (d, J = 136.2, –C@CP(O)), 117.05 (d, J = 135.9,
–C@CP(O)), 113.7 (s, Ar-C), 111.4 (s, Ar-C), 84.8 (d,
J = 16.3, quat), 84.7 (d, J = 16.3, quat), 60.7 (d, J = 5.8,
–OCH2CH3), 55.2 (s, –OMe), 49.6 (s, –CH–), 47.7 (s, quat),
47.6 (s, quat), 43.43 (s, –CH–), 43.37 (s, –CH–), 39.43 (s,
–CH–), 39.40 (s, –CH–), 37.3 (s, –CH2–), 32.6 (s, –CH2–),
32.5 (s, –CH2–), 29.7 (s, –CH2–), 27.4 (s, –CH2–), 26.2 (s,
–CH2–), 26.1 (s, –CH2–), 23.5 (s, –CH2–), 16.52 (d,
J = 6.5, –OCH2CH3), 16.50 (d, J = 6.7, –OCH2CH3),
14.2 (s, –CH3). 31P{1H} NMR (both diastereomers,
CDCl3, 25 °C): d 30.3 (s, one diastereomer), 30.2 (s, second
diastereomer).
(d, J = 6.1, Ar-C), 115.2 (d, J = 138.5, –C@CP(O)),
114.9 (d, J = 139.5, –C@CP(O)), 84.6 (d, J = 17.2, quat),
84.5 (d, J = 17.1, quat), 53.2 (s, –CH–), 53.1 (s, –CH–),
50.2 (s, –CH–), 49.9 (s, –CH–), 47.2 (d, J = 1.1, quat),
47.1 (d, J = 0.9, quat), 38.51 (s, quat), 38.50 (s, quat),
37.1 (s, –CH2–), 37.0 (s, –CH2–), 36.22 (s, –CH–), 36.19
(s, –CH–), 35.7 (s, –CH2–), 35.6 (s, –CH2–), 33.9 (s,
–CH2–), 32.6 (s, –CH2–), 32.3 (s, –CH2–), 32.0 (s,
–CH2–), 31.5 (s, –CH2–), 31.4 (s, –CH2–), 23.8 (s, –CH2–),
23.7 (s, –CH2–), 20.6 (s, –CH2–), 20.4 (s, –CH2–), 17.30
(s, –CH3), 17.2 (s, –CH3), 14.1 (s, –CH3), 14.0 (s, –CH3).
31P{1H} NMR (both diastereomers, CDCl3, 25 °C): d
23.2 (s, one diastereomer), 23.0 (s, second diastereomer).
4.7. Preparation of 7 (in water)
4.8. Preparation of 8 (in water)
A microwave reactor vial was charged with ethisterone
(0.10 g, 0.32 mmol), (Me2PhP)3RhMe3 (0.006 g, 10 lmol),
a magnetic stirring bar, DOPO (0.070 g, 0.32 mmol), and
water (1.5 mL). The reactor vial was sealed, placed in the
microwave, and irradiated. The microwave power held at
150 W (2.0 min) until the desired temperature was reached
(150 °C). The microwave power was decreased to 70–
80 W for the remainder of the experiment in order to
maintain the temperature. After a total irradiation time
of 15 min, the vial was cooled and extracted with CH2Cl2.
After drying with MgSO4 the volatiles were evaporated
under vacuum. The crude residue was purified by column
chromatography (40% THF in ether) to afford 0.071 g
(42%; 1:1.4 ratio of diastereomers) of the title compound
as an off-white solid. Anal. Calc. for C33H37O4P: C, 74.98;
H, 7.05. Found: C, 74.90, H, 7.06. ESI-MS: m/z = 529
(M + H+). 1H NMR (both diastereomers, CDCl3,
25 °C): d 8.01–7.92 (m, 2H, Ar-H), 7.82–7.70 (m, 2H,
Ar-H), 7.49 (m, 1H, Ar-H), 7.34 (m, 1H, Ar-H), 7.25
(m, 2H, Ar-H), 6.99 (dd, J = 16.8, 22.3, @CH–), 6.95
(dd, J = 17.0, 22.5, @CH–), 6.18 (dd, J = 16.8, 16.8,
@CH–), 6.10 (dd, J = 16.8, 16.8, @CH–), 5.77 (s, 1H,
@CH–), 2.45–2.30 (m, 4H, –CH– or –CH2–), 2.03 (m,
2H, –CH– or –CH2–), 1.85 (m, 2H, –CH– or –CH2–),
1.76–1.34 (m, 8H, –CH– or –CH2–), 1.20 (s, –CH3),
1.18 (s, –CH3), 0.96 (s, –CH3), 0.94 (s, –CH3), 0.93 (m,
A microwave reactor vial was charged with ethynyl
estradiol (0.10 g, 0.34 mmol), (PhMe2P)3RhMe3 (0.006 g,
10 lmol), a magnetic stirring bar, water (1.5 mL), and
DOPO (0.070 g, 0.32 mmol). The vial was sealed, placed
in the microwave, and irradiated. The microwave power
was held at 150 W (2.4 min) until the desired temperature
was reached (150 °C). The microwave power was decreased
to 70–80 W for the remainder of the experiment to main-
tain the temperature. After a total irradiation time of
15 min, the reaction mixture was cooled and extracted with
CH2Cl2. After drying with MgSO4 the volatiles were evap-
orated under vacuum. The crude residue was purified by
column chromatography (40% THF in ether) to afford
0.099 g (57%; 1:1.3 ratio of diastereomers) of the title com-
pound as a off-white solid. Anal. Calc. for C32H33O4P: C,
74.98; H, 6.49. Found: C, 75.25, H, 7.02. ESI-MS: m/z =
513 (M + H+). 1H NMR (both diastereomers, CDCl3,
25 °C): d 8.00 (m, 2H, Ar-H), 7.74 (m, 2H, Ar-H), 7.59–
7.26 (m, 5H, Ar-H and @CH–), 6.93 (m, 1H, Ar-H), 6.77
(m, 1H, Ar-H), 6.60 (m, 1H, Ar-H), 6.22 (dd, 1H,
J = 27.7, 16.8, @CH–), 2.75 (m, 2H, –CH– or –CH2–),
2.04 (m, 2H, –CH– or –CH2–), 1.90–1.67 (m, 3H, –CH–
or –CH2–), 1.54–1.15 (m, 6H, –CH– or –CH2–), 1.00 (m,
2H, –CH– or –CH2–), 0.87 (s, –CH3), 0.85 (s, –CH3–).
1H NMR (both diastereomers, DMSO-d6, 25 °C, only
–OH groups): d 9.03 (br s, –OH), 5.01 (br s, –OH).
13C{1H} NMR (both diastereomers, CDCl3, 25 °C): d
160.9 (d, 5.4, C@C–P(O)), 160.6 (d, 5.8, C@C–P(O)),
154.9 (s, quat), 148.9 (d, J = 2.4, quat), 148.8 (d, J = 2.4,
quat), 137.6 (s, quat), 135.5 (d, J = 5.0, quat), 135.4 (d,
J = 5.3, quat), 133.2 (d, J = 2.04, Ar-C), 131.3 (s, quat),
131.2 (s, quat), 130.6 (s, Ar-C), 130.4 (d, J = 12.8, Ar-C),
130.2 (d, J = 13.3, Ar-C), 128.43 (d, J = 14.1, Ar-C),
128.38 (d, J = 14.8, Ar-C), 125.9 (s, Ar-C), 125.8 (s, Ar-
C), 125.2 (s, Ar-C), 124.7 (s, Ar-C), 124.6 (d, J = 131.0,
quat), 124.55 (d, J = 130.6, quat), 124.0 (d, J = 10.2, Ar-
C), 123.8 (d, J = 10.2, Ar-C), 122.2 (d, J = 11.3, Ar-C),
122.1 (d, J = 11.5, Ar-C), 120.7 (d, J = 6.04, Ar-C), 115.3
(s, Ar-C), 115.2 (s, Ar-C), 113.4 (d, J = 142.2,
–C@CP(O)), 113.2 (d, J = 141.6, –C@CP(O)), 112.5 (s,
Ar-C), 112.4 (s, Ar-C), 85.2 (d, J = 16.9, quat), 85.16 (d,
1
3H, –CH– or –CH2–). H NMR (acetone-d6, 25 °C, only
alcohols listed): d 4.13 (br s, –OH, one diastereomer),
4.09 (br s,–OH, second diastereomer). 13C{1H} NMR
(both diastereomers, CDCl3, 25 °C): d 199.44 (s, –C@O),
199.42 (s, –C@O), 170.9 (s, quat), 170.8 (s, quat), 158.9
(d, J = 5.6, –C@CP(O)),158.4 (d, J = 5.1, –C@CP(O)),
149.1 (d, J = 8.4, quat), 149.0 (d, J = 8.5, quat), 135.6
(d, J = 5.5, quat), 133.1 (d, J = 2.3, Ar-C), 133.0 (d, 2.4,
Ar-C), 130.45 (s, Ar-C), 130.40 (s, Ar-C), 130.4 (d,
J = 11.8, Ar-C), 130.3 (d, J = 12.2, Ar-C), 128.31 (d,
J = 13.9, Ar-C), 128.27 (d, J = 14.0, Ar-C), 125.1 (s, Ar-
C), 125.0 (s, Ar-C), 124.8 (d, J = 129.4, quat), 124.53 (s,
Ar-C), 124.52 (s, Ar-C), 124.0 (s, Ar-C), 123.9 (s, Ar-C),
123.8 (d, J = 9.58, Ar-C), 122.5 (d, J = 11.0, Ar-C),
122.4 (d, J = 11.4, Ar-C), 120.6 (d, J = 6.0, Ar-C), 120.5

R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
4051
J = 17.1, quat), 49.7 (s, –CH–), 49.6 (s, –CH–), 47.7 (s,
quat), 42.1 (s, –CH–), 41.9 (s, –CH–), 38.8 (s, –CH–),
38.1 (s, –CH2–), 37.9 (s, –CH2–), 32.4 (s, –CH2–), 32.3 (s,
–CH2–), 29.64 (s, –CH2–), 29.59 (s, –CH2–), 27.1 (s,
–CH2–), 25.9 (s, –CH2–), 25.7 (s, –CH2–), 23.5 (s, –CH2–),
14.1 (s, –Me), 14.0 (s, –Me). 31P{1H} NMR (both diaste-
reomers, CDCl3, 25 °C): d 25.2 (s, one diastereomer),
24.1 (s, second diastereomer).
quat), 43.33 (s, –CH–), 43.27 (s, –CH–), 39.4 (s, –CH–),
39.3 (s, –CH–), 37.2 (s, –CH2–), 37.0 (s, –CH2–), 32.5
(s, –CH2–), 32.2 (s, –CH2–), 29.7 (s, –CH2–), 27.4 (s,
–CH2–), 26.2 (s, –CH2–), 26.1 (s, –CH2–), 23.5 (s,
–CH2–), 23.4 (s, –CH2–), 14.1 (s, -Me), 14.0 (s, –Me).
31P{1H} NMR (both diastereomers, CDCl3, 25 °C): d
24.0 (s, one diastereomer), 23.7 (s, second diastereomer).
4.10. Crystallographic studies
4.9. Preparation of 9 (in water)
Compounds 1 and 2. A colorless crystal was selected
under oil under ambient conditions and attached to the
tip of a nylon loop. The crystal was mounted in a stream
of cold nitrogen at 100(2) K and centered in the X-ray
beam by using a video camera. The crystal evaluation
and data collection were performed on a Bruker CCD-
A microwave reactor vial was charged with mestranol
(0.10 g, 0.32 mmol), (Me2PhP)3RhMe3 (0.006 g, 10 lmol),
a magnetic stirring bar, water (1.5 mL), and DOPO
(0.070 g, 0.32 mmol). The vial was sealed, placed in the
microwave reactor, and irradiated. The microwave power
was held at 150 W (2.2 min) until the desired temperature
was reached (150 °C). The microwave power was decreased
to 70–76 W for the remainder of the experiment to main-
tain the temperature. After a total irradiation time of
15 min, the reaction mixture was cooled and extracted
with CH2Cl2. After drying with MgSO4 the volatiles were
evaporated under vacuum. The crude residue was purified
by column chromatography (40% THF in ether) to afford
0.084 g (50%; 1:1.7 ratio of diastereomers) of the title
˚
1000 diffractometer with Mo Ka (k = 0.71073 A) radia-
tion and the diffractometer to crystal distance of 4.9 cm.
The initial cell constants were obtained from three series
of x scans at different starting angles. The reflections were
successfully indexed by an automated indexing routine
built in the SMART program. The final cell constants were
calculated from a set of strong reflections from the actual
data collection. The data were collected by using the
hemisphere data collection routine. The reciprocal space
was surveyed to the extent of a full sphere to a resolution
compound as
a
off-white solid. Anal. Calc. for
˚
C33H35O4P: C, 75.27; H, 6.70. Found: C, 75.45, H, 7.05.
ESI-MS: m/z = 527 (M + H+). 1H NMR (both
diastereomers, CDCl3, 25 °C): d 7.94 (m, 2H, Ar-H),
7.78 (m, 1H, Ar-H), 7.67 (m, 1H, Ar-H), 7.48 (m, 1H,
Ar-H), 7.35 (m, 1H, Ar-H), 7.26–7.05 (m, 4H, Ar-H
and @CH–), 6.73 (m, 1H, Ar-H), 6.65 (m, 1H, Ar-H),
6.21 (dd, J = 16.9, 24.3, @CH–), 6.13 (dd, J = 17.0,
24.8, @CH–), 3.79 (s, 3H, –OMe), 2.85 (m, 2H, –CH2–
or –CH–), 2.30–1.70 (m, 6H, –CH2– or –CH–), 1.6–1.0
(m, 7H, –CH2– or –CH–), 0.92 (s, –CH3), 0.91 (s,
of 0.80 A. The highly redundant datasets were corrected
for Lorentz and polarization effects. The absorption cor-
rection was based on fitting a function to the empirical
transmission surface as sampled by multiple equivalent
measurements [32]. A successful solution by the direct
methods provided most non-hydrogen atoms from the
E-map. The remaining non-hydrogen atoms were located
in an alternating series of least-squares cycles and differ-
ence Fourier maps. All non-hydrogen atoms were refined
with anisotropic displacement coefficients. All hydrogen
atoms were included in the structure factor calculation
at idealized positions and were allowed to ride on the
neighboring atoms with relative isotropic displacement
coefficients. For 1, the final least-squares refinement of
391 parameters against 6411 data resulted in residuals R
(based on F2 for I P 2r) and wR (based on F2 for all
data) of 0.0644 and 0.1315, respectively. There is also
one molecule of solvate (benzene) in the asymmetric unit
of 1. For 2, the final least-squares refinement of 328
parameters against 5476 data resulted in residuals R
(based on F2 for I P 2r) and wR (based on F2 for all
data) of 0.0381 and 0.0937, respectively. The final differ-
ence Fourier maps were featureless.
1
–CH3). H NMR (both diastereomers, DMSO-d6, 25 °C,
only –OH groups): d 5.08 (br s, –OH, one diastereomer),
5.03 (br s, –OH, second diastereomer). 13C{1H} NMR
(both diastereomers, CDCl3, 25 °C): d 159.3 (d, 5.7,
C@C–P(O)), 158.8 (d, 5.3, C@C–P(O)), 157.41 (s, quat),
157.40 (s, quat), 149.1 (d, J = 7.9, quat), 149.0 (d,
J = 7.3, quat), 137.84 (s, quat), 137.81 (s, quat), 135.63
(d, J = 5.9, quat), 135.61 (d, J = 5.51, quat), 133.0 (d,
J = 2.3, Ar-C), 132.9 (d, J = 2.3, Ar-C), 130.43 (s, Ar-
C), 130.38 (s, Ar-C), 130.38 (d, J = 11.9, Ar-C), 130.35
(d, J = 12.5, Ar-C), 128.3 (d, J = 14.0, Ar-C), 128.2 (d,
J = 14.0, Ar-C), 126.2 (s, Ar-C), 125.1 (s, Ar-C), 125.0
(s, Ar-C), 124.9 (d, J = 129.2, quat),124.5 (s, Ar-C),
123.74 (d, J = 9.6, Ar-C), 123.71 (d, J = 9.7, Ar-C),
122.6 (d, J = 11.1, quat), 122.5 (d, J = 11.3, quat), 120.7
(d, J = 6.0, Ar-C), 120.5 (d, J = 6.0, Ar-C), 115.1 (d,
J = 138.4, –C@C–P(O)), 114.9 (d, J = 139.5, –C@C–
P(O)), 113.7 (s, Ar-C), 111.5 (s, Ar-C), 84.75 (d, J =
17.2, quat), 84.73 (d, J = 17.1, quat), 55.2 (s, –OMe),
49.7 (s, –CH–), 49.4 (s, –CH–), 47.6 (s, quat), 47.5 (s,
Acknowledgements
The authors thank Bucknell University for a Graduate
Student Summer Research Fellowship (J.A.B), the Degen-
stein Foundation for a research fellowship (J.F.T), and
Bristol Myers Squibb for unrestricted support.

4052
R.A. Stockland Jr. et al. / Journal of Organometallic Chemistry 691 (2006) 4042–4053
(o) M.R. Douglass, M. Ogasawara, S. Hong, M.V. Metz, T.J.
Marks, Organometallics 21 (2002) 283;
Appendix A. Supporting information
(p) S. Gouault-Bironneau, S. Deprele, A. Sutor, J.L. Montchamp,
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(r) J.R. Moncarz, N.F. Laritcheva, D.S. Glueck, J. Am. Chem. Soc.
124 (2002) 13356;
Synthetic procedures and characterization data for 1–9 as
1
well as representative H and 31P{1H} NMR spectra. The
crystallographic data for the structures reported in this
paper have been deposited with the Cambridge Crystallo-
graphic Data Center (1: 604600, 2: 604601). This informa-
tion can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.jorganchem.2006.06.007.
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