Synthesis of enantiopure C1 symmetric diphosphines and phosphino-phosphonites with ortho-phenylene backbones

Article abstract of DOI:10.1016/S0957-4166(01)00175-6

Reaction of 2-(diphenylphosphino)phenylphosphonous acid tetramethyldiamide 1 with (+)-menthol, (1S,2S,3S,5R)-isopinocampheol and (1R,2R)-trans-cyclohexanediol affords enantiopure phosphino-phosphonite ligands 3-5. The X-ray structures of 1 (space group P2

Full text of DOI:10.1016/S0957-4166(01)00175-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1159–1169
Synthesis of enantiopure C1 symmetric diphosphines and
phosphino-phosphonites with ortho-phenylene backbones
Konstantin W. Kottsieper, Uwe Ku¨hner and Othmar Stelzer*
Fachbereich 9, Anorganische Chemie, Bergische Universita¨t-GH Wuppertal, D-42097 Wuppertal, Germany
Received 19 March 2001; accepted 19 April 2001
Abstract—Reaction of 2-(diphenylphosphino)phenylphosphonous acid tetramethyldiamide 1 with (+)-menthol, (1S,2S,3S,5R)-
isopinocampheol and (1R,2R)-trans-cyclohexanediol affords enantiopure phosphino-phosphonite ligands 3–5. The X-ray struc-
tures of
1 (space group P21/n) and 3 (space group P21) have been determined. The reaction of 1 with
(1R,2R,3S,5R)-(−)-pinanediol proceeds diastereoselectively to afford a novel type of enantiopure phosphino-phosphonite ligand 6
with an asymmetric substituted P atom. On reaction of (+)-cedryl alcohol with 1 the adduct 7 of the phosphonous acid
2-Ph2PꢀC6H4ꢀP(ꢁO)(H)OH 9 and its dimethylammonium salt is formed through elimination of water and subsequent hydrolysis.
(
The structure of 7 (space group P1) was elucidated by X-ray structural analysis. Reduction of the chlorophosphine 8 with LiAlH4
yields the novel primary–tertiary phosphine 10, which is a valuable starting material for the synthesis of the enantiopure C1
symmetric bidentate phospholane ligands 11 and 12. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
such as DIOP,2a DUPHOS2b and BINAP2c have played
a special role in the development of enantioselective
catalysis. C2 symmetry is not, however, a prerequisite
for the selectivity and the activity of diphosphines in
catalysis and C1 symmetric bidentate diphosphine lig-
ands also give excellent results. NORPHOS A,3a
BPPFA B,3b BPPM D,3c E3d and the Takaya phos-
phine–phosphite ligand (R,S)-BINAPHOS C2d–f may
be quoted as representative examples in this context.
However, diphosphine ligands with C1 symmetry con-
Asymmetric catalysis using coordination complexes of
transition metals is a rapidly developing research area
and in its present state is known to induce high efficien-
cies and selectivities surpassing in some cases those of
the equivalent enzyme-mediated reactions. This is
mainly due to the availability of a wide range of
enantiopure ligands1 promoting highly selective cata-
lytic reactions. Chiral diphosphines with C2 symmetry
Figure 1.
* Corresponding author. E-mail: stelzer@uni-wuppertal.de
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00175-6

1160
K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
taining ortho-phenylene backbones have been reported
amino)chlorophosphine
phino)-phenylphosphonous acid tetramethyldiamide 1,
the overall yield being 82% (Eqs. (1a, 1b)) (Scheme 1).
affords
2-(diphenylphos-
only scarcely in the literature to date (Fig. 1).4
Herein, we report on the syntheses of new enantiopure
C1 symmetric bidentate phosphine ligands of type F (Z,
Z%=OR*) containing cyclic and acyclic P(OR*)2 moi-
eties with chiral groups R*, of which only very few
examples have appeared in the recent literature.4 Those
containing an asymmetric PZZ% group with a stereo-
genic phosphorus center are unreported to the best of
our knowledge. The novel primary–tertiary arylphos-
phine F (Z, Z%=H) is also reported. It has great poten-
tial as synthon for the preparation of chiral tertiary
diphosphine ligands with a phospholane moiety, the
steric and electronic properties of which may be tuned
by appropriate choice of the substituents R or R% a or
b to phosphorus.
Reaction of 1 with excess iso-propanol, (+)-menthol,
(1S,2S,3S,5R)-(+)-isopinocampheol, (1R,2R)-trans-1,2-
cyclohexanediol and (1R,2R,3S,5R)-(−)-pinane-2,3-diol
in n-heptane under reflux gave 2 and the enantiopure
phosphino-phosphonite ligands 3–6 (Eqs. (2a–2e)).
These reactions proceeded stepwise, the aminophospho-
nites 2a–4a and 7a with unsymmetrically substituted
phosphorus atoms being formed as intermediates. They
have been identified by 31P{1H} NMR spectroscopy
and isolated in the case of 2a. On formation of acyclic
3 and 4 and cyclic 5 the configuration at the stereogenic
carbon atoms is retained, as indicated by analysis of the
31P{1H} and 13C{1H} NMR spectra and measurement
of the optical rotation (see Section 3). The reaction of 1
with (1R,2R,3S,5R)-(−)-pinanediol proceeded with high
diastereoselectivity and only one of the two possible
diastereoisomers 6a and 6b is formed. Due to the
asymmetric substitution in the organic backbone of the
1,3,2-dioxaphospholane moiety the phosphorus atom
Pa was stereogenic in both diastereoisomers. Com-
pounds 6a and 6b were interrelated by an interchange
of the C6H4–2-PPh2 substituent and the lone pair at the
phosphorus atom Pa (Fig. 2). The 31P{1H} NMR spec-
trum showed only one pair of doublets at lP=158.2
ppm (PO2, Pa) and −18.7 ppm (PPh2, Pb), 3J(PP)=
112.3 Hz. Accordingly a single set of ten resonances
(some of them showing P–C coupling fine structure) for
the ten chemically different aliphatic carbon atoms were
2. Results and discussion
2.1. Synthesis of C1 symmetric phosphino-phosphonite
ligands with ortho-phenylene backbones
For the synthesis of C1 symmetric phosphino-phospho-
nite ligands ortho-bromophenyl-diphenylphosphine 1a5
was used as the starting material. It may be obtained in
large quantities and high yield by Pd-catalyzed P–C
coupling6 of diphenylphosphine and ortho-bro-
moiodobenzene, as developed by us. Halogen–metal
exchange on 1a with n-BuLi yields the lithio derivative
1b,7
which
on
reaction
with
bis(dimethyl-
Scheme 1.

K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
1161
phosphines Ph2P–R* with a chiral group R*9 and also
applies to 6, which according to the 31P{1H} NMR
spectrum was obtained as one diastereoisomer only.
One set of ten resonances was observed in the 13C{1H}
NMR spectrum of 6 for the aliphatic carbon atoms
C(11)–C(20) and an eight line set for the aromatic
carbon atoms of the two diastereotopic Ph groups of
the PPh2 units. The assignment of the 13C{1H} NMR
signals in 3–6 was achieved by using DEPT NMR
Figure 2. One possible diastereoisomer of 6 (6a).
observed in the 13C{1H} NMR spectrum. Structure 6a
with the energetically favorable equatorial position of
the bulky C6H4–2-PPh2 group is consistent with the
1
spectra and H,1H or 13C,1H correlated spectra.10
3
small coupling constant J(PaC) for C(17)H3, which is
2.2. X-Ray structural analysis of 1, 3 and 7
remote from the lone pair at Pa (for indication of the
carbon atoms see Fig. 2). While this coupling could not
be resolved in the 13C{1H} NMR spectrum, for carbon
atoms C(13) and C(16) values of 4.6 and 3.8 Hz were
found for 3J(PaC). Generally, coupling constants
3J(PC) between carbon and three valent phosphorus are
small if the lone pair at P is remote, and large if it is in
the proximity of the g-carbon atom.8a
In order to obtain detailed information on the mutual
orientation of the PPh2 and the PZ2 units (Z=NMe2,
OMen) with respect to the plane of the disubstituted
aromatic ring system, a crystal structure of 1 and 3 was
obtained. The results for 1 are shown in Fig. 3. Impor-
tant bond lengths and angles are collected in Table 1.
As expected, the phosphorus atoms P(1) and P(2) are
almost coplanar with the best plane through C(11)–
C(16), the dihedral angle P(1)–C(11)–C(12)–P(2) being
1.18(20)°. The PPh2 group is not in a symmetric posi-
tion with respect to this plane, as indicated by the
different dihedral angles C(21)–P(1)–C(11)–C(16)
(–81.95(16)°) and C(31)–P(1)–C(11)–C(16) (23.52(17)°).
The same applies to the P(NMe2)2 moiety with almost
planar arrangements of the substituents at N(1) and
N(2), the sum of the bond angles being 355.44 and
352.34°, respectively. The C(m)–N(1)–P(2) and C(n)–
N(2)–P(2) bond angles for m=1, 3 and n=2, 4 are
rather different.
Attempts to synthesize C1 symmetric phosphino-phos-
phonite ligands derived from bulky tertiary alcohols
using the method applied for 2–6 with secondary alkoxy
groups were unsuccessful. Thus, reaction of 1 with
(+)-cedrol gave the salt 7 instead of the expected phos-
phino-phosphonite ligand of type F (Z=OR*). The
X-ray structural analysis showed 7 to be the 1:1 adduct
of the phosphonous acid 9 and its dimethylammonium
salt. The formation of 7 is obviously a result of elimina-
tion of water from (+)-cedrol and subsequent hydrolysis
of 1. The reaction proceeds via the intermediate
aminophosphonite 7a with an asymmetric phosphorus
atom and a chiral OR group. It is formed as a 1:1
mixture of two diastereoisomers, which in the 31P{1H}
NMR spectrum show the line pattern of two AX-type
spectra [isomer I: lP(A)=104.4 ppm, lP(X)=−18.7
ppm (3J(PP)=145.3 Hz); isomer II: lP(A)=103.6 ppm,
lP(B)=−18.8 ppm (3J(PP)=136.5 Hz)].
While the dihedral angle C(11)–C(12)–P(2)–N(1) is
−67.73(15)°, a value of 179.76(14)° was found for
C(11)–C(12)–P(2)–N(2). The bisectors of the N(1)–P(2)–
N(2) and the C(21)–P(1)–C(31) moieties are rotated
against each other in order to release repulsion of the
lone pairs at the phosphorus atoms P(1) and P(2). The
geometrical parameters of the PPh2–C6H4 and the
(Me2N)2P–C6H4 fragment in 1 may well be compared
In the 31P{1H} NMR spectra the phosphino-phospho-
nite ligands 2–6 show two resonances with 31P–31P
coupling fine structure in the lP range of about −20
ppm and 150–160 ppm, which may be assigned to the
PPh2 groups and the phosphonite moieties, respectively.
with those in PPh3 or (Me2N)2PPh,12 respectively.
11
The unit cell of 3 contains two crystallographically
different molecules, the geometrical parameters of
which differ slightly. Therefore the structure of
molecule 2 (shown in Fig. 4) will only be discussed. As
in 1 both phosphorus atoms P(3) and P(4) are almost
coplanar with the aromatic ring system C(51)–C(56).
The absolute configuration at the stereogenic carbon
atoms (C(80), C(90): (S)-; C(81), C(91): (R)-; C(84),
C(94): (S)-) of both menthyl groups is the same as in
the (+)-menthol employed in the synthesis of 3, the
Flack-parameter x13 being 0.022(68). In order to mini-
mize the steric interaction between the lone pairs and
the bulky groups at P(3) and P(4) the two PZ2 units
(Z=Ph, O–Men) in the ortho-position are not arranged
in a symmetrical manner with respect to the aromatic
plane C(51)–C(56), with the phosphorus lone pairs
pointing towards each other. The bisectors of the O(3)–
P(3)–O(4) and the C(61)–P(4)–C(71) moieties form
angles of 30 and 25° with the C(51)–C(52) bond vector.
3
The values of J(PP) vary in the range between 112 and
190 Hz, reflecting the differences in the mutual orienta-
tion of the lone pairs on both phosphorus atoms in the
different P–C rotamers contributing to the rotamer
equilibrium. As in the structurally related tetra-
3
phosphines, the coupling constants J(PP) are large if
the terminal lone pairs are close and small if they are
3
remote.8b,8c For 1 a much smaller value of J(PP) was
found (91.6 Hz) than in 3 (189.6 Hz). This may, how-
ever, be due in part to the different electronic effects of
the nitrogen and oxygen substituents.
The chiral substituents R* in the P(OR*)2 moieties
render the Ph groups of the Ph2P units in 3–5
diastereotopic, two sets of lines being observed for the
aromatic carbon atoms in the 13C{1H} NMR spectra.
This has been observed for the other Ph2P units in

1162
K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
Figure 3. X-Ray structure of 1.
may be assigned, are comparable to those found in
For 1 and 3 bearing PZ2 groups with rather different
steric demands, the PꢀC bond lengths and CꢀPꢀC bond
angles do not differ significantly (1: P(1)ꢀC(11)=
1.842(2), P(1)ꢀC(21)=1.835(2), P(1)ꢀC(31)=1.839(2)
14b
,
piperidinomethyl phosphonous acid (1.469(2) A) and
phosphinic acids R2P(O)OH.16 The steric interaction of
the hydrogen atoms and the P(H)(ꢁO)O groups ortho to
the phosphorus atoms is minimized by a propeller-type
arrangement of the aromatic ring systems.
,
A, C(11)ꢀP(1)ꢀC(21)=102.93(8), C(21)ꢀP(1)ꢀC(31)=
101.98(8), C(11)ꢀP(1)ꢀC(31)=102.05(8)°; 3 (molecule
2): P(4)ꢀC(51)=1.837(3), P(4)ꢀC(61)=1.829(4), P(4)ꢀ
2.3. Synthesis of the primary–tertiary phosphine 10
,
C(71)=1.839(4)A,C(51)ꢀP(4)ꢀC(61)=102.12(16), C(61)ꢀ
P(4)ꢀC(71)=100.78(16),C(51)ꢀP(4)ꢀC(71)=102.55(16)°)
In contrast to the well known primary diphosphine
(Table 2).
17
1,2-C6H4(PH2)2 (which is commercially available) and
18
the secondary diphosphines 1,2-C6H4(PRH)2 (R=Me
Recrystallization of product 7 obtained on reaction
between 1 and (+)-cedryl alcohol from iso-propanol
gave crystals of 7 suitable for X-ray structural analysis.
According to the X-ray structure determination (Fig.
5), the elemental analysis and the NMR data, it is a 1:1
mixture of the phosphonous acid 9 and its dimethyl-
ammonium salt 9a. X-Ray structural analysis reveals
that in the solid state 9 and 9a are interconnected by
N+ꢀH···O hydrogen bridges14a with the dimethylammo-
nium cation, the distance of the hydrogen bridged N
or iso-Pr) primary–tertiary 1,2-diphosphinobenzenes
1,2-C6H4(PH2)(PR2) have not been reported to date. As
shown above, the reactivity of the PꢀN bonds renders 1
a useful starting material for the preparation of C1
symmetric phosphine–phosphonite ligands. It may also
be employed for the synthesis of primary–tertiary phos-
phines, e.g. 10, which turned out to be quite valuable
synthons in the preparation of chiral chelating tertiary
,
Table 1. Selected interatomic distances (A) and angles (°)
,
and O atoms being 2.710(6) A (N(1)···O(2)) and
2.773(5) A (N(1)···O(3)). These values, although short,
of 1
,
may be compared with those in piperidinomethyl phos-
phonous acid.14b The molecules of 7 are linked by
NꢀH···O and strong OꢀH···O hydrogen bridges forming
endless zig-zag chains along the crystallographic a-axis
(Table 3).
Bond lengths
P(1)–C(11)
P(1)–C(21)
P(1)–C(31)
N(1)–C(1)
N(1)–C(3)
C(11)–C(12)
1.842(2)
1.835(2)
1.839(2)
1.457(3)
1.455(2)
1.409(2)
P(2)–N(1)
P(2)–N(2)
P(2)–C(12)
N(2)–C(2)
N(2)–C(4)
1.684(2)
1.696(2)
1.841(2)
1.463(3)
1.451(3)
The CꢀC and PꢀC bond lengths are within the typical
range.15 Within the P(H)(ꢁO)O groups, both with a
Bond angles
C(11)–P(1)–C(21) 102.93(8)
C(11)–P(1)–C(31) 102.05(8)
C(21)–P(1)–C(31) 101.98(8)
P(1)–C(11)–C(12) 118.73(13)
C(12)–P(2)–N(1)
C(12)–P(2)–N(2)
N(1)–P(2)–N(2)
98.50(8)
101.94(9)
109.87(9)
strongly
distorted
geometry
(O(1)ꢀP(1)ꢀO(2)=
118.04(16)°, C(11)ꢀP(1)ꢀO(2)=111.11(14)°, C(11)ꢀ
P(1)ꢀO(1)=106.20(15)°), the bond distances P(1)ꢀO(2)
P(2)–C(12)–C(11) 118.85(13)
,
,
(1.470(2) A) and P(3)ꢀO(3) (1.473(2) A) are significantly
C(1)–N(1)–C(3)
C(1)–N(1)–P(2)
C(3)–N(1)–P(2)
112.22(16)
126.40(14)
116.76(13)
C(2)–N(2)–C(4)
C(2)–N(2)–P(2)
C(4)–N(2)–P(2)
112.43(18)
123.56(15)
116.29(16)
,
shorter than P(1)ꢀO(1) (1.514(2) A) or P(3)ꢀO(4)
,
(1.511(2) A), respectively. These PꢀO bond lengths, to
which a higher degree of PꢁO double bond character

K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
1163
Figure 4. X-Ray structure of 3.
diphosphines. Thus, treatment of 1 with ethereal HCl at
low temperature yielded the chlorophosphine 84 (Eq.
(3a)), which could be reduced with LiAlH4 to give the
novel primary–tertiary phosphine 10 in good yield (Eq.
(3c)). In the 31P{1H} NMR spectrum, 10 shows two
resonances at lP=−9.3 and −125.0 ppm, each split by
31P–31P coupling into doublets (3J(PP)=93.7 Hz). The
resonance at lP=−125.0 ppm shows additional triplet
fine structure in the 31P NMR spectrum (1J(PH)=202.2
recovered quantitatively (Eq. (3g)). Using the same
procedure as employed for the synthesis of 11, ligand
12 could be obtained using (R,R)-(+)-1,4-di-O-p-tolue-
nesulfonyl-2,3-O-isopropylidene-D-threitol as the alkyl-
ating agent.
The enantiopure C2 symmetric phosphine ligand G
containing two phospholane moieties with 1,3-diox-
olane groups was synthesized from 1,2-C6H4(PH2)2 by
Lappert et al.20
n
Hz). The triplet lines are split further by J(PH) cou-
pling (n=3, 4). In solution, 10 is moderately sensitive
towards oxygen, the phosphonous acid 9 being formed.
It could be obtained independently by hydrolysis of the
chlorophosphine 8 at 0°C (Eq. (3b)). The nitrogen
analog of 10 was obtained by Cooper and Downes19 in
a laborious multistage synthesis and later by us in a
single step by employing Pd-catalyzed P–C coupling
reactions.6a,6b It may also be obtained in a straightfor-
ward manner from N-BOC aniline.6c
The specific rotation values for 11 and 12 are [h]2D0=
−171.8 (c=0.815, CHCl3) and [h]2D0=+61.3 (c=1.435,
CHCl3), respectively. It is generally accepted that a
complete inversion of configuration at the stereogenic
centers of the cyclic sulfate occurs in phosphination
reactions. This has been proved for the synthesis of
DUPHOS,2b which is analogous to 11. The conforma-
tion of the chiral carbon atoms in (+)-1,4-di-O-p-tolue-
nesulfonyl-2,3-O-isopropylidene-D-threitol on forma-
tion of 12 does not change. This has been shown by
2.4. Synthesis of the C1 symmetric tertiary
diphosphines 11 and 12
us21 and others22,23 for similar phosphination reactions.
,
Table 2. Selected interatomic distances (A) and angles (°)
Using the consecutive metallation–alkylation proce-
dure, as developed by Burk et al.2b for the synthesis of
DUPHOS-type ligands, the C1 symmetric tertiary
diphosphines 11 and 12 could be obtained from the
primary–tertiary phosphine 10 in satisfactory to good
yield (Scheme 2, Eqs. (3d and 3e)). The cyclic sulfate of
(2S,5S)-(+)-hexane-2,5-diol 10a was used for alkylation
of the intermediate lithium phosphide. The crude 11
was purified via its dihydrochloride salt 11a, which was
prepared by treatment of 11 with excess ethereal HCl
(Eq. (3f)). In contrast to the oily crude 11, the dihy-
drochloride was obtained as a white crystalline material
(which is stable to oxygen but hygroscopic). On treat-
ment with aqueous NaHCO3 the free phosphine was
of 3 (molecule 2)
Bond lengths
P(3)–O(3)
P(3)–O(4)
P(3)–C(52)
P(4)–C(51)
P(4)–C(61)
1.634(2)
1.619(2)
1.842(3)
1.837(3)
1.829(4)
P(4)–C(71)
O(3)–C(90)
O(4)–C(80)
C(51)–C(52)
1.839(4)
1.466(3)
1.455(4)
1.411(4)
Bond angles
O(3)–P(3)–O(4)
O(3)–P(3)–C(52)
O(4)–P(3)–C(52)
101.97(13)
94.24(13)
97.86(14)
C(51)–P(4)–C(61) 102.12(16)
C(51)–P(4)–C(71) 102.55(16)
C(61)–P(4)–C(71) 100.78(16)
P(3)–O(3)–C(90)
P(3)–O(4)–C(80)
P(3)–C(52)–C(51) 120.06(26)
P(4)–C(51)–C(52) 118.59(26)
118.78(18)
119.53(20)

1164
K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
Figure 5. X-Ray structure of 7.
The 31P{1H} NMR spectra of 11 and 12 show the line
pattern of only one AB-type spectrum (11: lP=1.0,
3.2. Procedures
3
3.2.1. Synthesis of 1. To a solution of 1a (30.0 g, 88.1
mmol) in diethyl ether (500 mL) a solution of n-BuLi in
n-hexane (1.6 M, 55.1 mL, 88.1 mmol) was added over
a period of 20 min at ambient temperature. The sol-
vents were separated by decantation from the pre-
cipitate formed, which was washed with diethyl ether
(40 mL) and dissolved in toluene (400 mL). To this
−9.8 ppm; J(PP)=159.8 Hz; 12: lP=7.0, −13.0 ppm;
3J(PP)=155.4 Hz). Correspondingly only one set of
lines was observed for the aliphatic carbon atoms of 11
and 12 in the 13C{1H} NMR spectra. Again the Ph
substituents of the Ph2P groups are diastereotopic, as
indicated by the increased number of 13C{1H} NMR
resonances.
residue was added
a
solution of bis(diethyl-
amino)chlorophosphine (11.6 g, 74.8 mmol) at −78°C
and the reaction mixture was stirred for 10 min. The
coolant was removed and the reaction mixture was
stirred for a further 50 min. After addition of a solu-
tion of dimethylamine in THF (2.0 M, 10 mL) to
3. Experimental
3.1. Apparatus and materials
All manipulations were carried out employing standard
vacuum line and inert atmosphere techniques. The 31P
and 13C NMR spectra were obtained on JEOL FX 90Q
and Bruker AC 250 and AC 400 spectrometers
,
Table 3. Selected interatomic distances (A) and angles (°)
of 7
Bond lengths
1
equipped with standard H, 31P and 13C probe acces-
P(1)–O(1)
P(1)–O(2)
1.514(2)
1.470(2)
1.799(3)
1.845(3)
1.833(3)
1.829(4)
1.409(4)
1.458(5)
1.483(6)
P(3)–O(3)
P(3)–O(4)
P(3)–C(41)
P(4)–C(42)
P(4)–C(51)
P(4)–C(61)
C(41)–C(42)
N(1)–O(2)
N(1)–O(3)
1.473(2)
1.511(2)
1.800(3)
1.844(3)
1.827(3)
1.825(4)
1.403(4)
2.710(6)
2.773(5)
1
sories. 31P (relative to external 85% H3PO4) and 13C, H
(relative to internal Me4Si) chemical shifts downfield
from the standard are given positive values. Mass spec-
tra were determined on a Varian MAT 311a instrument
at 70 eV. Optical rotations were recorded on a Perkin
Elmer 241 polarimeter. Solvents were dried immediately
before use. Compound 1a was prepared by the method
as developed by us.5 (2S,5S)-(+)-Hexane-2,5-diol cyclic
sulfate 10a was prepared according to the literature
method,2b (2S,5S)-(+)-hexane-2,5-diol was purchased
P(1)–C(11)
P(2)–C(12)
P(2)–C(21)
P(2)–C(31)
C(11)–C(12)
N(1)–C(71)
N(1)–C(72)
Bond angles
O(1)–P(1)–O(2)
C(11)–P(1)–O(2)
C(11)–P(1)–O(1)
118.04(16)
111.11(14)
106.20(15)
O(4)–P(3)–O(3)
C(41)–P(3)–O(3)
C(41)–P(3)–O(4)
C(42)–P(4)–C(51) 102.99(15)
C(42)–P(4)–C(61) 101.49(15)
C(51)–P(4)–C(61) 103.18(16)
118.31(15)
113.04(14)
105.94(15)
from
Ju¨lich
Fine
Chemicals.
(+)-Menthol,
(1S,2S,3S,5R)-isopinocampheol, (1R,2R)-trans-cyclo-
hexanediol, (1R 2R,3S,5R)-(−)-pinanediol, (+)-cedryl
alcohol and (R,R)-(+)-1,4-di-O-p-toluoenesulfonyl-2,3-
C(12)–P(2)–C(21) 102.33(15)
C(12)–P(2)–C(31) 100.82(14)
C(21)–P(2)–C(31) 102.97(15)
C(71)–N(1)–C(72) 114.25(39)
isopropylidene-
D-threitol were obtained from Aldrich
Chemicals and used without purification.

K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
1165
Scheme 2.
1
bind unreacted bis(diethylamino)chlorophosphine, the
reaction mixture was filtered through a suction funnel
and the solvent was removed in vacuo (50°C, 0.01
Analytical data for 2a: H NMR (C6D6): l 6.9–8.2 (m,
14H), 4.14 (dsp, 1H, J=8.1, 6.1, 6.3 Hz), 2.40 (d, 3H,
J=8.6 Hz), 1.22 (d, 3H, J=6.1 Hz), 1.20 (d, 3H, J=6.3
Hz); 13C{1H} NMR (C6D6): l 149.5 (dd, J=6.6, 27.5
Hz), 140.6 (dd, J=15.5, 27.7 Hz), 140.0 (dd, J=10.9,
1.3 Hz), 137.3 (dd, J=15.0, 6.9 Hz), 135.5 (dd, J=4.1,
1.5 Hz), 134.2 (d, J=20.3 Hz), 133.7 (d, J=18.8 Hz),
130.8 (dd, J=9.2, 6.1 Hz), 128.8, 128.54 (d, J=6.1 Hz),
128.52 (d, J=6.1 Hz), 128.4 (d, J=7.1 Hz), 128.1, 70.5
(d, J=23.9 Hz), 38.6 (d, J=15.8 Hz), 24.9 (d, J=4.1
Hz), 24.4 (d, J=6.6 Hz); 31P{1H} NMR (C6D6): l 122.8
(d, J=129.2 Hz), −16.2 (d, J=129.2 Hz); MS: m/z (%)
396 (17, [M+H]+), 395 (65, M+), 352 (100, [M−
H3CCHCH3]+). Anal. calcd for C23H27NOP2: C, 69.86;
H, 6.88; P, 15.67; N, 3.54. Found: C, 69.67; H, 6.93; P,
15.70; N, 3.67%.
1
mBar) to afford 1 (27.4 g, 96%). H NMR (C6D6): l
6.99–6.67 (m, 14H), 2.50 (d, 12H, J=8.9 Hz); 13C{1H}
NMR (C6D6): l 148.0 (dd, J=7.1, 27.2 Hz), 141.1 (dd,
J=17.8, 24.7 Hz), 139.0 (dd, J=14.5, 2.8 Hz), 136.2
(dd, J=3.3, 1.0 Hz), 134.2 (d, J=20.6 Hz), 131.1 (t,
J=7.4 Hz), 128.5 (d, J=6.6 Hz), 128.4, 128.3, 128.1 (d,
J=1.5 Hz), 41.7 (dd, J=17.3, 1.5 Hz); 31P{1H} NMR
(C6D6): l 99.9 (d, J=91.6 Hz), −11.5 (d, J=91.6 Hz);
MS: m/z (%) 380 (58, M+), 337 (37, [M−CH2NCH3]+),
336 (100, [M−NMe2]+), 183 (99, [9-phosphafluorenyl]+).
Anal. calcd for C22H26N2P2: C, 69.46; H, 6.89; N, 7.36;
P, 16.28. Found: C, 69.47; H, 7.14; N, 7.32; P, 16.08%.
3.2.2. Synthesis of 2 and 2a. A solution of 1 (1.5 g, 4.0
mmol) in iso-propanol (15 mL) was heated under reflux
for 24 h. The solvent was removed in vacuo (40°C, 0.01
mBar) and the residue obtained was washed with two
aliquots of iso-propanol (3 mL each). An oily residue
was obtained, which crystallized on standing. For the
analogous synthesis of 2a, a solution of 1 (1.0 g, 2.7
mmol) in iso-propanol (20 mL) was heated for 3.5 h at
85°C. The work-up procedure was as for 2. Yields: 2
(0.90 g, 55%); 2a (1.02 g, 96%).
3.2.3. Synthesis of 3. To a solution of 1 (0.50 g, 1.3
mmol) in n-heptane (20 mL) was added (+)-menthol
(0.40 g, 2.6 mmol). The resultant mixture was heated
under reflux for 24 h. The solvent was removed in
vacuo and the remaining residue was washed with
iso-propanol (5 mL). Evaporation of all volatiles in
vacuo gave 3 as a colorless powder (0.68 g, 87%). For
further purification 3 was recrystallized from iso-
1
propanol at −18°C. Compound 3: H NMR (C6D6): l
8.3–6.9 (m, 14H), 3.95–3.75 (m, 2H), 2.64 (m, 1H,
J=7.0, 2.5 Hz), 2.43–2.34 (m, 2H), 2.25 (m, 1H, J=
7.0, 2.6 Hz), 2.18–2.10 (m, 2H), 1.6–0.6 (m, 12H), 0.97
(d, 3H, J=7.1 Hz), 0.91 (d, 3H, J=6.1 Hz), 0.88 (d,
3H, J=6.9 Hz), 0.82 (d, 3H, J=7.1 Hz), 0.80 (d, 3H,
J=7.1 Hz), 0.77 (d, 3H, J=6.6 Hz); 13C{1H} NMR
(C6D6): l 150.5 (dd, J=17.0, 27.7 Hz), 140.5 (dd,
J=15.0, 34.3 Hz), 138.5 (dd, J=13.0, 6.4 Hz), 138.4
(dd, J=13.5, 7.9 Hz), 134.4 (d, J=18.8 Hz), 134.3 (d,
J=19.3 Hz), 133.2 (dd, J=6.1, 1.0 Hz), 130.3, 130.0
(dd, J=9.2, 4.1 Hz), 129.0 (d, J=1.0 Hz), 128.72 (d,
J=6.1 Hz), 128.71 (d, J=7.1 Hz), 128.62, 128.58, 79.0
(d, J=18.3 Hz), 77.6 (d, J=15.3 Hz), 49.7 (d, J=5.1
Hz), 49.6 (d, J=5.1 Hz), 44.9 (d, J=3.6 Hz), 44.5 (dd,
J=5.6, 1.5 Hz), 34.7, 34.6, 32.1, 31.8, 25.7, 25.5, 23.4,
1
Analytical data for 2: H NMR (C6D6): l 6.9−8.3 (m,
14H), 4.23 (m, 2H, J=8.2, 6.2, 6.1 Hz), 1.14 (d, 6H,
J=6.1 Hz), 1.09 (d, 6H, J=6.2 Hz); 13C{1H} NMR
(C6D6): l 149.7 (dd, J=17.3, 29.0 Hz), 140.8 (dd,
J=15.3, 32.3 Hz), 138.3 (dd, J=12.7, 5.8 Hz), 134.3 (d,
J=1.5 Hz), 134.2 (d, J=19.3 Hz), 130.1, 129.7 (dd,
J=9.9, 4.8 Hz), 129.0, 128.6 (d, J=6.6 Hz), 128.5, 71.1
(d, J=18.3 Hz), 24.70 (d, J=4.6 Hz), 24.65 (d, J=3.8
Hz); 31P{1H} NMR (C6D6): l 150.6 (d, J=164.6 Hz),
−14.4 (d, J=164.6 Hz); MS: m/z (%) 410 (57, M+), 367
(17, [M−CH3CHCH3]+), 326 (39, [M−2CH2CHCH3]+),
183 (100, [9-phosphafluorenyl]+). Anal. calcd for
C24H28O2P2: C, 70.23; H, 6.89; Found: C, 70.57; H,
7.08%.

1166
K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
3.2.6. Synthesis of 6. The compound was synthesized
by the same procedure as for 5. Heating 1 (4.79 g,
12.6 mmol) and (1R,2R,3S,5R)-(−)-pinanediol (2.15 g,
12.6 mmol) in n-heptane (100 mL) for 24 h at 95°C
gave 6 as a white pasty material. It was recrystallised
methanol. After drying in vacuo 6 was obtained
as a white powder (3.70 g, 64%). 1H NMR (C6D6):
l 7.74–6.98 (m, 14H), 4.15 (d, 1H, J=7.6 Hz), 2.19 (dd,
1H, J=14.6, 3.2 Hz), 2.09–1.92 (m, 2H), 1.89 (t, 1H,
J=5.7 Hz), 1.67–1.58 (m, 2H), 0.97 (3H), 0.58 (3H),
0.42 (3H); 13C{1H} NMR (C6D6): l 153.6 (dd, J=
31.3, 58.0 Hz), 140.6 (dd, J=14.2, 20.9 Hz), 138.9 (dd,
J=10.9, 5.3 Hz), 136.3 (dd, J=10.3, 1.4 Hz), 135.5 (d,
J=1.8 Hz), 135.4 (d, J=20.1 Hz), 133.4 (d, J=17.8
Hz), 129.6, 129.1, 129.0, 128.54 (d, J=6.1 Hz), 128.49
(d, J=7.4 Hz), 128.2, 127.8 (dd, J=13.0, 7.6 Hz), 88.3
(d, J=10.7 Hz), 78.4 (dd, J=8.1, 2.0 Hz), 52.5 (d,
J=3.8 Hz), 40.1, 37.6, 34.8 (d, J=4.6 Hz), 27.7, 27.0,
25.8, 23.8; 31P{1H} NMR (C6D6): l 158.2 (d, J=112.3
Hz), −18.7 (d, J=112.3 Hz); MS: m/z (%) 461 (17,
[M+H]+), 460 (58, M+), 326 (75, [M+−C10H14]+), 325
(100, M−C10H14−H]+), 183 (77, [9-phosphafluorenyl]+);
[h]2D0=+26.4 (c=5, toluene). Anal. calcd for
C28H30O2P2: C, 73.03; H, 6.57; P, 13.45. Found: C,
73.16; H, 6.60; P, 13.43%.
23.3, 22.4, 22.3, 21.5, 21.3, 16.5, 16.2 (dd, J=3.3, 1.8
Hz); 31P{1H} NMR (C6D6): l 154.9 (d, J=189.6 Hz),
−11.9 (d, J=189.6 Hz); MS: m/z (%) 603 (3, [M+H]+),
602 (4, M+), 326 (100, [M−2C10H18]+), 183 (24, [9-
phosphafluorenyl]+); [h]2D0=+61.5 (c=2, toluene). Anal.
calcd for C38H52O2P2: C, 75.72; H, 8.70; P, 10.27.
Found: C, 75.66; H, 8.32; P, 9.78%.
3.2.4. Synthesis of 4. Compound 4 was synthesized
according to the same procedure as for 3. Thus, from
1
(0.99 g, 2.6 mmol) and (1S,2S,3S,5R)-(+)-
isopinocampheol (0.80 g, 5.2 mmol), dissolved in n-
heptane (40 mL), 4 was formed after heating for 72 h
under reflux. The product obtained after evaporation
of the solvent was washed with iso-propanol (10 mL)
and dried in vacuo affording 4 as a colorless solid
1
(1.25 g, 80%). Compound 4: H NMR (C6D6): l 8.35–
6.95 (14H), 4.57 (sp, 1H, J=4.8 Hz), 4.53 (sp, 1H,
J=4.7 Hz), 2.58–2.01 (m, 6H), 1.83 (sp, 1H, J=3.1
Hz), 1.79 (sp, 1H, J=3.0 Hz), 1.72 (td, 1H, J=5.8,
1.9 Hz), 1.66 (td, 1H, J=5.8, 1.8 Hz), 1.22–1.08 (m,
4H), 1.20 (d, 3H, J=7.6 Hz), 1.13 (d, 3H, J=7.4 Hz),
1.10 (6H), 0.82 (3H), 0.81 (3H); 13C{1H} NMR (C6D6)
l 150.1 (dd, J=19.1, 28.7 Hz), 140.9 (dd, J=15.0,
32.3 Hz), 138.34 (dd, J=12.7, 6.1 Hz), 138.30 (dd,
J=12.7, 6.1 Hz), 134.3 (d, J=19.3 Hz), 134.2 (d,
J=19.3 Hz), 134.0 (dd, J=5.1, 1.5 Hz), 130.3, 129.8
(dd, J=9.9, 4.8 Hz), 129.0, 128.7 (d, J=6.6 Hz), 128.6
(d, J=6.6 Hz), 128.54, 128.53, 78.9 (d, J=16.8 Hz),
78.0 (d, J=15.8 Hz), 48.2, 46.8 (d, J=4.1 Hz), 46.5
(d, J=3.6 Hz), 42.1, 38.5 (d, J=2.8 Hz), 38.4, 38.3
(dd, J=4.5, 0.9 Hz), 34.2, 34.0, 27.7, 23.91, 23.87,
20.7, 20.6 (t, J=1.9 Hz); 31P{1H} NMR (C6D6) l
156.8 (d, J=168.4 Hz), −13.3 (d, J=168.4 Hz); MS:
m/z (%) 598 (7, M+), 462 (3, [M−C10H16]+), 325 (100,
M−2C10H16−H]+), 183 (27, [9-phosphafluorenyl]+);
[h]2D0=+43.5 (c=1, toluene). Anal. calcd for
C38H48O2P2: C, 76.23; H, 8.08; P, 10.34. Found: C,
76.13; H, 8.21; P, 10.83%.
3.2.7. Reaction of 1 with (+)-cedrol. To a solution of 1
(0.99 g, 2.6 mmol) in toluene (40 mL) was added
(+)-cedrol (1.16 g, 5.2 mmol) and the reaction mixture
was heated at reflux. After 100 h, the mono-substitu-
tion product 7a was formed, as indicated by two sets
of doublets for the two diastereoisomers in the
31P{1H} NMR spectrum (isomer I: lP(A)=104.4 ppm,
lP(X)=−18.7 ppm (3J(PP)=145.3 Hz); isomer II:
lP(A)=103.6 ppm, lP(B)=−18.8 ppm (3J(PP)=136.5
Hz)). Further heating of the reaction mixture for 3
days afforded the hydrolysis product 7 exclusively.
Evaporation of the solvent in vacuo afforded 7 as a
colorless solid (0.73 g, 80%). On repeated recrystalliza-
tion from iso-propanol, 7 could be obtained as color-
less crystals, which were identified by X-ray structural
analysis.
3.2.5. Synthesis of 5. Using the same procedure as
outlined above, 1 (1.5 g, 3.9 mmol) and (1R,2R)-trans-
1,2-cyclohexanediol (0.45 g, 3.9 mmol) in n-heptane
(60 mL) afforded 5 after heating for 20 h under reflux.
The crude material was washed with iso-propanol (1×5
mL and 1×2 mL) and dried in vacuo to afford 5 (1.34
3.2.8. Synthesis of 9. A solution of 1 (0.99 g, 2.6 mmol)
in toluene (20 mL) was cooled to −78°C and a solution
of HCl in diethyl ether (1 M, 11 mL) was added. After
stirring for 15 min the coolant was removed and the
reaction mixture was stirred for 90 min at ambient
temperature. The precipitate formed was removed by
filtration and water (0.2 mL) was added at 0°C to the
filtrate. After stirring for 2 h the solvent was removed
in vacuo. The evaporation residue was recrystallized
from benzene to afford 9 (0.76, 90%). 1H NMR
(CDCl3): l 12.37 (broad, 1H), 8.13 (d, 1H, J=585.2
Hz), 8.1–7.1 (m, 14H); 13C{1H} NMR (CDCl3): l 140.8
(dd, J=14.7, 20.3 Hz), 136.9 (dd, J=135.8, 29.5 Hz),
136.0 (d, J=9.7 Hz), 134.7 (dd, J=12.2, 1.3 Hz), 133.7
(d, J=19.3 Hz), 132.3 (d, J=2.5 Hz), 131.8 (t, J=9.7
Hz), 128.9 (d, J=12.2 Hz), 128.7, 128.5 (d, J=12.2
Hz); 31P{1H} NMR (CDCl3): l 22.6 (d, J=61.2 Hz),
−15.3 (d, J=61.2 Hz); MS: m/z (%) 326 (4, M+), 325 (9,
[M−H]+), 183 (100, [9-phosphafluorenyl]+). Anal. calcd
1
g, 85%). H NMR (C6D6): l 7.9–6.9 (14H), 3.19–3.10
(1H), 2.96–2.87 (1H), 2.04–1.93 (1H), 1.53–1.44 (1H),
1.29–0.98 (4H), 0.79–0.64 (1H), 0.61–0.46 (1H);
13C{1H} NMR (C6D6): l 152.0 (dd, J=30.0, 55.9 Hz),
140.5 (dd, J=14.8, 21.9 Hz), 138.2 (dd, J=11.2, 4.6
Hz), 137.8 (dd, J=9.7, 2.5 Hz), 135.0 (d, J=1.5 Hz),
134.2 (d, J=18.8 Hz), 134.0 (d, J=18.3 Hz), 130.0,
129.2 (dd, J=12.5, 8.4 Hz), 128.65, 128.59 (d, J=6.1
Hz), 128.47 (d, J=7.1 Hz), 128.46, 82.5 (dd, J=5.6,
2.0 Hz), 78.8 (d, J=7.1 Hz), 30.7, 29.8 (d, J=4.6 Hz),
24.0, 23.8; 31P{1H} NMR (C6D6): l 163.3 (d, J=111.5
Hz), −17.6 (d, J=115.5 Hz); MS: m/z (%) 406 (43,
M+), 325 (17, [M+−C6H8−H]+), 183 (100, [9-phos-
phafluorenyl]+); [h]D20=+8.6 (c=5, toluene). Anal calcd
for C24H24O2P2: C, 70.93; H, 5.95; P, 15.24. Found: C,
70.32; H, 6.04; P, 14.74%.

K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
1167
for C18H16O2P2: C, 66.26; H, 4.94. Found: C, 66.39; H,
5.19%.
11a that precipitated on addition of n-hexane was
collected by filtration, washed with three aliquots of
n-hexane (15 mL) and dried in vacuo to afford 11a
(4.40 g, 96%). Compound 11 could be retained from the
dihydrochloride 11a quantitatively by treatment with
NaHCO3 in a two-phase H2O/CH2Cl2 system.
3.2.9. Synthesis of 10. To a solution of 1 (60.0 g, 157.7
mmol) in toluene (800 mL) was added an ethereal
solution of HCl in diethyl ether (2 M, 320 mL, 4.06
equiv.) at −78°C over 1 h. After stirring the mixture for
10 min the cooling bath was removed and the reaction
mixture was stirred at ambient temperature for a fur-
ther 45 min. Most of the ether was evaporated in vacuo
(20°C, 0.01 mbar) and the mixture was filtered through
a glass fritted suction funnel with exclusion of air and
moisture. The solvents were completely evaporated in
vacuo. The residue 8 was dissolved in THF (400 mL)
and this solution was added over 2 h at 0°C to a
solution of LiAlH4 in THF (1 M, 100 mL, 2.54 g, 100
mmol) diluted with THF (400 mL). After 45 min the
reaction mixture was quenched with conc. HCl (10 mL)
and the solvents were removed in vacuo. The residue
was partitioned between dichloromethane (1 L) and
dilute aqueous HCl (1 L water+15 mL conc. HCl). The
organic phase was separated and dried over magnesium
sulfate. After filtration the solvents were evaporated
and the residue was recrystallized from iso-propanol to
1
Analytical data for 11: H NMR (C6D6): l 7.50–6.93
(m, 14H), 2.51–2.39 (m, 1H), 2.39–2.22 (m, 1H), 2.04–
1.91 (m, 1H), 1.89–1.76 (m, 1H), 1.49–1.28 (m, 1H),
1.21–1.1 (m, 1H), 1.09 (dd, 3H, J=18.3, 7.1 Hz), 0.99
(dd, J=9.2, 7.1 Hz); 13C{1H} NMR (C6D6): l 146.4
(dd, J=32.6, 11.2 Hz), 143.7 (dd, J=29.5, 28.5 Hz),
139.2 (dd, J=16.3, 10.7 Hz), 138.4 (dd, J=11.7, 4.1
Hz), 134.8 (dd, J=19.8, 1.0 Hz), 134.3 (dd, J=18.8, 1.0
Hz), 133.8 (d, J=7.1 Hz), 133.1 (dd, J=6.1, 2.5 Hz),
129.0 (d, J=0.9 Hz), 128.7 (d, J=6.1 Hz), 128.57 (d,
J=7.1 Hz), 128.56, 128.5, 128.4, 37.1 (d, J=2.0 Hz),
36.4 (J=3.1 Hz), 35.6 (dd, J=13.0, 9.4 Hz), 35.0 (dd,
J=14.8, 1.0 Hz), 20.6 (d, J=36.1 Hz), 17.2 (dd, J=5.1,
2.0 Hz); 31P{1H} NMR (C6D6): l 1.0 (d, J=159.8 Hz),
−9.8 (d, J=159.8 Hz); MS: m/z (%) 377 (27, [M+H]+),
376 (99, M+), 375 (44, [M−H]+), 299 (65, [M−Ph]+), 183
(100, [9-phosphafluorenyl]+); [h]D20=−171.8 (c=0.815,
CHCl3). Anal. calcd for C24H26P2: C, 76.58; H, 6.96; P,
16.46. Found: C, 76.69; H, 6.86; P, 15.88%.
1
afford 10 (34.4 g, 74%). H NMR (C6D6): l 7.38–6.87
(m, 14H), 4.03 (dd, 2H, J=202.2, 11.7 Hz); 13C{1H}
NMR (C6D6): l 142.2 (dd, J=14.5, 10.9 Hz), 137.5 (dd,
J=35.9, 10.4 Hz), 136.8 (dd, J=11.4, 2.8 Hz), 136.1
(dd, J=9.7, 6.6 Hz), 134.3 (d, J=19.3 Hz), 133.8 (d,
J=3.1 Hz), 129.0, 128.9 (d, J=7.1 Hz), 128.8 (d, J=3.6
Hz), 128.6; 31P{1H} NMR (C6D6): l −9.3 (d, J=93.7
Hz), −125.0 (d, J=93.7 Hz); 31P NMR (C6D6): l −9.3
(d, J=93.7), −125.0 (m, J=202.2, 93.5, 6.3, 2.6 Hz);
MS: m/z (%) 295 (41, [M+H]+), 294 (100, M+), 293 (64,
[M−H]+), 292 (23, [M−2H]+), 186 (43, [M−PPh]+), 185
(49, [M−PPh−H]+), 183 (97, [9-phosphafluorenyl]+).
Anal. calcd for C18H16P2: C, 73.47; H, 5.48; P, 21.05.
Found: C, 73.38; H, 5.28; P, 20.87%.
Analytical data for 11a: 1H NMR (CDCl3): l 9.24
(broad, 2H), 8.35–7.15 (m, 14H), 3.72–3.58 (m, 1H),
3.45–3.27 (m, 1H), 2.66–2.38 (m, 2H) 2.18–2.00 (m,
2H), 1.37 (dd, 3H, J=19.8, 6.6 Hz), 1.18 (dd, 3H,
J=19.8, 7.1 Hz); 13C{1H} NMR (CDCl3): l 143.9 (dd,
J=14.8, 9.7 Hz), 137.6 (dd, J=12.5, 9.4 Hz), 136.3 (d,
J=10.7 Hz), 135.0 (d, J=3.1 Hz), 133.6 (d, J=18.8
Hz), 133.5 (d, J=18.8 Hz), 133.3 (d, J=5.6 Hz), 133.1
(d, J=5.6 Hz), 131.2 (d, J=12.2 Hz), 130.0 (d, J=1.5
Hz), 129.3 (d, J=7.1 Hz), 129.2 (d, J=7.6 Hz), 121.1
(d, J=38.1 Hz), 120.3 (d, J=37.6 Hz), 35.0 (dd, J=6.6,
3.6 Hz), 34.1 (dd, J=44.8, 11.2 Hz), 33.8 (d, J=9.7
Hz), 31.1 (dd, J=45.8, 2.0 Hz), 14.5, 14.4 (d, J=2.5
Hz); 31P{1H} NMR (CDCl3) 33.5 (d, J=42.5 Hz),
−10.0 (d, J=43.0 Hz). Anal. calcd for C24H28Cl2P2: C,
64.15; H, 6.28. Found: C, 64.11; H, 6.93%.
3.2.10. Synthesis of 11 and 11a. To a solution of 10 (4.0
g, 13.6 mmol) in THF (250 mL) at 0°C was added a
solution of n-BuLi in n-hexane (1.6 M, 8.5 mL, 13.6
mmol). After stirring the mixture for 30 min a solution
of the cyclic sulfate of (2S,5S)-hexane-2,5-diol (2.45 g,
13.6 mmol) in THF (20 mL) was added at 0°C. After
removal of the coolant, the reaction mixture was stirred
for 2 h at ambient temperature and treated with a
solution of n-BuLi in n-hexane (10.2 mL, 16.3 mmol) at
0°C. The reaction mixture was stirred at ambient tem-
perature for 2 h and the excess n-BuLi was quenched
by addition of methanol (1 mL). The waxy solid left
after all volatiles had been removed in vacuo was
extracted at 60°C with n-hexane (2×200 mL). After
evaporation of the solvent in vacuo 11 was obtained as
a pale yellow oil (3.93 g, 77%).
3.2.11. Synthesis of 12. To a solution of 10 (2.0 g, 6.8
mmol) in THF (120 mL) was added a solution of
nBuLi in n-hexane (1.6 M, 4.3 mL) at 0°C and the
reaction mixture was stirred for 30 min. Thereafter a
solution of (R,R)-(+)-1,4-di-O-p-toluenesulfonyl-2,3-O-
isopropylidene-D-threitol (3.20 g, 6.8 mmol) in THF (20
mL) was added over 5 min and the reaction mixture
was stirred for 2 h at ambient temperature. After
cooling to 0°C a nBuLi solution in n-hexane (1.6 M,
5.5 mL, 8.8 mmol) was added. The reaction mixture
was then stirred for 2 h at room temperature and excess
nBuLi was quenched by addition of methanol (1 mL).
The residue obtained after evaporation of all volatiles
in vacuo was dissolved in dichloromethane (120 mL)
and washed with saturated aqueous NaHCO3 solution
(3×100 mL) and saturated solution of NaCl (50 mL).
The organic phase was separated and dried over
MgSO4. The oily residue left after removal of the
solvent was recrystallized from methanol to afford 12
For the preparation of 11a, a solution of 11 (3.84 g,
10.2 mmol) in n-hexane (60 mL) was treated with a
solution of HCl in diethyl ether (2 M, 15 mL). An oily
product separated from the reaction mixture. After
removal of the solvent in vacuo a second equivalent of
HCl in diethyl ether was added. The colorless solid of

1168
K. W. Kottsieper et al. / Tetrahedron: Asymmetry 12 (2001) 1159–1169
Table 4. Crystal and refinement data for 1, 3 and 7
Compound
1
3
7
Chemical formula
Formula weight
Crystal system
Space group
C
380.39
22H26N2P2
C38H52O2P2
602.74
Monoclinic
P21
11.1787(12)
26.8194(37)
12.7123(19)
90
107.206(10)
90
C38H39NO4P4
697.58
Triclinic
Monoclinic
P21/n
9.0861(14)
19.7870(37)
11.5829(22)
90
93.266(14)
90
2079.1(6)
4
(
P1
,
a (A)
10.9756(14)
12.1468(16)
16.2695(23)
94.499(11)
108.935(11)
114.149(10)
1815.2(4)
2
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
V (A )
3640.7(8)
4
Z
Temperature (K)
295(2)
1.215
294(2)
1.100
297(2)
1.276
Dcalcd (g cm−3
)
Radiation
Mo Ka
0.71073
0.217
808
Mo Ka
0.71073
0.149
Mo Ka
0.71073
0.248
732
,
Wave length (A)
v (mm−1
F(000)
)
1304
Crystal size (mm)
2q Range (°)
Index range
0.74×0.42×0.35
4.08–50.00
05h510, 05k523,
−115l513
3788
0.80×0.36×0.27
4.10–44.98
0.59×0.52×0.23
4.10–40.00
−125h512, −285k528, −135l513 05h510, −115k510, −155l514
Reflections collected
Independent reflections
Rint
10328
9494
0.0165
3622
3387
0.0212
3568
0.0211
Absorption correction
Max./min. transmission
Data/restraints/parameters 3563/0/243
Semi-empirical
0.26937–0.24833
Semi-empirical
0.34374–0.32906
9494/1/769
Semi-empirical
0.99124–0.91677
3387/0/435
Goodness-of-fit
0.880
0.909
1.073
Final indices [I\2|(I)]
R1=0.0340, wR2=0.0827
R1=0.0531, wR2=0.0895
0.153 to −0.260
None
R1=0.0357, wR2=0.0797
R1=0.0511, wR2=0.0840
0.155 to −0.177
0.02(7)
R1=0.0372, wR2=0.1026
R1=0.0427, wR2=0.1057
0.605 to −0.175
None
R indices (all data)
−3
,
DF (e A
)
Flack parameter x
1
(0.89 g, 31%). H NMR (C6D6): l 7.39–6.88 (m, 14H),
4.25 (ddd, 1H, J=12.1, 9.3, 6.2 Hz), 3.80 (dddd, 1H,
J=12.4, 9.2, 6.0, 1.3 Hz), 2.23 (ddd, 1H, J=29.0, 11.0,
6.1 Hz), 1.92 (dd, 1H, J=13.1, 6.2 Hz), 1.85–1.66 (m,
2H), 1.42 (3H), 1.40 (3H); 13C{1H} NMR (C6D6): l
146.4 (dd, J=31.7, 27.2 Hz), 142.7 (dd, J=29.8, 11.6
Hz), 137.7 (dd, J=12.4, 1.0 Hz), 137.6 (d, J=12.3 Hz),
134.7 (d, J=5.7 Hz), 134.4 (d, J=19.7 Hz), 134.2 (d,
J=19.5 Hz), 129.5, 129.3 (d, J=7.8 Hz), 128.83, 128.80
(d, J=6.4 Hz), 128.77 (d, J=6.7 Hz), 128.77, 128.70,
118.6 (d, J=1.3 Hz), 84.7 (dd, J=2.0, 1.8 Hz), 83.9
(dd, J=7.4, 1.6 Hz), 27.73, 27.67, 24.8 (dd, J=19.5, 7.4
Hz), 20.9 (dd, J=20.9, 11.4 Hz); 31P{1H} NMR (C6D6):
l 7.0 (d, J=155.4 Hz), −13.0 (d, J=155.5 Hz); MS:
m/z (%): 422 (70, [M+2H]+), 421 (30, [M+H]+), 420 (60,
M+), 362 (20, [M+−Me2CO]+), 305 (21, [M−2Me2CO+
H]+), 294 (81, [M−C7H10O2]+), 183 (100, [9-phos-
phafluorenyl]+); [h]D20=+61.3 (c=1.435, CHCl3). Anal.
calcd for C25H26O2P2: 71.42; H, 6.23; P, 14.73. Found:
C, 70.77; H, 6.40; P, 13.75%.
ter employing graphite monochromated Mo Ka radia-
tion (u=0.71073 A).
,
The structures were solved by direct methods and
refined against F2 on all data by full-matrix least-
squares with SHELXTL-93 programs.24,25 H atoms of
the organic groups were included at geometrically cal-
culated positions using the riding model (CꢀH=0.95
,
A). Experimental data for the X-ray structure determi-
nation and refinement details for 1, 3 and 7 are col-
lected in Table 4.
Acknowledgements
This work was supported by Symyx Technologies Inc.,
Santa Clara, USA, and the Fonds der Chemischen
Industrie.
3.3. X-Ray crystallography
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