Towards chiral non-racemic cis-1,3-disubstituted cyclopentane 1,4-diphosphines

Article abstract of DOI:10.1016/S0957-4166(02)00184-2

Reaction of dialkyl- or diaryl-trans-(3,4-epoxycyclopentyl)phosphine oxides 2 with the lithium derivative of methyldiphenylphosphine oxide gives a mixture of (±)-t-4- and (±)-c-4-(disubstituted phosphinoyl)-t-2-(diphenylphosphinoylmethyl)-r-1-cyclopentanol derivatives 13a-c and 16a-c, which could be obtained in pure form by separation of the corresponding acetates 14a-c and 17a-c followed by methanolysis. Compounds 13b and 16b were transformed into the corresponding dehydroxy derivatives 19 and 21 through the Barton procedure. Additionally, 16a was transformed into a diastereomeric mixture of carbamates 22 and 23 on reaction with (S)-α-phenylethylisocyanate which could be separated by repeated crystallization. The relative configuration of compounds 13b, 17a, 21 and 22 was established by X-ray diffraction analysis.

Full text of DOI:10.1016/S0957-4166(02)00184-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 759–778
Towards chiral non-racemic cis-1,3-disubstituted cyclopentane
1,4-diphosphines
Pelayo Camps,a,* Gisela Colet,a Merce` Font-Bardia,b Victoria Mun˜oz-Torrero,a Xavier Solansb and
Santiago Va´zqueza
aLaboratori de Qu´ımica Farmace`utica (Unitat Associada al CSIC), Facultat de Farma`cia, Universitat de Barcelona,
Av. Diagonal 643, E-08028 Barcelona, Spain
bDepartament de Cristal·lografia i Dipo`sits Minerals, Facultat de Geologia, Universitat de Barcelona, Av. Mart´ı i Franque´s s/n,
E-08028 Barcelona, Spain
Received 4 April 2002; accepted 17 April 2002
Abstract—Reaction of dialkyl- or diaryl-trans-(3,4-epoxycyclopentyl)phosphine oxides 2 with the lithium derivative of
methyldiphenylphosphine oxide gives a mixture of ( )-t-4- and ( )-c-4-(disubstituted phosphinoyl)-t-2-(diphenylphosphinoyl-
methyl)-r-1-cyclopentanol derivatives 13a–c and 16a–c, which could be obtained in pure form by separation of the corresponding
acetates 14a–c and 17a–c followed by methanolysis. Compounds 13b and 16b were transformed into the corresponding dehydroxy
derivatives 19 and 21 through the Barton procedure. Additionally, 16a was transformed into a diastereomeric mixture of
carbamates 22 and 23 on reaction with (S)-a-phenylethylisocyanate which could be separated by repeated crystallization. The
relative configuration of compounds 13b, 17a, 21 and 22 was established by X-ray diffraction analysis. © 2002 Elsevier Science
Ltd. All rights reserved.
1. Introduction
and b-amino ketones of interest in connection with the
synthesis of drugs such as (S)-levamisol,5 (S)-propra-
nolol,6 the stereoisomers of epronizol,7 and (R)-fluox-
etine,8 among others. However, the industrial
application of these diphosphines is greatly conditioned
by their lengthy syntheses [15 steps for (S,S)-MCCPM3
and 17 steps for (R,R)-MCCPM,4 in both cases starting
from (2S,4R)-4-hydroxyproline]. Consequently, the
synthesis of analogs of (S,S)- and (R,R)-MCCPM
through shorter synthetic sequences is of great interest.
Chiral diphosphines have been extensively used as lig-
ands for transition metals in catalytic asymmetric pro-
cesses,1 of interest for the synthesis of enantiopure
drugs.2 Among them, cis-1,4-diphosphines derived from
(2S,4R)-4-hydroxyproline, containing a five-membered
pyrrolidine ring, such as (2S,4S)-4-(dicyclohexylphos-
phino)-2-[(diphenylphosphino)methyl]-1-(methylamino-
carbonyl)pyrrolidine [(S,S)-MCCPM]3 (Fig. 1) and its
enantiomer [(R,R)-MCCPM]4 give Rh(I) complexes
which perform highly enantioselective reductions of a-
Taking into account that lithiated alkyldiphenylphos-
phine oxides react with epoxides to give g-(hydroxy-
alkyl)phosphine oxides in good yields,9 and that
chlorodisubstituted phosphines react with a,b-unsatu-
rated carbonyl compounds in very good yields,10 we
planned the synthesis of cyclopentane diphosphines,
analogs of MCCPM, through the retrosynthetic analy-
sis shown in Fig. 2.
C6H11
C6H5
P
P
C6H5
C6H11
N
NHCH3
(S,S)-MCCPM
O
Herein we describe a synthesis of ( )-t-4-(disubstituted
phosphinoyl) - t - 2 - [(diphenylphosphinoyl)methyl] - r - 1-
cyclopentanol derivatives 16a–c and the dehydroxylated
derivative 21, as well as the enantiomerically pure car-
bamates 22 and 23 derived from alcohol 16a and (S)-a-
Figure 1. Structure of (S,S)-MCCPM.
* Corresponding author. Tel.: +34-93-402-4536; fax: +34-93-403-5941;
e-mail: camps@farmacia.far.ub.es
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00184-2

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P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
cyclopentanol (probably derived from cyclopentadiene
PO(C6H5)2
O
P(C6H5)2
X
by hydroboration/protonolysis plus hydroboration/oxi-
dation) and n-butanol (probably formed by borane
reduction of THF). This mixture could not be sepa-
rated by distillation and was reacted directly with phos-
phorus tribromide in pentane to give impure
3-cyclopentenyl bromide 1 in about 70% yield.
X
P(O)R2
O
P(O)R2
O
PR2
Reaction of impure 1 (2.5 equiv.) with magnesium
turnings in anhydrous THF followed by treatment of
the thus formed organomagnesium reagent with
chlorodiisopropylphosphine (1 equiv.) and atmospheric
oxidation during the work-up gave a mixture the main
components of which were 3-cyclopentenyldiisopropyl-
phosphine oxide, cyclopentyldiisopropylphosphine
oxide and n-butyldiisopropylphosphine oxide (59, 12
and 26% relative areas by GC/MS). This mixture could
neither be separated by distillation nor by column
chromatography (neutral aluminum oxide) and was
reacted as such with m-chloroperbenzoic acid (m-
CPBA) in CH2Cl2 to give impure 2a, which was
purified by flash silica gel column chromatography.
Although the yield of 2a from chlorodiisopropylphos-
phine was only about 10%, we could prepare enough
material in this way to carry out the next reactions.
P(O)R2
P(O)R2
R = alkyl, aryl or cycloalkyl
X = H, OH or O-derivatives
+
ClPR2
MgBr
Figure 2. Retrosynthetic analysis to MCCPM analogs.
phenylethylisocyanate, as precursors of the title
diphosphines.
2. Results and discussion
The synthesis of compounds 16a–c involved reaction of
epoxides 2 with the lithium derivative of methyl-
diphenylphosphine oxide as shown in Fig. 2. Firstly, we
prepared epoxide 2a starting from the known 3-
cyclopentenyl bromide11 1 (Scheme 1). As described,
cyclopentadiene12 was submitted to hydroboration fol-
lowed by hydrogen peroxide oxidation to give the
desired 3-cyclopentenol in 31% yield, somewhat higher
than that described in the literature.11 However, the
product was contaminated (1H and 13C NMR) with
Taking into account the low yield in the preparation of
2a, compounds 2b and 2c were prepared by the alterna-
tive route shown in Scheme 2. Reaction of 2-cyclopen-
tenone 3 with chlorodiphenylphosphine in glacial acetic
acid afforded 3-diphenylphosphorylcyclopentanone10 4b
in 99% yield. NaBH4 reduction of this compound in
methanol gave a mixture of cis-3-(diphenylphospho-
ryl)cyclopentanol 6b and the corresponding trans-
diastereomer in an approximate ratio of 6:1 (96%
yield), from which pure 6b was isolated by crystalliza-
tion. Curiously, in one case, a compound that was
characterized as the dimethyl acetal of 4b (compound
5b) was obtained as the main product from the above
reaction. Since formation of acetal 5b from 4b requires
acid catalysis, formation of 5b was avoided by carrying
out the reduction of 4b in methanol pre-treated with
NaBH4 to destroy possible traces of acid. Mesylation of
a mixture of 6b and its trans-stereoisomer gave the
corresponding mixture of mesylates in high yield, from
O
i, ii, iii, iv
Br
PO(isoPr)2
2a
1
Scheme 1. Preparation of epoxide 2a. Reagents and condi-
tions: (i) Mg, anh. THF; (ii) ClP(i-Pr)2; (iii) air; (iv) m-
chloroperbenzoic acid, CH2Cl2.
OH
OMs
O
O
MeO
OMe
iv
iii
i
ii
+
P(O)R2
6 + stereoisomer
P(O)R2
7 + stereoisomer
P(O)R2
PO(C6H5)2
3
4
5b
O
OH
O
O
v
+
+
+
P(O)R2
vi
+
2
P(O)R2
P(O)R2
P(O)R2
10
P(O)R2
8
9
P(O)R2
2
11
12
2b, 4b and 6b-12b, R = C6H5; 2c, 4c and 6c-12c, R = cyclopentyl
,
Scheme 2. Preparation of epoxides 2. Reagents and conditions: (i) ClPR2, AcOH, 4 A molecular sieves, rt, 2 h; (ii) NaBH4, MeOH;
(iii) MsCl, Et3N, DMAP (10% M), CH2Cl2; (iv) pyrolysis; (v) m-chloroperbenzoic acid, CH2Cl2; (vi) KOH, EtOH.

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
761
Since we could not obtain an adequate single crystal of
any of the epoxides 2 to perform an X-ray diffraction
analysis, the relative configuration of 2b was proposed
which pure cis-mesylate 7b could be isolated by crystal-
lization. Pyrolysis of the above mixture of 7b and its
trans-stereoisomer gave a high yield of a mixture of
alkenes 8b and 9b in a ratio of ca. 1.8:1, which could
not be separated by column chromatography and was
characterized ‘as is’. Compound 9b has been prepared
previously by our group through a different route.13
Additionally, we knew13 that on epoxidation 9b gives a
mixture of epoxides 10b and 11b, which on reaction
with ethanolic KOH are transformed into the allylic
alcohol 12b. Consequently, to obtain epoxide 2b, we
reacted the mixture of alkenes 8b and 9b with m-CPBA
and the mixture of epoxides 2b, 10b and 11b, thus
obtained, was treated with ethanolic KOH to give a
mixture of epoxide 2b and allylic alcohol 12b, which
was easily separated by silica gel column chromatogra-
phy. In this way, epoxide 2b was obtained in 26%
overall yield from 2-cyclopentenone 3. Alcohol 12b was
also isolated in 20% overall yield from 3. The use of
alcohols 12 for the synthesis of precursors of 1,3-
diphosphines was described recently.13
1
on the basis of their H and 13C NMR data, including
NOESY experiments. The absence of NOE enhance-
ment between 1-H and the 3(4)-H protons is indicative
of the trans-configuration of 2b: 1-H and 3(4)-H
showed NOE with both 2-Ha and 2-Hb. The observed
coupling constant values between atoms (1H, 31P and
13C) separated by three s bonds, according to the
Karplus relationships, suggest the preferred conforma-
tion of 2b in CDCl3 solution to have an envelope
cyclopentane ring in which C1 is out of the plane
determined by the rest of cyclopentane carbon atoms
on the same side of the epoxide oxygen atom, in such a
way that the C(1)-substituent occupies a pseudoequato-
rial arrangement (Fig. 3). Molecular mechanics calcula-
tions also suggests this conformation to be the more
stable one.15 Reasonably, the relative configuration of
epoxides 2a and 2c must be the same, although in the
1
case of 2a, overlapping of the H NMR signals pre-
cluded NOESY experiments and the determination of
several coupling constant values.
Having developed an efficient access to epoxide 2b, we
then applied a similar procedure to prepare the dicy-
clopentyl analog 2c. In this case, the starting chlorodi-
cyclopentylphosphine was prepared as described, by
reaction of cyclopentylmagnesium chloride with PCl3 in
the appropriate ratio.14 Compound 4c and the mixtures
of 6c and 7c and their trans-stereoisomers showed to be
viscous oily products which could not be purified by
column chromatography and were used directly in the
following steps.
Next, anhydrous epoxide 2a (azeotropic distillation of
its water content with toluene) was reacted with the
lithium derivative of methyldiphenylphosphine oxide in
anhydrous THF (Scheme 3). Contrary to our expecta-
tions a mixture of stereoisomeric alcohols 13a and 16a
in a ratio of about 3:1 (1H NMR, HPLC) was obtained
in 62.5% yield. In other runs, the ratio of 13a/16a was
around 2:1. Since this mixture could not be separated
by silica gel column chromatography or by crystalliza-
tion, it was transformed into a mixture of the corre-
3J(C3/31P) = 12.7 Hz
3J(2-Hα/31P) = 14.5 Hz
Hα
Pyrolysis of the mixture of 7c and its trans-stereoisomer
gave a mixture of 8c and 9c13 in a ratio of ca. 2.8:1, in
which the desired alkene 8c was somewhat more abun-
dant than 8b in the above mixture of 8b and 9b.
Epoxidation of this mixture, followed by silica gel
column chromatography of the thus formed mixture of
epoxides 2c, 10c and 11c allowed the isolation of epox-
ide 2c in 37% overall yield from 3.
H
3J(2-Hβ/31P) = 1.0 Hz
2
PO(C6H5)2
3J(2-Hα/2-Hβ) = 14.5 Hz
3J(1-H/2-Hβ) = 8.0 Hz
3J(1-H/2-Hα) = 10.0 Hz
1
Hβ
O
H
Figure 3. Configuration, preferred conformation and several
coupling constant values of epoxide 2b.
PO(C6H5)2
PO(C6H5)2
AcO
HO
i
ii
2
P(O)R2
iii
14
13
P(O)R2
iv
+
+
O
PO(C6H5)2
PO(C6H5)2
AcO
HO
ii or v
P(C6H5)2
15
P(O)R2
P(O)R2
16
17
13a, 14a, 16a, 17a, R = isoPr; 13b,14b, 16b, 17b, R = C6H5; 13c,14c, 16c, 17c, R = cyclopentyl
Scheme 3. Synthesis of cis-1,3-disubstituted cyclopentane 1,4-diphosphines dioxides. Reagents and conditions: (i)
methyldiphenylphosphine oxide, THF, 1.6 M n-BuLi (in hexanes), −78°C; then 2, rt for 3 h and reflux for 15 h; (ii) NaMeO,
MeOH, reflux, 2 h; (iii) (EtO)3SiH, Ti(OisoPr)4, THF, reflux, 7 h; (iv) Ac2O, reflux, 2 h; (v) KCN, EtOH, reflux, 12 h.

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P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
sponding acetates 14a and 17a on reaction with acetic
anhydride. The mixture of acetates 14a and 17a could
be separated by flash silica gel column chromatogra-
phy, thus obtaining pure samples of both compounds,
which were fully characterized. The complexity of the
1H NMR spectra of these compounds did not allow us
to establish their relative configurations. Fortunately,
we could obtain a single crystal of acetate 17a whose
X-ray diffraction analysis was conclusive to establish
the cis-configuration of the phosphinoyl substituents
(Fig. 4). Reaction of these acetates with methanol cata-
lyzed by sodium methoxide gave the corresponding
alcohols 13a and 16a, which were fully characterized.
chromatography or crystallization. However, as before,
we were able to separate the corresponding mixture of
acetates 14b and 17b, which were obtained in pure
form. Reaction of acetates 14b and 17b with sodium
methoxide in methanol gave the corresponding alcohols
13b and 16b. X-Ray diffraction analysis of a single
crystal of 13b allowed us to clearly establish the relative
trans-configuration of its phosphinoyl substituents (Fig.
5).
A mixture of alcohols 13c and 16c (approximate ratio
2.5:1) was also obtained from epoxide 2c. Separation of
the mixture was carried out via the corresponding
acetates 14c and 17c, whose methanolysis gave back the
corresponding alcohols. Worthy of note, methanolysis
of acetate 17c with sodium methoxide in methanol took
place with partial epimerization to 13c. However,
In a similar way, starting from 2b, a mixture of alcohols
13b and 16b in an approximate ratio of 3:2 (1H NMR)
was obtained, which could not be separated by column
Figure 4. X-Ray diffraction structure (ORTEP) of 17a.
Figure 5. X-Ray diffraction structure (ORTEP) of 13b.

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
763
in good yield (80%) the corresponding phosphine 15
(Scheme 3). Attempted reduction of 2b with
trichlorosilane3,19 led mainly to the corresponding
chlorohydrin, phosphine 15 being not observed. Con-
trary to expectations, all attempts to open the epoxide
function of 15 by reaction with the lithium derivative of
methyldiphenylphosphine oxide [(a) in the standard
way used for epoxides 2, (b) in the presence of BF3
etherate20 to activate the epoxide, (c) in the presence of
tetramethylethylenediamine to increase the reactivity of
the lithium derivative, or (d) in the presence of CeCl3,
to activate the epoxide and to increase the nucleophilic
reactivity of the organometallic reagent21] were fruitless.
In all cases, most of the starting phosphine was recov-
ered unchanged.
methanolysis of 17c to 16c could be cleanly carried out
on reaction with potassium cyanide in ethanol (83%
yield).16
1
Comparison of the H and 13C NMR data for alcohols
13a–c and 16a–c allowed us to clearly establish that in
all cases the opening of epoxides 2a–c gave the unex-
pected alcohols 13a–c as the main products, the
expected stereoisomers 16a–c always being the minor
components. As expected for the epoxide opening in all
of the alcohols 13a–c and 16a–c, the hydroxyl and the
diphenylphosphinoylmethyl substituents are in a trans-
arrangement. Since epoxides 2a–c correspond to only
one stereoisomer, an explanation of the experimental
results could be related to the acidity of the a-phosphi-
noyl protons of 2, which would allow epimerization at
C(4) (the carbon atom bearing the dialkyl- or diaryl-
phosphinoyl substituent) in the opened product.
Alcohols 13b and 16b were dehydroxylated to com-
pounds 19 and 21, respectively, through the Barton
procedure via the corresponding imidazolylthiocar-
bonyl derivatives 18 and 20, respectively,22 which were
reduced with tri-n-butyltin hydride23 (Scheme 5).
Taking into account the assigned configuration and the
preferred conformation of epoxides 2, the alkoxide
initially formed by nucleophilic addition to the epoxide
ring of 2 could abstract the close acidic hydrogen atom
(4-H) to give an a-phosphinoyl anion whose protona-
tion can take place in two ways to give alcohols 16 or
their epimers 13 (Scheme 4).
N
PO(C6H5)2
PO(C6H5)2
N
O
i
ii
13b
S
PO(C6H5)2
19
18
Nu
Nu
PO(C6H5)2
PO(C6H5)2
iv
P(O)R2
P(O)R2
N
O
PO(C6H5)2
O
H
H
N
O
2
iii
Nu-H = CH3PO(C6H5)2
16b
S
Nu
PO(C6H5)2
20
21
PO(C6H5)2
13 and / or 16
HO
P(O)R2
Scheme 5. Dehydroxylation of diphosphine dioxides 13b and
16b. Reagents and conditions: (i) thiocarbonydiimidazole, tol-
uene, reflux, 1 h; (ii) (n-Bu)3SnH, AIBN, toluene, reflux, 4 h;
(iii) thiocarbonydiimidazole, CH2Cl2, reflux, 4 h; (iv) (n-
Bu)3SnH, AIBN, benzene, reflux, 6 h.
Scheme 4. Possible mechanism for the formation of alcohols
13 and 16 from epoxides 2.
The preferential formation of the trans-derivatives 13
could be indicative of their greater stability. In fact, as
stated before, partial epimerization of C(4) was
observed during the methanolysis of acetate 17c using
sodium methoxide in methanol.
Although the relative configuration of compounds 19
and 21 should be the same as their precursors 13b and
16b, respectively, we were able to carry out an X-ray
diffraction analysis of a single crystal of 21, which
confirmed its cis-configuration.
Since the desired diphosphines should contain both
phosphino substituents in a cis-arrangement, only the
minor products from these reactions are of interest. To
solve the problem of the epimerization in the above
reaction we carried out the reaction of 2b with the
lithium derivative of methyldiphenylphosphine oxide in
THF in the presence of an excess of trimethylsilyl
chloride (TMSCl) with the aim of trapping the initially
formed alkoxide.17 However, the only observed product
seemed to be the corresponding chlorohydrin, probably
formed during the aqueous work up by reaction of 2
with the HCl formed by hydrolysis of the TMSCl.
Alternatively, epoxide 2b was reduced with triethoxy-
silane18 catalyzed by titanium tetraisopropoxide to give
To prepare non-racemic precursors of the cis-1,3-disub-
stituted cyclopentane-1,4-diphosphines, racemic alcohol
16a was reacted with excess (S)-a-phenylethyliso-
cyanate (Scheme 6) to give a diastereomeric mixture of
the corresponding carbamates, 22 and 23. The product
was separated from N,N%-bis-(1-phenylethyl)urea by
flash column chromatography (silica gel, ethyl acetate/
methanol mixtures), and then submitted to a series of
crystallizations from ethyl acetate/methanol mixtures.
In this way, pure samples of both diastereomers (22 and
23) could be obtained in enough quantity to fully
characterize them.

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P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
H
N
13C and 31P NMR and MS) and elemental analysis
PO(C6H5)2
C6H5
O
(except phosphine 15). Assignment of the NMR spectra
1
have been carried out with the aid of COSY H/1H,
H
H
Me
Me
O
HETCOR 1H/13C, NOESY and DEPT experiments.
The relative configurations of alcohols 13 and 16 and
acetates 14 and 17 were assigned by comparison of their
NMR data with those of alcohol 13b and acetate 17a,
whose relative configurations were established by X-ray
diffraction analysis.
C6H5
NCO
22
PO(isoPr)2
PO(C6H5)2
+
H
Me
16a
H
N
Anh. Benzene,
Et3N, reflux, 24 h
C6H5
O
O
The NMR data for acetates 17 in CDCl3 solution are in
accord for a preferred conformation similar to that
observed in the solid state for 17a (Fig. 3). This confor-
mation corresponds to an envelop in which the C(1),
C(2), C(4) and C(5) carbon atoms are essentially copla-
nar (dihedral angle C(4)ꢀC(5)ꢀC(1)ꢀC(2)=−3.90°), with
the C(3) atom out of this plane in such a way that the
phosphinoyl substituents are in pseudoequatorial
arrangements. One of the protons of the exocyclic
methylene group (Hanti) is nearly antiperiplanar to 2-H
(dihedral angle 2-HꢀC(2)ꢀCꢀHanti=177.1°), while the
phosphinoyl substituent connected to this methylene
group is anti to C(1) and the other hydrogen atom
(Hsyn) is anti to C(3). Table 1 collects significant 3J(13C–
31P) for compounds 17a–c and dihedral angles for 17a,
from the X-ray diffraction analysis. Also, the observed
3J(13C–31P) values are in accord with the assumed
conformation (see Table 1), taking into account a
Karplus relationship.24
23
PO(isoPr)2
Scheme 6. Preparation of carbamates 22 and 23.
Although, only very minor differences were observed in
the IR, NMR (1H, 13C and 31P) and MS spectra of
compounds 22 and 23, both diastereomers are clearly
distinguishable by chiral HPLC using a Chiralcel OD-H
column containing the chiral stationary phase cellulose
tris(3,5-dimethylphenylcarbamate) and show very dif-
ferent optical rotations. The relative configuration of 23
could be obtained by X-ray diffraction analysis (Fig. 6).
Knowing, the absolute (S)-configuration of the starting
a-phenylethylisocyanate, the absolute configuration of
23 should be (aS,1R,2R,4S) while that of 22 should be
(aS,1S,2S,4R).
All of the new compounds described herein have been
fully characterized by spectroscopic techniques (IR, H,
1
Figure 6. X-Ray diffraction structure of 23.
3
Table 1. Significant J(13C–31P) values (Hz) for acetates 17a–c and corresponding alcohols 16a–c and dihedral angles (°)
from the single-crystal X-ray diffraction structure of 17a
3J(13C–31P) (dihedral angle)
17a
17b
17c
16a
16b
16c
3.3
7.7
10.4
13.7
C1ꢀPO(C6H5)2 (C1ꢀC2ꢀCH2ꢀP)
C1ꢀC4ꢀPOR2 (C1ꢀC5ꢀC4ꢀP)
C2ꢀC4ꢀPOR2 (C2ꢀC3ꢀC4ꢀP)
C3ꢀPO(C6H5)2 (C3ꢀC2ꢀCH2ꢀP)
14.6 (170.2)
8.5 (146.6)
8.9 (164.4)
2.4 (−71.7)
14.2
8.7
8.6
14.8
9.3
8.6
2.9
7.5
9.6
1.9
6.3
10.2
14.6
:0
:0
14.4

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
765
In the case of alcohols 16, a conformation of the
cyclopentane ring similar to that of acetates was
assumed, but the CH2–PO(C6H5)2 bond is rotated by
ca. 120° in order to establish an intramolecular hydro-
gen bond between the phosphinoyl and hydroxyl
groups, as previously observed in closely related com-
pounds.13 In doing so, the Hsyn proton of an acetate 17
becomes the Hanti proton in the corresponding alcohol
16, and vice versa. This conformation is supported by
the significant reduction of the 3J(13C–31P) value
between C(1) and the phosphor atom of the CH2PO
group and the significant increase of the 3J(13C–31P)
value for C(3) in these alcohols (see Table 1).
quint, quintuplet; h, heptuplet. For the different
cyclopentanes, the terms Ha or Hb are assigned to
hydrogen atoms which are cis or trans relative to the
reference substituent (usually at position 1), respec-
tively. IR spectra were recorded on a FT/IR Perkin–
Elmer spectrometer, model 1600; only significant
absorption bands are given. Routine MS spectra were
taken on a Hewlett–Packard 5988A spectrometer, the
sample was introduced directly or through a gas chro-
matograph, Hewlett–Packard model 5890 Series II,
equipped with a 30 m HP-5 (5% diphenyl–95%
dimethylpolysiloxane) column [conditions A: 10 psi,
initial temperature: 100°C (2 min), then heating at a
rate of 15°C/min until 250°C, then isothermal; condi-
tions B: 10 psi, initial temperature: 200°C (2 min), then
heating at a rate of 15°C/min until 300°C, then isother-
mal; conditions C: 10 psi, initial temperature: 100°C (2
min), then heating at a rate of 8°C/min until 250°C,
then isothermal] and the electron impact technique (70
eV). Only significant ions are given: those with higher
relative abundance, except for the ions with higher m/z
values. Silica gel SDS 60 (70–200 mm) or (35–70 mm)
was utilized for the standard and flash column chro-
matography, respectively. Optical rotations were mea-
sured on a Perkin–Elmer, model 241 polarimeter.
Chiral HPLC analyses were performed on a Waters
model 600 liquid chromatograph provided with vari-
able u detector, working at u=220 nm and using a
Chiralcel OD-H column (25×0.46 cm) containing the
chiral stationary phase cellulose tris-(3,5-dimethyl-
phenylcarbamate), conditions A: hexane/isopropanol in
the ratio of 90:10 as eluent, flow 0.5 mL/min. Chlorodi-
isopropylphosphine and chlorodiphenylphosphine were
purchased from Aldrich Chemical Co. and chlorodicy-
clopentylphosphine was prepared according to the
method previously described.14 NMR and routine MS
spectra were performed at the Serveis Cient´ıfico-Te`cnics
of the University of Barcelona, while elemental analyses
were carried out at the Microanalysis Service of the
Centro de Investigacio´n y Desarrollo (C.I.D.), C.S.I.C.,
Barcelona, Spain.
However, it is difficult to propose a preferred confor-
mation from the NMR data for alcohols 13, acetates 14
and compounds 19, 21, 22 and 23.
Preliminary studies have shown that trichlorosilane
reduction of the phosphine oxide groups of ( )-16a
takes place without epimerization at any stereogenic
center and that reduction of enantioenriched 23 with
trichlorosilane takes place with simultaneous carbamate
deprotection,19 which opens the way to enantioenriched
cis-1,3-disubstituted
cyclopentane-1,4-diphosphines.
Work is in progress to develop improved methods to
prepare this class of compounds and to study the
catalytic activity of the corresponding diphosphines.
3. Conclusions
In conclusion, we have developed a synthetic route to
prepare advanced precursors of chiral non-racemic cis-
1,3-disubstituted cyclopentane-1,4-diphosphines which
are of potential interest as ligands for asymmetric cata-
lysts. In spite of the lack of stereoselectivity in the
reaction of epoxides 2 with the lithium derivative of
methyldiphenylphosphine oxide, the diastereomeric
mixtures can be separated via the corresponding
acetates, while the enantiomeric mixtures of alcohols 16
can be separated by crystallization of the diastereo-
meric mixtures of the corresponding carbamates
derived from (S)-a-phenylethylamine. The relative
configuration of representative compounds of this series
has been ascertained by X-ray diffraction analysis.
4.1.1. trans-(3,4-Epoxycyclopentyl)diisopropylphosphine
oxide 2a
4.1.1.1. 3-Cyclopentenol.11 To a solution of freshly
distilled cyclopentadiene (30 g, 455 mmol) in anhydrous
THF (100 mL) was added dropwise a solution of
BH3·THF (100 mL, 1 M in THF, 100 mmol) keeping
the temperature below 25°C. When the addition was
complete, the solution was stirred at room temperature
for 2 h. The mixture was concentrated under reduced
pressure and the residue was treated with 3N NaOH
(40 mL), diethyl ether (100 mL). Then, aqueous solu-
tion of H2O2 (40 mL, 30%) was added dropwise and
when the addition was over, the mixture was stirred for
30 min. The organic phase was separated and the
aqueous one was extracted with diethyl ether (2×40
mL). The combined organic phase and extracts were
dried (Na2SO4), filtered and concentrated under moder-
ate vacuum to give impure 3-cyclopentenol as a yellow
oil (7.69 g, 31% approx. yield), which was kept at
4. Experimental
4.1. General methods
Melting points were determined with a MFB 595010 M
Gallenkamp melting point apparatus. Unless otherwise
stated, NMR spectra were recorded in CDCl3 in the
1
following spectrometers: H NMR (500 MHz, Varian
VXR 500), 13C NMR (75.4 MHz, Varian Gemini 300),
1
31P NMR (121.4 MHz, Varian Unity 300 Plus). H and
13C NMR chemical shifts (l) are reported in ppm with
respect to internal tetramethylsilane (TMS) and 31P
NMR chemical shifts (l) are reported in ppm relative
to 85% H3PO4 as external standard. The multiplicity of
the signals is: s, singlet; d, doublet; t, triplet; q, quartet;
1
−30°C, and was used as such in the next step. The H
and 13C NMR spectra of this product suggested the
presence of cyclopentanol and n-butanol.

766
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
4.1.1.2. 3-Cyclopentenyl bromide. To a solution of
mg, 28% approx. yield). IR (KBr) 1172, 1147 (PꢁO st)
cm−1; 1H NMR 3.52 [s, 2H, 3(4)-H], 2.18–1.97 [complex
signal, 7H, 1-H, 2(5)-Ha, 2(5)-Hb [l 2.02, dh, J=12.5
3-cyclopentenol (7.00 g, 83 mmol approx.) in pentane
(27 mL) at −20°C was added a solution of PBr3 (3.2
mL, 33.2 mmol) in pentane (5 mL) and the mixture was
heated under reflux for 12 h. The mixture was allowed
to cool to room temperature, cold (0°C) H2O (50 mL)
was added and the organic phase was separated. The
aqueous phase was extracted with pentane (3×30 mL)
and the combined organic extracts were dried
(Na2SO4), filtered and concentrated under moderate
vacuum to give impure 3-cyclopentenyl bromide as an
oil (8.5 g, 70% approx. yield, containing bromocyclo-
pentane and 1-bromobutane (1H and 13C NMR).
Hz, J%=7.0 Hz, 2H, 2 CH
6 (CH3)2]], 1.18 (dd, J=7.5 Hz,
J%=14.5 Hz, 6H) and 1.16 (dd, J=7.0 Hz, J%=14.5 Hz,
3
6H) [2 CH(CH3 2
Hz, C3(4)], 28.3 [CH2, s, C2(5)], 27.0 (CH, d, JCꢀP
6
) ]; 13C NMR 56.6 [CH, d, JCꢀP=11.1
1
=
1
63.1 Hz, C1), 26.4 [CH, d, JCꢀP=63.2 Hz, C
16.8 (CH3, broad s) and 16.5 (CH3, broad s) [2
CH(C
H3)2]; 31P NMR 53.7; GC/MS (EI) (conditions C,
tr=6.88 min), m/z (%): 217 [(M+H) , 4], 216 (M , 2),
6 H(CH3)2],
6
+
+
’
+
+
’
215 [(M−H) , 7], 174 [(M−C3H6) , 85], 146 [(M−C3H6−
+
’
+
’
CO) , 70], 134 [(M−C5H6O) , 79], 131 [(M−C3H6−
+
+
’
C3H7) , 34], 113 (73), 92 [(M−C5H6O−C3H6) , 74], 83
[(C5H7O)+, 51], 67 (C5H+7, 100). Anal. calcd for
C11H21O2P·0.5H2O: C, 58.65; H, 9.85. Found: C, 58.53;
H, 9.83%.
4.1.1.3. (3-Cyclopentenyl)diisopropylphosphine oxide.
To a suspension of dried Mg (662 mg, 27.2 mmol) in
anhydrous THF (5 mL), a crystal of I2 was added and
the mixture was stirred for 10 min. Then, a solution of
3-cyclopentenyl bromide (4.0 g, 27.2 mmol approx.) in
anhydrous THF (10 mL) was added dropwise and the
mixture was stirred at room temperature for 5 h. This
solution was added through a transfer to a cold (ice-
bath) solution of chlorodiisopropylphosphine (1.7 mL,
1.57 g, 96% content, 10.3 mmol) in anhydrous THF (8
mL) and the mixture was stirred for 18 h, while it was
allowed to slowly reach room temperature. Aqueous
saturated solution of NH4Cl (20 mL) and 2N H2SO4 (6
mL) were added and the mixture was concentrated in
vacuo to dryness. The yellow residue was washed with
hot diethyl ether (200 mL) for 1 h. The solution was
discarded and the residue was dissolved in H2O (50
mL), was made basic with 5N NaOH (16 mL), and
extracted with ethyl acetate (9×100 mL). The combined
organic extracts were dried (Na2SO4), filtered and con-
centrated under vacuum to give a dark oil (1.75 g),
which was submitted to flash column chromatography
[silica gel (70 g), ethyl acetate/methanol mixtures]. On
elution with a mixture of ethyl acetate/methanol in the
ratio of 96.5:3.5, a mixture of products was obtained.
GC/MS (conditions C) showed it to contain: n-butyldi-
isopropylphosphine oxide (tr=9.3 min), (3-cyclopen-
tenyl)diisopropylphosphine oxide (tr=11.9 min) and
cyclopentyldiisopropylphosphine oxide (tr=12.0 min),
whose relative areas were 26:59:12. This mixture could
not be separated by distillation (50°C/0.5 Torr) or by
neutral aluminum oxide column chromatography and
4.1.2. 3-(Diphenylphosphinoyl)cyclopentanone 4b. A mix-
ture of 2-cyclopentenone (1.00 g, 1.02 mL, 12.2 mmol),
acetic acid (99.7%, 1.00 mL, 17.4 mmol) and molecular
,
sieves (4 A, 200 mg) was stirred at room temperature
for 1 h. The mixture was cooled (ice-bath) and
chlorodiphenylphosphine (95%, 2.25 mL, 11.9 mmol)
was added dropwise. When the addition was over, the
ice-bath was removed and the mixture was stirred at
room temperature for 2 h. The solution was poured
into H2O (10 mL) and the mixture was extracted with
CHCl3 (4×7 mL). The combined organic phases were
washed with NaHCO3 (saturated aqueous solution, 4×4
mL), dried (Na2SO4) filtered and evaporated under
reduced pressure to give pure 4b as a yellow viscous oil
(3.35 g, 99% yield). IR (NaCl) 1738 (CꢁO st), 1184,
1
1119 (PꢁO st) cm−1; H NMR 7.80–7.70 (complex sig-
nal, 4H, Ar-Hortho), 7.54–7.42 (complex signal, 6H,
Ar-Hpara, Ar-Hmeta), 3.07–2.98 (m, 1H, 3-H), 2.58
(dddd, J=1.0 Hz, J%=11.0 Hz, J%%=16.0 Hz, J%%%=18.5
Hz, 1H, 2-Ha), 2.45–2.36 (m, 1H, 5-Ha), 2.32–2.21
(complex signal, 2H, 2-Hb, 4-Hb), 2.18 (dd, J=8.5 Hz,
J%=18.0 Hz, 5-Hb), 1.98 (m, 1H, 4-Ha); 13C NMR 215.8
3
4
(C, d, JCꢀP=12.6 Hz, C1), 131.9 (CH, d, JCꢀP=2.7
1
Hz, Ar-CHpara), 131.7 (C, d, JCꢀP=98.2 Hz) and 131.1
1
2
(C, d, JCꢀP=98.2 Hz) (Ar-Cipso), 130.8 (CH, d, JCꢀP
=
2
9.3 Hz) and 130.6 (CH, d, JCꢀP=8.8 Hz) (Ar-CHortho),
3
128.7 (CH, d, JCꢀP=11.5 Hz, Ar-CHmeta), 38.0 (CH2,
d, 3JCꢀP=6.0 Hz, C5), 37.9 (CH2, d, 2JCꢀP=2.2 Hz, C2),
1
2
was used as such in the next step. Compound of
35.2 (CH, d, JCꢀP=76.8 Hz, C3), 22.5 (CH2, d, JCꢀP
=
+
’
tr=11.9 min: GC/MS (EI), m/z (%): 200 (M , 4), 157
2.2 Hz, C4); 31P NMR 30.0; MS (EI), m/z (%): 285
+
+
+
+
+
’
’
[(M−C3H7) , 4], 134 [(M−C5H6) , 69], 92 [(M−C3H6−
[(M+H) , 7], 284 (M , 17), 283 [(M−H) , 13], 202
+
+
’
’
C5H6) , 100].
[[HPO(C6H5)2] , 100], 201 (70). Anal. calcd for
C17H17O2P·0.5H2O: C, 69.61; H, 6.19. Found: C, 69.62;
H, 6.07%.
4.1.1.4. Epoxide 2a. To a solution of (3-cyclopen-
tenyl)diisopropylphosphine oxide (from a different run
to that described under 4.1.1.3.) (1.53 g, 47% relative
area by GC/MS, 3.6 mmol approx.) in CH2Cl2 (30 mL),
m-CPBA (4.63 g, 57% content, 15.3 mmol) was added
and the mixture was stirred at room temperature for 18
h. More CH2Cl2 (20 mL) was added and the solution
was washed with 5N NaOH (15 mL) and brine (30
mL). The organic phase was dried (Na2SO4), filtered
and evaporated under reduced pressure to give a yellow
residue (1.21 g). Flash column chromatography [silica
gel (75 g), ethyl acetate/methanol] gave 2a as an oil (220
4.1.3. 3-(Dicyclopentylphosphinoyl)cyclopentanone 4c.
From 2-cyclopentenone (3.04 g, 3.16 mL, 37.0 mmol),
,
acetic acid (5 mL), molecular sieves (4 A, 200 mg) and
chlorodicyclopentylphosphine14 (7.57 g, 37.1 mmol) and
following the procedure described for 4b, pure 4c was
obtained as a yellow viscous oil (9.90 g, quantitative
yield). IR (NaCl) 1740 (CꢁO st), 1155, 1118 (PꢁO st)
cm−1; 1H NMR 2.59–2.48 (m, 1H, 2-Ha), 2.48–2.35
(complex signal, 3H, 2-Hb, 3-H, 5-Ha), 2.26–2.00 (com-
plex signal, 5H, cyclopentyl CH, 4-Ha, 4-Hb, 5-Hb),

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
767
1.96–1.52 (complex signal, 16H, cyclopentyl CH2); 13C
temperature for 18 h. The solvent was evaporated
under reduced pressure, the residue was treated with
aqueous 5N NaOH (220 mL) and the mixture was
heated under reflux for 30 min. The mixture was
allowed to cool to room temperature, 6N HCl (300 mL)
was added until neutral pH and the solution was
extracted with CHCl3 (3×245 mL). The combined
organic phases were dried (Na2SO4), filtered and evapo-
rated under reduced pressure to give a mixture of 6b
and its trans-stereoisomer in the ratio of 6:1 (1H NMR)
as a pale brown solid (19.4 g, 96%). An analytical
sample of 6b was obtained by crystallization, mp 145–
146°C (ethyl acetate). IR (KBr) 3321 (OH st), 1152,
3
NMR 216.2 (C, d, JCP=12.7 Hz, C1), 38.6 (CH2, s,
C2), 37.5 (CH2, d, 1JCP=6.0 Hz, C5), 36.7 (CH, d,
1JCP=67.0 Hz) and 36.5 (CH, d, 1JCP=67.0 Hz)
(cyclopentyl CH), 34.0 (CH, d, 1JCP=67.0 Hz, C3),
26.8–26.6 (CH2, complex signal, cyclopentyl C2 and
C5), 26.0–25.7 (CH2, complex signal, cyclopentyl C3
2
and C4), 23.3 (CH2, d, JCꢀP=2.4 Hz, C4); 31P NMR
+
+
’
’
50.2; MS (EI), m/z (%): 268 (M , 4), 200 [(M−C5H8) ,
+
’
20], 186 [[HPO(C5H9)2] , 36], 119 (41), 118
+
’
+
[[H2POC5H9] , 45], 83 [[M−PO(C5H9)2] , 100]. Anal.
calcd for C15H25O2P·0.75H2O: C, 63.92; H, 9.48. Found
C, 64.03; H, 9.52%.
1
1120 (PꢁO st) cm−1; H NMR 7.80–7.73 (complex sig-
4.1.4.
(3,3-Dimethoxycyclopentyl)diphenylphosphine
nal, 4H, Ar-Hortho), 7.53–7.42 (complex signal, 6H,
Ar-Hmeta, Ar-Hpara), 5.20–4.80 (broad s, 1H, OH), 4.28
(broad s, 1H, 1-H), 3.02–2.94 (m, 1H, 3-H), 2.14–1.96
(complex signal, 3H, 2-Ha, 2-Hb, 4-Hb or 4-Ha), 1.94–
1.82 (complex signal, 2H, 4-Ha or 4-Hb, 5-Ha), 1.77–
1.68 (m, 1H, 5-Hb); 13C NMR 132.9 (C, higher l signal
of a d) and 131.5 (C, d, 1JCꢀP=97.7 Hz) (Ar-Cipso),
oxide 5b. To a cold (ice-bath) solution of 4b (3.07 g,
10.8 mmol) in methanol (35 mL), solid NaBH4 (0.79 g,
20.9 mmol) was added portionwise for 1 h. When the
addition was over, the ice-bath was removed and the
mixture was stirred at room temperature for 18 h. The
solvent was evaporated under reduced pressure, the
residue was treated with aqueous 5N NaOH (21 mL)
and the mixture was heated under reflux for 30 min.
The mixture was allowed to cool to room temperature,
6N HCl (18 mL) was added and the solution was
extracted with CHCl3 (6×10 mL). The combined
organic phases were dried (Na2SO4), filtered and evapo-
rated under reduced pressure to give a brown viscous
4
4
131.7 (CH, d, JCꢀP=2.7 Hz) and 131.6 (CH, d, JCꢀP
=
2
2.8 Hz) (Ar-CHpara), 130.8 (CH, d, JCꢀP=8.8 Hz) and
2
130.7 (CH, d, JCꢀP=8.8 Hz) (Ar-CHortho), 128.6 (CH,
3
d, JCꢀP=11.0 Hz, Ar-CHmeta), 72.7 (CH, s, C1), 36.6
(CH2, d, JCꢀP=4.5 Hz, C5), 35.8 (CH2, d, JCꢀP=1.7
3
2
1
Hz, C2), 34.7 (CH, d, JCꢀP=71.3 Hz, C3), 23.4 (CH2,
d, JCꢀP=2.8 Hz, C4); 31P NMR 39.9; MS (EI), m/z
2
1
oil mixture of 5b and alcohol 6b (ratio 2.6:1, H NMR)
+
’
+
(%): 286 (M , 2), 285 [(M−H) , 2], 243 (22), 229 (32),
202 [[HPO(C6H5)2] , 100], 201 (34). Anal. calcd for
(2.84 g, 59.7% yield of 5b and 23% yield of 6b).
Standard column chromatography [silica gel (150 g),
ethyl acetate] allowed clean separation of the products.
An analytical sample of 5b was obtained as a white
solid by crystallization, mp 144–144.5°C (ethyl acetate).
IR (KBr) 1181, 1119 (PꢁO st) cm−1; 1H NMR 7.77–7.72
(m, 4H, Ar-Hortho), 7.50–7.40 (complex signal, 6H, 4
Ar-Hmeta, 2 Ar-Hpara), 3.16 (s, 3H) and 3.14 (s, 3H) (2
OCH3), 2.94–2.85 (m, 1H, 1-H), 2.10–1.97 (complex
signal, 2H, 2-Hb, 5-Hb), 1.97–1.89 (complex signal, 2H,
+
’
C17H19O2P·0.25H2O: C, 70.21; H, 6.76. Found: C,
70.24; H, 6.68%.
4.1.6. Mixture of cis-3-(dicyclopentylphosphinoyl)-
cyclopentanol 6c and its trans-stereoisomer. From
NaBH4 (4.32 g, 114 mmol), methanol (230 mL) and
ketone 4c (10.21 g, 38.1 mmol) and following the
procedure described for 6b, a mixture of 6c and its
trans-stereoisomer in the ratio of 9:1 (1H NMR) was
obtained (8.91 g, 87%) as a pale brown oil, which was
characterized and used as such in the next step. IR
(NaCl) 3377 (OH st), 1144 (PꢁO st) cm−1; MS (EI), m/z
2-Ha, 4-Hb or 4-Ha), 1.86–1.80 (m, 1H, 4-Ha or 4-Hb),
1
1.80–1.72 (m, 1H, 5-Ha); 13C NMR 132.8 (C, d, JCꢀP
=
1
96.6 Hz) and 132.5 (C, d, JCꢀP=97.1 Hz) (Ar-Cipso),
4
131.5 (CH, d, JCꢀP=1.5 Hz, Ar-CHpara), 130.8 (CH, d,
+
+
’
2JCꢀP=8.8 Hz) and 130.7 (CH, d, JCꢀP=8.2 Hz) (Ar-
2
(%): 270 (M , 2), 202 (41), 201 [(M−C5H9) , 34], 186
+
’
+
CHortho), 128.5 (CH, d, 3JCꢀP=11.5 Hz, Ar-CHmeta),
[[HPO(C5H9)2] , 100], 145 [(M−C5H8O–C3H5) , 40],
134 [(M−2 C5H8) , 36]. Anal. calcd for C15H27PO2·
+
’
111.1 (C, d, 3JCꢀP=12.6 Hz, C3), 50.2 (CH3, s) and 48.6
1
0.5H2O: C, 64.49; H, 10.10. Found: C, 64.69; H,
10.17%. Data for 6c from the spectra of the mixture: 1H
NMR 4.50–4.30 (broad s, 1H, OH), 4.27 (m, 1H, 1-H),
2.30–2.04 (complex signal, 6H, cyclopentyl CH, 2-Ha,
2-Hb, 3-H, 4-Ha), 2.00–1.55 (complex signal, 19H,
cyclopentyl CH2, 4-Hb, 5-Ha, 5-Hb); 13C NMR 72.4
(CH3, s) (2 OCH3), 35.0 (CH, d, JCꢀP=76.3 Hz, C1),
2
3
34.0 (CH2, d, JCꢀP=1.7 Hz, C2), 33.5 (CH2, d, JCꢀP
=
6.6 Hz, C4), 22.9 (CH2, s, C5); 31P NMR 31.5; MS (EI),
+
’
+
m/z (%): 330 (M , 0,5), 329 [(M−H) , 0,6], 299 [(M−
CH3O)+, 6], 202 [[HPO(C6H5)2] , 17], 201
+
’
[[PO(C6H5)2]+, 17], 129 [[M−PO(C6H5)2]+, 56], 97 [[M−
3
1
CH3OH−PO(C6H5)2]+,
100].
Anal.
calcd
for:
(CH, d, JCꢀP=5.5 Hz, C1), 36.8 (CH, d, JCꢀP=65.9
1
Hz) and 36.6 (CH, d, JCꢀP=66.4 Hz) (cyclopentyl C1),
36.2 (CH2, broad s, C2), 35.9 (CH2, d, JCꢀP=6.6 Hz,
C5), 34.3 (CH, d, JCꢀP=63.7 Hz, C3), 27.4 (2 CH2, s),
C19H23O3P: C, 69.07; H, 7.02. Found C, 69.32; H,
7.01%.
3
1
27.2 (CH2, s) and 27.1 (CH2, s) (cyclopentyl C2 and
4.1.5.
cis-3-(Diphenylphosphinoyl)cyclopentanol
6b.
3
C5), 26.3 (CH2, d, JCꢀP=9.9 Hz) and 26.2 (CH2, d,
Methanol (375 mL) was treated with NaBH4 (2.66 g,
70.3 mmol) for 30 min. The mixture was cooled (ice-
bath) and was added to solid 4b (20.0 g, 70.4 mmol).
More NaBH4 (5.30 g, 140 mmol) was added portion-
wise for 1 h. When the addition was over, the ice-bath
was removed and the mixture was stirred at room
3JCꢀP=9.9 Hz) (cyclopentyl C3 and C4), 26.0 (CH2, d,
3JCꢀP=9.9 Hz), 25.9 (CH2, d, 3JCꢀP=9.9 Hz), 24.1
2
(CH2, d, JCꢀP=2.7 Hz, C4); 31P NMR 56.0. Data for
the trans-stereoisomer of 6c from the spectrum of the
mixture: 31P NMR 52.5.

768
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
3
4.1.7. cis-3-(Diphenylphosphinoyl)cyclopentyl methane-
sulfonate 7b. To a cold (ice-bath) solution of a mixture
of 6b and its trans-stereoisomer (19.4 g, 67.8 mmol) in
anhydrous CH2Cl2 (345 mL), anhydrous triethylamine
(23.7 mL, 17.2 g, 170 mmol) and 4-(dimethyl-
amino)pyridine (830 mg, 6.8 mmol) were added. The
solution was stirred for 5 min and methanesulfonyl
chloride (6.44 mL, 98% content, 81 mmol) was added
dropwise and the mixture was stirred for 6 h. The
ice-bath was removed, the mixture was diluted with
CH2Cl2 (170 mL) and the solution was washed with
NH4Cl (saturated aqueous solution, 2×345 mL) and 2N
HCl (2×250 mL). The organic phase was dried
(Na2SO4), filtered and evaporated in vacuo to give a
mixture of 7b and its trans-stereoisomer in the ratio of
6:1 (1H NMR) as a foamy brown solid (21.1 g, 82%).
An analytical sample of 7b was obtained by crystalliza-
tion, mp 129–130°C (ethyl acetate). IR (KBr) 1346 (SO2
C2), 33.4 (CH2, d, JCꢀP=9.3 Hz, C5), 27.0–26.9 (CH2,
complex signal, cyclopentyl C2 and C5), 26.1–25.9
(CH2, complex signal, cyclopentyl C3 and C4), 24.5
(CH2, d, JCꢀP=1.1 Hz, C4); 31P NMR 54.2.
2
4.1.9. Mixture of (2-cyclopentenyl)diphenylphosphine
oxide 9b and (3-cyclopentenyl)diphenylphosphine oxide
8b. The above mixture of 7b and its trans-stereoisomer
(21.1 g, 55.5 mmol) was heated in vacuo (135°C/1.0
Torr) for 6 h. The dark brown oil product formed was
dissolved in CH2Cl2 (200 mL) and the solution was
washed with aqueous 2N NaOH (2×175 mL), dried
(Na2SO4), filtered and evaporated to dryness to give a
solid mixture of 9b,13 and 8b (14.6 g, 98% yield) in the
1
approximate relative ratio of 1:1.8 by H NMR. An
analytical sample of 8b was obtained as a solid by
standard column chromatography [silica gel (70 g),
ethyl acetate] followed by crystallization, mp 151.5–
152.5°C (ethyl acetate). IR (KBr) 1185, 1118 (PꢁO st)
1
st), 1180, 1121 (PꢁO st and SO2 st) cm−1; H NMR
1
7.77–7.70 (complex signal, 4H, Ar-Hortho), 7.53–7.42
(complex signal, 6H, Ar-Hmeta, Ar-Hpara), 5.14 (broad
pseudo quint, J=6.0 Hz, 1H, 1-H), 2.96 (s, 3H,
SO2CH3), 2.76 (pseudo dq, J=9.0 Hz, J%=3.5 Hz, 1H,
3-H), 2.31–2.03 (complex signal, 4H, 2-Ha, 2-Hb, 4-Hb,
5-Ha), 2.03–1.94 (m, 1H, 5-Hb), 1.86–1.74 (m, 1H,
4-Ha); 13C NMR 133.0 (C, higher l signal of a d) and
cm−1; H NMR 7.78–7.73 (m, 4H, Ar-Hortho), 7.51–7.46
(m, 2H, Ar-Hpara), 7.46–7.41 (m, 4H, Ar-Hmeta), 5.66
[broad s, 2H, 3(4)-H], 3.12 (dtt, J=4.5 Hz, J%=8.5 Hz,
J%%=10.0 Hz, 1H, 1-H), 2.83–2.71 [m, 2H, 2(5)-Ha],
2.57–2.47 [m, 2H, 2(5)-Hb]; 13C NMR 133.0 (C, d,
1JCꢀP=96.7 Hz, Ar-Cipso), 131.4 (CH, d, JCꢀP=2.8 Hz,
4
2
Ar-CHpara), 130.9 (CH, d, JCꢀP=8.8 Hz, Ar-CHortho),
1
132.1 (C, d, JCꢀP=97.7 Hz) (Ar-Cipso), 131.7 (CH, d,
129.3 [CH, d, 3JCꢀP=7.9 Hz, C3(4)], 128.4 (CH, d,
4JCꢀP=2.2 Hz, Ar-CHpara), 130.8 (CH, d, 2JCꢀP=9.4
Hz) and 130.7 (CH, d, 2JCꢀP=9.3 Hz) (Ar-CHortho),
128.62 (CH, d, 3JCꢀP=11.5 Hz) and 128.59 (CH, d,
3JCꢀP=11.3 Hz, Ar-CHmeta), 35.0 (CH, d, JCꢀP=75.3
1
Hz, C1), 33.2 [CH2, C2(5)]; 31P NMR 32.8; MS (EI),
+
’
+
’
m/z (%): 268 (M , 5), 202 [[HPO(C6H5)2] , 100], 201
(28), 155 (34). Anal. calcd for: C17H17OP: C, 76.10; H,
6.39. Found: C, 75.97; H, 6.56%.
3
3JCꢀP=11.5 Hz) (Ar-CHmeta), 81.6 (CH, d, JCꢀP=11.0
1
Hz, C1), 38.7 (CH3, s, SO2CH3), 35.5 (CH, d, JCꢀP
=
3
75.8 Hz, C3), 33.5 (CH2, d, JCꢀP=8.8 Hz, C5), 32.8
(CH2, s, C2), 23.5 (CH2, d, 2JCꢀP=1.1 Hz, C4); 31P
4.1.10. Mixture of (2-cyclopentenyl)dicyclopentyl-
phosphine oxide 9c and (3-cyclopentenyl)dicyclopentyl-
phosphine oxide 8c. Heating a mixture of 7c and its
trans-stereoisomer (38.0 g, 0.11 mol) at 120°C/0.5 Torr
for 12 h, and following the work-up procedure
described for 7b, a mixture of 9c and 8c in a ratio of
1:2.8 (1H NMR) was obtained (26.4 g, 96%). The two
compounds could not be separated by column chro-
matography and were characterized as a mixture. An
oily analytical sample of the mixture was obtained by
distillation (100°C/0.5 Torr). IR (NaCl) 1158 (PꢁO st)
cm ; MS (EI), m/z (%): 252 (M , 2), 186 [[(HPO-
(C5H9)2] , 51], 145 (48), 119 (75), 118 [[(H2POC5H9) ,
84], 69 (C5H9 , 41), 67 (C5H7 , 100). Data for 8c from
the spectra of the mixture: H NMR 5.70 (broad s, 2H,
3(4)-H), 2.74–2.54 (complex signal, 5H, 1-H, 2(5)-Ha,
2(5)-Hb), 2.20–1.95 (complex signal, cyclopentyl CH),
1.94–1.48 (complex signal, 16H, cyclopentyl CH2); 13C
NMR 30.7; MS (EI), m/z (%): 269 [(M−SO3CH3)+, 24],
+
’
268 (17), 203 (24), 202 [[HPO(C6H5)2] , 100], 201 (93).
Anal. calcd for: C18H21O4PS·0.25H2O: C, 58.60; H,
5.88. Found: C, 58.83; H, 5.79%.
4.1.8. Mixture of cis-3-(dicyclopentylphosphinoyl)cyclo-
pentyl methanesulfonate 7c and its trans-stereoisomer.
From a mixture of 6c and its trans-stereoisomer in the
ratio of 9:1 (7.93 g, 29.4 mmol), anhydrous CH2Cl2
(200 mL), anhydrous triethylamine (10.3 mL, 74
mmol), 4-(dimethylamino)pyridine (359 mg, 2.94 mmol)
and methanesulfonyl chloride (2.78 mL, 98% content,
35.2 mmol) and following the procedure described for
6b, a mixture of 7c and its trans-stereoisomer was
obtained as a brown oil (8.94 g, 87%), which was
characterized and used as such in the next step. IR
(NaCl) 3416 (OH st, H2O), 1349 (SO2 st), 1197, 1177
(PꢁO st and SO2 st) cm−1; spectroscopic data for 7c:
GC/MS (conditions B, tr=7.62 min), m/z (%): 252
−1
+
’
+
’
+
’
+
+
1
3
NMR 129.3 [CH, d, JCꢀP=6.6 Hz, C3(4)], 36.7 [CH, d,
1JCꢀP=66.3 Hz, cyclopentyl CH], 34.2 (CH, d, JCꢀP
=
1
+
+
’
’
[(M−CH3SO3H) , 9], 186 [[HPO(C5H9)2] , 96], 185
65.3 Hz, C1), 33.7 [CH2, s, C2(5)], 26.9 (CH2, s,
+
1
3
’
(33), 145 (61), 119 (87), 118 [[H2PO(C5H9)] , 100]; H
NMR 5.17 (m, 1H, 1-H), 3.04 (s, 3H, CH3SO3), 2.45–
2.35 (m, 1H, 3-H), 2.30–2.00 (complex signal, 6H,
cyclopentyl CH, 2-Hb or 2-Ha, 4-Hb, 5-Ha, 5-Hb), 2.00–
1.50 (complex signal, 18H, cyclopentyl CH2, 2-Ha or
cyclopentyl C2 and C5), 25.99 (CH2, d, JCꢀP=9.6 Hz)
3
and 25.95 (CH2, d, JCꢀP=9.6 Hz) (cyclopentyl C3 and
C4); 31P NMR 52.2.
4.1.11. trans-(3,4-Epoxycyclopentyl)diphenylphosphine
oxide 2b. To a cold (ice-bath) solution of the above
mixture of 8b and 9b in the ratio of 1.8:1 (2.82 g, 10.6
mmol) in CH2Cl2 (50 mL), m-CPBA (8.9 g, 57% con-
tent, 29.4 mmol) was added and the mixture was stirred
2-Hb, 4-Ha); 13C NMR 82.1 (CH, d, JCꢀP=10.5 Hz,
3
1
C1), 38.4 (CH3, s, CH3SO3), 36.8 (CH, d, JCꢀP=66.9
Hz) and 36.7 (CH, d, 1JCꢀP=66.4 Hz) (cyclopentyl
1
CH), 35.1 (CH, d, JCꢀP=65.3 Hz, C3), 33.8 (CH2, s,

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
769
at room temperature for 18 h. The solution was diluted
with CH2Cl2 (50 mL), was washed with aqueous 10%
NaHSO3 (3×75 mL), H2O (75 mL) and brine (75 mL).
The organic phase was dried (Na2SO4), filtered and
concentrated under reduced pressure to give a foamy
yellow solid (2.72 g, 90%), mixture of 11b,13 10b13 and
2b in the approximate ratio of 1:4:9 (1H NMR). To a
solution of the above mixture (2.72 g, 9.58 mmol) in
ethanol (150 mL) was added a solution of KOH in
ethanol (4.3 mL, 1.6 M, 6.88 mmol) and the mixture
was stirred at room temperature for 18 h. The solution
was evaporated at reduced pressure to give a residue,
which was dissolved in H2O (50 mL). The solution was
made acidic (pH 1) with 5N HCl and was extracted
with CH2Cl2 (3×40 mL). The combined organic extracts
were dried (Na2SO4), filtered and concentrated in vacuo
to give a mixture of 2b and 12b (2.59 g, 95% yield) in
the approximate ratio of 2:1 (1H NMR) as a foamy
brown solid. Standard column chromatography of the
above mixture [silica gel (70 g), ethyl acetate] gave 2b as
a white solid (1.01 g, 52% overall yield from the
amount of 8b present in the mixture), 12b13 (780 mg,
73% overall yield from the amount of 9b present in the
mixture) and 240 mg of a mixture of 2b and 12b. An
analytical sample of 2b was obtained by crystallization
(ethyl acetate), mp 120–121°C. IR (KBr) 1184, 1118
J=8.0 Hz, J%=13.5 Hz, 2H, 2(5)-Hb], 2.10–2.00 [com-
plex signal, 4H, cyclopentyl CH, 2(5)-Ha [l 2.06, dt,
J=10.5 Hz, J%=13.0 Hz]], 2.00–1.91 [m, 1H, 1-H],
1.90–1.80 (complex signal, 8H), 1.78–1.64 (complex sig-
nal, 4H) and 1.63–1.50 (complex signal, 4H)
3
(cyclopentyl CH2); 13C NMR 56.5 [CH, d, JCꢀP=11.2
1
Hz, C3(4)], 37.4 [CH, d, JCꢀP=67.3 Hz, cyclopentyl
C1], 29.6 [CH, d, 1JCꢀP=65.8 Hz, C1], 28.7 [CH2, broad
2
s, C2(5)], 27.1 [CH2, d, JCꢀP=2.4 Hz, cyclopentyl C2
3
and C5], 26.2 (CH2, d, JCꢀP=10.2 Hz) and 26.1 (CH2,
3
d, JCꢀP=10.1 Hz) [cyclopentyl C3 and C4]; 31P NMR
+
+
’
51.3. MS (EI), m/z (%): 268 (M , 2), 267 [(M−H) , 3],
+
’
+
’
200 [(M−C5H8) , 18], 186 [[HPO(C5H9)2] , 10], 134
(47), 67 (100). Anal. calcd for: C15H25O2P·0.6H2O: C,
64.54; H, 9.47. Found: C, 64.58; H, 9.59%.
4.1.13. c-4-(Diisopropylphosphinoyl)-t-2-[(diphenylphos-
phinoyl)methyl]-r-1-cyclopentyl acetate 14a and t-4-
(diisopropylphosphinoyl) - t - 2 - [(diphenylphosphinoyl)-
methyl]-r-1-cyclopentyl acetate 17a
4.1.13.1. Mixture of alcohols 13a and 16a. To a cold
solution (ice-bath) of methyldiphenylphosphine oxide
(220 mg, 1.00 mmol) in anhydrous THF (3.0 mL) was
added dropwise n-butyllithium (0.75 mL, 1.6 M in
hexanes, 1.2 mmol). The suspension was cooled to
−78°C and a solution of anhydrous epoxide 2a (216 mg,
1.00 mmol, azeotropic distillation of the water content
with toluene in a Dean–Stark equipment) in anhydrous
toluene (1 mL) was added dropwise. The mixture was
allowed to warm to room temperature for 3 h, and then
was heated under reflux for 15 h. The mixture was
allowed to cool to room temperature, saturated
aqueous solution of NH4Cl (6 mL) was added, and the
organic phase was separated and evaporated to dryness
in vacuo. The residue was dissolved in water (15 mL)
and extracted with CH2Cl2 (3×30 mL). The combined
organic phases were dried (Na2SO4) and concentrated
in vacuo to give a dark oily residue (410 mg). Flash
column chromatography of the above solid [silica gel
(21 g), ethyl acetate/methanol mixtures] gave a mixture
of 13a and 16a (270 mg, 62%) in a ratio of 3:1 (1H
NMR). Attempted separation of a mixture of these
alcohols from a higher scale batch, gave only mixtures
of these alcohols in different ratio.
1
(PꢁO st) cm−1; H NMR 7.76–7.71 (m, 2H, Ar-Hortho),
7.51–7.46 (m, 2H, Ar-Hpara), 7.46–7.41 (m, 4H, Ar-
Hmeta), 3.53 (s, 2H, 3(4)-H), 2.64 (dtt, J=2.0 Hz, J%=
8.0 Hz, J%%=10.0 Hz, 1H, 1-H), 2.11 (dt, J=10.0 Hz,
J%=14.5 Hz, 2H, 2(5)-Ha), 2.01 (ddd, J=1.0 Hz, J%=
8.0 Hz, J%%=14.5 Hz, 2H, 2(5)-Hb); 13C NMR 132.5 (C,
1
4
d, JCꢀP=97.7 Hz, Ar-Cipso), 131.5 (CH, d, JCꢀP=2.6
Hz, Ar-CHpara), 130.4 (CH, d, 2JCꢀP=9.1 Hz, Ar-
CHortho), 128.5 (CH d, 3JCꢀP=11.6 Hz, Ar-CHmeta),
56.8 [CH, d, 3JCꢀP=12.7 Hz, C3(4)], 31.0 (CH, d,
1JCꢀP=76.5 Hz, C1), 27.8 [CH2, s, C2(5)]; 31P NMR
+
+
’
25.6; MS (EI), m/z (%): 285 [(M+H) , 2], 284 (M , 1),
+
+
’
283 [(M−H) , 4], 256 [(M−CO) , 17], 255 (23), 228
+
’
+
[(M−C3H4O) , 33], 202 (76), 201 [[PO(C6H5)2] , 100].
Anal. calcd for: C17H17O2P: C, 71.82; H, 6.03. Found:
C, 71.90; H, 6.10%.
4.1.12. trans-(3,4-Epoxycyclopentyl)dicyclopentylphos-
phine oxide 2c. From a mixture of 8c and 9c in the ratio
of 2.8:1 (23.4 g, 93 mmol) in CH2Cl2 (500 mL) and
m-CPBA (58.4 g, 57%, 0.19 mol) and following a
similar procedure to that described for 2b, a mixture of
10c,13 11c13 and 2c (23.0 g, 93%) in the ratio of 1:2:7
(1H NMR) was obtained. Flash column chromatogra-
phy of the mixture [silica gel (270 g), ethyl acetate/
methanol mixtures] gave a mixture of 10c and 11c (1.16
g), a mixture of the three epoxides (10.8 g) and 2c (8.28
g) on elution with a mixture of ethyl acetate/methanol
in the ratio of 95:5. The mixture of the three epoxides
was submitted to a new flash column chromatography
[silica gel (100 g), ethyl acetate/methanol mixtures] to
give a mixture of 10c and 11c (2.68 g), a mixture of the
three epoxides (2.42 g) and 2c (4.01 g). Overall yield of
2c from the amount of 8c present in the starting
mixture: 62%. Analytical data for 2c: mp:25°C (wax
at room temperature). IR (NaCl) 1186, 1143 (PꢁO st)
4.1.13.2. Acetylation of the mixture of 13a and 16a. A
solution of a mixture of 13a and 16a [in the ratio of
65:35 (HPLC), 800 mg, 1.85 mmol] in acetic anhydride
(9.5 mL) was heated under reflux for 2 h. The solution
was allowed to cool to room temperature and then
evaporated to dryness. The residue was dissolved in
CH2Cl2 (80 mL) and was washed with H2O (3×40 mL).
The organic phase was dried (Na2SO4), filtered and
concentrated in vacuo to give a solid residue (820 mg).
Flash column chromatography of the above solid [silica
gel (90 g), ethyl acetate/methanol mixtures] gave pure
17a (200 mg), a mixture of 14a and 17a (160 mg) and
pure 14a (350 mg, 81% overall yield). Analytical sam-
ples of 14a and 17a were obtained by crystallization
from ethyl acetate.
4.1.13.3. Analytical and spectroscopic data for 14a.
Mp 158.5–159.5°C (ethyl acetate). IR (KBr) 1726 (CꢁO
1
cm−1; H NMR 3.52 [s, 2H, 3(4)-H], 2.16 [broad dd,

770
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
1
1
st), 1178, 1149 (PO st) cm−1; H NMR 7.75–7.70 (com-
plex signal, 4H, Ar-Hortho), 7.53–7.41 (complex signal,
6H, Ar-Hmeta, Ar-Hpara), 4.78 (pseudo q, J=6.5 Hz,
1H, 1-H), 2.57 (ddd, J=4.0 Hz, J%%=10.5 Hz, J%%%=14.5
Hz, 1H, CHsynP), 2.41 (m, 1H, 2-H), 2.34–2.20 (com-
plex signal, 3H, 3-Ha, 4-H and 5-Hb), 2.15 (ddd, J=
10.5 Hz, J%=13.0 Hz, J%%=15.0 Hz, 1H, CHantiP),
26.0 [CH, d, JCꢀP=62.8 Hz, [C
6
H(CH3)2]a], 21.1 (CH3,
2
s, OCOC6 H3), 16.8 (CH3, d, JCꢀP=2.4 Hz) and 16.7
2
(CH3, d, JCꢀP=2.4 Hz) [[CH(C
2JCꢀP=2.5 Hz) and 16.5 (CH3, d, 2JCꢀP=2.4 Hz)
[[CH(C
H3)2]a]; 31P NMR 56.3 [PO(i-Pr)2], 30.3
[PO(C6H5)2]; MS (EI), m/z (%): 475 [(M+H)+, 5], 474
6 H3)2]b], 16.6 (CH3, d,
6
+
’
+
(M , 3), 431 [(M−CH3CO) , 25], 389 [(M−CH3CO–
C3H6)+, 32], 341 [[M−(i-Pr)2PO]+, 74], 281 [[M−
CH3COOH−(i-Pr)2PO]+, 70], 201 [[PO(C6H5)2]+, 100].
Anal. calcd for C26H36O4P2: C, 65.81; H, 7.65. Found:
C, 65.63; H, 7.61%.
2.06–1.93 [complex signal, 5H, 2 CH6 (CH3)2 and 1.97 (s,
OCOCH3)], 1.94–1.78 (complex signal, 2H, 3-Hb, 5-Ha),
1.14 (dd, J=7.5 Hz, J%=15.0 Hz, 6H), 1.13 (dd, J=7.5
Hz, J%=14.0 Hz, 3H) and 1.12 (dd, J=7.5 Hz, J%=15.0
Hz, 3H) [2 CH(CH
6
3)2]; 13C NMR 171.0 (C, s,
1
OC
6
OCH3), 133.7 (C, d, JCꢀP=93.6 Hz) and 132.4 (C,
4.1.14. c-4-(Diphenylphosphinoyl)-t-2-[(diphenylphosphi-
noyl)methyl]-r-1-cyclopentyl acetate 14b and t-4-(di-
phenylphosphinoyl) - t - 2 - [(diphenylphosphinoyl)methyl]-
r-1-cyclopentyl acetate 17b
1
4
d, JCꢀP=94.0 Hz) (Ar-Cipso), 131.8 (CH, d, JCꢀP=3.0
Hz) and 131.7 (CH, d, 4JCꢀP=2.6 Hz) (Ar-CHpara),
2
2
130.7 (CH, d, JCꢀP=9.1 Hz) and 130.5 (CH, d, JCꢀP
=
9.7 Hz) (Ar-CHortho), 128.7 (CH, d, 3JCꢀP=11.7 Hz)
4.1.14.1. Mixture of alcohols 13b and 16b. From
methyldiphenylphosphine oxide (472 mg, 98% content,
2.14 mmol) in anhydrous THF (12 mL), n-butyllithium
(2.14 mL, 1.6 M in hexanes, 3.42 mmol) and anhydrous
epoxide 2b (607 mg, 2.14 mmol, azeotropic distillation
of the water content with toluene in a Dean–Stark
equipment) in anhydrous THF (21 mL), and following
the above described procedure for 2a, a mixture of 13b
and 16b in the ratio of 3:2 (1H NMR) was obtained as
a foamy brown solid (960 mg, 90%), which could
neither be separated by column chromatography nor by
crystallization.
3
and 128.6 (CH, d, JCꢀP=11.7 Hz) (Ar-CHmeta), 80.5
(CH, dd, 3JCꢀP=10.4 Hz, 3JCꢀP=14.4 Hz, C1), 38.8
2
3
(CH, dd, JCꢀP=3.5 Hz, JCꢀP=6.0 Hz, C2), 32.7 [CH2,
1
2
d, JCꢀP=71.4 Hz, CH2P], 31.3 (CH2, d, JCꢀP=2.6 Hz,
C5), 29.8 (CH, d, 1JCꢀP=62.8 Hz, C4), 29.3 (CH2,
pseudo t, 2JCꢀP=3JCꢀP=2.5 Hz, C3), 26.2 (CH, d,
1JCꢀP=62.3 Hz) and 25.9 (CH, d, JCꢀP=62.8 Hz) [2
1
C6
H(CH3)2], 21.1 (CH3, s, OCOC
6 H3), 16.8 (CH3, d,
2JCꢀP=2.0 Hz), 16.7 (CH3, d, 2JCꢀP=2.6 Hz), 16.6
2
2
(CH3, d, JCꢀP=2.5 Hz) and 16.5 (CH3, d, JCꢀP=2.5
Hz) [2 CH(C
H3)2]; 31P NMR 56.9 [PO(i-Pr)2], 30.4
[PO(C6H5)2]; MS (EI), m/z (%): 475 [(M+H)+, 2], 474
(M , 2), 415 [(M−CH3COO) , 8], 389 [(M−CH3CO−
C3H6)+, 39], 341 [[M−(i-Pr)2PO]+, 34], 281 [[M−
CH3COOH−(i-Pr)2PO]+, 65], 215 [[CH2PO(C6H5)2]+,
14], 201 [[PO(C6H5)2]+, 100]. Anal. calcd for
C26H36O4P2: C, 65.81; H, 7.65. Found: C, 65.63; H,
7.86%.
6
+
’
+
4.1.14.2. Acetylation of the mixture of 13b and 16b.
From a mixture of 13b and 16b in the ratio of 3:2 (1.12
g, 2.25 mmol) and acetic anhydride (9.5 mL) and
following a similar procedure to that described above
for the mixture of 13a and 16a, a mixture of acetates
14b and 17b (1.15 g) was obtained. Flash column
chromatography of the above mixture [silica gel (100 g),
ethyl acetate/methanol mixtures] gave pure 17b (350
mg, 30% overall yield from 2b), a mixture of 14b and
17b (60 mg) and pure 14b (470 mg, 41% overall yield
from 2b). Analytical samples of 14b and 17b were
obtained by crystallization (ethyl acetate).
4.1.13.4. Analytical and spectroscopic data for 17a.
Mp 184.5–185.5°C (ethyl acetate). IR (KBr) 1731 (CꢁO
st), 1168, 1147 (PꢁO st) cm−1; 1H NMR 7.79–7.71
(complex signal, 4H, Ar-Hortho), 7.51–7.41 (complex
signal, 6H, Ar-Hmeta, Ar-Hpara), 4.90 (ddd, J=3.5 Hz,
J%=5.5 Hz, J%%=7.0 Hz, 1H, 1-H), 2.64 [ddd, J=3.0
Hz, J%=13.0 Hz, J%%=14.5 Hz, 1H, CHsyn-P], 2.52 (m,
1H, 2-H), 2.45–2.34 [complex signal, 2H, 5-Hb, CHanti
P], 2.27 (tt, J=10.0 Hz, J%=10.5 Hz, 1H, 4-H), 2.03–
1.82 [complex signal, 6H, 3-Ha, 2 CH(CH3)2 and 1.96
(s, 3H, OCOCH3)], 1.77 (m, 1H, 5-Ha), 1.49 (tt, J=10.0
Hz, J%=11.0 Hz, 1H, 3-Hb), 1.14 (dd, J=7.5 Hz,
J%=14.5 Hz, 3H) and 1.13 (dd, J=7.5 Hz, J%=14.5 Hz,
3H) [[CH(CH6 3)2]b], 1.06 (dd, J=7.5 Hz, J%=14.5 Hz,
3H) and 0.99 (dd, J=7.5 Hz, J%=14.5 Hz, 3H)
3)2]a]; 13C NMR 170.6 (C, s, OC
[[CH(CH OCH3), 133.3
4.1.14.3. Analytical and spectroscopic data for 14b.
Mp 233.5–234°C (ethyl acetate). IR (KBr) 1725 (CꢁO
st), 1181, 1119 (PꢁO st) cm−1; 1H NMR 7.71–7.62
(complex signal, 8H, Ar-Hortho), 7.51–7.37 (complex
signal, 12H, Ar-Hmeta, Ar-Hpara), 4.77 (q, J=7.5 Hz,
1H, 1-H), 2.89–2.80 (m, 1H, 4-H), 2.54 (ddd, J=4.0
Hz, J%=10.5 Hz, J%%=15.0 Hz, 1H, CHsyn-P), 2.48–2.38
(m, 1H, 2-H), 2.31–2.19 (complex signal, 2H, 3-Ha,
5-Hb), 2.15 (ddd, J=10.0 Hz, J%=12.5 Hz, J%%=15.0
Hz, 1H, CHanti-P), 1.92 (s, 3H, CH3), 1.86 (dddd,
J=8.5 Hz, J%=10.5 Hz, J%%=13.5 Hz, J%%%=18.0 Hz,
1H, 5-Ha), 1.73 (pseudo ddt, J=8.0 Hz, J%=14.0 Hz,
J%%=10.0 Hz, 1H, 3-Hb); 13C NMR 170.8 (C, s, CꢁO),
-
6
6
6
1
1
(C, d, JCꢀP=97.6 Hz) and 133.2 (C, d, JCꢀP=98.8 Hz)
(Ar-Cipso), 131.7 (CH, d, 4JCꢀP=2.4 Hz) and 131.6 (CH,
4
2
d, JCꢀP=3.0 Hz) (Ar-CHpara), 130.8 (CH, d, JCꢀP=9.8
Hz) and 130.6 (CH, d, 2JCꢀP=9.1 Hz) (Ar-CHortho),
128.7 (CH, d, 3JCꢀP=11.6 Hz) and 128.6 (CH, d,
1
1
133.4 (C, d, JCꢀP=98.2 Hz), 132.4 (C, d, JCꢀP=98.2
Hz), 132.3 (C, d, 1JCꢀP=98.2 Hz) and 131.8 (C, d,
1JCꢀP=98.2 Hz) (Ar-Cipso), 131.7 (CH, d, 4JCꢀP=1.5
Hz) and 131.6 (CH, d, 4JCꢀP=1.5 Hz) (Ar-CHpara),
3JCꢀP=11.6 Hz) (Ar-CHmeta), 81.1 (CH, dd, JCꢀP=8.5
3
3
2
Hz, JCꢀP=14.6 Hz, C1), 40.2 (CH, dd, JCꢀP=4.0 Hz,
3JCꢀP=8.9 Hz, C2), 32.8 [CH2, d, 1JCꢀP=70.7 Hz,
2
2
130.9 (CH, d, JCꢀP=9.1 Hz), 130.7 (CH, d, JCꢀP=8.1
CH2P], 32.2 (CH2, t, JCꢀP=3JCꢀP=2.4 Hz, C3), 31.9
Hz), 130.6 (CH, d, JCꢀP=8.6 Hz) and 130.4 (CH, d,
2
2
1
2
3
(CH, d, JCꢀP=62.8 Hz, C4), 31.7 (CH2, d, JCꢀP=2.4
Hz, C5), 26.4 [CH, d, JCꢀP=62.8 Hz, [C
2JCꢀP=9.1 Hz) (Ar-CHortho), 128.6 (CH, d, JCꢀP=11.2
1
3
6
H(CH3)2]b],
Hz) and 128.5 (CH, d, JCꢀP=11.2 Hz) (Ar-CHmeta),

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
771
80.1 (CH, dd, 3JCꢀP=10.6 Hz, 3J% ꢀP=13.7 Hz, C1),
13a and 16a, a mixture of 14c and 17c (920 mg) was
obtained. Flash column chromatography of the above
mixture [silica gel (70 g), ethyl acetate/methanol mix-
tures] gave, on elution with a mixture of ethyl acetate/
methanol in the ratio of 92:8 and in order of elution:
pure 17c (120 mg), a mixture of 14c and 17c (250 mg)
and pure 14c (200 mg). The overall yield of 14c plus 17c
from starting 2c was 45.5% (9.5% of pure 14c, 16% of
pure 17c and 20% of a mixture of 14c and 17c).
Analytical samples of 14c and 17c were obtained by
crystallization (ethyl acetate).
C
38.8 (CH, pseudo t, 2JCꢀP=3JCꢀP=4.1 Hz, C2), 33.1
1
1
(CH, d, JCꢀP=75.0 Hz, C4), 32.6 (CH2, d, JCꢀP=71.4
Hz, CH2-P), 30.4 (CH2, s, C5), 28.8 (CH2, s, C3), 21.0
(CH3, s, C
6
H3COO); 31P NMR 31.7 [Cy-PO(C6H5)2],
+
’
28.0 [CH2PO(C6H5)2]. MS (EI), m/z (%): 542 (M , 6),
483 [(M−CH3COO)+, 6], 341 [[M−PO(C6H5)2]+, 30], 281
[[M−PO(C6H5)2−AcOH]+,
48],
202
(28),
201
[[PO(C6H5)2]+, 100]. Anal. calcd for: C32H32O4P2: C,
70.84; H, 5.92. Found: C, 70.65; H, 5.86%.
4.1.14.4. Analytical and spectroscopic data for 17b.
Mp 239–239.5°C (ethyl acetate). IR (KBr) 1721 (CꢁO
st), 1181, 1119 (PꢁO st) cm−1; 1H NMR 7.74–7.66
(complex signal, 6H) and 7.58–7.53 (m, 2H) (Ar-Hortho),
7.50–7.31 (complex signal, 12H, Ar-Hmeta, Ar-Hpara),
4.92 (ddd, J=4.0 Hz, J%=5.5 Hz, J%%=7.0 Hz, 1H,
1-H), 2.84 (d quint, J=2.0 Hz, J%=9.5 Hz, 1H, 4-H),
2.62–2.53 (complex signal, 2H, 2-H, CHsyn-P), 2.44–
2.34 (complex signal, 2H, 5-Hb and CHanti-P), 1.93 (s,
3H, CH3COO), 1.86 (m, 1H, 3-Ha), 1.69 (dddd, J=4.5
Hz, J%=5.5 Hz, J%%=9.5 Hz, J%%%=14.0 Hz, 1H, 5-Ha),
4.1.15.3. Analytical and spectroscopic data for 14c.
Mp 197–198°C (ethyl acetate). IR (KBr) 1730 (CꢁO st),
1
1179, 1121 (PꢁO st) cm−1; H NMR 7.75–7.69 (complex
signal, 4H, Ar-Hortho), 7.53–7.41 (complex signal, 6H,
Ar-Hmeta, Ar-Hpara), 4.78 (pseudo q, J=7.0 Hz, 1H,
1-H), 2.56 (ddd, J=3.5 Hz, J%=10.5 Hz, J%%=14.5 Hz,
1H, CHsyn-P), 2.43–2.10 (complex signal, 5H, 2-H, 3-
6
Ha, 4-H, 5-Hb, CHanti-P), 2.02–1.91 (complex signal,
2H, cyclopentyl CH), 1.98 (s, 3H, CH3COO), 1.87–1.60
(complex signal, 14H) and 1.57–1.45 (complex signal,
4H) (cyclopentyl CH2, 3-Hb, 5-Ha); 13C NMR 170.7 (C,
1.51 (ddt, J=13.5 Hz, J%=15.0 Hz, J%%=9.0 Hz, 1H,
1
3-Hb); 13C NMR 170.3 (C, s, CO), 133.2 (C, d, JCꢀP
=
s, CO), 133.5 (C, d, 1JCꢀP=98,7 Hz) and 133.1 (C,
1
4
98.7 Hz) and 132.9 (C, d, JCꢀP=97.7 Hz), 133.0 and
132.8 (C, higher l signals of two d) (Ar-Cipso), 131.7
(CH, broad s) and 131.5 (CH, broad s) (Ar-CHpara),
higher l signal of a d) (Ar-Cipso), 131.7 (CH, d, JCꢀP
=
4
2.5 Hz) and 131.6 (CH, d, JCꢀP=2.5 Hz) (Ar-CHpara),
2
2
130.6 (CH, d, JCꢀP=9.1 Hz) and 130.4 (CH, d, JCꢀP
=
2
2
130.7 (CH, d, JCꢀP=9.1 Hz) and 130.5 (CH, d, JCꢀP
=
9.1 Hz) (Ar-CHortho), 128.6 (CH, d, 3JCꢀP=11.1 Hz)
9.1 Hz) (Ar-CHortho), 128.6 (CH, d, 3JCꢀP=11.6 Hz)
and 128.5 (CH, d, JCꢀP=11.7 Hz) (Ar-CHmeta), 80.4
3
3
and 128.4 (CH, d, JCꢀP=11.7 Hz) (Ar-CHmeta), 81.1
(CH, dd, 3JCꢀP=10.6 Hz, 3J%CꢀP=14.2 Hz, C1), 38.7
(CH, dd, 3JCꢀP=8.7 Hz, 3J% ꢀP=14.2 Hz, C1), 40.0
(CH, dd, JCꢀP=3.5 Hz, JCꢀP=6.6 Hz, C2), 36.9 (CH,
1 1
2
3
C
2
3
(CH, dd, JCꢀP=3.5 Hz, JCꢀP=8.6 Hz, C2), 35.4 (CH,
d, JCꢀP=66.8 Hz) and 36.6 (CH, d, JCꢀP=66.7 Hz)
1
1
1
d, JCꢀP=75.9 Hz, C4), 32.6 (CH2, d, JCꢀP=71.4 Hz,
(cyclopentyl CH), 32.56 (CH2, d, JCꢀP=69.9 Hz, CH2-
P), 32.5 (CH, d, JCꢀP=65.8 Hz, C4), 31.6 (CH2, s, C5),
1
CH2-P), 31.0 (CH2, s, C3), 30.9 (CH2, s, C5), 21.1
(CH3, s, C
6
H3COO); 31P NMR 30.8 [Cy-PO(C6H5)2],
29.5 (CH2, s, C3), 27.2 (CH2, broad s), 27.01 (CH2,
broad s) and 26.95 (2 CH2, broad s) (cyclopentyl C2
+
’
28.0 [CH2PO(C6H5)2]; MS (EI), m/z (%): 542 (M , 3),
483 [(M−CH3COO)+, 4], 341 [[M−PO(C6H5)2]+, 54], 281
[[M−PO(C6H5)2−CH3COOH]+, 40], 215 [[CH2PO-
(C6H5)2]+, 11], 202 (28), 201 [[PO(C6H5)2]+, 100]. Anal.
calcd for: C32H32O4P2: C, 70.84; H, 5.92. Found: C,
70.93; H, 5.80%.
3
and C5), 26.10 (CH2, d, JCꢀP=9.7 Hz), 26.05 (CH2, d,
3
3JCꢀP=10.1 Hz) and 26.01 (2 CH2, d, JCꢀP=9.7 Hz)
(cyclopentyl C3 and C4), 21.0 (CH3, s, C6
H3COO); 31P
NMR 51.2 [PO(C5H9)2], 28.0 [PO(C6H5)2]; MS (EI),
m/z (%): 467 [(M−CH3COO)+, 4], 389 [(M−C5H8–
C5H9)+, 31], 341 [(M−PO(C5H9)2)+, 24], 281 [[M−
PO(C5H9)2–CH3COOH]+, 59], 265 [[M−PO(C6H5)2–
CH3COOH]+, 17], 215 [[CH2PO(C6H5)2]+, 14], 201
[[PO(C6H5)2]+, 100], 185 [[PO(C5H9)2]+, 16]. Anal. calcd
for: C30H40O4P2: C, 68.42; H, 7.66. Found: C, 68.17; H,
7.68%.
4.1.15.
c-4-(Dicyclopentylphosphinoyl)-t-2-[(diphenyl-
phosphinoyl)methyl]-r-1-cyclopentyl acetate 14c and t-4-
(dicyclopentylphosphinoyl) - t - 2 - [(diphenylphosphinoyl)-
methyl]-r-1-cyclopentyl acetate 17c
4.1.15.1. Mixture of alcohols 13c and 16c. From
methyldiphenylphosphine oxide (716 mg, 3.3 mmol) in
anhydrous THF (100 mL), n-butyllithium (3.25 mL, 1.6
M in hexanes, 5.2 mmol) and anhydrous epoxide 2c
(870 mg, 3.25 mmol, azeotropic distillation of the water
content with toluene in a Dean–Stark equipment) in
anhydrous THF (150 mL), and following the above
described procedure for 2a, a mixture of 13c and 16c (in
4.1.15.4. Analytical and spectroscopic data for 17c.
Mp 200–200.5°C (ethyl acetate). IR (KBr) 1722 (CꢁO
1
st), 1181, 1162, 1120 (PꢁO st) cm−1; H NMR 7.78–7.70
(complex signal, 4H, Ar-Hortho), 7.51–7.41 (complex
signal, 6H, Ar-Hmeta, Ar-Hpara), 4.89 (ddd, J=3.0 Hz,
J%=5.5 Hz, J%%=8.0 Hz, 1H, 1-H), 2.71 (ddd, J=2.7
Hz, J%=12.5 Hz, J%%=15.0 Hz, 1H, CHsyn-P), 2.52–2.44
(m, 1H, 2-H), 2.44–2.36 (m, 1H, 5-Hb), 2.33 (ddd,
J=9.0 Hz, J%=10.5 Hz, J%%=15.0 Hz, 1H, CHanti-P),
2.24–2.16 (m, 1H, 4-H), 2.02–1.38 [complex signal,
24H, cyclopentyl CH and CH2, 3-Ha, 3-Hb, 5-Ha,
CH3COO (s, 1.97)]; 13C NMR 170.5 (C, s, CO), 133.2
1
the ratio of 2.5:1, H NMR) was obtained as a foamy
brown solid (1.16 g, 74%), which could not be sepa-
rated
by
column
chromatography
nor
by
crystallization.
4.1.15.2. Acetylation of the mixture of 13c and 16c.
From a solution of a mixture of 13c and 16c (860 mg,
1.77 mmol) in acetic anhydride (13.4 mL) and following
a similar procedure to that described for the mixture of
1
1
(C, d, JCꢀP=97.7 Hz) and 133.1 (C, d, JCꢀP=97.8 Hz)
(Ar-Cipso), 131.6 (CH, d, 4JCꢀP=2.2 Hz) and 131.5 (CH,
d, JCꢀP=2.2 Hz) (Ar-CHpara), 130.7 (CH, d, JCꢀP=9.3
4
2

772
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
Hz) and 130.4 (CH, d, 2JCꢀP=9.3 Hz) (Ar-CHortho),
128.6 (CH, d, 3JCꢀP=11.5 Hz) and 128.5 (CH, d,
2.6 Hz) [2 CH(C
[PO(C6H5)2]; MS (EI), m/z (%): 433 [(M+H)+, 4], 432
(M , 2), 347 [(M−C3H6–C3H7) , 5], 299 [(M−(i-
Pr)2PO]+, 33], 281 [[M−H2O–(i-Pr)2PO]+, 13], 231 [[M−
PO(C6H5)2]+, 100], 215 [[CH2PO(C6H5)2]+, 11], 201
[[PO(C6H5)2]+, 59]. Anal. calcd for C24H34O3P2·2.5H2O:
C, 60.36; H, 8.24. Found: C, 60.09; H, 8.17%.
6
H3)2]; 31P NMR 59.2 [PO(i-Pr)2], 35.5
3
+
’
+
3JCꢀP=11.5 Hz) (Ar-CHmeta), 80.9 (CH, dd, JCꢀP=9.3
3
2
Hz, J%CꢀP=14.8 Hz, C1), 40.5 (CH, dd, JCꢀP=3.5 Hz,
3JCꢀP=9.6 Hz, C2), 37.5 (CH, d, JCꢀP=66.9 Hz) and
1
36.9 (CH, d, 1JCꢀP=66.9 Hz) (cyclopentyl CH), 34.9
1
1
(CH, d, JCꢀP=65.8 Hz, C4), 32.9 (CH2, d, JCꢀP=71.3
Hz, CH2-P), 32.9 (CH2, s, C3), 32.0 (CH2, broad s, C5),
27.2 (CH2, broad s), 27.1 (CH2, broad s), 27.0 (CH2,
broad s) and 26.8 (CH2, broad s) (cyclopentyl C2 and
C5), 26.13 (CH2, d, 3JCꢀP=9.9 Hz), 26.10 (CH2, d,
3JCꢀP=9.7 Hz), 26.05 (CH2, d, 3JCꢀP=9.9 Hz) and 26.01
(CH2, d, 3JCꢀP=9.9 Hz) (cyclopentyl C3 and C4),
4.1.17. c-4-(Diphenylphosphinoyl)-t-2-[(diphenylphosphi-
noyl)methyl]-r-1-cyclopentanol 13b. From a solution of
14a (890 mg, 1.64 mmol) in methanol (60 mL) and
NaOCH3 (195 mg, 3.6 mmol) and following the proce-
dure described for 13a, 13b (820 mg, quantitative yield)
was obtained as a foamy brown solid. An analytical
sample of 13b was obtained by crystallization, mp
108–108.5°C (ethyl acetate). IR (KBr) 3380 (OH st),
21.1 (CH3, s, C6
H3COO); 31P NMR 50.8 [PO(C5+H9)2],
’
27.9 [PO(C6H5)2]; MS (EI), m/z (%): 526 (M , 1),
467 [(M−CH3COO)+, 7], 389 [(M−C5H8–C5H9)+, 84],
341 [[M−PO(C5H9)2]+, 75], 281 [[M−PO(C5H9)2–
CH3COOH]+, 73], 215 [[CH2PO(C6H5)2]+, 15], 201
[[PO(C6H5)2]+, 100], 185 [[PO(C5H9)2]+, 15]. Anal. calcd
for: C30H40O4P2: C, 68.42; H, 7.66. Found: C, 68.24; H,
7.81%.
1
1174, 1119 (PꢁO st) cm−1; H NMR 7.73–7.64 (complex
signal, 8H, Ar-Hortho), 7.53–7.37 (complex signal, 12H,
Ar-Hpara, Ar-Hmeta), 3.96 (pseudo q, J=7.0 Hz, 1H,
1-H), 2.96–2.87 (m, 1H, 4-H), 2.39–2.28 [complex sig-
nal, 2H, 3-Ha and CHsyn-P [l 2.36 (ddd, J=5.0 Hz,
J%=10.5 Hz, J%%=14.5 Hz)]], 2.20 (ddd, J=9.0 Hz,
J%=13.0 Hz, J%%=15.0 Hz, 1H, CHanti-P), 2.18–2.07
(complex signal, 2H, 2-H and 5-Hb), 1.98 (dddd, J=8.5
Hz, J%=9.0 Hz, J%%=13.0 Hz, J%%%=17.5 Hz, 1H, 5-Ha),
1.78 (ddt, J=7.5 Hz, J%=13.5 Hz, J%%=11.0 Hz, 1H,
4.1.16. c-4-(Diisopropylphosphinoyl)-t-2-[(diphenylphos-
phinoyl)methyl]-r-1-cyclopentanol 13a. To a solution of
14a (1.03 g, 2.2 mmol) in methanol (30 mL) was added
solid NaOCH3 (227 mg, 4.2 mmol) and the solution
was heated under reflux for 2 h. The mixture was
allowed to cool to room temperature and the solvent
was evaporated to dryness. The residue was dissolved in
CH2Cl2 (100 mL) and the solution was washed with
saturated aqueous solution of NH4Cl (2×30 mL). The
organic phase was dried (Na2SO4) and concentrated in
vacuo to give 13a as a very hygroscopic foamy white
solid (880 mg, 94%), which could not be crystallized. IR
(KBr, film) 3334 (OH st), 1169 (PꢁO st) cm−1; 1H NMR
7.73–7.68 (complex signal, 4H, Ar-Hortho), 7.53–7.49
(complex signal, 2H, Ar-Hpara), 7.48–7.43 (complex sig-
nal, 4H, Ar-Hmeta), 3.93 (pseudo q, J=7.5 Hz, 1H,
3-Hb); 13C NMR 133.0 (C, higher l signal of a d),
1
132.05 (C, higher l signal of a d), 132.05 (C, d, JCꢀP
=
1
97.2 Hz) and 131.95 (C, d, JCꢀP=97.2 Hz) (Ar-Cipso),
4
4
132.0 (2 CH, d, JCꢀP=2.5 Hz), 131.7 (CH, d, JCꢀP
=
4
4.1 Hz) and 131.6 (CH, d, JCꢀP=3.0 Hz) (Ar-CHpara),
2
2
130.92 (CH, d, JCꢀP=9.1 Hz), 130.88 (CH, d, JCꢀP
=
2
9.1 Hz), 130.8 (CH, d, JCꢀP=9.7 Hz) and 130.5 (CH,
2
3
d, JCꢀP=9.7 Hz) (Ar-CHortho), 128.8 (CH, d, JCꢀP
=
3
11.6 Hz), 128.7 (CH, d, JCꢀP=11.6 Hz), 128.6 (CH, d,
3JCꢀP=11.6 Hz) and 128.5 (CH, d, 3JCꢀP=11.6 Hz)
3
3
(Ar-CHmeta), 78.4 (CH, dd, JCꢀP=5.6 Hz, JCꢀP=9.1
Hz, C1), 42.1 (CH, t, JCꢀP=3JCꢀP=4.1 Hz, C2), 34.6
2
1
1-H), 2.49–2.38 [complex signal, 2H, 3-Ha and CHsyn
P
(CH2, d, JCꢀP=69.9 Hz, CH2-P), 33.8 (CH2, broad s,
1
[l 2.42, ddd, J=4.0 Hz, J%=11.0 Hz, J%%=15.0 Hz]],
2.35 (m, 1H, 4-H), 2.24 [ddd, J=9.5 Hz, J%=13.5 Hz,
J%%=15.0 Hz, 1H, CHantiP], 2.19 (ddt, J=5.5 Hz, J%=
7.5 Hz, J%%=13.0 Hz, 1H, 5-Hb), 2.14–1.97 [complex
C5), 32.7 (CH, d, JCꢀP=74.4 Hz, C4), 31.1 (CH2, dd,
2JCꢀP=2.3 Hz, 3JCꢀP=13.5 Hz, C3); 31P NMR 33,8
[CH-PO(C6H5)2], 32.3 [CH2PO(C6H5)2]; MS (EI), m/z
+
’
+
(%): 500 (M , 2), 299 [[M−PO(C6H5)2] , 72], 281 [[M−
PO(C6H5)2−H2O]+, 10], 215 [[CH2PO(C6H5)2]+, 13], 202
(41), 201 [[PO(C6H5)2]+, 100], 77 (70). Anal. calcd for:
C30H30O3P2·0.5H2O: C, 70.72; H, 6.14. Found: C,
70.76; H, 6.10%.
signal, 3H, 2 CH6 (CH3)2 and 2-H], 1.94 (dddd, J=8.5
Hz, J%=10.0 Hz, J%%=12.5 Hz, J%%%=14.0 Hz, 1H, 5-Ha),
1,74 (ddt, J=8.0 Hz, J%=10.5 Hz, J%%=13.0 Hz, 1H,
3-Hb), 1.17 (dd, J=7.2 Hz, J%=14.3 Hz, 3H), 1.15 (dd,
J=7.5 Hz, J%=14.5 Hz, 3H), 1.146 (dd, J=7.0 Hz,
J%=14.3 Hz, 3H), 1.14 (dd, J=7.5 Hz, J%=14.5 Hz,
4.1.18.
c-4-(Dicyclopentylphosphinoyl)-t-2-[(diphenyl-
1
3H) [2 CH(CH
6
3)2]; 13C NMR 132.3 (C, d, JCꢀP=101.1
phosphinoyl)methyl]-r-1-cyclopentanol 13c. From a solu-
tion of 14c (77 mg, 0.15 mmol) in methanol (6 mL) and
NaOCH3 (17.8 mg, 0.33 mmol) and following the pro-
cedure described for 13a, 13c (68 mg, 94%) was
obtained as a brown solid. An analytical sample of 13c
was obtained by crystallization, mp 144.5–145.5°C
(ethyl acetate). IR (KBr) 3393 (OH st), 1167, 1120 (PꢁO
st) cm−1; 1H NMR 7.74–7.68 (complex signal, 4H,
Ar-Hortho), 7.55–7.50 (complex signal, 2H, Ar-Hpara),
7.49–7.44 (complex signal, 4H, Ar-Hmeta), 6.20–6.00
(broad signal, 1H, OH), 3.93 (dt, J=8.5 Hz, J%=6.0
Hz, 1H, H-1), 2.50–2.40 [complex signal, 2H, 3-Ha,
CHsyn-P (l 2.48, ddd, J=3.5 Hz, J%=7.5 Hz, J%%=15.0
1
Hz) and 131.2 (C, d, JCꢀP=100.3 Hz) (Ar-Cipso), 132.0
(CH, d, 4JCꢀP=2.5 Hz, Ar-CHpara), 130.8 (CH, d,
2JCꢀP=9.6 Hz) and 130.4 (CH, d, JCꢀP=9.1 Hz) (Ar-
2
3
CHortho), 128.8 (CH, d, JCꢀP=12.2 Hz) and 128.7 (CH,
3
2
d, JCꢀP=11.6 Hz) (Ar-CHmeta), 78.2 (CH, dd, JCꢀP
=
=
3
2
4.5 Hz, JCꢀP=9.7 Hz, C1), 41.5 (CH, pseudo t, JCꢀP
4JCꢀP=3.8 Hz, C2), 34.6 (CH2, d, JCꢀP=3.0 Hz, C5),
2
1
34.58 (CH2, d, JCꢀP=69.9 Hz, CH2P), 31.4 (CH2, dd,
2JCꢀP=3.3 Hz, 3JCꢀP=13.4 Hz, C3), 28.9 (CH, d,
1JCꢀP=61.7 Hz, C4), 25.8 (CH, d, JCꢀP=62.8 Hz) and
1
25.6 (CH, d, 1JCꢀP=62.3 Hz) [2 C
6 H(CH3)2], 16.73
2
2
(CH3, d, JCꢀP=2.6 Hz), 16.67 (CH3, d, JCꢀP=2.0 Hz),
2
2
16.6 (CH3, d, JCꢀP=2.6 Hz) and 16.4 (CH3, d, JCꢀP
=
Hz)], 2.36–2.15 [complex signal, 3H, 4-H, 5-Hb, CHantiP

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
773
(l 2.26, ddd, J=10.5 Hz, J%=14.5 Hz, J%=15.0 Hz)],
2.08–1.94 (complex signal, 3H, cyclopentyl CH, 2-H),
1.88–1.44 (complex signal, 18H, cyclopentyl CH2, 3-Hb,
5-Ha); 13C NMR 132.4 (C, d, 1JCꢀP=100.7 Hz) and
2.2 Hz) [2 CH(C
[PO(C6H5)2]; MS (EI), m/z (%): 433 [(M+H)+, 3], 432
6
H3)2]; 31P NMR 56.7 [PO(i-Pr)2], 34.9
+
’
+
(M , 1), 347 [(M−C3H6–C3H7) , 13], 299 [(M−(i-
Pr)2PO]+, 68], 281 [[M−H2O–(i-Pr)2PO]+, 47], 231 [[M−
PO(C6H5)2]+, 95], 217 [[M−CH2PO(C6H5)2]+, 70], 215
[[CH2PO(C6H5)2]+, 24], 201 [[PO(C6H5)2]+, 100], 135
[(i-Pr)2POH2]+, 64]. Anal. calcd for C24H34O3P2·H2O:
C, 63.98; H, 8.06. Found: C, 64.18; H, 7.69%.
1
131.1 (C, d, JCꢀP=97.2 Hz) (Ar-Cipso), 132.0 (CH, d,
4
4JCꢀP=4.1 Hz) and 131.9 (CH, d, JCꢀP=3.0 Hz) (Ar-
2
CHpara), 130.8 (CH, d, JCꢀP=9.6 Hz) and 130.4 (CH,
2
3
d, JCꢀP=9.1 Hz) (Ar-CHortho), 128.73 (CH, d, JCꢀP
=
11.6 Hz) and 128.68 (CH, d, 3JCꢀP=11.6 Hz) (Ar-
3
3
CHmeta), 78.2 (CH, dd, JCꢀP=3.3 Hz, J%CꢀP=10.8 Hz,
4.1.20. t-4-(Diphenylphosphinoyl)-t-2-[(diphenylphosphi-
noyl)methyl]-r-1-cyclopentanol 16b. From a solution of
17b (530 mg, 0.98 mmol) in methanol (40 mL) and
NaOCH3 (116 mg, 2.15 mmol) and following the proce-
dure described for 13a, 16b (480 mg, 98%) was obtained
as a foamy brown solid. An analytical sample of 16b
was obtained by crystallization, mp 175–176.5°C (ethyl
acetate). IR (KBr) 3422 (OH st), 1188, 1167, 1118 (PꢁO
st) cm−1; 1H NMR 7.73–7.64 (complex signal, 8H,
C1), 41.4 (CH, t, JCꢀP=3JCꢀP=3.8 Hz, C2), 37.0 (CH,
2
1
1
d, JCꢀP=66.8 Hz) and 36.3 (CH, d, JCꢀP=66.3 Hz)
(cyclopentyl CH), 35.1 (CH2, s, C5), 34.7 [CH2, d,
2
1JCꢀP=69.8 Hz, CH2P], 31.8 (CH21, dd, JCꢀP=2.6 Hz,
3JCꢀP=14.2 Hz, C3), 31.7 (CH, d, JCꢀP=65.3 Hz, C4),
2
2
27.3 (CH2, d, JCꢀP=1.1 Hz), 27.1 (CH2, d, JCꢀP=1.1
2
Hz), 26.8 (CH2, d, JCꢀP=1.5 Hz) and 26.7 (CH2, d,
2JCꢀP=1.5 Hz) (cyclopentyl C2 and C5), 26.12 (CH2, d,
3JCꢀP=9.1 Hz), 26.06 (CH2, d, JCꢀP=9.6 Hz), 25.99
Ar-Hortho), 7.53–7.38 (complex signal, 12H, Ar-Hpara,
3
3
3
(CH2, d, JCꢀP=10.1 Hz) and 25.96 (CH2, d, JCꢀP=9.7
Hz) (cyclopentyl C3 and C4); 31P NMR 52.3
[PO(C5H9)2], 33.1 [PO(C6H5)2]; MS (EI), m/z (%): 485
[(M+H)+, 1], 347 [(M−C5H8−C5H9)+, 7], 299 [[M−
PO(C5H9)2]+, 29], 283 [[M−PO(C6H5)2]+, 100], 281 [[M−
PO(C5H9)2–H2O]+, 25], 215 [[CH2PO(C6H5)2]+, 20], 202
(30), 201 [[PO(C6H5)2]+, 88], 185 [[PO(C5H9)2]+, 17].
Anal. calcd for: C28H38O3P2: C, 69.41; H, 7.90. Found:
C, 69.61; H, 8.12%.
Ar-Hmeta), 6.00–5.20 (broad signal, 1H, OH), 4.10 (dt,
J=8.5 Hz, J%=7.5 Hz, 1H, 1-H), 2.90 (dtt, J=2.5 Hz,
J%=8.0 Hz, J%%=10.5 Hz, 1H, 4-H), 2.50–2.40 [complex
signal, 2H, 5-Hb and CHsyn-P (l 2.48, ddd, J=2.5 Hz,
J%=7.0 Hz, J%%=15.0 Hz)], 2.30 (dt, J=11.0 Hz, J%=
15.0 Hz, 1H, CHanti-P), 2.11–2.01 (m, 1H, 2-H), 1.85–
1.76 (complex signal, 3H, 3-Ha, 3-Hb, 5-Ha); 13C NMR
1
1
132.8 (C, d, JCꢀP=96.6 Hz), 132.7 (C, d, JCꢀP=100.2
Hz), 132.3 (C, d, 1JCꢀP=97.7 Hz) and 131.3 (C, d,
1JCꢀP=99.8 Hz) (Ar-Cipso), 132.0 (CH, d, 4JCꢀP=2.7
Hz), 131.9 (CH, d, 4JCꢀP=3.2 Hz), 131.6 (CH, d,
4.1.19. t-4-(Diisopropylphosphinoyl)-t-2-[(diphenylphos-
phinoyl)methyl]-r-1-cyclopentanol 16a. From a solution
of 17a (430 mg, 0.91 mmol) in methanol (12 mL) and
NaOCH3 (108 mg, 2.0 mmol) and following the proce-
dure described for 13a, 16a (380 mg, 97%) was obtained
as a foamy white solid. An analytical sample of 16a was
obtained by crystallization, mp 170–172°C (ethyl ace-
tate). IR (KBr) 3299 (OH st), 1175, 1150 (PꢁO st) cm−1;
1H NMR 7.77–7.68 (complex signal, 4H, Ar-Hortho),
7.55–7.43 (complex signal, 6H, Ar-Hmeta, Ar-Hpara),
5.74 (d, J=1.5 Hz, 1H, OH), 4.09 (pseudo dq, J=1.5
Hz, J%=7.0 Hz, 1H, 1-H), 2.52 (ddd, J=3.0 Hz, J%=7.0
Hz, J%%=15.0 Hz, 1H, CHsynP), 2,48 (tt, J=9.0 Hz,
J%=14.0 Hz, 1H, 5-Hb), 2.42–2.32 (m, 1H, 4-H), 2.34
(ddd, J=10.5 Hz, J%= 14.5 Hz, J%%=15.0 Hz, 1H,
4
4JCꢀP=2.8 Hz) and 131.5 (CH, d, JCꢀP=2.2 Hz) (Ar-
2
CHpara), 131.0 (CH, d, JCꢀP=9.4 Hz), 130.8 (CH, d,
2
2JCꢀP=9.4 Hz), 130.7 (CH, d, JCꢀP=8.8 Hz) and 130.3
(CH, d, 2JCꢀP=9.4 Hz) (Ar-CHortho), 128.75 (CH, d,
3JCꢀP=11.5 Hz), 128.73 (CH, d, 3JCꢀP=11.5 Hz),
128.54 (CH, d, 3JCꢀP=10.9 Hz) and 128.48 (CH, d,
3
3JCꢀP=11.0 Hz) (Ar-CHmeta), 77.7 (CH, dd, JCꢀP=1.9
3
2
Hz, JCꢀP=6.3 Hz, C1), 44.0 (CH, dd, JCꢀP=3.6 Hz,
3JCꢀP=10.2 Hz, C2), 34.6 (CH, dd, 4JCꢀP=1.0 Hz,
1JCꢀP=77.4 Hz, C4), 33.7 (CH2, d, 1JCꢀP=69.2 Hz,
2
CH2-P), 33.3 (CH2, d, JCꢀP=1.9 Hz, C5), 33.2 (CH2,
2
3
dd, JCꢀP=2.6 Hz, JCꢀP=14.6 Hz, C3); 31P NMR 32.7
[PO(C6H5)2], 31.3 [CH2PO(C6H5)2]; MS (EI), m/z (%):
+
+
’
500 (M , 1), 299 [[M−PO(C6H5)2] , 60], 281 [[M−H2O−
PO(C6H5)2]+, 14], 217 (23), 215 [[CH2PO(C6H5)2]+, 19],
203 (43), 202 (45), 201 [[PO(C6H5)2]+, 100]. Anal. calcd
for: C30H30O3P2·0.25H2O: C, 71.35; H, 6.09. Found: C,
71.31; H, 6.04%.
CHantiP), 2.09–1.91 [complex signal, 4H, 2 CH6 (CH3)2,
2-H, 3-Ha], 1.83 (m, 1H, 5-Ha), 1.77 (pseudo q, J=11.5
Hz, 1H, 3-Hb), 1.16 (dd, J=7.5 Hz, J%=14.5 Hz, 3H),
1.15 (dd, J=7.5 Hz, J%=14.5 Hz, 3H), 1,14 (dd, J=7.5
Hz, J%=14.5 Hz, 3H) and 1.12 (dd, J=7.5 Hz, J%=14.5
1
Hz, 3H) [2 CH(CH
6
3)2]; 13C NMR 132.9 (C, d, JCꢀP
=
4.1.21.
t-4-(Dicyclopentylphosphinoyl)-t-2-[(diphenyl-
1
100.4 Hz) and 131.6 (C, d, JCꢀP=97.6 Hz) (Ar-Cipso),
phosphinoyl)methyl]-r-1-cyclopentanol 16c. To a solu-
tion of 17c (50 mg, 0.095 mmol) in ethanol (10 mL) was
added KCN (0.5 mg, 7.7 mmol) and the mixture was
heated under reflux for 12 h. The mixture was allowed
to cool to room temperature and the solvent was
evaporated in vacuo to dryness. The residue was dis-
solved in H2O (10 mL) and was extracted with CH2Cl2
(3×5 mL). The combined organic extracts were dried
(Na2SO4), filtered and concentrated in vacuo to give
18c (38 mg, 83%) as a brown solid. An analytical
sample of 16c was obtained by crystallization, mp
148–149°C (ethyl acetate). IR (KBr) 3292 (OH st),
4
4
132.0 (CH, d, JCꢀP=2.7 Hz) and 131.9 (CH, d, JCꢀP
=
2
2.8 Hz) (Ar-CHpara), 131.0 (CH, d, JCꢀP=9.1 Hz) and
2
130.4 (CH, d, JCꢀP=9.5 Hz) (Ar-CHortho), 128.8 (CH,
3
3
d, JCꢀP=11.9 Hz, Ar-CHmeta), 77.6 (CH, dd, JCꢀP
=
3
2
2.9 Hz, JCꢀP=7.5 Hz, C1), 43.9 (CH, dd, JCꢀP=3.8
3
2
Hz, JCꢀP=9.6 Hz, C2), 34.3 (CH2, dd, JCꢀP=3.1 Hz,
3JCꢀP=14.4 Hz, C3), 33.58 [CH2, d, 1JCꢀP=69.9 Hz,
2
CH2P], 33.55 (CH2, d, JCꢀP=2.4 Hz, C5), 31.2 (CH, d,
1JCꢀP=63.5 Hz, C4), 26.2 (CH, d, JCꢀP=62.6 Hz) and
1
26.0 (CH, d, 1JCꢀP=62.6 Hz) [2 C
6 H(CH3)2], 16.75
2
2
(CH3, d, JCꢀP=2.5 Hz), 16.73 (CH3, d, JCꢀP=2.1 Hz),
2
2
1
16.6 (CH3, d, JCꢀP=2.4 Hz) and 16.5 (CH3, d, JCꢀP
=
1180, 1163, 1119 (PꢁO st) cm−1; H NMR 7.76–7.67

774
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
(complex signal, 4H, Ar-Hortho), 7.55–7.44 (complex
signal, 6H, Ar-Hmeta, Ar-Hpara), 5.72 (d, J=1.0 Hz, 1H,
OH), 4.08 (q, J=7.0 Hz, 1H, 1-H), 2.55 (ddd, J=2.5
Hz, J%=6.5 Hz, J%%=15.2 Hz, 1H, CHsyn-P), 2.44 (tt,
J=9.0 Hz, J%=14.0 Hz, 1H, 5-Hb), 2.36–2.24 [complex
signal, 2H, 4-H, CHantiP (l 2.30, dt, J=10.5 Hz, J%=
15.0 Hz)], 2.09–1.94 (complex signal, 4H, cyclopentyl
CH, 2-H, 3-Ha), 1.88–1.48 (complex signal, 18H,
cyclopentyl CH2, 3-Hb, 5-Ha); 13C NMR 132.7 (C, d,
a white solid. An analytical sample of 18 was obtained
by crystallization (ethyl acetate), mp 192–193°C. IR
1
(KBr) 1182, 1120 (PꢁO st) cm−1; H NMR 8.23 (s, 1H,
imidazole 2-H), 7.71–7.66 (complex signal, 8H, Ar-
Hortho), 7.62 (broad s, 1H, imidazole 5-H), 7.52–7.38
(complex signal, 12H, Ar-Hmeta, Ar-Hpara), 6.98 (broad
s, 1H, imidazole 4-H), 5.55 (q, J=5.5 Hz, 1H, 1-H),
3.06 (dq, J=3.5 Hz, J%=9.0 Hz, 1H, 4-H), 2.83–2.74
(m, 1H, 2-H), 2.53–2.44 (complex signal, 2H, 5-Hb,
CHsyn-P), 2.43–2.33 (m, 1H, 3-Ha), 2.25 (ddd, J=10.0
Hz, J%=13.0 Hz, J%%=15.0 Hz, 1H, CHanti-P), 2.14
(dddd, J=5.5 Hz, J%=8.5 Hz, J%%=14.0 Hz, J%%%=18.0
Hz, 1H, 5-Ha), 2.06–1.98 (m, 1H, 3-Hb); 13C NMR
183.6 (C, s, CS), 137.2 (CH, s, imidazole C2), 133.1 (C,
1
1JCꢀP=99.9 Hz) and 131.4 (C, d, JCꢀP=97.7 Hz) (Ar-
4
Cipso), 131.9 (CH, d, JCꢀP=2.8 Hz) and 131.8 (CH, d,
2
4JCꢀP=2.8 Hz) (Ar-CHpara), 130.9 (CH, d, JCꢀP=9.9
Hz) and 130.2 (CH, d, 2JCꢀP=9.9 Hz) (Ar-CHortho),
3
128.7 (CH, d, JCꢀP=11.5 Hz, Ar-CHmeta), 77.6 (CH,
3
3
1
1
dd, JCꢀP=3.3 Hz, JCꢀP=7.7 Hz, C1), 43.8 (CH, dd,
2JCꢀP=3.8 Hz, 3JCꢀP=10.4 Hz, C2), 37.1 (CH, d,
1JCꢀP=66.4 Hz) and 36.8 (CH, d, 1JCꢀP=66.4 Hz)
d, JCꢀP=96.6 Hz), 132.2 (C, d, JCꢀP=97.6 Hz), 131.8
1 1
(C, d, JCꢀP=96.6 Hz) and 131.7 (C, JCꢀP=97.7 Hz)
(Ar-Cipso), 131.9–131.7 (CH, complex signal, Ar-
(cyclopentyl CH), 34.6 (CH2, dd, 2JCꢀP=2.8 Hz, 3JCꢀP
=
CHpara), 130.9–130.2 (CH, complex signal, Ar-CHortho,
imidazole C4), 128.8–128.5 (CH, complex signal, Ar-
2
13.7 Hz, C3), 33.8 (CH, d, JCꢀP=66.4 Hz, C4), 33.7
2
1
(CH2, d, JCꢀP=1.1 Hz, C5), 33.6 (CH2, d, JCꢀP=69.7
Hz, CH2P), 27.1 (2 CH2, s), 27.0 (CH2, s) and 26.9
(CH2, s) (cyclopentyl C2 and C5), 26.2 (2 CH2, d,
CHmeta), 117.8 (CH, s, imidazole C5), 88.6 (CH, dd,
3
3JCꢀP=7.7 Hz, JCꢀP=12.6 Hz, C1), 39.6 (CH, broad s,
1
C2), 33.3 (CH, d, JCꢀP=74.7 Hz, C4), 31.7 (CH2, d,
3JCꢀP=9.9 Hz), 26.1 (CH2, d, JCꢀP=9.2 Hz) and 26.0
1JCꢀP=70.9 Hz, CH2-P), 30.0 (CH2, s, C5), 29.4 (CH2,
broad s, C3); 31P NMR 32.2 [Cy−PO(C6H5)2], 27.9
[CH2PO(C6H5)2]; MS (EI), m/e (%): 483 [[M−(C3H3N2)-
C(S)O]+, 3], 482 (3), 281 [[M−(C3H3N2)C(S)O−
PO(C6H5)2]+, 66], 202 (34), 201 [[PO(C6H5)2]+, 100].
Anal. calcd for C34H32N2O3P2S·0.5H2O: C, 65.90; H,
5.37. Found: C, 65.91; H, 5.15%.
3
3
(CH2, d, JCꢀP=9.3 Hz) (cyclopentyl C3 and C4); 31P
NMR 52.8 [PO(C5H9)2], 34.7 [PO(C6H5)2]; MS (EI),
m/z (%): 485 [(M+H)+, 4], 347 [(M−C5H8−C5H9)+, 34],
299 [[M−PO(C5H9)2]+, 63], 283 [[M−PO(C6H5)2]+, 100],
281
[[M−PO(C6H5)2−H2O]+,
32],
269
[[M−
CH2PO(C6H5)2]+, 26], 217 (27), 215 [[CH2PO(C6H5)2]+,
24], 202 (36), 201 [[PO(C6H5)2]+, 98]. Anal. calcd for:
C28H38O3P2: C, 69.40; H, 7.91. Found: C, 69.44; H,
8.03%.
4.1.24. trans-1-(Diphenylphosphinoyl)-3-[diphenylphos-
phinoyl)methyl]cyclopentane 19. To a solution of 18 (155
mg, 0.25 mmol) in anhydrous toluene (70 mL) was
added dropwise (n-Bu)3SnH (0.35 mL, 1.25 mmol) and
azobis(isobutyronitrile) (AIBN) (8.38 mg, 0.05 mmol)
and the mixture was heated under reflux for 4 h. The
mixture was allowed to cool to room temperature and
the solvent was removed under vacuum to give a solid
residue (860 mg), which was submitted to flash column
chromatography [silica gel (8 g), ethyl acetate/methanol
mixtures] to give pure 19 (68 mg, 56%), as a white solid,
on elution with a mixture ethyl acetate/methanol in the
ratio of 90:10. An analytical sample was obtained by
crystallization, mp 55–56°C (ethyl acetate). IR (KBr)
4.1.22. trans-(3,4-Epoxycyclopentyl)diphenylphosphine
15. To a solution of 2b (200 mg, 0.70 mmol) in anhy-
drous THF (4 mL), triethoxysilane (0.41 mL, 2.22
mmol) and titanium tetraisopropoxide (20 mg, 0.07
mmol) were added and the mixture was stirred under
reflux for 7 h. The solvent was evaporated under
reduced pressure. Standard column chromatography of
the residue [silica gel (4 g), hexane/ethyl acetate mix-
tures] gave 15 as a colorless oil (150 mg, 80%). 1H
NMR 7.46–7.39 (m, 4H, Ar-Hortho), 7.33–7.29 (complex
signal, 6H, Ar-Hmeta, Ar-Hpara), 3.49 (d, J=2.0 Hz, 2H,
3(4)-H), 2.54 (tq, J=10.5 Hz, J%=7.5 Hz, 1H, H-1),
2.10 (dd, J=7.5 Hz, J%=14.5 Hz, 2H, 2(5)-Hb), 1.62
(dt, J=10.5 Hz, J%=14.0 Hz, 2H, 2(5)-Ha); 13C NMR
1
1176, 1119 (PꢁO st) cm−1; H NMR 7.71–7.65 (complex
signal, 8H, Ar-Hortho), 7.49–7.37 (complex signal, 12H,
Ar-Hmeta, Ar-Hpara), 2.88–2.79 (m, 1H, 1-H), 2.35–2.25
(complex signal, 3H, CH2-P, 3-H), 2.24–2.14 (m, 1H,
2-Ha), 2.03–1.95 (m, 1H, 4-Hb or 4-Ha), 1.90–1.77
(complex signal, 2H, 5-Ha, 5-Hb), 1.63 (ddt, J=6.5 Hz,
J%=13.5 Hz, J%%=10.5 Hz, 1H, 2-Hb), 1.42–1.34 (m, 1H,
4-Ha or 4-Hb); 13C NMR 133.27 (C, d, 1JCꢀP=98.2 Hz),
1
137.5 (C, d, JCꢀP=13.2 Hz, Ar-Cipso), 132.9 (CH, d,
2JCꢀP=19.3 Hz, Ar-CHortho), 128.8 (CH, s, Ar-CHpara),
3
128.3 (CH, d, JCꢀP=7.1 Hz, Ar-CHmeta), 57.5 [CH, d,
2
3JCꢀP=12.7 Hz, C3(4)], 32.5 [CH2, d, JCꢀP=20.3 Hz,
C2(5)], 28.7 (CH, d, 1JCꢀP=8.1 Hz, C1); 31P NMR −7.0.
1
1
132.99 (C, d, JCꢀP=97.7 Hz), 132.86 (C, d, JCꢀP=96.1
1
4.1.23. O-[c-4-(Diphenylphosphinoyl)-t-2-[(diphenylphos-
phinoyl)methyl]-r-cyclopentyl] imidazole-1-carbothioate
18. To a solution of alcohol 13b (200 mg, 0.40 mmol) in
anhydrous toluene (15 mL) was added thiocarbonyldi-
imidazole (120 mg, 90% content, 0.61 mmol) and the
mixture was heated under reflux for 1 h. The mixture
was allowed to cool to room temperature and the
separated solid (a mixture of 18 and imidazole) was
collected by filtration. Elimination of imidazole by sub-
limation (60°C/1 Torr) gave pure 18 (161 mg, 65%) as
Hz) and 132.76 (C, d, JCꢀP=96.7 Hz) (Ar-Cipso), 131.5
(CH, broad signal) and 131.4 (CH, d, JCꢀP=2.2 Hz)
(2+2 Ar-CHpara), 130.86 (CH, d, JCꢀP=8.7 Hz), 130.79
(CH, d, JCꢀP=8.8 Hz), 130.55 (CH, d, JCꢀP=8.7 Hz)
4
2
2
2
2
and 130.51 (CH, d, JCꢀP=9.3 Hz) (Ar-CHortho), 128.54
(CH, d, 3JCꢀP=11.0 Hz), 128.52 (CH, d, 3JCꢀP=9.8 Hz),
128.41 (CH, d, 3JCꢀP=10.9 Hz) and 128.38 (CH, d,
3JCꢀP=10.9 Hz) (Ar-CHmeta), 35.8 (CH, d, JCꢀP=84.5
1
1
Hz, C1), 35.4 (CH2, s, C2), 35.2 (CH2, d, JCꢀP=71.4
Hz, CH2-P), 34.6 (CH, dd, JCꢀP=3.8 Hz, JCꢀP=6.0
2
3

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
775
3
Hz, C3), 33.6 (CH2, broad d, JCꢀP=8.7 Hz, C4), 26.0
nal, 2H, 2-Hb, 4-Hb), 1.74–1.64 (m, 1H, 5-Hb), 1.50
(ddt, J=12.5 Hz, J%=17.0 Hz, J%%=10.0 Hz, 1H, 2-Ha),
1.36 (dq, J=9.5 Hz, J%=12.5 Hz, 1H, 4-Ha); 13C NMR
(CH2, d, 2JCꢀP=1.7 Hz, C5); 31P NMR 33.3 [Cy-
PO(C6H5)2], 28.6 [CH2PO(C6H5)2]; MS (EI), m/e (%):
484 (M , 5), 284 (20), 283 [[M−PO(C6H5)2] , 100], 215
[[CH2PO(C6H5)2]+, 19], 202 (24), 201 [[PO(C6H5)2]+, 83];
Anal. calcd for C30H30O2P2·1.5H2O: C, 70.44; H, 6.51.
Found: C, 70.24; H, 6.38%.
+
’
+
1
1
133.4 (C, d, JCꢀP=97.7 Hz), 133.2 (C, d, JCꢀP=97.2
Hz), 132.9 (C, d, 1JCꢀP=96.1 Hz) and 132.8 (C, d,
1JCꢀP=96.6 Hz) (Ar-Cipso), 131.6 (CH, d, 4JCꢀP=2.8
4
Hz), 131.5 (2 CH, d, JCꢀP=2.8 Hz) and 131.3 (CH, d,
2
4JCꢀP=2.8 Hz) (Ar-CHpara), 130.73 (CH, d, JCꢀP=8.8
4.1.25. O-[t-4-(Diphenylphosphinoyl)-t-2-[(diphenylphos-
phinoyl)methyl]-r-cyclopentyl imidazole-1-carbothioate
20. To a solution of alcohol 16b (50 mg, 0.10 mmol) in
anhydrous CH2Cl2 (8 mL) was added thiocarbonyldi-
imidazole (30 mg, 90% content, 0.15 mmol) and the
mixture was heated under reflux for 4 h. The solvent
was evaporated under reduced pressure to give a yellow
residue (77 mg) mixture of 20 and imidazole. An ana-
lytical sample of 20 was obtained by crystallization, mp
170.5–171°C (ethyl acetate/methanol, 10:1). IR (KBr)
Hz), 130.64 (CH, d, 2JCꢀP=9.3 Hz), 130.55 (CH, d,
2JCꢀP=9.3 Hz) and 130.50 (CH, d, 2JCꢀP=9.3 Hz)
(Ar-CHortho), 128.52 (CH, d, 3JCP=11.5 Hz), 128.49
3
3
(CH, d, JCꢀP=11.5 Hz), 128.42 (CH, d, JCꢀP=11.5
3
Hz) and 128.37 (CH, d, JCꢀP=10.9 Hz) (Ar-CHmeta),
36.4 (CH, d, 1JCꢀP=75.2 Hz, C1), 35.0 (CH, dd, 2JCꢀP
=
3
1
4.4 Hz, JCꢀP=10.5 Hz, C3), 34.5 (CH2, d, JCꢀP=70.8
Hz, CH2P), 34.4 (CH2, broad s, C4), 34.3 (CH2, dd,
3
2JCꢀP and JCP=1.5 and 2.5 Hz, C2), 24.9 (CH2, s, C5);
31P NMR l: 32.6 [Cy-PO(C6H5)2], 28.4 [CH2PO-
1180 (PꢁO st) cm−1; H NMR 8.15 (s, 1H, imidazole
(C6H5)2]; MS (EI), m/z (%): 484 (M , 5), 283 [[M−
1
+
’
2-H), 7.73–7.60 (complex signal, 8H, Ar-Hortho), 7.52–
7.34 (complex signal, 13H, Ar-Hmeta, Ar-Hpara, imida-
zole 5-H), 6.99 (broad s, 1H, imidazole 4-H), 5.55
(broad pseudo dt, J=3.5 Hz, J%=6.5 Hz, 1H, 1-H),
2.97–2.87 (complex signal, 2H, 2-H, 4-H), 2.65 (dddd,
J=7.5 Hz, J%=9.5 Hz, J%%=15.0 Hz, J%%%=17.0 Hz, 1H,
5-Hb), 2.60–2.50 [complex signal, 2H, CH2P], 2.09–2.02
(m, 1H, 3-Ha), 1.92–1.85 (m, 1H, 5-Ha), 1.80–1.70 (m,
1H, 3-Hb); 13C NMR 182.8 (C, s, CS), 136.7 (CH, s,
PO(C6H5)2]+, 100], 269 [[M−CH2PO(C6H5)2]+, 15], 215
[[CH2PO(C6H5)2]+, 12], 201 [[PO(C6H5)2]+, 44]. Anal.
calcd for C30H30O2P·H2O: C, 71.70; H, 6.42. Found: C,
71.72; H, 6.55%.
4.1.27. (1S,2S,4R)- and (1R,2R,4S)-4-(Diisopropylphos-
phinoyl)-2-[(diphenylphosphinoyl)methyl]cyclopentyl N-
[(S)-a-phenylethyl]carbamate 22 and 23
4.1.27.1. Mixture of carbamates 22 and 23. To a
solution of 16a (360 mg, 0.83 mmol) in anhydrous
benzene (15 mL) was added dropwise anhydrous Et3N
(0.145 mL, 1.04 mmol) and (–)-(S)-a-phenylethyliso-
cyanate (96% e.e., 0.147 mL, 1.04 mmol) and the
mixture was heated under reflux for 6 h. The mixture
was allowed to cool to room temperature, more (−)-(S)-
a-phenylethylisocyanate (0.147 mL, 1.04 mmol) was
added dropwise and the mixture was heated under
reflux for 18 h. The mixture was cooled to room
temperature and was concentrated in vacuo to give a
solid residue (642 mg), which was submitted to flash
column chromatography [silica gel (30 g), ethyl acetate/
methanol mixtures] to give a mixture of 22 and 23 (420
mg, 87%) on elution with a mixture of ethyl acetate/
methanol in the ratio of 90:10. Repeated crystallization
of this mixture from ethyl acetate/methanol in the
approximate ratio of 15:1) allowed the separation of
both diastereomers. The different fractions were ana-
lyzed by Chiral HPLC [conditions A: 23: tr=34.9 min
1
imidazole C2), 133.1 (C, d, JCꢀP=99.2 Hz), 133.1 (C,
higher l signal of a d), 132.1 (C, d, 1JCꢀP=98.2 Hz) and
131.9 (C, d, 1JCꢀP=98.7 Hz) (Ar-Cipso), 131.9–131.6
(CH, complex signal, Ar-CHpara), 130.8–130.4 (CH,
complex signal, Ar-CHortho, imidazole C4), 128.9–128.5
(CH, complex signal, Ar-CHmeta), 117.9 (CH, s, imida-
3
3
zole C5), 89.5 (CH, dd, JCꢀP=9.1 Hz, J%CꢀP=11.1 Hz,
C1), 39.7 (CH, dd, JCꢀP=3.5 Hz, JCꢀP=9.1 Hz, C2),
35.4 (CH, d, JCꢀP=75.4 Hz, C4), 32.5 [CH2, d, JCꢀP
2
3
1
1
=
3
70.9 Hz, CH2P], 31.5 (CH2, broad d, JCꢀP=5.5 Hz,
C3), 30.9 (CH2, s, C5); 31P NMR 30.5 [Cy-PO(C6H5)2],
27.4 [CH2PO(C6H5)2]; MS (EI), m/e (%): 482 [[(M−
+
’
(C3H3N2)C(S)OH)] , 2], 281 [[M−(C3H3N2)C(S)OH)–
PO(C6H5)2]+, 61], 202 (26), 201 [[PO(C6H5)2]+, 100], 77
(97). Anal. calcd for C34H32N2O3P2S·0.75H2O: C, 65.43;
H, 5.41. Found: C, 65.41; H, 5.25%.
4.1.26. cis-1-(Diphenylphosphinoyl)-3-(diphenylphosphi-
noylmethyl)cyclopentane 21. To a solution of 20 (61 mg,
0.10 mmol) in anhydrous benzene (15 mL) was added
dropwise (n-Bu)3SnH (0.14 mL, 0.5 mmol) and AIBN
(3.3 mg, 0.02 mmol) and the mixture was heated under
reflux for 6 h. The mixture was allowed to cool to room
temperature and the solvent was removed under vac-
uum. The residue was dissolved in acetonitrile (8 mL),
the solution was washed with hexane (3×8 mL) and the
acetonitrile evaporated under reduced pressure to give
impure 21 as a brown solid (64 mg). An analytical
sample of 21 was obtained by crystallization, mp 172–
173°C (ethyl acetate). IR (KBr) 1177, 1120 (PꢁO st)
cm−1; 1H NMR 7.73–7.65 (complex signal, 6H) and
7.61–7.57 (complex signal, 2H) (Ar-Hortho), 7.49–7.33
(complex signal, 12H, Ar-Hpara, Ar-Hmeta), 2.74–2.65
(m, 1H, 1-H), 2.43–2.38 (complex signal, 3H, CH2P,
3-H), 2.05–1.94 (m, 1H, 5-Ha), 1.84–1.74 (complex sig-
and 22: tr=42.3 min, k%=4.0, k%=5.0, h=1.43 and
1
Rs=0.9] and were conveniently2 combined, finally
obtaining: fraction I (67 mg, pure 23), fraction II (130
mg, pure 22) and fraction III (209 mg, mixture of 23
and 22 enriched in 23).
4.1.27.2. Analytical and spectroscopic data for 22. Mp
210–212°C (ethyl acetate/methanol in a ratio close to
6:1). IR (KBr) 3425, 3223 (NH st and OH st, H2O),
1709 (CꢁO st), 1183, 1148 (PꢁO st) cm−1; 1H NMR
7.82–7.64 (complex signal, 4H, Ar-Hortho), 7.52–7.40
(complex signal, 6H, Ar-Hmeta, Ar-Hpara), 7.36–7.14
(complex signal, 5H, benzyl Ar-H), 4.99 (broad signal,
1H, NH), 4.83 (broad signal, 1H, 1-H), 4.78 (broad
signal, 1H, a-H), 2.74 (pseudo t, J=13.0 Hz, 1H,
CHsynP), 2.51 (broad signal, 1H, 2-H), 2.44–2.29 [com-

776
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
2
plex signal, 2H, 5-Hb, CHantiP (l 2.33 dt, J=7.0 Hz,
J%=13.5 Hz)], 2.24 (broad signal, 1H, 4-H), 2.00–1.80
broad s, a-CH3), 16,81 (CH3, d, JCꢀP=2.5 Hz), 16.75
2
2
(CH3, d, JCꢀP=2.5 Hz), 16.6 (CH3, d, JCꢀP=2.5 Hz)
and 16.5 (CH3, d, 2JCꢀP=2.5 Hz) [2 CH(CH3)2]; 31P
[complex signal, 3H, 2 CH
6
(CH3)2, 3-Ha], 1.79 (broad s,
6
3H, 5-Ha, H2O), 1.54–1.30 [complex signal, 4H, 3-Hb,
a-CH3 (l 1.45, d, J=5.5 Hz)], 1.12 (dd, J=7.5 Hz,
J%=14.5 Hz, 3H), 1.11 (dd, J=7.5 Hz, J%=14.5 Hz,
3H), 1.05 (dd, J=7.0 Hz, J%=14.5 Hz, 3H) and 0.98
NMR 54.9 and 54.2 [PO(i-Pr)2, 2 rotamers], 28.4
+
’
[PO(C6H5)2]; MS (EI), m/z (%): 579 (M , 0.1), 446
[(M−(i-Pr)2PO]+, 4], 299 [[M−C8H9NCO−(i-Pr)2PO]+,
16], 281 [M−C8H9NHCOOH−(i-Pr)2PO]+, 88], 231
[[M−C8H9NCO−PO(C6H5)2]+, 14], 217 [[M−C8H9-
NCO−CH2PO(C6H5)2]+, 18], 215 [[CH2PO(C6H5)2]+,
(dd, J=7.2 Hz, J%=14.2 Hz, 3H) [2 CH(CH3 2
NMR 155.0 (C, s, OCONH), 143.3 (C, s, Ar-Cipso
6
) ]; 13C
6
1
+
+
’
benzyl), 133.3 (C, d, JCꢀP=95.8 Hz) and 133.2 (C, d,
11], 201 [[PO(C6H5)2] , 100], 147 [(C8H9NCO) , 34],
132 [(C6H5CHNCO)+, 85). Anal. calcd for C33H43NO4P2:
C, 68.38; H, 7.48; N, 2.42. Found: C, 68.20; H, 7.62; N,
2.41%. [h]2D5=−52.0 (CHCl3, c=0.9).
1JCꢀP=97.7 Hz) (Ar-Cipso), 131.6 (CH, JCꢀP=3.0 Hz)
4
4
and 131.5 (CH, JCꢀP=2.3 Hz) (Ar-CHpara), 130.8 (CH,
d, 2JCꢀP=9.6 Hz) and 130.6 (CH, d, 2JCꢀP=9.1 Hz)
(Ar-CHortho), 128.56 (CH, d, 3JCꢀP=11.6 Hz, Ar-
CHmeta), 128.55 (CH, s, Ar-CHmeta benzyl), 128.51 (CH,
d, 3JCꢀP=11.6 Hz, Ar-CHmeta), 127.2 (CH, broad s,
Ar-CHpara benzyl), 125.8 (CH, broad s, Ar-CHortho ben-
zyl), 81.6 (CH, broad signal, C1), 50.6 (CH, s, Ca), 40.4
4.1.28. X-Ray crystal structure determinations of 13b,
17a, 21, 23 (Table 2)
4.1.28.1. Crystal data for 13b·AcOEt. A prismatic
crystal was selected and mounted on a MAR345 dif-
fractometer with an image plate detector. Unit-cell
parameters were determined from automatic centering
of 9124 reflections (12<q<21°) and refined by least-
squares method. Intensities were collected with
graphite-monochromatizedMo-Karadiation,usingꢀ/2q
scan-technique. Reflections were measured in the range
1.975q528.87° and were assumed as observed apply-
ing the condition I>2|(I). Lorentz polarization but no
absorption corrections were made. The structure was
solved by direct methods, using the SHELXS computer
program26 and refined by full-matrix least-squares
method with the SHELX-97 computer program,27 (very
negative intensities were not assumed). The function
2
3
(CH, dd, JCꢀP=3.0 Hz, JCꢀP=8.2 Hz, C2), 32.7 (CH2,
1
d, JCꢀPꢀ75 Hz, CH2P), 32.2 (CH2, broad s, C5), 32.0
(CH, d, JCꢀP=63.3 Hz, C4), 31.8 (CH2, broad s, C3),
26.3 (CH, d, JCꢀP=62.7 Hz) and 26.0 (CH, d, JCꢀP
1
1
1
=
62.8 Hz) [2 C
16.8 (CH3, d, JCꢀP=2.0 Hz), 16.7 (CH3, d, JCꢀP=2.0
6
H(CH3)2], 22.5 (CH3, broad s, a-CH3),
2
2
2
Hz), 16.67 (CH3, d, JCꢀP=2.6 Hz) and 16.58 (CH3, d,
2JCꢀP=2.5 Hz) [2 CH(C
6
H3)2]; 31P NMR 54.1 [PO(i-
+
’
Pr)2], 28.3 [PO(C6H5)2]; MS (EI), m/z (%): 579 (M ,
0,4), 415 [(M−C8H9NHCOO)+, 4], 299 [[M−C8H9NCO–
(i-Pr)2PO]+, 17], 281 [M−C8H9NHCOOH−(i-Pr)2PO]+,
90], 231 [[M−C8H9NCO−PO(C6H5)2]+, 14], 217 [[M−
C8H9NCO−CH2PO(C6H5)2]+, 19], 201 [[PO(C6H5)2]+,
100], 147 [(C8H9NCO) , 29], 132 [(C6H5CHNCO) ,
62]. Anal. calcd for C33H43NO4P2·H2O: C, 66.31; H,
7.59; N, 2.34. Found: C, 66.19; H, 7.33; N, 2.40%.
[h]2D5=+4.5 (CHCl3, c=1.1).
minimized was ꢀwꢁꢁFoꢁ −ꢁFcꢁ ꢁ , where w=[|2(I)+
+
+
2
2 2
’
2
2
(0.1177P)2]−1, and P=(ꢁFoꢁ +2ꢁFcꢁ )/3, f, f % and f %% were
taken from the literature.28 Hydrogen atoms were
located from a difference synthesis with the exception
to those linked to ethyl acetate. Hydrogen atoms linked
to carbon atoms were refined using a riding model and
an isotropic temperature factor equal to 1.2 times the
equivalent isotropic temperature factor of the atom
linked to hydrogen. The ethyl acetate molecules are
disordered. These were refined with all bond angle and
length constrained and a global isotropic temperature
factor for each molecule. Goodness of fit=0.903 for all
observed reflections.
4.1.27.3. Analytical and spectroscopic data for 23. Mp
237–240°C (ethyl acetate/methanol in a ratio close to
6:1). IR (KBr) 3228 (NH st), 1710 (CꢁO st), 1179, 1148
(PꢁO st) cm−1; 1H NMR 7.82–7.64 (complex signal, 4H,
Ar-Hortho), 7.50–7.38 (complex signal, 6H, Ar-Hmeta
,
Ar-Hpara), 7.38–7.10 (complex signal, 5H, benzyl Ar-H),
4.93 (broad signal, 1H, NH), 4.86–4.74 (complex signal)
and 4.56–4.44 (broad signal) (2H, 1-H, a-H), 2.65
(pseudo t, J=13.0 Hz, 1H, CHsynP), 2.6–2.2 (complex
signal, 4H, 2-H, 4-H, 5-Ha, CHantiP), 2.2–1.7 [complex
4.1.28.2. Crystal data for 17a. A prismatic crystal was
selected and mounted on an Enraf–Nonius CAD4 four-
circle diffractometer. Unit-cell parameters were deter-
mined from automatic centering of 25 reflections
(12<q<21°) and refined by least-squares method. Inten-
sities were collected with graphite-monochromatized
Mo-Ka radiation, using ꢀ/2q scan-technique. 6164
reflections were measured in the range 2.005q529.96°,
6112 of which were non-equivalent by symmetry
[Rint(on I)=0.007] and 5472 reflections were assumed as
observed applying the condition I>2|(I). Three reflec-
tions were measured every 2 h as orientation and
intensity control, significant intensity decay was not
observed. Lorentz polarization but no absorption cor-
rections were made. The structure was solved by direct
methods, using the SHELXS computer program26 and
refined by full-matrix least-squares method with the
SHELX-93 computer program,29 using 6062 reflections
signal, 4H, 5-Hb, 2 CH
plex signal, 4H, 3-Hb, a-CH3), 1.2–0.9 [complex signal,
12H, 2 CH(CH3 2
) ]; 13C NMR 155.0 (C, s, OCONH),
143.3 (C, broad s, benzyl Ar-Cipso), 133.3 (C, d, JCꢀP
6 (CH3)2 and 3-Ha], 1.6–1.3 (com-
6
1
=
1
96.7 Hz) and 129.9 (C, d, JCꢀP=96.7 Hz) (Ar-Cipso),
4
4
131.62 (CH, JCꢀP=3.5 Hz) and 131.58 (CH, JCꢀP=3.1
Hz) (Ar-CHpara), 130.8 (CH, d, 2JCꢀP=10.1 Hz) and
2
130.6 (CH, d, JCꢀP=9.1 Hz) (Ar-CHortho), 128.6 (CH,
3
broad s, benzyl Ar-CHmeta), 128.58 (CH, d, JCꢀP=11.7
Hz) and 128.53 (CH, d, JCꢀP=11.7 Hz) (Ar-CHmeta),
3
127.3 (CH, broad s, benzyl Ar-CHpara), 125.9 (CH,
broad s, benzyl Ar-CHortho), 81.6 (CH, broad signal,
C1), 50.7 (CH, s, Ca), 40.5 (CH, broad m, C2), 33.1
(CH2, d, 1JCꢀP:75 Hz, CH2P), 32.1 (CH2, broad s, C5),
31.9 (CH, broad d, 1JCꢀP=63.3 Hz, C4), 31.7 (CH2,
1
broad s, C3), 26.3 (CH, d, JCꢀP=62.7 Hz) and 26.0
(CH, d, 1JCꢀP=62.7 Hz) [2 C
6 H(CH3)2], 22.5 (CH3,

P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
777
(very negative intensities were not assumed). The func-
temperature factor equal to 1.2 times the equivalent
temperature factor of the atom to which are linked.
Goodness of fit=1.115 for all observed reflections.
Max. shift/esd=0.00, mean shift/esd=0.00.
2
2 2
tion minimized was ꢀwꢁꢁFoꢁ −ꢁFcꢁ ꢁ , where w=[|2(I)+
2
2
(0.0634P)2+0.1524P]−1 and P=(ꢁFoꢁ +2ꢁiFcꢁ )/3, f, f %
and f %% were taken from the literature.28 The extinction
coefficient was 0.037(3). All H atoms were located from
a difference synthesis and refined, with an overall
isotropic temperature factor. Goodness of fit=1.069 for
all observed reflections. Max. shift/esd=0.00, mean
shift/esd=0.00.
4.1.28.4. Crystal data for 23. A prismatic crystal was
selected and mounted on a Enraf–Nonius CAD4 four-
circle diffractometer. Unit-cell parameters were deter-
mined from automatic centering of 25 reflections
(12<q<21°) and refined by least-squares method. Inten-
sities were collected with graphite-monochromatized
Mo-Ka radiation. 3123 reflections were measured in the
range 2.225q529.97°. 2334 reflections were assumed
as observed applying the condition I>2|(I). Three
reflections were measured every 2 h as orientation and
intensity control, significant intensity decay was not
observed. Lorentz polarization but no absorption cor-
rections were made. The structure was solved by direct
methods, using the SHELXS computer program26 and
refined by full-matrix least-squares method with the
SHELX-97 computer program,27 using 3123 reflections
(very negative intensities were not assumed). The func-
4.1.28.3. Crystal data for 21 monohydrate. A pris-
matic crystal was selected and mounted on a MAR345
diffractometer with an image plate detector. Unit-cell
parameters were determined from automatic centering
of 6833 reflections (3<q<31°) and refined by least-
squares method. Intensities were collected with
graphite-monochromatized Mo-Ka radiation. 9952
reflections were measured in the range 2.415q531.65°,
3758 of which were non-equivalent by symmetry
[Rint(on I)=0.0185]. 2453 reflections were assumed as
observed applying the condition I>2|(I). Lorentz
polarization but no absorption corrections were made.
The structure was solved by direct methods, using the
SHELXS computer program26 and refined by full-
matrix least-squares method with the SHELX-97 com-
puter program,27 using 3758 reflections (very negative
intensities were not assumed). The function minimized
2
2 2
tion minimized was ꢀwꢁꢁFoꢁ −ꢁFcꢁ ꢁ , where w=[|2(I)+
2
2
(0.0650P)2]−1, and P=(ꢁFoꢁ +2ꢁFcꢁ )/3, f, f % and f %% were
taken from the literature.28 The chirality of the struc-
ture was defined from the Flack coefficient, which is
equal to 0.04 (12) for the given results.30 The extinction
coefficient was 0.037(3). Four hydrogen atoms were
located from a difference synthesis and refined with an
overall isotropic temperature factor and 39 hydrogen
atoms were computed and refined with an overall
2
2 2
was ꢀwꢁꢁFoꢁ −ꢁFcꢁ ꢁ , where w=[|2(I)+(0.1184P)2+
2
2
0.0133P]−1 and P=(ꢁFoꢁ +2ꢁFcꢁ )/3, f, f % and f %% were
taken from the literature.28 All H atoms were computed
and refined, using a riding model, with an isotropic
Table 2. Experimental data for the X-ray crystal-structure determination of compounds 13b, 17a, 21 and 2325
Compound
13b·AcOEt
17a
21·H2O
23
Molecular formula
Molecular mass
Crystal system
Space group
C34H38O5P2
588.58
Monoclinic
C2/c
C26H36O4P2
474.49
Triclinic
C30H32O3P2
502.50
Monoclinic
P21/c
C33H43NO4P2
579.62
Monoclinic
P21
(
P1
Cell parameters
,
a (A)
33.42000(10)
20.31000(10)
25.50700(10)
90
130.7810(10)
90
10.515(2)
10.646(11)
12.286(4)
89.86(5)
99.27(2)
101.51(3)
1329(2)
2
9.4930(10)
14.2010(10)
11.0620(10)
90
117.15
90
8.625(3)
17.385(10)
11.027(5)
90
101.19(6)
90
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
V (A )
13109.70(9)
16
1327.0(2)
2
1622.0(13)
2
Z
F(000)
4992
1.193
508
1.185
532
1.258
620
1.187
Dcalcd (Mg m−3
)
Size of crystal (mm)
Measured reflections
Independent reflections
Observed reflections
0.1×0.1×0.2
10042
10042
5820
0.171
0.1×0.1×0.2
6164
6112
5472
0.191
0.1×0.1×0.2
9952
3758
2453
0.193
0.1×0.1×0.2
3123
3123
2334
0.170
v(Mo-Ka) (mm−1 a
)
R
0.052
0.043
0.046
0.042
Rw
Dzmax (e A
Dzmin (e A
Refined parameters
Max. shift/e.s.d.
0.150
0.535
−0.291
713
0.00
0.106
0.302
−0.311
434
0.00
0.181
0.277
−0.314
184
0.00
0.101
0.318
−0.152
415
0.00
b
−3
,
)
c
−3
,
)
a
,
v(Mo-Ka) linear absorption coefficient. Radiation Mo-Ka (u=0.71069 A).
b Maximun peaks in final difference synthesis.
c Minimum peaks in final difference synthesis.

778
P. Camps et al. / Tetrahedron: Asymmetry 13 (2002) 759–778
isotropic temperature factor using a riding model.
Goodness of fit=0.947 for all observed reflections.
Max. shift/esd=0.00, mean shift/esd=0.00.
D. Tetrahedron Lett. 1977, 1065–1068; (c) Bell, A.;
Davidson, A. H.; Earnshaw, C.; Norrish, H. K.; Torr, R.
S.; Trowbridge, D. B.; Warren, S. J. Chem. Soc., Perkin
Trans. 1 1983, 2879–2891; (d) Mikolajczyk, M.; Zatorski,
A. J. Org. Chem. 1991, 56, 1217–1223.
11. Maercker, A.; Greuß, R. Chem. Ber. 1973, 106, 773–797.
12. Moffett, R. B. Org. Synth. Coll. Vol. IV 1963, 238–241.
13. Camps, P.; Colet, G.; Font-Bardia, M.; Mun˜oz-Torrero,
V.; Solans, X.; Va´zquez, S. Tetrahedron 2002, 58, 3473–
3484.
14. Roucoux, A.; Thieffry, L.; Carpentier, J. F.; Devocelle,
M.; Me´liet, C.; Agbossou, F.; Mortreux, A.
Organometallics 1996, 15, 2440–2449.
15. Molecular mechanics calculations were performed by
using PCModel, which employs the MMX force field.
Gilbert, K. PCModel V5.0; Serena Software: Box 3076,
Bloomington, IN 47402–3076, USA, 1995.
Acknowledgements
Financial support from the Direccio´n General de Inves-
tigacio´n of Ministerio de Ciencia y Tecnolog´ıa (project
QUI1999-0512) and a fellowship from the Generalitat
de Catalunya (to G.C.) are gratefully acknowledged.
We thank the Serveis Cient´ıfico-Te`cnics of the Univer-
sity of Barcelona for the NMR and MS facilities, and
Ms. P. Dome`nech from the Centro de Investigacio´n y
Desarrollo (C.I.D.) (Barcelona, Spain) for carrying out
the elemental analyses.
16. Mori, K.; Tominaga, M.; Takigawa, T.; Matsui, M.
Synthesis 1973, 790–791.
17. Cooke, M. P., Jr. J. Org. Chem. 1986, 51, 951–953.
18. Coumbe, T.; Lawrence, N. J.; Muhammad, F. Tetra-
hedron Lett. 1994, 35, 625–628.
19. (a) Paquette, L. A. Encyclopedia of Reagents for Organic
Synthesis; John Wiley and Sons: Chichester, 1995; Vol. 7,
pp. 5080–5081; (b) Takaya, H.; Akatagawa, S.; Noyori,
R. Org. Synth. Coll., Vol. VIII 1993, 57–63.
20. Manabe, S.; Ito, Y.; Ogawa, T. Chem. Lett. 1998, 919–
920.
21. Imamoto, T.; Sugiura, Y.; Takiyama, N. Tetrahedron
References
1. (a) Noyori, R. Asymmetric Catalysis in Organic Synthe-
sis; Wiley: New York, 1994; (b) Ojima, I. Catalytic
Asymmetric Synthesis, 2nd ed.; Wiley-VCH: Weinheim,
2000; (c) Methods of Organic Synthesis, Houben-Weyl:
Stereoselective Synthesis; Helmchen, G.; Hoffmann, R.
W.; Mulzer, J.; Schaumann, E., Eds.; Georg Thieme
Verlag: New York, 1996; (d) Jacobsen, E. N.; Pfalz, A.;
Yamamoto, H. Comprehensive Asymmetric Catalysis I–
III; Springer Verlag: Berlin, 1999; (e) Noyori, R.;
Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40–73.
2. (a) Collins, A. N.; Sheldrake, G. N.; Crosby, J. Chirality
in Industry I; John Wiley & Sons: Chichester, 1992; (b)
Collins, A. N.; Sheldrake, G. N.; Crosby, J. Chirality in
Industry II; John Wiley & Sons: Chichester, 1997; (c)
Sheldon, R. A. Chirotechnology; Marcel Dekker: New
York, 1993.
Lett. 1984, 25, 4233–4236.
22. (a) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc.,
Perkin Trans. 1 1975, 1574–1585; (b) Corey, E. J.; Gosh,
A. K. Tetrahedron Lett. 1988, 29, 3205–3206.
23. Motherwell, W. B.; Crich, D. Free Radical Chain Reac-
tions in Organic Synthesis; Academic Press: London,
1992.
24. (a) Gue´guen, C.; O’Brien, P.; Powell, H. R.; Raithby, P.
R.; Warren, S. J. Chem. Soc., Perkin Trans. 1 1995,
3405–3417; (b) Breitmeier, E.; Voelter, W. Carbon-13
NMR Spectroscopy, 3rd ed.; VCH: Weinheim, 1990; p.
413.
3. Morimoto, T.; Takahashi, H.; Achiwa, K. Chem. Pharm.
Bull. 1994, 42, 481–488.
4. Sakuraba, S.; Takahashi, H.; Takeda, H.; Achiwa, K.
Chem. Pharm. Bull. 1995, 43, 738–747.
25. Crystallographic data (excluding structure factors) for the
structures of 13b, 17a, 21 and 23 have been deposited
with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 182484,
182482, 180717 and 182483, respectively. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
+44 (0) 1223–336033 or e-mail: deposit@ccdc.cam.ac.uk].
26. Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46,
467–473.
27. Sheldrick, G. M. SHELX-97: A Computer Program for
Determination of Crystal Structure, University of Go¨ttin-
gen, Germany, 1999.
28. International Tables of X-ray Crystallography; Ibers, J.
A.; Hamilton, W. C., Eds.; Kynoch Press: Birmingham,
1974; Vol. IV, pp. 99–100 and 149.
5. Takeda, H.; Tachinami, T.; Aburatani, M.; Takahashi,
H.; Morimoto, T.; Achiwa, K. Tetrahedron Lett. 1989,
30, 363–366.
6. Takahashi, H.; Sakuraba, S.; Takeda, H.; Achiwa, K. J.
Am. Chem. Soc. 1990, 112, 5876–5878.
7. Sakuraba, S.; Nakajima, N.; Achiwa, K. Tetrahedron:
Asymmetry 1993, 4, 1457–1460.
8. Sakuraba, S.; Achiwa, K. Synlett 1991, 689–690.
9. (a) Horner, L.; Klink, W. Tetrahedron Lett. 1964, 2467–
2473; (b) O’Brien, P.; Warren, S. Tetrahedron Lett. 1995,
36, 2681–2684; (c) Clayden, J.; Warren, S. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 241–270; (d) Gue´guen, C.;
O’Brien, P.; Warren, S.; Wyatt, P. J. Organomet. Chem.
1997, 529, 279–283; (e) Gue´guen, C.; O’Brien, P.; Powell,
H. R.; Raithby, P. R.; Warren, S. J. Chem. Soc., Perkin
Trans. 1 1998, 3405–3417; (f) Nelson, A.; Warren, S. J.
Chem. Soc., Perkin Trans. 1 1999, 1963–1982.
29. Sheldrick, G. M. SHELX-93: A Computer Program for
Determination of Crystal Structure, University of Go¨ttin-
gen, Germany, 1994.
30. Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876–
881.
10. For precedents on the reaction of chlorodiphenylphos-
phine with a,b-unsaturated carbonyl compounds, see: (a)
Conant, J. B.; Braverman, J. B. S.; Hussey, R. E. J. Am.
Chem. Soc. 1923, 45, 165–171; (b) Miller, J. A.; Stewart,