Rigid P-chiral mono and diphosphines. Configurative stability and P-inversion barrier

Article abstract of DOI:10.1016/j.tetasy.2006.05.005

A group of P-chiral monophosphine oxides and one diaryl diphosphine oxide based on the dibenzophosphole skeleton have been synthesized. Preparative enantioselective chromatography of 4-trimethylsilyl-5-phenyl-5H-dibenzophosphol oxide followed by a simple transformation with exchange of substituents (and a homo-coupling reaction in one case) and a stereoselective reduction step furnished the corresponding phosphines in fair to good yield. Their relative and absolute configurations were determined by crystal structure analysis. It turned out that racemization of the phosphines through P-inversion takes place at ambient temperature and depends markedly on ortho substituents (104-114 kJ mol^-1). In the case of the diphosphine, racemization can be suppressed when forming a chelate with Pd(II) or Ni(II) complexes.

Full text of DOI:10.1016/j.tetasy.2006.05.005

Tetrahedron: Asymmetry 17 (2006) 1355–1369
Rigid P-chiral mono and diphosphines. Configurative stability
and P-inversion barrier
Michael Widhalm,a,* Lothar Breckera and Kurt Mereiterb
aInstitute for Organic Chemistry, University of Vienna, Wa¨hringer Strasse 38, A-1090 Vienna, Austria
bInstitute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164SC, A-1060 Vienna, Austria
Received 22 March 2006; revised 3 May 2006; accepted 8 May 2006
Abstract—A group of P-chiral monophosphine oxides and one diaryl diphosphine oxide based on the dibenzophosphole skeleton have
been synthesized. Preparative enantioselective chromatography of 4-trimethylsilyl-5-phenyl-5H-dibenzophosphol oxide followed by a
simple transformation with exchange of substituents (and a homo-coupling reaction in one case) and a stereoselective reduction step fur-
nished the corresponding phosphines in fair to good yield. Their relative and absolute configurations were determined by crystal struc-
ture analysis. It turned out that racemization of the phosphines through P-inversion takes place at ambient temperature and depends
markedly on ortho substituents (104–114 kJ molꢀ1). In the case of the diphosphine, racemization can be suppressed when forming a che-
late with Pd(II) or Ni(II) complexes.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
discovered, which are better catalyzed by monodentate
ligands.3 To counterbalance the lack of conformational
stability in transition metal catalysts with monodentate
ligands, frequently concomitant with decreased asymmetric
induction, P-chiral phosphines,4 which display their chiral
interaction in immediate proximity to the metal center
are of high interest. These compounds are typically
prepared either by (1) resolution of preceding phosphine
oxides, (2) stepwise attachment of three electronically
and/or sterically different aryl or alkyl substituents to a
sp3 P-center replacing a chiral auxiliary, (3) by asymmetric
deprotonation of enantiotopic CH3 or CH2 groups in cor-
responding phosphine oxides or borane complexes, or (4)
via dynamic kinetic resolution of secondary phosphine bor-
ane complexes under the influence of BuLi/(ꢀ)sparteine or
chiral transition metal complexes.5 A sufficiently high
inversion barrier provided stable enantiomers. Several cal-
culations and empirical determinations of the barrier for
the pyramidal inversion have been performed both, for
open chain and cyclic phosphines,6 including P-aromatic
systems.7
The dramatically increased importance of transition metal
catalyzed asymmetric transformations1 over the last few
decades has been paralleled by the growing desire for chiral
ligands. Among these especially P(III)-compounds have
proven to be versatile modifiers, useful in numerous
types of transition metal catalyzed reactions. An impres-
sive number of applications have been reported where
almost enantiopure products were obtained in high chemi-
cal yield.
Nevertheless, it became obvious that a perfect fit of ligand
and substrate is a prerequisite for high asymmetric induc-
tion. This stimulated an intensive and continuous search
for new and more efficient ligand structures. Since it is gen-
erally accepted that conformational stability, best accom-
plished through the formation of 5–7 membered chelates,
is a favorable feature for efficient chiral catalysts, preferen-
tially bidentate P-ligands have been applied. In contrast,
the number of chiral monophosphines2 is still comparably
small, which might be due to the fact that only rather
recently transition metal catalyzed reactions have been
For rigid compounds of general structures depicted in Fig-
ure 1, the inversion of P will be markedly influenced by the
ring strain and the aromatic character of the heteroring (if
n = 0). For the first investigation, we chose the dibenzo-
phosphole unit (Fig. 1: R = aryl, n = 0) as a rigid prochiral
*
Corresponding author. Tel.: +43 1 4277 52111; fax: +43 1 4277 9521;
e-mail: m.widhalm@univie.ac.at
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.05.005

1356
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
metallation of one of the diastereotopic positions 4 or 6 fol-
R
P
R
P
Z'
Z
lowed by reaction with electrophiles yields rigid P-chiral
phosphine oxides.8e After resolution of a suitable inter-
mediate, the substituent at position 4 could be modified
or exchanged before a final reduction step would afford
the phosphine. Alternatively, a homo-coupling reaction
resulted in a bidentate biaryl diphosphine ligand with
P-chirality, a low rotational barrier, and—tentatively—
with less conformational freedom than BINAP.10 Struc-
tural variations are possible either with replacing P–Ph
by other aromatic or aliphatic moieties or by introducing
additional substituents at positions 6 and 60.
X
X
n
n
R = Ar, alkyl
Z = Ar, Het-ar, SiR3, COOR, CH2NR2, etc.
X = CR2, O, S
n = 0,1
Figure 1. Examples of P-chiral auxiliaries through desymmetrization of P
heterocycles.
Herein we report the synthesis of several P-chiral mono
and the first diphosphine ligand as well as their oxides
containing dibenzophosphole units, their preparation in
enantiomerically pure or enriched form, determination of
absolute configuration, and investigation of their racemiza-
tion barrier due to P-inversion. Moreover, we describe the
preparation and structure of a palladium complex.
precursor,8 which can be conveniently desymmetrized by
ortho substitution yielding P-chiral monophosphines.
Based on the results of the calculations,7 we expected mod-
erate configurative stability, which eventually increased due
to the presence of annelated benzene rings in a range of 100
and 150 kJ molꢀ1
.
In a subsequent homo-coupling reaction, C2-symmetrical
biaryl ligands9 will be accessible (Scheme 1). With these
ligands, sterically demanding metal complexes will be
formed, in particular with Z1 5 H in the case of biaryls,
which can be applied as chiral catalysts. We expected an
increased asymmetric induction in several reaction types,
especially in cases where small and/or monocoordinating
substrate molecules are involved, due to a more pro-
nounced steric interaction with improved conformational
stability in substrate complexes.
2. Results and discussion
2.1. Syntheses
The synthesis started from 5-phenyl-dibenzophosphole
oxide 1, which is easily prepared from triphenylphosphine
oxide and Ph–Li in two steps (Scheme 2). As reported by
Ogawa et al.8e 1 can be ortho metallated with LDA giving
preferentially the 4-lithio compound, which reacts with
various electrophiles. Quenching with TMS-Cl yielded 4.
In our hands, the yields were rather low (28%). A modified
procedure with a shorter reaction time and excess of LDA
P-Phenyl-5H-dibenzophosphole oxide 1 appeared to be an
inexpensive and versatile starting material since ortho
12
13
Z2
11
Z1
Z3
10
14
P
O
4a
15
P
6
4
5a
5
3
7
9b 9a
2
8
1
9
ortho metallation
stucture
optical resolution
"fine tuning"
1
Ph
Ph
exchange/
Ph
O
O
X
Y
modification
Y
P
P
P
of substituents
reduction
homo coupling,
reduction
stucture
"fine tuning"
Z2
Ph
Z1
P
P
P
P
Z2
Z1
Ph
Scheme 1.

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
1357
O
Ph
O
Ph
I
P
P
Ph3P
2
1
Me3Si
O
O
Ph
Ph
O
Me3Si
Me3Si
SiMe3
P
P
P
3
5
4
Scheme 2.
afforded 4 in 41% yield, together with some disubstituted
product 5 (27%) and starting material 1 (9%). Treatment
of 4 with excess of ICl gave 4-iodo-5-phenyl-dibenzophosp-
hole oxide 2 (97%), which proved to be a versatile key
intermediate for the synthesis of several P-chiral com-
pounds (see below). Attempts to increase the yield of 4
by using the in situ trap protocol11 (Li-TMP/TMS-Cl,
ꢀ78 ꢁC) resulted in a 1:1 mixture of 3 and 4 indicating that
4 is the thermodynamically favored species, while both
ortho positions are attacked by LDA with equal ease.
Attempts to access 2 directly from 1 failed. Under the
conditions investigated [LDA, TMP-MgBr, (TMP)2Mg;
electrophile I2 or 1,2-diiodoethane] only complex mixtures
were obtained from which no 2 could be isolated.
straightforward; while quenching with CO2 gave 6 in good
yield, the reaction with benzophenone afforded comparable
quantities of 7 and 8 in low yield. Their structures were
confirmed by X-ray crystallography (see below). Both Pd
mediated reactions, the introduction of the cyano group
(Pd(PPh3)4, KCN, CuCN, 12)15 and arylation (Suzuki cou-
pling with Ar–B(OH)2, 9, 10) proceeded smoothly in good
yield.16
Not unexpected, the introduction of the 9-anthryl unit was
difficult; 11 could be isolated in only 11%, which was attrib-
uted to the steric hindrance and low stability of 9-anthryl
boronic acid. An attempted coupling reaction with 9-phen-
anthryl boronic acid led to an inseparable mixture of
(atropisomeric) products.
For the preparation of enantiomerically pure phosphines,
an economic access either to 2 or 4 was desired. Attempted
resolution procedures via fractional crystallization of dia-
stereomeric clathrates with 2,20-binaphthol,12 O,O-di-
benzoyltartrate,13 mandelic acid,14 or camphor sulfonic
acid13 were unsuccessful. Fortunately, enantiomeric phos-
phine oxides 2 and 4 could be easily separated by enantio-
selective chromatography using a Chiralcel OD column.
For 4, with an extremely large separation factor
(a = 4.6), separation on a large scale was practical. Using
a preparative column (5 · 50 cm, 20 lm), 300 mg samples
per injection could be resolved within 1 h. The absolute
configuration of the preferentially eluted enantiomer (ꢀ)-
4 was determined to be (S)P by crystal structure analysis
of (ꢀ)-2 (see below).
While the reduction of a non-stereogenic P@O group with
various reagents are available (HSiCl3/amine, polysiloxane,
AlH3, LiAlH4, with or without Lewis acids, etc.)17 the pres-
ence of a stereogenic center requires a stereoselective trans-
formation in order to conserve P-chirality.18 A mild
method using MeOTf/LiAlH4 in DME was recently shown
to reduce several P-chiral mono and diphosphine oxides
with a high degree of stereo inversion.18b With all phos-
phine oxides, including 4, the final reduction step pro-
ceeded smoothly yielding phosphines 13–15 as moderately
air stable compounds.
2.2. Racemization kinetics and configurative stability
During work-up of the phosphines, it was noticed that the
specific rotation varied markedly depending on duration,
temperature, and method of isolation. Hence, it became
evident that significant racemization took place at ambient
temperature. In a kinetic study on 13, 14, and 15, rate con-
stants of the pyramidal inversion of P and activation
parameters were determined by following the decay of
the specific rotation at 436 nm for 0.5–4 half lives. With
these data and on the basis of a first order kinetics with
vrac = 2 · vinv, rate constants kinv and DG5 were calcu-
lated for three temperatures (Table 1). After graphical
From 2, P-chiral monophosphine oxides with various sub-
stituents at position 4 were obtained (Scheme 3). In view of
their intended use in asymmetric catalysis either ‘trans-
formable’ substituents (useful in further transformations)
such as carboxyl or cyano group, or bulky substituents
with increased steric interaction near to the P-center were
synthesized. The corresponding Grignard intermediate
with MgX at position 4 was not accessible directly from
1 but could be easily obtained from 2 by reaction with iso-
propyl magnesium chloride. However, the reaction was not

1358
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
HO
Ph
Ph
O
Ph
HOOC
O
Ph
P
P
R
6
O
Ph
R = H
Cl
I
7
8
P
2
O
Ph
O
Ph
Ar
NC
P
P
Ar = Ph
9
10
11
12
2-Naphthyl
9-Anthryl
4
Ph
Ph
Ar
Me3Si
P
P
13
14
Ar = Ph
2-Naphthyl
15
Scheme 3.
determination of DEA from the Arrhenius plot, DH5 and
DS5 were obtained.ꢀ For further details see the Experimen-
tal. It turned out that the donor/acceptor ability of 4-
substituents had a marked influence on the ease of racemi-
zation. While a trimethylsilyl group stabilized the P config-
uration (t1/2 = 338 h at 313 K), aromatic substituents with
delocalization ability promoted the inversion (t1/2 = 19 h at
313 K), eventually through stabilization of a polar transi-
tion state as depicted in Figure 2. This is in qualitative
agreement with the experimental findings and theoretical
studies on the benzophosphol system.6,7
C2 symmetrical diphosphine 17 was attempted (Scheme
4). Various procedures for homo-coupling reactions19 have
been developed beginning with the ‘classical’ high temper-
ature Ullmann coupling (Cu bronze, neat) and variants
thereof (in DMF, NMP, pyridine or with Ni complexes
and reducing agents). Also, the cross coupling methodol-
ogy and Fe and Cu promoted coupling reactions of lithi-
ated precursors can be adapted in order to obtain
symmetrical products.16,20 While the Cu catalyzed Ull-
mann coupling proved to be rather insensitive to steric hin-
drance, yielding tetra-ortho substituted biphenyls or 2,20-
substituted binaphthyls in high yield, the corresponding
Pd and Ni catalyzed reaction often suffers from low yields
accompanied by the formation of a dehalogenated sub-
strate.21 Conditions have been worked out which proved
to be particularly useful for the coupling of Ar–P(O)R2.22
A minor stabilizing effect from the incorporation of P into
a ring is overcompensated by formation of a heteroaro-
matic structure and a low-energy polar transition state with
delocalization of the negative charge.
From these findings, we concluded that configurative sta-
bility in this system could be reached if the P-centers are
part of a chelate structure. Therefore the synthesis of the
In our case, the Ullmann type Ni catalyzed reaction using
excess phosphine ligand, zinc dust, and NaH gave the most
promising results.23 Replacing Ph3P with 1,10-bis(diphen-
ylphosphino)ferrocene (dppf) and applying ultrasonifica-
tion afforded the desired C2-symmetrical dioxide dl-16.
Under optimized conditions, 47% of dl-16 was isolated
as the exclusive stereoisomer. No NMR evidence for the
ꢀ The slight temperature dependence observed is attributed to insufficient
accurancy of T measurement.

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
Table 1. Kinetics of P-inversion and activation parameters
1359
Compd
T (K)
kinv · 10ꢀ6 sꢀ1
DEA (kJ molꢀ1
)
DG5 (kJ molꢀ1
)
DH5 (kJ molꢀ1
)
DS5 (J molꢀ1 Kꢀ1
)
13a
303
313
323
2.95
10.26
33.60
106.3
106.6
106.9
96.1
96.0
96.0
ꢀ33
ꢀ34
ꢀ34
ꢀ30
ꢀ31
ꢀ31
ꢀ9
ꢀ8
ꢀ9
59
59
59
59
98.6
14a
303
313
323
2.84
10.11
33.10
106.4
106.7
107.0
97.2
97.1
97.1
99.7
114
15a
313
323
333
0.569
2.53
7.94
114.1
113.9
114.3
111.4
111.3
111.2
dl-17b
293
296
303
308
1.55
2.73
8.57
104.2
104.1
103.6
103.4
121.7
121.6
121.6
121.5
124
18.37
a Based on the decay of the specific rotation at 436 nm.
b Based on integration of corresponding signals of dl-17 and meso-17 in 1H NMR spectra.
Ph
P
Ph
P
Ph
X
X
X
P
Figure 2.
O
Ph
I
P
Ph
P
P
2
Ph
dl-17
O
Ph
P
Ph
O
P
C2
P
O
Ph
1
dl-16
Ph
Ph
O
P
P
P
P
Ci
O
Ph
Ph
meso-17
meso-16
Scheme 4.

1360
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
presence of meso-16 could be detected;ꢁ repetition with
enantiomeric (ꢀ)-(S)-2 improved the yield of (+)-(S,S)-16
to 69% (13% of 1 was recovered). To elucidate the
preferred biaryl torsion of dl-16, its crystal structure was
determined (see below) showing a relative configuration
(S*,S*)P(S*)axial with a biaryl angle of 54.5(3)ꢁ. However,
at room temperature no evidence from the NMR spectra
for a restricted rotation around the biaryl axis could be
found. Reduction of dl-16 proceeded smoothly at low
temperature to afford 66% of crude 17. Analysis by
NMR revealed that a (slow) epimerization of the predomi-
nating and obviously primarily formed diastereoisomer
dl-17 was taking place to give meso-17. By conducting the
reduction with racemic dl-16, the main product could be
selectively precipitated with MeOH. Its relative configura-
tion was confirmed by crystal structure analysis of the
corresponding PdCl2 complex to be (S*,S*)P (see below).§
In situ decomplexation of dl-17ÆPdCl2 with KCN in a
NMR tube yielded the spectrum of the original ligand
dl-17. The epimer meso-17 could be only obtained as an
enriched mixture after chromatography together with
dl-17 (60:40). This process of epimerization resulted in
the population of meso-17 by P-inversion in a reversible
reaction reaching equilibrium with a 1:1 mixture of the
stereoisomers which was somewhat surprising but reflects
the lack of steric or electronic interaction of P-centers. If
enantiomerically pure 16 was used in the reduction, this
process also resulted in a racemization of 17 through two
P-inversions in sequence according to Eq. 1.
tion (NMR, specific rotation) even at elevated temperature
(up to 6 h at 50 ꢁC).
2.3. Crystal structure analysis and solid state stereochemis-
try of (S)-2, 7, 8, (S,S)-16ÆCH2Cl2, and dl-17ÆPdCl2ÆCHCl3
In order to ascertain molecular structures, the absolute
configuration in the case of (ꢀ)-(S)-2 and (S,S)-16ÆCH2Cl2,
and the stereochemistry of new compounds, crystal struc-
tures of five representatives were determined by X-ray
diffraction. Technical details on this work are reported in
the Experimental, and crystallographic data are shown in
Table 2. Crystallographic data of a sixth compound,
meso-16, are reported only in the supporting information
(CCDC-294527). Selected geometric data are compiled in
Table 3, views of the molecular structures are shown in Fig-
ures 3–7. All structures are based on the 4H-dibenzophos-
phol moiety which consists of a biphenyl entity bridged by
phosphorus under the formation of a flat five-membered
ring. The phosphorus imposes a significant in-plane bend-
ing of the biphenyl entity causing the inner angles C2–
C1–C7/C8–C7–C1 to be smaller by about 12ꢁ than the out-
er angles C6-C1–C7/C12–C7–C6 (cf. Fig. 3). The bond
lengths and bond angles in the phosphol rings are fairly
constant (Table 3), showing mean values of P–C =
˚
˚
1.809(14) A, aromatic C–C = 1.403(9) A, aliphatic C–
˚
C = 1.477(4) A, C–P–C = 92.5(4)ꢁ, P–C–C = 109.8(9)ꢁ,
and C–C–C = 113.9(5)ꢁ for the four phosphol oxides and
similar values for the phosphol complex dl-17ÆPdCl2Æ
CHCl3 (Table 3). In all five compounds are the terminal
phenyl rings [e.g., C13 though C18 in (S)-2] essentially per-
pendicular to the dibenzophosphol moieties and in bisect-
ing orientations, as can be seen from the torsion angles
C14–C13–P1–O1 in Table 3. Particularly regular in this
respect is (S)-2, which served to fix the absolute configura-
tion of the chiral members of the compounds presented
here. The distinctly anisotropic displacement ellipsoids of
the outer biphenyl atoms of this compound at 173 K (cf.
Fig. 3) are in context with a pending phase transition,
which at lower temperature leads to a change in the unit
cell (see Experimental).
k1
k
ꢀ1
ðS; SÞP-17 ꢀ meso-17 ꢀ ðR; RÞP-17 k1 ꢁ k
ð1Þ
ꢀ1
k
k1
ꢀ1
1
The kinetics were followed by H NMR between 293 and
308 K, from which activation parameters were calculated
and a half-life for the interconversion t1/2 = 120 h at
293 K (Table 1). Note: the half-life for the epimerization
is 60 h.
Similarly a Ni(II) complex was prepared in the NMR tube;
adding a methanolic solution of NiCl2Æ7H2O to dl-17 in
CDCl3 gave an immediate color change to deep violet.
NMR spectra showed the formation of a single species with
C2 symmetry for which in analogy to the Pd complex, a
dicoordinated Ni(II) complex was postulated. However,
its structure remains undiscovered yet. Attempts to crystal-
lize the compound remained unsuccessful and MS spectra
(electrospray and MALDI) were not conclusive, showing
fragments of m/e 576 and 1095 corresponding to a (P–
P)M and (P–P)2M. Since this species displays a pronounced
solubility in polar solvents, either a monomeric or dimeric
cationic species with coordination of solvate molecules is
supposed. Both complexes are air stable compounds and
no epimerization/racemization could be observed in solu-
A remarkable situation was encountered with the two di-
phenylhydroxymethyl compounds 7 and 8, which differ in
constitution by only the Cl atom attached to C4 of com-
pound 8. In 7, the phenyl rings C13–C18 and C20–C25
are oriented in such a fashion which permits a pronounced
intramolecular arene–arene p-stacking interaction with a
˚
ring–ring separation of about 3.3 A (shortest C–C distance
˚
is 3.34 A and mutual ring inclination is 4.9ꢁ). This stereo-
chemistry brings the hydroxy group of O2 in close vicinity
of O1 and both are linked by a straight intramolecular
˚
hydrogen bond to O1ꢂ ꢂ ꢂO2 = 2.735(2) A (Fig. 4). In
compound 8, the chlorine attached to C4 hinders the
diphenylhydroxymethyl group from adopting the same
orientation as in 7 and consequently 8 is lacking an intra-
molecular arene–arene p-stacking. Because of this stereo-
chemistry, the hydroxy oxygen O2 is now coplanar with
the dibenzophosphol moiety and shows a remarkably short
ꢁ In a preliminary coupling experiment using Ph3P instead of dppf, also
meso-16 was isolated as a side product (ꢁ5%). Its structure was
confirmed by X-ray crystallography.
§ Note that the stereochemical descriptors are unchanged although the
configuration at P is inverted since the substituent ‘@O’ is replaced by a
lone pair changing the priority of substituents.
˚
intramolecular distance to P1, P1–O2 = 2.581(2) A (in
˚
˚
7 this distance is 3.31 A, that is, close to 3.35 A, the sum
of van der Waals radii), while the accompanying intra-

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
1361
Table 2. Details for the crystal structure determinations of compounds (S)-2, 7, 8, (S,S)-16ÆCH2Cl2, and dl-17ÆPdCl2ÆCHCl3
(S)-2
7
8
(S,S)-16ÆCH2Cl2
dl-17ÆPdCl2ÆCHCl3
Formula
fw
C18H12IOP
402.15
C31H23O2P
458.46
C31H22ClO2P
492.91
C37H26Cl2O2P2
635.42
C37H25Cl5P2Pd
815.16
Cryst. size, mm
Crystal system
Space group
0.55 · 0.52 · 0.33
Orthorhombic
P212121 (no. 19)
8.2459(4)
13.0882(7)
14.7084(8)
90
1587.39(14)
4
1.683
0.58 · 0.28 · 0.22
Monoclinic
P21/c (no. 14)
15.1403(11)
9.1133(7)
16.5383(12)
92.524(1)
2279.7(3)
4
1.336
173(2)
0.148
960
0.65 · 0.08 · 0.07
Monoclinic
P21/c (no. 14)
12.8448(6)
16.5073(8)
12.0212(6)
110.414(1)
2388.8(2)
4
1.371
297(2)
0.255
1024
0.69 · 0.45 · 0.40
Orthorhombic
P212121 (no. 19)
10.0076(4)
15.4231(6)
20.0818(8)
90
3099.6(2)
4
1.362
0.48 · 0.35 · 0.07
Orthorhombic
Pca21 (no. 29)
21.4238(11)
10.8201(5)
14.5902(7)
90
3382.1(3)
4
1.601
˚
a (A)
˚
b (A)
˚
c (A)
b (ꢁ)
3
˚
V (A )
Z
qcalcd (g cmꢀ3
T (K)
)
173(2)
2.113
784
173(2)
0.346
1312
173(2)
1.066
1632
l (mmꢀ1) (Mo Ka)
F(000)
hmax (ꢁ)
30
9708
4537
4203
190
0.0422
0.0457
27
26350
4971
4276
311
0.0382
0.0463
27
23738
5202
3889
320
0.0499
0.0699
30
27740
9005
8612
388
0.0357
0.0376
30
48454
9872
9124
406
0.0230
0.0270
No. of rflns measd
No. of unique rflns
No. of rflns I > 2r(I)
No. of params
R1 (I > 2r(I))a
R1 (all data)
wR2 (all data)
Diff. four peaks min/max (e A
0.1020
ꢀ1.64/1.09
0.1092
0.1300
ꢀ0.18/0.48
0.0944
ꢀ0.25/0.64
0.0545
ꢀ0.56/0.68
ꢀ3
˚
)
ꢀ0.32/0.47
P
P
P
2
2
1=2
a R1 = RkFoj ꢀ jFck/ jFoj, wR2 ¼ ½ ððwðF 2o ꢀ F c2Þ Þ= ðwðF 2oÞ Þꢃ
.
˚
Table 3. Selected geometric data of compounds (S)-2, 7, 8, (S,S)-16ÆCH2Cl2, and dl-17ÆPdCl2ÆCHCl3 (A, ꢁ)
a
a
(S)-2
7
8
(S,S)-16ÆCH2Cl2
dl-17ÆPdCl2ÆCHCl3
Pd–Cl1, Pd–Cl2
P1–O1 or –Pd
P1–C2
P1–C8
P1–C13
C1–C2
C7–C8
C1–C7
C2–P1–C8
2.342(1), 2.347(1)
2.240(1), 2.246(1)
1.824(2), 1.817(2)
1.814(2), 1.809(2)
1.812(2), 1.801(2)
1.404(3), 1.405(3)
1.397(3), 1.398(3)
1.475(3), 1.472(3)
91.7(1), 91.6(1)
1.489(2)
1.805(4)
1.798(4)
1.799(3)
1.411(6)
1.387(7)
1.470(8)
92.2(2)
1.493(1)
1.816(1)
1.794(1)
1.803(2)
1.409(2)
1.403(2)
1.483(2)
93.1(1)
1.483(1)
1.844(2)
1.811(2)
1.802(2)
1.413(3)
1.388(3)
1.477(3)
92.0(1)
1.493(1), 1.486(1)
1.813(1), 1.818(1)
1.801(1), 1.793(1)
1.794(1), 1.802(2)
1.408(2), 1.410(2)
1.402(2), 1.402(2)
1.476(2), 1.478(2)
92.5(1), 92.5(1)
C2–P1–O1 or –Pd
C8–P1–O1 or –Pd
C13–P1–O1 or –Pd
C2–P1–C13
C8–P1–C13
C14–C13–P1–O1 or Pd
118.9(2)
117.1(2)
112.7(2)
106.5(2)
107.2(2)
2.7(4)
114.9(1)
118.2(1)
113.7(1)
110.1(1)
104.8(1)
19.2(1)
122.0(1)
111.2(1)
116.1(1)
107.6(1)
104.0(1)
ꢀ15.0(2)
0.027
116.2(1), 118.5(1)
115.4(1), 114.8(1)
111.6(1), 113.9(1)
110.7(1), 107.3(1)
109.1(1), 107.5(1)
ꢀ5.3(1), 30.2(1)
0.072, 0.030
121.4(1), 113.7(1)
114.7(1), 115.7(1)
112.1(1), 113.3(1)
104.9(1), 111.9(1)
110.1(1), 108.8(1)
31.7(2), ꢀ23.8(3)
0.074, 0.105
b
˚
rms planarity (A)
0.026
0.070
C3–X
X = I 2.099(5)
X = C19 1.550(2)
2.735(2)
3.310(1)
ꢀ57.9(2)
X = C19 1.545(3)
2.781(2)
2.581(2)
ꢀ0.5(2)
X = C21 1.484(2)
X = C21 1.483(3)
O1. . .O2 intramol.
P1. . .O2 intramol.
C2–C3–C19–O2
C2–C3–C21–C20
127.7(1)
54.5(3)
a Pairs of values for first and second dibenzophosphol moiety (atom numbers for second dibenzophosphol moiety increase by 18 for C and by 1 for P and
O).
b rms deviation from a common least-squares plane of the C and P atoms of the dibenzophosphol moiety.
˚
molecular O2–O1 distance of 2.781(2) A is now not a
hydrogen bond because the hydrogen atom is exo-oriented.
Referring to systematic studies of Holmes et al.,24 P1–O2 =
a trigonal bipyramidal geometry. Consistent with this are
the trends in the bond angles around P1 when compared
with those of 7 (cf. C2–P1–O1 and C8–P1–O1 of 7 and 8
in Table 3). In order to show how outstanding
P1–O2 = 2.581 A in 8 is, the corresponding P–O donor
bond lengths in diphenylposphinoylbenzoic acid, P–O =
˚
2.581(2) A in 8 has to be classified as a P–O donor coordi-
nation by which an oxygen enters the coordination of a
tetrahedral phosphorus and changes it gradually toward
˚

1362
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
Figure 5. Structural view of 8 showing 20% thermal ellipsoids. The open
˚
bond P1–O2 = 2.581(2) A represents a P–O donor coordination. Hydro-
gen bonds with O10 and O20 of a centrosymmetric neighbor molecule are
0
0
˚
shown as broken lines, O2ꢂ ꢂ ꢂO1 = O2 ꢂ ꢂ ꢂO1 = 2.715(2) A.
Figure 3. Structural view of (S)-2 showing 20% thermal ellipsoids.
Figure 6. Structural view of (S,S)-16ÆCH2Cl2 (40% thermal ellipsoids, H
atoms and CH2Cl2 omitted for clarity).
phosphol moieties is about 128ꢁ and results in an intra-
˚
molecular P1–P2 distance of 5.67 A. The distinct basicity
Figure 4. Structural view of 7 showing 40% thermal ellipsoids. Hydrogen
of the phosphol oxide oxygen atoms is evident in this com-
pound from the presence of hydrogen bond interactions
with the CH2Cl2 solvent molecule, which bridges two mole-
cules of 16 with C–Hꢂ ꢂ ꢂO hydrogen bonds of Cꢂ ꢂ ꢂO1 =
˚
bond O1ꢂ ꢂ ꢂO2 = 2.735(2) A shown as broken line.
˚
˚
3.075(2) A, and its diethylammonium salt, P–O =
25
˚
2.863(2) A, can be quoted as examples. The obvious
shortness of P1–O2 in 8 may be at least in part attributable
to the formation of a pair of intermolecular hydrogen bond
3.18 and Cꢂ ꢂ ꢂO2 = 3.68 A, both C–H—O angles being near
165ꢁ. When dl-17 is reacted with Pd(CH3CN)2Cl2, the
chelate complex dl-17ÆPdCl2 is formed, which crystallizes
from chloroform as a stable stoichiometric CHCl3 solvate.
The molecular structure depicted in Figure 7 shows an
essentially C2-symmetric bis-dibenzophosphol moiety, but
the PdCl2 unit, as well as the two P-bound phenyl rings
C13–C18 and C31–C36 deviate notably from this symme-
try. The angle between the two dibenzophosphol moieties
is about 55ꢁ and results in an intramolecular P1–P2 dis-
˚
from O2 to O1 [O2ꢂ ꢂ ꢂO1 = 2.715(2) A] of a neighboring
molecule under formation of a hydrogen bonded dimer
(Fig. 5). Moreover a push effect of the Cl at the ortho-posi-
tion to O2 may be effective.
The stereochemistry of (S,S)-16ÆCH2Cl2 is shown in Figure
6 with geometric data in Table 3. Note that this solid state
compound is formed from dl-16 by spontaneous crystalli-
zation resolution under the formation of a conglomerate
of both enantiomers. The angle between the two dibenzo-
˚
tance of 3.21 A. Pd has a moderately twisted square-planar
coordination by two P and two Cl with bond angles
between 85.9ꢁ and 93.2ꢁ. The CHCl3 molecule forms an

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
1363
Coupling patterns are designated as s (singlet), d (doublet),
t (triplet), p (pseudo), m (multiplet), and br (broad). 13C
NMR spectra are recorded in a J-modulated mode; signals
are assigned as CH3, CH2 or C for quaternary carbon;
undesignated signals refer to CH-resonances. In spectral
areas with extensive signal overlapping multiplets could
not be identified; these signals of unclear relationship are
underlined, ignoring probable multiplet structures. MS:
MAT 8230 (EI, 70 eV) and MAT 900 (electrospray). Petro-
leum ether and ethyl acetate were distilled, absolute THF,
dioxane, and DME from sodium benzophenone ketyl,
Et2O from LiAlH4. Commercially available solutions were
used of PhLi (1.9 M, in dibutylether, Fluka), LDA (1.5 M
as THF complex in cyclohexane, Aldrich), and 2-PrMgCl
(2.0 M in THF). All other chemicals were of analytical
grade and used without further purification. dppf26 and
27
Ni(PPh3)2Cl2 were prepared according to published pro-
cedures. Zinc dust was activated by treatment with diluted
HCl and stored under argon.28
4.2. Syntheses
4.2.1. 5-Phenyl-5H-dibenzophosphol oxide 1. The synthe-
sis followed a literature procedure with modifications using
triphenylphosphine8c and commercially available phenyl-
lithium in dibutylether. The reaction proceeded with
moderate yield (52%) and gave a product slightly contam-
inated with biphenyl, which was pure enough for the next
step. For the oxidation with hydrogen peroxide, acetic acid
was replaced by a mixture of toluene/methanol (9:1) as the
solvent (100 mL/10 g of crude 5-phenyl-5H-dibenzophosp-
hole oxide). After work-up the crude product was leached
several times with boiling pentane to remove biphenyl.
The remaining white powder given, was almost pure 1 as
evidenced by NMR.
Figure 7. Structural view of dl-17ÆPdCl2ÆCHCl3 (40% thermal ellipsoids,
most H atoms omitted for clarity) including the C–Hꢂ ꢂ ꢂCl hydrogen
bonded CHCl3 molecule.
asymmetrically bifurcated C–H–Cl hydrogen bond with
˚
the two PdCl2 chlorine atoms, H37ꢂ ꢂ ꢂCl1 = 2.51 A. and
˚
H37ꢂ ꢂ ꢂCl2 = 2.86 A (Fig. 7).
3. Conclusions
In conclusion we have synthesized a group of P-chiral
monophosphine oxides and one biaryl diphosphine oxide,
all based on the dibenzophosphole skeleton as well as the
corresponding phosphines. Preparative separation of the
enantiomers of the key intermediate 4 by chromatography
enabled their synthesis in enantiomerically pure form and
determination of absolute configurations. It turned out
that racemization of phosphines through P-inversion takes
place at ambient temperature and depends markedly on the
ortho substituents (104–114 kJ molꢀ1). In the case of
diphosphine 17, racemization can be suppressed when
forming a chelate with either Pd(II) or Ni(II) complexes.
4.2.2. 4-Trimethylsilyl-5-phenyl-5H-dibenzophosphol oxide
4 and 4,6-bis(trimethylsilyl)-5-phenyl-5H-dibenzophosphol
oxide 5. 5-Phenyl-5H-dibenzophosphol oxide 1 (11.28 g,
40.9 mmol) was placed in a three-necked flask equipped
with dropping funnel and gas inlet. Freshly distilled abs
THF (350 mL) was added and the solution degassed and
set under argon. The reaction was cooled to ꢀ78 ꢁC and
1.5 equiv LDA (40.9 mL, 61.4 mmol) was added dropwise
over 10 min. After 1 h at the same temperature, TMS-Cl
(17.77 g, 164 mmol, 4 equiv, 20.8 mL) was added over
15 min. The mixture was kept at ꢀ78 ꢁC for 2 h and then
warmed up to ꢀ40 ꢁC over 1 h. The deep red solution
was stirred for further 30 min and water (5 mL) was added.
After removing the solvent under vacuum, the residue was
treated with HCl (100 mL, 2%) and CH2Cl2 (100 mL). The
aqueous phase was extracted with CH2Cl2 (2 · 100 mL)
and the combined organic phases washed with satd NaH-
CO3 (50 mL), water (2 · 100 mL), and satd NaCl solution
(100 mL). After drying over MgSO4 and removal of solvent
the mixture was chromatographed (column 5 · 40 cm,
ethyl acetate (50% ! 100%)/petroleum ether). Yield:
4.27 g (27%) of 5, 5.82 g (41%, 45% relative to recovered
starting material) of 4, and 1.06 g (9%) of 1.
4. Experimental
4.1. General
Melting points were determined on a Kofler melting point
apparatus and are uncorrected. NMR: Bruker DRX 400
spectrometer at 400.13 MHz for protons (1H),
161.92 MHz for phosphorus (31P), and 100.57 MHz for
carbon (13C) as well as Bruker DRX 600 spectrometer at
600.13 MHz for protons (1H), 242.88 MHz for phosphorus
(31P) and 150.86 MHz for carbon (13C) in CDCl3 if not
otherwise stated. Chemical shifts d are reported in parts
per million rel to CHCl3 (7.24 or 77.00 ppm, respectively).
Compound 4: 1H NMR (CDCl3) d: 0.15 (s, 9H); 7.29 (ptdd,
J = 7.4, 3.8, 0.8 Hz, 1H); 7.33 (m, 2H); 7.43 (m, 1H); 7.49

1364
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
(ptpt, J = 7.6, 1.2 Hz, 1H); 7.54–7.62 (m, 5H); 7.76 (dd,
J = 7.8, 2.9 Hz; 1H); 7.83 (ddd, J = 7.3, 2.8, 1.3 Hz, 1H).
13C NMR (CDCl3) d: 0.05 (CH3); 120.79 (d, J = 9.9 Hz);
121.47 (d, J = 9.9 Hz); 128.50 (d, J = 13.0 Hz); 129.06;
129.16; 129.21; 129.32 (2 · d); 130.94 (d, J = 10.7 Hz);
131.74 (d, J = 3.1 Hz); 132.11 (d, J = 2.3 Hz); 132.86 (d,
J = 2.3 Hz); 133.36 (C, d, J = 50.5 Hz); 134.70 (C);
135.80 (d, J = 13.8 Hz); 137.09 (C); 140.61 (C, d,
J = 21.4 Hz); 142.51 (C, d, J = 25.0 Hz); 145.62 (C, d,
J = 16.2 Hz). 31P NMR (CDCl3) d: 35.24 (s).
(0.8 mL, 1.6 mmol) at ꢀ20 ꢁC and the heterogeneous violet
mixture stirred for 15 min. After cooling to ꢀ50 ꢁC, excess
solid CO2 was added and the reaction was allowed to warm
to ꢀ10 ꢁC. Concd HCl (0.2 mL) was added and stirring
was continued for 30 min. The white crystalline precipitate
formed was separated, washed with distilled water and
dried in vacuo to yield 365 mg (85%) of 6. Mp: >310 ꢁC
(dec). 1H NMR (DMSO-d6) d: 7.36–7.51 (m, 6H); 7.56
(br pt, J = 8.0 Hz, 1H); 7.66 (ptpt, J = 7.6, 1.3 Hz, 1H);
7.86 (ptd, J = 7.9, 1.3 Hz, 1H); 7.98 (ddd, J = 7.6, 4.3,
0.8 Hz, 1H); 8.14 (dd, J = 7.6, 2.5 Hz, 1H); 7.40 (ddd,
J = 7.6, 2.5, 0.8 Hz, 1H); 13.41 (br s, 1H). 13C NMR
(DMSO-d6) d: 121.78 (d, J = 9.2 Hz); 125.85 (d,
J = 9.2 Hz); 128.28 (d, J = 12.2 Hz); 129.19 (d, J =
9.2 Hz); 130.10; 130.25; 130.25 (d, J = 10.7 Hz); 130.33;
131.34 (C); 131.40 (d, J = 2.3 Hz); 132.11 (C); 132.43 (C);
133.10; 133.25 (C); 134.22; 134.36 (C); 135.41 (C); 139.17
(C, d, J = 20.5 Hz); 143.40 (C, d, J = 20.7 Hz); 165.44
(C). 31P NMR (DMSO-d6) d: 33.52 (s). MS (electrospray):
319.1 (100, Mꢀ1+). HRMS: calcd for C19H12O3P:
319.0624, found: 319.0538.
Chromatographic separation of enantiomers, (S)-4 and
(R)-4: Chiralcel ODꢂ (5 · 50 cm, 20 lm), solvent: 2-
PrOH/petroleum ether (30:70), sample size: 200–300 mg
per run, dissolved in 10 mL, flow: 40 mL minꢀ1, rt, fraction
20
1: tR ꢁ 20 min, (ꢀ)-(S)-4, ½aꢃD ¼ ꢀ276 (c 1.15, CHCl3);
20
fraction 2: tR ꢁ 40 min, (+)-(R)-4, ½aꢃD ¼ þ281 (c 1.21,
CHCl3); recovery rate: 95%.
1
Compound 5: H NMR (CDCl3) d: 0.16 (s, 18H); 7.29 (m,
2H); 7.38 (m, 1H); 7.47–7.63 (m, 6H); 7.82 (ddd, J = 7.5,
2.8, 1.3 Hz, 2H). 13C NMR (CDCl3) d: 0.27 (CH3);
121.17 (d, J = 9.9 Hz); 128.18 (d, J = 12.2 Hz); 131.44 (d,
J = 2.3 Hz); 131.76 (d, J = 2.3 Hz); 132.10 (C, d, J =
95.8 Hz); 132.30 (d, J = 9.9 Hz); 135.86 (d, J = 13.8 Hz);
138.99 (C, d, J = 106.7 Hz); 141.42 (C, d, J = 25.2 Hz);
144.39 (C, d, J = 17.4 Hz). 31P NMR (CDCl3) d: 36.31
(s). MS (40 ꢁC) m/z (rel%): 420 (2.5, M+); 405 (85,
MꢀCH3); 329 (100). HRMS: calcd for C23H26OPSi2:
405.1260, found: 405.1267.
4.2.5. 4-Diphenylhydroxymethyl-5-phenyl-4H-dibenzophos-
phol oxide 7 and 3-chloro-4-diphenylhydroxymethyl-5-phen-
yl-4H-dibenzophosphol oxide 8. To a degassed solution
of 4-iodo-5-phenyl-dibenzophosphol oxide 2 (201 mg,
0.5 mmol) in abs THF (3 mL) was added 2-propylmagne-
sium chloride (0.3 mL of a 2 M solution in THF, 0.6 mmol)
at ꢀ20 ꢁC and the heterogeneous violet mixture was stirred
at the same temperature for 20 min. Benzophenone
(146 mg, 0.8 mmol) was added and the reaction slowly
warmed up to rt overnight. To the yellow solution contain-
ing some white precipitate was added HCl (2 mL, 2%) and
the mixture extracted with ethyl acetate (2 · 10 mL). The
organic phase was washed with water and brine and dried
over MgSO4. The crude mixture obtained after evapora-
tion was subjected to column chromatography (SiO2,
60 · 2 cm, ethyl acetate) to yield 34 mg (15%) of 7 and
36 mg (14%) of 8 as crystalline solids.
4.2.3. 4-Iodo-5-phenyl-5H-dibenzophosphol oxide 2. To a
stirred solution of 4 (5.50 g, 15.8 mmol) in CH2Cl2
(230 mL) was added dropwise iodomonochloride (15.4 g,
94.7 mmol, 6 equiv) in CH2Cl2 (100 mL) at 0 ꢁC over 1 h.
Stirring was continued at room temperature and the pro-
gress followed by TLC. After complete consumption of
starting material (approx. 48 h), NaHSO3 solution (10%,
100 mL) was added. The organic phase was separated,
washed with water (100 mL) and brine (100 mL), and dried
over MgSO4. Evaporation left a pale yellow solid which
was found to be pure by NMR. Yield: 5.99 g (94%); mp:
191–194 ꢁC. 1H NMR (CDCl3) d: 7.22 (ptd, J = 7.8,
1.3 Hz, 1H); 7.38 (m, 3H); 7.50 (m, 1H); 7.58 (m, 1H);
7.65–7.73 (m, 4H); 7.78 (br ptd, J = 7.8, 3.0 Hz, 2H). 13C
NMR (CDCl3) d: 97.00 (C, d, J = 7.4 Hz); 120.54 (d,
J = 9.2 Hz); 121.07 (d, J = 9.9 Hz); 128.55 (d,
J = 13.0 Hz); 128.77 (C, d, J = 105.3 Hz); 129.95; 130.03;
130.06, 130.14 (2 · d); 131.89 (d, J = 11.5 Hz); 132.24
(d, J = 3.1 Hz); 133.13 (C, d, J = 109 Hz); 133.44
(d, J = 1.5 Hz); 134.34 (d, J = 1.5 Hz); 139.43 (d,
J = 8.4 Hz); 140.12 (C, d, J = 19.6 Hz); 144.70 (C, d,
J = 21.6 Hz). 31P NMR (CDCl3) d: 36.57 (s). MS: (40 ꢁC)
m/z (rel%): 401.9 (69, M+); HRMS: calcd for C18H12IOP:
401.9670, found: 401.9682.
1
Compound 7: Mp: 235–240 ꢁC. H NMR (CDCl3) d: 5.83
(s, 1H); 6.86–7.00 (m, 6H); 7.15–7.38 (m, 11H); 7.44
(ptm, J = 7.8 Hz, 1H); 7.54 (m, 2H); 7.78 (dd, J = 7.6,
2.5 Hz, 1H); 7.82 (dd, J = 7.6, 2.5 Hz, 1H). 13C NMR
(CDCl3) d: 83.21 (C, d, J = 1.9 Hz); 120.03 (d,
J = 9.9 Hz); 120.92 (d, J = 9.9 Hz); 127.20; 127.51;
127.60; 127.80; 128.02; 128.32 (d, J = 13.0 Hz); 128.48;
129.56 (d, J = 3.8 Hz); 129.57 (d, J = 17.6 Hz); 129.72 (C,
d, J = 105.8 Hz); 130.38 (d, J = 11.5 Hz); 130.85 (d, J =
9.2 Hz); 130.94 (d, J = 3.1 Hz); 131.90 (C, d, J =
108.0 Hz); 132.75 (d, J = 2.3 Hz); 133.05 (d, J = 2.3 Hz);
133.81 (C, d, J = 108.0 Hz); 140.80 (C, d, J = 20.9 Hz);
143.28 (C, d, J = 23.4 Hz); 145.24 (C); 146.49 (C);
152.57 (C, d, J = 6.9 Hz). 31P NMR (CDCl3) d: 40.14 (s).
MS (190 ꢁC) m/z (rel%): 458 (84, M+); 381 (100,
MꢀPh). HRMS: calcd for C13H23O2P: 458.1436, found:
458.1428.
The same procedure applied to (S)-4 yielded (S)-2; mp:
20
195–198 ꢁC; ½aꢃD ¼ ꢀ77:2 (c 1.03, CHCl3).
1
Compound 8: Mp: 210–214 ꢁC. H NMR (CDCl3) d: 5.00
4.2.4. 5-Phenyl-5H-dibenzophosphol oxide-4-carbonic acid
6. To a degassed solution of 2 (539 mg, 1.34 mmol) in
THF abs (5 mL) was added 2-propylmagnesium chloride
(s, 1H); 6.86 (m, 2H); 6.98 (m, 2H); 7.08 (ptt, J = 7.2,
1.4 Hz, 1H); 7.28–7.43 (m, 9H); 7.52–7.62 (m, 5H); 7.82
(m, 2H); 13C NMR (CDCl3) d: 84.05 (C); 120.71 (d,

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
1365
J = 9.9 Hz); 121.63 (d, J = 11.5 Hz); 126.84; 126.90 (d,
J = 13.0 Hz); 128.06; 128.19; 128.23; 128.37; 128.88;
129.51; 129.67; 129.77; 129.85; 129.96; 130.34 (d,
J = 10.7 Hz); 131.19 (d, J = 3.1 Hz); 132.25 (C); 132.30
(C); 132.96 (d, J = 2.0 Hz); 133.31 (C); 133.41 (C); 134.12
(C); 134.69 (C); 134.81 (C); 135.19 (C); 137.00 (d,
J = 1.2 Hz); 139.41 (C, d, J = 20.0 Hz); 142.45 (C);
142.49 (C); 142.67 (C, d, J = 23.0 Hz); 149.36 (C, d,
J = 6.2 Hz). 31P NMR (CDCl3) d: 40.17 (s). MS (200 ꢁC)
m/z (rel%): 492 (100, M+); 415 (45, MꢀPh). HRMS: calcd
for C31H22ClO2P: 492.1046, found: 492.1057.
(C); 131.56 (d, J = 2.3 Hz); 132.46 (C); 132.78 (C); 132.85
(C); 133.23 (d, J = 2.2 Hz); 133.39 (d, J = 2.0 Hz); 133.54
(C); 136.59 (C); 136.62 (C); 141.69 (C, d, J = 21.0 Hz);
142.50 (C, d, J = 22.3 Hz); 146.68 (C, d, J = 8.6 Hz). 31P
NMR (CDCl3) d: 35.46 (s). MS (120 ꢁC) m/z (rel%):
402.3 (6, M+); 401.3 (9, Mꢀ1). HRMS: calcd for
C28H19OP: 402.1174, found: 402.1145. (ꢀ)-(S)-10; mp:
20
86–89 ꢁC; ½aꢃD ¼ ꢀ357 (c 1.01, CHCl3).
1
Compound 11: 11%; pale yellow foam. H NMR (CDCl3)
d: 6.52 (dd, J = 12.9, 1.3 Hz, 1H); 6.54 (dd, J = 13.1,
1.3 Hz, 1H); 6.60 (m, 2H); 6.70 (ptdm, J = 8.3, 3.3 Hz,
2H); 6.98 (ptq, J = 7.6, 1.5 Hz, 1H); 7.12 (ddd, J = 8.6,
5.3, 2.3 Hz, 1H); 7.27 (ddd, J = 7.6, 4.3, 0.8 Hz, 1H); 7.36
(ptdd, J = 7.3, 3.5, 0.8 Hz, 1H); 7.41 (m, 1H); 7.48 (m,
1H); 7.52 (m, 1H); 7.63 (ptt, J = 7.6, 1.3 Hz, 1H); 7.70
(dm, J = 8.8 Hz, 1H); 7.74 (dd, J = 7.6, 1.3 Hz, 1H); 7.85
(br d, J = 8.6 Hz, 1H); 7.95 (ddm, J = 7.8, 2.8 Hz, 1H);
7.99 (ddd, J = 7.8, 2.3, 0.8 Hz, 1H); 8.04 (dm, J = 8.3 Hz,
1H); 8.49 (s, 1H). 13C NMR (CDCl3) d: 120.54 (d,
J = 9.9 Hz); 121.13 (d, J = 9.9 Hz); 124.18; 124.82;
125.30; 125.54; 125.67; 127.44; 127.61 (d, J = 13.0 Hz);
127.81; 127.94; 129.20 (C, d, J = 67 Hz); 129.35 (C);
129.57 (d, J = 10.8 Hz); 130.08 (d, J = 9.2 Hz); 130.44 (d,
J = 11.5 Hz); 130.59 (C); 131.18 (C); 131.22 (d,
J = 3.1 Hz); 132.14 (C); 132.23 (d, J = 9.2 Hz); 132.35
(C); 133.35 (d, J = 1.4 Hz); 133.41 (C); 133.76 (C); 134.80
(C); 141.89 (C, d, J = 22.3 Hz); 142.22 (C, d, J =
21.2 Hz); 142.75 (C, d, J = 9.0 Hz). 31P NMR (CDCl3) d:
33.33 (s). MS (190 ꢁC) m/z (rel%): 452.1 (100, M+). HRMS
4.2.6. 4,5-Diphenyl-4H-dibenzophosphol oxide 9. To a
solution of 2 (201 mg, 0.5 mmol) in toluene (5 mL) was
added phenyl boronic acid (122 mg, 1 mmol) dissolved in
the minimum amount of EtOH (0.3 mL) and 2 M Na2CO3
(1.05 mL, 2.1 mmol) and the mixture degassed. A catalytic
amount of Pd(Ph3P)4 (10 mg) was added and the mixture
refluxed under Ar for 16 h. TLC indicated the complete ab-
sence of the starting material. Water (10 mL) was intro-
duced and the mixture extracted with ethyl acetate
(20 mL) and the organic phase washed with water and satd
NaCl solution. After drying with MgSO4 and evaporation,
the crude product was chromatographed on SiO2. Elution
with ethyl acetate afforded 138 mg (78%) of 9; mp: 210–
1
211 ꢁC. H NMR (CDCl3) d: 7.14 (ptd, J = 7.6, 3.3 Hz,
2H); 7.21 (dm, J = 6.8 Hz, 1H); 7.24 (dm, J = 6.8 Hz,
1H); 7.30–7.38 (m, 5H); 7.43 (ptd, J = 7.6, 3.8 Hz, 1H);
7.54 (m, 2H); 7.64 (m, 2H); 7.72 (br dd, J = 8.6, 7.5H,
1H); 7.86 (dd, J = 7.8, 2.5 Hz, 1H); 7.90 (dd, J = 7.8,
2.8 Hz, 1H). 13C NMR (CDCl3) d: 119.78 (d, J = 9.9 Hz);
121.04 (d, J = 10.7 Hz); 127.86; 127.93 (d, J = 12.2 Hz);
127.94; 129.29; 129.48 (d, J = 10.7 Hz); 129.83 (d,
J = 9.9 Hz); 130.27 (C, d, J = 104 Hz); 130.50 (d, J =
9.2 Hz); 130.74 (d, J = 11.4 Hz); 131.54 (d, J = 3.1 Hz);
131.67 (C, d, J = 103 Hz); 132.80 (C, d, J = 109 Hz);
133.17 (d, J = 2.3 Hz); 133.29 (d, J = 2.2 Hz); 139.17 (C,
d, J = 2.6 Hz); 141.67 (C, d, J = 21.6 Hz); 142.26 (C, d,
J = 21.6 Hz); 146.73 (C, d, J = 7.9 Hz). 31P NMR (CDCl3)
d. 35.54 (s). MS (120 ꢁC) m/z (rel%): 351.0 (100, Mꢀ1).
HRMS: calcd for C24H17OP: 352.1017, found: 352.0976.
calcd for C23H21OP: 452.1330, found: 452.1327. (+)-(S)-11:
20
Mp: 302–306 ꢁC, ½aꢃD þ 45 (c 0.43, CHCl3).
4.2.8. 4-Cyano-5-phenyl-5H-dibenzophosphol oxide 12. To
a solution of 2 (201 mg, 0.5 mmol) in THF (5 mL) was
added KCN (98 mg, 1.5 mmol) and a catalytic amount of
CuCN (5 mg). The mixture was degassed and after the
addition of Pd(PPh3)4 (58 mg, 10 mol %) was heated under
argon at reflux until TLC (CHCl3/MeOH, 9:1) indicated
complete conversion. The dark brown solution was diluted
with CH2Cl2 (20 mL) and water (10 mL) was added. The
aqueous phase was repeatedly extracted with CH2Cl2
(3 · 5 mL) and the combined organic extracts washed with
water, satd NaCl solution, and dried over MgSO4. Evapo-
ration of the solvent left 12 as a crystalline white powder;
Applying the same procedure to (ꢀ)-(S)-2 afforded (ꢀ)-(S)-
20
9; mp: 198–202 ꢁC, ½aꢃD ¼ ꢀ199 (c 1.03, CHCl3).
4.2.7. 4-(2-Naphthyl)-5-phenyl-4H-dibenzophosphol oxide
10 and 4-(9-anthryl)-5-phenyl-4H-dibenzophosphol oxide
11. Similar procedures as used for the preparation of 9
were applied using naphthalene-2-boronic acid and anthra-
cene-9-boronic acid, respectively, instead of phenyl boronic
acid to afford 10 and 11. Analogue procedures using enan-
tiopure iodide (ꢀ)-(S)-2 gave (ꢀ)-(S)-10 and (+)-(S)-11.
Compound 10: 87%; mp: 104–107 ꢁC; 1H NMR (CDCl3) d:
7.00 (m, 2H); 7.14 (m, 2H); 7.23 (ptq, J = 7.3, 1.3 Hz, 1H);
7.36–7.42 (m, 2H); 7.43–7.49 (m, 2H); 7.54 (dd, J = 8.6,
1.8 Hz, 1H); 7.57–7.68 (m, 3H); 7.73–7.89 (m, 5H); 7.98
(d, J = 1.2 Hz, 1H). 13C NMR (CDCl3) d: 119.89 (d,
J = 9.2 Hz); 121.08 (d, J = 9.9 Hz); 126.10; 126.20;
126.97; 127.49; 127.70; 128.00 (d, J = 13.0 Hz); 128.58;
128.79; 129.58 (d, J = 11.5 Hz); 129.84 (d, J = 9.9 Hz);
130.02 (C); 130.78 (2(!)d, J = 10.7 Hz); 131.05 (C); 131.41
1
yield: 127 mg (84%); mp: 216–217 ꢁC. H NMR (CDCl3)
d: 7.38–7.41 (m, 2H); 7.47 (ptdd, J = 7.3, 3.5, 0.8 Hz,
1H); 7.52 (m, 1 Hz, 1H); 7.54 (ddd, J = 7.6, 3.8, 1.0 Hz,
1H); 7.60–7.72 (m, 4H); 7.75 (br dd, J = 9.9, 7.3 Hz, 1H);
7.84 (dd, J = 7.8, 3.0 Hz; 1H); 7.99 (ddd, J = 7.8, 2.3,
1.0 Hz, 1H). 13C NMR (CDCl3) d: 113.76 (C, d,
J = 5.9 Hz); 115.63 (C, d, J = 4.5 Hz); 121.59 (d,
J = 9.9 Hz); 124.94 (d, J = 9.2 Hz); 127.70 (C, part of d);
128.83 (d, J = 13.0 Hz); 130.45 (d, J = 9.9 Hz); 130.62 (d,
J = 11.5 Hz); 131.50 (d, J = 11.5 Hz); 132.53 (C, part of
d); 132.84 (d, J = 6.9 Hz); 132.92 (d, J = 3.1 Hz); 133.57
(d, J = 1.5 Hz); 133.98 (d, J = 2.3 Hz); 136.85 (C, d,
J = 100 Hz); 140.18 (C, d, J = 20.0 Hz); 142.74 (C, d,
J = 20.0 Hz). 31P NMR (CDCl3) d: 33.18 (s). MS (electro-
spray) m/z (rel%): 324.1 (100, M+23). HRMS: calcd for
C19H12NOP: 301.0657, found: 301.0662.

1366
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
4.2.9. Reduction of enantiopure phosphol oxides (R)-4, (S)-9,
and (S)-10 (general procedure). The phosphol oxide
(0.7 mmol) was dissolved in dry DME (10 mL) and de-
gassed. Methyltriflate (1.0 mmol, 113 lL) was added and
the mixture stirred at rt for 2 h. After cooling to ꢀ55 ꢁC,
LiAlH4 (137 mg, 1.75 mmol) was added and the reaction
warmed up to +10 ꢁC for 4 h. TLC control indicated com-
plete consumption of the substrate and the reaction was
quenched by careful addition of degassed dil HCl (2%,
10 mL) followed by degassed ethyl acetate (10 mL). The
aqueous phase was washed with a second portion of ethyl
acetate (10 mL) and the combined extracts were washed
with water and satd NaCl solution and dried with MgSO4.
After removal of solvent, the crude product was chromato-
graphed with degassed solvents on SiO2 (10 · 2 cm, ethyl
acetate/petroleum ether (50:50)).
(C, d, J = 2.4 Hz); 143.50 (C, d, J = 24.4 Hz); 144.42 (C);
144.46 (C); 144.47 (C); 144.50 (C); 147.93 (C, d,
J = 5.1 Hz). 31P NMR (CDCl3) d: ꢀ9.87 (s). MS (50 ꢁC)
m/z (rel%): 332 (100, M+); 317 (55, MꢀCH3). HRMS:
calcd for C21H21PSi: 332.1150, found: 332.1154.
20
½aꢃD ¼ þ291 (c 0.74, CHCl3).
4.2.10. dl-5,50-Diphenyl-4,40-bis(5H-dibenzophosphol oxide)
dl-16. NaH (960 mg, 40 mmol), Ni(PPh3)2Cl2 (1.64 g,
2.5 mmol), Zn dust (activated, 980 mg, 15 mmol), and 2
(2.01 g, 5 mmol) were placed in a Schlenk tube under argon
and abs toluene (100 mL) was added through a rubber sep-
tum. After stirring for 10 min, dppf (1.39 g, 2.5 mmol) was
added and the mixture degassed. The carefully sealed
Schlenk tube was sonificated in an ultrasonic bath at 75–
80 ꢁC for 4 h with occasional shaking. During this time,
the color of the reaction mixture changed from green to
dark yellow. Subsequently the reaction was stirred for
10–12 h at 80 ꢁC. After cooling to room temperature,
HCl (5%, 50 mL) was added carefully followed by CHCl3
(300 mL) and the mixture stirred for 30 min. Filtration re-
moved remaining Zn dust and Ni residues and the organic
phase was separated and dried with MgSO4. Evaporation
of solvent left a semi-solid mixture which was triturated
with CH2Cl2/ethyl acetate (1:4) to give dl-16 as a crystalline
powder which was filtered off and washed with ethyl ace-
tate and Et2O (>95% pure by NMR). The mother liquor
was subjected to column chromatography (SiO2,
40 · 4 cm, acetone/CH2Cl2, 1:1) to give a further crop of
dl-16. Total yield: 631 mg (46%); mp: 237–240 ꢁC.
1
Compound (S)-13: 84%, turbid oil. H NMR (CDCl3) d:
6.92 (ptm, J = 8.3 Hz, 2H); 7.05 (ptm, J = 7.3 Hz, 2H);
7.17 (m, 1H); 7.29 (ddd, J = 7.6, 4.0, 1.0 Hz, 1H); 7.29–
7.36 (m, 4H); 7.39–7.43 (m, 2H); 7.49 (ptd, J = 7.6,
1.3 Hz, 1H); 7.56 (pt, J = 7.8 Hz, 1H); 7.65 (br dd,
J = 7.6, 4.8 Hz, 1H); 7.98 (d, J = 7.8 Hz, 1H); 8.01 (br d,
J = 7.8 Hz, 1H). 13C NMR (CDCl3) d: 120.22; 121.47;
127.37; 127.65 (d, J = 7.6 Hz); 127.94 (d, J = 3.8 Hz);
128.12 (d, J = 7.6 Hz); 128.16; 128.50; 128.76 (d,
J = 3.8 Hz); 128.97; 129.34; 130.21 (d, J = 22.9 Hz);
133.14 (d, J = 20.7 Hz); 135.22 (C, d, J = 19.4 Hz);
141.84 (C); 142.08 (C, d, J = 6.0 Hz); 143.13 (C, d, J =
1.6 Hz); 143.68 (C, d, J = 2.4 Hz); 144.27 (C, d, J =
2.9 Hz); 145.11 (C, d, J = 16.2 Hz). 31P NMR (CDCl3) d:
ꢀ9.79 (s). MS (40 ꢁC) m/z (rel%): 336.1 (100, M+).
1H NMR (CDCl3) d: 6.70 (br dd, J = 13.1, 8.3 Hz, 4H);
6.85 (br td, J = 7.8, 3.0 Hz, 4H); 7.11 (m, 2H); 7.34 (ptdd,
J = 7.6, 3.8, 0.8 Hz, 2H); 7.50 (br dd, J = 9.3, 7.2 Hz, 2H);
7.58 (ptpt, J = 7.6, 1.3 Hz, 2H); 7.78 (ptd, J = 7.6, 1.3 Hz,
2H); 7.83 (m, 4H); 8.35 (br dd, J = 6.8, 5.6 Hz, 2H). 13C
NMR (CDCl3) d: 120.85 (d, J = 9.9 Hz); 121.02 (d,
J = 9.9 Hz); 128.02 (d, J = 12.2 Hz); 129.15 (C, d, J =
103 Hz); 129.43 (d, J = 11.5 Hz); 129.83 (d, J = 9.9 Hz);
130.61 (d, J = 10.7 Hz); 131.29 (d, J = 3.1 Hz); 131.42 (C,
d, J = 101 Hz); 132.15 (C, d, J = 110 Hz); ꢁ133.3 (m);
141.68; 141.89; 141.95; 142.17 (2 · C, 2 · d); ꢁ142.96 (C,
m). 31P NMR (CDCl3) d: 36.76 (s). MS (electrospray)
m/z (rel%): 573.1 (70, M+Na); 551.1 (60, M+H); 473.1
(100, MꢀPh). HRMS: calcd for C30H19O2P2 (MꢀPh):
473.0860, found: 473.0871. The same procedure applied
HRMS: calcd for C24H17P: 336.1068, found: 336.1061.
20
½aꢃD ¼ ꢀ164 (c 1.00, CHCl3).
Compound (S)-14: 96%, pale yellow oil. 1H NMR (CDCl3)
d: 6.89 (ptm, J = 8.2 Hz, 2H); 6.99 (ptm, J = 7.5 Hz, 2H);
7.14 (ptm, J = 7.4 Hz, 1H); 7.29 (ptdd, J = 7.3, 2.8,
1.0 Hz, 1H); 7.36 (ddd, J = 7.6, 4.0, 1.0 Hz, 1H); 7.42–
7.49 (m, 3H); 7.51 (dd, J = 8.6, 1.8 Hz, 1H); 7.56–7.62
(m, 3H); 7.67 (br s, 1H); 7.79 (d, J = 8.6 Hz, 1H); 7.83
(m, 1H); 7.99 (dm, J = 7.8 Hz, 2H). 13C NMR (CDCl3)
d: 120.32; 121.49; 125.96; 126.05; 127.01 (d, J = 3.1 Hz);
127.61; 127.74 (d, J = 6.9 Hz); 127.84; 127.94 (d,
J = 3.8 Hz); 128.23; 128.27 (d, J = 8.4 Hz); 128.33 (d,
J = 3.8 Hz); 128.49; 129.10; 129.45; 130.18 (d, J =
22.2 Hz); 132.62 (C); 133.04 (C); 133.35 (d, J = 19.9 Hz);
135.78 (C, d, J = 18.6 Hz); 139.32 (C); 142.17 (C, d,
J = 5.6 Hz); ꢁ143.5 (C, m); ꢁ144.6 (C, m); 145.19 (C, d,
J = 16.2 Hz). 31P NMR (CDCl3) d: ꢀ10.31 (s). MS
(110 ꢁC) m/z (rel%): 366.0 (100, M+). HRMS of BH3 com-
to (S)-2 yielded 69% of (S,S)-16; mp: >345 ꢁC;
20
½aꢃD ¼ þ213 (c 0.736, CH2Cl2).
4.2.11. 5,50-Diphenyl-4,40-bis(5H-dibenzophosphol) 17.
Bis(phosphine oxide) dl-16 (330 mg, 0.6 mmol) was
suspended in abs DME (20 mL) in a Schlenk tube and
degassed. To this was added MeOTf (390 mg, 1.8 mmol,
267 lL) and the mixture was stirred under Ar to give, after
1.5 h, an orange solution. After cooling to ꢀ50 ꢁC LiAlH4
(183 mg, 5.1 mmol) was added in one portion. The reaction
was warmed up within 3 h to ꢀ10 ꢁC and quenched with
HCl (3 mL, 1 M). The cold mixture was filtered over Celite
which was carefully washed with ethyl acetate (15 mL) and
the filtrate evaporated at rt. The residue was treated with
MeOH (3 mL) and kept overnight to give a white crystal-
line precipitate which was separated and dried. Yield:
plex: calcd for C28H19PÆBH3: 400.1557, found: 400.1546.
20
½aꢃD ¼ ꢀ162 (c 1.00, CHCl3).
1
Compound (R)-15: 89%, oil. H NMR (CDCl3) d: 0.15 (s,
9H); 7.13–7.29 (m, 6H); 7.38 (ptm, J = 7.5 Hz, 1H); 7.49
(pt, J = 7.5 Hz, 1H); 7.53–7.59 (m, 2H); 7.91 (br d,
J = 7.8 Hz, 1H); 7.99 (br d, J = 7.6 Hz, 1H). 13C NMR
(CDCl3) d: ꢀ0.17 (CH3), 121.14; 121.93; 127.54 (d,
J = 7.6 Hz); 128.09; 128.24; 128.56 (d, J = 7.6 Hz);
129.36; 129.51 (d, J = 22.9 Hz); 133.51 (d, J = 20.7 Hz);
133.86 (d, J = 9.2 Hz); 136.89 (C, d, J = 19.0 Hz); 142.46

M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
1367
174 mg (56%, 90–95% pure racem form, mp: ꢁ325 ꢁC). The
mother liquor was chromatographed (ethyl acetate/petro-
leum ether, 1:9, SiO2 deactivated with 13% of water) to give
an additional product (33 mg, 10%) which was a mixture of
racemate (40%) and meso (60%) forms.
solution. This was followed by the addition of EtOH
(5 mL) and the slightly turbid mixture was concentrated
in vacuo to afford a yellow precipitate. The crude complex
was collected, washed with Et2O and dried. The solid was
dissolved in CHCl3, filtered over Celite, and evaporated
to yield 56 mg (80%) of the pure complex. 1H NMR
(CDCl3) d: 6.69 (dd, J = 7.3, 4.8 Hz, H-3); 7.07 (ptd,
J = 7.7, 1.6 Hz, H-12, H-14); 7.26 (br t, J = 7.5 Hz, H-
13); 7.36–7.45 (m, H-2, H-7, H-11, H-15); 7.61 (pt,
J = 7.6 Hz, H-8); 7.73 (d, J = 7.8 Hz, H-1); 7.84 (br d,
J = 7.6 Hz, H-9); 8.64 (pt, J = 7.8 Hz, H-6). 13C NMR
(CDCl3) d: 121.11 (m, C-1); 121.27 (m, C-9); 124.63 (d,
J = 52 Hz, C-10); 128.56 (m, C-12, C-14); 129.06 (m, C-
7k); 129.23 (m, C-3); 131.96 (C-13); 132.67 (C-8); 132.97–
133.58 (m, Cquat.); 133.70 (C-2k); 134.01 (m, C-11, C-15);
136.36 (m, C-6); 141.31 (m, Cquat.); 142.66 (m, C). 31P
NMR (CDCl3) d: 17.27 (s). MS (electro spray, sample in
CH3CN): m/z (rel%) 698 (40), 699 (20), 700 (95), 701
(50), 702 (100), 703 (43), 704 (50), 705 (21), 706 (10); the
isotopic pattern is in agreement with C38H27ClNP2Pd cor-
responding to the fragment [17ÆPdClÆCH3CN]+.
Compound dl-17: 1H NMR– (600 MHz, CDCl3) d: 6.90 (br
m, H-3); 6.98 (br m, H-12, H-14); 7.14 (pt, J = 7.5 Hz, H-
13); 7.20 (br pt, J = 7.4 Hz, H-2); 7.27 (ptq, J = 7.3,
1.4 Hz, H-7); 7.47 (ptd, J = 7.6, 1.2 Hz, H-8); 7.57 (dm,
J = 7.4 Hz, H-6); 7.60 (br m, H-11, H-15); 7.92 (dd,
J = 7.9, 1.0 Hz, H-1); 7.80 (d, J = 7.5 Hz, H-9). 13C
NMR– (600 MHz, CDCl3) d: 120.42 (C-1); 121.34 (C-9);
127.53 (pt, J = 3.9 Hz, C-7); 127.97 (pt, J = 4.5 Hz, C-12,
C-14); 128.38 (C-8); 128.53 (C-2); 128.60 (pt, J = 3.1 Hz,
C-3); 129.01 (C-13); 130.52 (pt, J = 11.5 Hz, C-6); 133.67
(pt, J = 10.9 Hz, C-11, C-15); 142.43 (pt, J = 2.4 Hz, C-
4a); 143.41 (C-5a); 143.49 (C-4); 143.94 (pt, J = 1.2 Hz,
C-9a, C-9b); C-10 was not observed. 31P NMR
(600 MHz, CDCl3) d: ꢀ10.03 (s). MS (150 ꢁC) m/z (rel%):
518 (55, M+); 441 (100, MꢀPh). HRMS: calcd for
C36H24P2: 518.1353, found: 518.1362.
The same procedure applied to (S,S)P-17 (90% d.e.) affor-
20
Compound meso-17: 1H NMR– (600 MHz, CDCl3) d: ꢁ6.5
(br m, H-3); 6.76 (br m, H-12, H-14); 6.88 (br m, H-11, H-
15); 6.98 (br m, H-13); 7.25 (ptdd, J = 7.3, 2.8, 1.1 Hz, H-
7); 7.38 (br m, H-2); 7.44 (ptd, J = 7.6, 1.3 Hz, H-8); 7.46
(m, H-6); 7.94 (d, J = 8.2 Hz, H-1); 7.96 (d, J = 8.6 Hz,
H-9). 13C NMR– (600 MHz, CDCl3) d: 120.51 (C-1);
121.21 (C-9); 127.45 (d, J = 7.3 Hz, C-7); 127.91 (d,
J = 8.1 Hz, C-12, C-14); 128.26 (C-8); 128.36 (d,
J = 6.8 Hz, C-3); 129.02 (C-13); 130.10 (d, J = 12.7 Hz;
C-6); 133.59 (d, J = 21.6 Hz, C-11, C-15); 142.42 (d,
J = 1.9 Hz, C-4a); 143.38 (C-5a); 143.68 (C-9a); 143.74
(C-9b); 143.81 (C-4); signals due to C-2 and C-10 were
not observed. 31P NMR (600 MHz, CDCl3) d: ꢀ11.54 (br
s).
ded stereoselectively (S,S)P-17ÆPdCl2; ½aꢃD ¼ ꢀ373 (c 0.105,
CH2Cl2,).
4.3. Kinetics
Kinetics of racemization for compounds 13–15 during
0.5–4 half lives was followed by polarimetry at 436 nm
using a thermostated 1 dm cell. Thek calculations were
1
based on a first order rate law29 for ½Rꢃ ꢀ ½Sꢃ with [R] > [S].
k
ꢀ1
½Rꢃ0 ꢀ ½Rꢃequ
½Rꢃt ꢀ ½Rꢃequ
ðk1 þ kꢀ1Þt ¼ ln
with k = k1 = kꢀ1 and taking into account that the specific
rotation decreases with a rate twice the P-inversion, this
transforms to
4.2.12. Nickel dichloride complex of dl-17. To a solution
of 5.2 mg (0.01 mmol) of dl-17 in CDCl3 (0.7 mL) was
added 1.1 equiv NiCl2Æ6H2O (0.1 M solution in CD3OD)
immediately giving a dark violet solution. 1H NMR
(CDCl3/CD3OD, ꢁ7:1) d: 6.54 (d, J = 7.6 Hz, H-3); 6.99
(pt, J = 7.6 Hz, H-12, H-14); 7.16 (t, J = 7.3 Hz, H-13);
7.29 (pt, J = 7.8 Hz, H-7); 7.31 (pt, J = 7.8 Hz, H-2); 7.42
(d, J = 7.8 Hz, H-11, H-15); 7.59 (pt, J = 7.6 Hz, H-8);
7.72 (d, J = 7.8 Hz, H-1); 7.87 (d, J = 7.8 Hz, H-9); 8.31
(d, J = 7.6 Hz, H-6). 13C NMR (CDCl3/CD3OD, ꢁ7:1) d:
120.92 (C-1); 121.40 (C-9); 128.29 (C-12, C-14); 128.78
(C-3); 129.16 (C-7); 131.50 (C-13); 132.56 (C-8); 133.38
(C-2); 133.50 (C-11, C-15); 135.90 (C-6); 141.70–142.22
(m, C). 31P NMR (CDCl3/CD3OD, ꢁ7:1) d: ꢁ15 (br s).
amax
2kt ¼ ln
at
A linear plot ln(amax/at) versus t yielded the rate constant
kinv from which DG5 was calculated. From rate constants
at three temperatures the slope of the Arrhenius plot (lgk
vs 1/T) yielded the activation energy EA and therefrom
DH5 = EA ꢀ RT and DS5 = (DH5 ꢀ DG5)/T.
The kinetics of the epimerization of dl-17 was followed by
1H NMR (600 MHz) using the integration ratio of signals
at 7.99 ppm (dl) and 7.95 ppm (meso). The determination
of thermodynamic parameters was performed as described
above. For all plots, R2 P 0.996 was found.
4.2.13. Palladium dichloride complexes of dl-17 and (S,S)-
17. Ligand dl-17 (52 mg, 0.1 mmol) was dissolved in
degassed CH2Cl2 (1 mL) and a solution of Pd(CH3CN)2Cl2
(26 mg, 0.1 mmol) in 2.5 mL of the same solvent was added
dropwise with stirring over 5 min to give a clear yellow
4.4. Crystallography
Crystals of (S)-2,7,8, dl-16, and dl-17ÆPdCl2 were obtained
either by evaporation ((S)-2 from acetone, 7 from DMF) or
by diffusion of pentane into CH2Cl2 (8, dl-16 crystallizing
as chiral (S,S)-16ÆCH2Cl2) or CHCl3 solutions (dl-17ÆPdCl2
– Assignment was made by 2D NMR methods and numbering refers to
Scheme 1.
k Exchangeable.

1368
M. Widhalm et al. / Tetrahedron: Asymmetry 17 (2006) 1355–1369
Lett. 2002, 43, 7735–7737; (g) Maienza, F.; Spindler, F.;
Thommen, M.; Pugin, B.; Malan, C.; Mezzetti, A. J. Org.
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Miyazaki, T.; Imamoto, T. Tetrahedron Lett. 2003, 44, 3467–
3469; (i) Danjo, H.; Higuchi, M.; Yada, M.; Imamoto, T.
Tetrahedron Lett. 2004, 45, 603–606; (j) Katagiri, K.; Danjo,
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649.
giving dl-17ÆPdCl2ÆCHCl3). X-ray data were collected on a
Bruker Smart CCD area detector diffractometer with
graphite monochromated Mo Ka radiation, k =
˚
0.71073 A, and 0.3ꢁ x-scan frames covering mostly entire
spheres of the reciprocal space. After frame data integra-
tion with program SAINT, the reflection data were corrected
for absorption by the multi-scan method and for k/2 effects
with program SADABS.30 Space group assignments were
made on the basis of systematic absences and intensity sta-
tistics by using the XPREP program.30 The structures were
then solved by direct methods and refined by full-matrix
least-squares on F2 using the program suite SHELX97.31
The non-hydrogen atoms were refined with anisotropic
thermal parameters and carbon-bound hydrogen atoms
were included in idealized positions. The hydrogen atoms
of the OH-groups in 7 and 8 were refined in x, y, z, and
Uiso. Crystallographic data are presented in Table 2, se-
lected geometric data are given in Table 3, and views of
the molecular structures are shown in Figures 3–7. The
structure of (S)-2 showed at T = 173 K, strongly aniso-
tropic displacement parameters for the phenyl carbon
atoms indicating disorder. On cooling below T = 173 K,
a phase transformation occurred, which caused the b-axis
and the unit cell volume to double, but this low tempera-
ture structure could not be solved as yet. Another feature
of interest is that racemic 16 crystallized as a CH2Cl2-sol-
vate in the chiral space group P212121 and formed a con-
glomerate of enantiopure left- and right-handed crystals,
one of which with an (S,S)-configuration was investigated
by X-ray diffraction. Therefore, the term racemic was omit-
ted for the solid state material. In addition, compound
meso-16 was studied with X-ray diffraction, but is reported
only in the supplementary material. CCDC 294522-294527
contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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