A flexible approach to different families of bidentate P,P ligands as highly efficient ligands for asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.200500937

A novel and versatile approach has led to the synthesis of various classes of mono- and bidentate phospholane and phosphinite ligands based on a benzothiophene scaffold. The ligand functions in the bidentate ligands can be introduced independently and consecutively. A bis-phospolane ligand as well as its rhodium complex have been characterized by crystal-structure determinations. The bis-phospholane ligands were tested in the catalysed asymmetric homogeneous hydrogenation of dehydroamino acid derivatives, enamides and itaconates and gave ee values of up to 98.7 %. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500937

FULL PAPER
DOI: 10.1002/ejoc.200500937
A Flexible Approach to Different Families of Bidentate P,P Ligands as Highly
Efficient Ligands for Asymmetric Catalysis
Ulrich Berens,*[a] Ulli Englert,[b] Stefan Geyser,[b] Jan Runsink,[c] and Albrecht Salzer*[b]
Keywords: Asymmetric catalysis / Benzothiophene / Hydrogenation / Phospholane ligands / Rhodium
A novel and versatile approach has led to the synthesis of
various classes of mono- and bidentate phospholane and
phosphinite ligands based on a benzothiophene scaffold. The
ligand functions in the bidentate ligands can be introduced
independently and consecutively. A bis-phospolane ligand as
well as its rhodium complex have been characterized by
crystal-structure determinations. The bis-phospholane li-
gands were tested in the catalysed asymmetric homogeneous
hydrogenation of dehydroamino acid derivatives, enamides
and itaconates and gave ee values of up to 98.7%.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
Chiral phosphanes play an important role as ligands in
transition-metal-catalyzed asymmetric hydrogenation reac-
tions and many very successful representatives such as
DIOP,[1] DIPAMP[2] and BINAP[3] have been designed and
synthesized over the past three decades.
More recently, with the BPE[4] (1) and especially the
DuPHOS ligands[5] (2), a class of ligands that afford excel-
lent selectivity in the RhI-catalyzed asymmetric hydrogena-
tion of olefins has emerged.[6] The flexible design of these
ligands with respect to variations of the backbone and/or
of the phospholane allows in many cases a representative to
be quickly identified that provides excellent hydrogenation
results for a given substrate. Up to now, compared with the
BPE ligands, the DuPHOS ligands with their rigid back-
bone have appeared to be more useful, and by changing the
phospholane part of the DuPHOS ligand, numerous ana-
logues with the same backbone have been prepared by the
groups of Börner,[7] Zhang,[8] Rajanbabu[9] and others.[10]
In all these ligands the relative electronic properties as
well as the bite angle remain almost constant.[11] Changing
the backbone requires extra synthetic effort as the required
bis-primary phosphanes are not commercially available.
Such a change will alter the electronic nature of one or both
of the phosphorus atoms and only relatively few phos-
pholane-phosphane ligands of this type have been de-
scribed.[12] As the bite angle is also affected, which has a
profound effect on the performance of a ligand,[13] such
variations in DuPHOS offer new handles for fine-tuning
and thus have the potential to broaden the scope of phos-
pholane-derived ligands.
Our objective in this work was to be flexible with respect
to the bite angle of our ligands and also to prepare biden-
tate ligands in which the electronic nature of the phospho-
rus could be modified in order to allow ligands of type 3 to
be accessed in the most flexible manner.
This led us to consider heterocycles such as benzothio-
phene, N-alkylindoles and benzofuran as useful novel li-
gand backbones. In our strategy, attaching the first phos-
phorus atom P1 is achieved through electrophilic bromina-
tion at the 3-position followed by the reaction of the corre-
sponding organometallic reagent with a suitable phospho-
rus electrophile. In the next step, the second phosphorus
atom P2 is introduced either directly of after further func-
tionalisation of P1 by heteroatom-assisted metallation of
the backbone in the 2-position and the reaction of this spe-
cies with a second phosphorus electrophile.
This strategy requires slight modifications for each of the
particular backbones. For benzofuran, the derived 3-Grig-
nard reagent is prone to fragmentation,[14] whereas for
benzothiophene metal migration from the 3- to the 2-posi-
tion is known to occur readily.[15] Apart from this, with
some further adaptations other donor atoms instead of
phosphorus can also be attached to the backbone in either
[a] CIBA SC, K-420.2.20,
4002 Basel, Switzerland
E-mail: ulrich.berens@cibasc.com
[b] Institut für Anorganische Chemie, RWTH Aachen,
52056 Aachen, Germany
Fax: +49-241-8092644
E-mail: albrecht.salzer@ac.rwth-aachen.de
[c] Institut für Organische Chemie, RWTH Aachen,
52056 Aachen, Germany
2100
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Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis
FULL PAPER
step and thus an enormous variety of ligands becomes ac- mediate species. In order to suppress this, we decided to
cessible by our approach. trap the corresponding Grignard reagent immediately with
For geometrical reasons, the bite angle for all of these the phosphorus electrophile. Thus, when an equimolar mix-
ligands can be expected to be larger than for ligands derived ture of 5 and chlorobis(dimethylamino)phosphane[20] (6) in
from 1,2-bis(phosphanyl)benzene such as DuPHOS and THF was added to excess magnesium turnings, the 3-substi-
should increase from benzothiophene- through indole- to tuted benzothiophene 7 was obtained in ca. 75–85% yield
benzofuran-derived ligands. As for ligands with a large bite in a vigorous reaction. Very little product resulting from
angle, irrespective of the electron density of the specific li- metal migration (Ͻ5% by GC) was formed under these
gand, unusually high activities have been observed in asym- conditions and thus 7 was not purified prior to the next
metric hydrogenation reactions with the derived RhI cata- step (Scheme 1).
lysts, for example, for Phanephos,[16] DiPFc[17] and the
Ferrotane ligands.[18] This was considered to be a desirable TMEDA is facile and the intermediate formed was
feature of the new ligands. quenched by the addition of a slight excess of 6 to give 9.
The metallation of 7 with nBuLi in the presence of
Also, depending on the heteroatom in the backbone, the If desired, this intermediate can be isolated, but we found
electron densities at the two phosphorus atoms will be affec- it more convenient to treat it directly with gaseous HCl to
ted. It is difficult to predict this effect, but ligands derived give 10 in a typical yield of ca. 75% based on 7 (Scheme 2).
from the benzothiophene backbone can be expected to be
more electron-rich than ligands derived from the 1,2-bis-
(phosphanyl)benzene backbone.[12e,12f]
In the following the synthesis of some mono- and biden-
tate P,P ligands derived from benzothiophene will be de-
scribed. Also, the results of some initial hydrogenation reac-
tions with cationic RhI catalysts derived from these ligands
will be presented.
Results and Discussion
Scheme 2. Synthesis of 10. Reagents and conditions: (a) 1.1 equiv.
The bromination of benzothiophene 4 in the presence of
nBuLi, 1.2 equiv. TMEDA, Et2O, 2 h room temp.; (b) 1.1 equiv. 6;
sodium or potassium acetate has previously been report- (c) excess HClg, 75% overall.
ed,[19a,19b] but we found it more convenient to perform the
bromination reaction in the absence of acetate.[19c] It was
noticed that even when a slight excess (ca. 10%) of bromine
was employed, conversion of benzothiophene was still in-
complete. In the end, we chose to use an excess of 10%
bromine as a compromise to obtain a good conversion of 4
into 5 (Scheme 1) without losing too much product due to
over-bromination. The selectivity towards bromination at
the 3-position is good and only a small quantity of 2-bro-
mobenzothiophene was formed (ca. 3% by GC).
Compound 10 is a crystalline solid which can be handled
in air for a short time without special precautions. It is an
extremely versatile ligand precursor as it reacts with
alcohols to give bis(phosphinite) ligands or with secondary
amines to give, for example, diazaphospholidine ligands of
the ESPHOS type.[21] Further, bidentate phosphanes are
readily available from 10 by reaction with organometallic
reagents. Interestingly, the only known analogue of 10 is 11,
which has a backbone related to that of DuPHOS. How-
ever, 11 is, by far, not as readily available as 10 as its synthe-
sis either involves the use of mercury compounds[22a] or
poses safety problems as ortho-lithiobromobenzene is
formed as an intermediate.[22b]
Scheme 1. Synthesis of 7. Reagents and conditions: (a) 1.05 equiv.
Br2, 0–15 °C, 46%; (b) 1 equiv. 5 + 1.05 equiv. 6 added to 3 equiv.
Mg in THF, 66%.
The reduction of 10 with lithium aluminium hydride pro-
vides bis(phosphane) 12 in 60% yield. From 12 the
For the subsequent introduction of a phosphorus electro- DuPHOS analogues 13, 14a and 14b were prepared essen-
phile into the 3-position it is crucial that no migration of tially as described by Burk.[23] However, especially in large-
the metal from the 3- to the 2-position occurs in the inter- scale preparations of DuPHOS and other ligands with pro-
Eur. J. Org. Chem. 2006, 2100–2109
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U. Berens, U. Englert, S. Geyser, J. Runsink, A. Salzer
FULL PAPER
longed dwell times the reaction of n-butyllithium and also Initial Hydrogenation Results
the deprotonated phosphane with THF becomes significant
From ligands 13 and 14 the cationic RhI complexes
and causes considerable losses in yield as a result of the
consumption of the base or the phosphane.[24] Thus, instead
of n-butyllithium we selected lithium diethylamide (LDA)
as the base because this was expected to result in a lower
stationary concentration of the deprotonated phosphane
and suppress phosphane consumption by “THF alky-
lation”. As it turned out, at least on a small scale, the yields
are similar to the reported yields[23] and in the course of the
development of a process for the production of commercial
quantities of these ligands a suitable approach was iden-
tified at Solvias AG.[25]
In order to demonstrate the synthetic flexibility of our
strategy some other ligands were also prepared. From 7,
the corresponding dichlorophosphane 15 is readily available
and reduction with lithium aluminium hydride provided 16
in 86% yield (Scheme 3).
[(COD)Rh(ligand)]+BF4– were prepared as precatalysts and
then tested in the hydrogenation reactions of a selected set
of hydrogenation substrates.
In the hydrogenation of the standard dehydroamino acid
derivatives 20a and 20b a slight increase in the ee was ob-
served at increased pressure and temperature for the first
substrate, whereas the opposite trend was noticed for the
second substrate (Scheme 5, Table 1). Enamides with a car-
bamate group at the nitrogen, such as 20c, can be challeng-
ing because they do not coordinate well to the RhI cata-
lyst.[5b] Thus we were pleased to notice that the hydrogena-
tion of this substrate was complete within 6 hours under the
given conditions providing the product in excellent optical
purity.
Scheme 3. Synthesis of ligands 16 and 17. Reagents and conditions:
(a) LiAlH4, THF, 87 %; (b) (2R,5R)-hexanediol cyclic sulfate
(1 equiv.), 2.2 equiv. KOtBu, 64%.
Scheme 5. Substrates for hydrogenation reactions.
Some interesting trends were observed in the hydrogena-
tion of enamide 20d. Use of [Rh(MeDuPhOS)(COD)]BF4
gave the product with a much higher ee than the catalyst
derived from ligand 13. Interestingly, the opposite trend was
observed when the catalyst derived from EtDuPHOS was
compared with the catalyst derived from 14. Importantly,
the ees achieved are well in line with results obtained with
other ligand–metal systems with these types of sub-
strates.[27]
This was converted into the crystalline monophosphol-
ane ligand 17. Lithiation of 17 at the 2-position and reac-
tion with 6 gave ligand 18, which was treated with either
the (S) or the (R) enantiomer of BINOL to give the corre-
sponding phosphinite/phospholane ligands 19a or 19b (not
drawn) essentially in quantitative yields (Scheme 4).
The utility of the RhI-derived catalysts was next tested
in the hydrogenation of enamides leading to β-amino acid
derivatives. With the (E)-enamides 20e and 20f the hydro-
genation products were obtained in good-to-excellent ee
and are in line with values reported by other groups.[28] The
fact that the (Z)-enamide 20g was also hydrogenated with
high ee is important as usually the products from these en-
amides have a much lower ee and can be difficult to sepa-
rate from the mixture of diastereoisomers of enamides usu-
ally obtained.
Hydrogenation of dimethyl itaconate (22) with the pre-
catalyst derived from ligand 13 gave the (S) product in
94.8% ee and also the “inverse itaconate”[18a] 23 was hydro-
genated rapidly with the same catalyst to give the product
in 98.7% ee (Scheme 5, Table 1). Hydrogenation of 24 with
this precatalyst was sluggish even at 40 bar at S/C = 100
and the product had an ee of only 34%. This relatively lim-
Scheme 4. Synthesis of ligands 18 and 19. Reagents and conditions:
(a) 2 equiv. TMEDA, 1.2 equiv. nBuLi, room temp., 2 h, then
1 equiv. 6, 75 %; (b) 1 equiv. (S)-BINOL, toluene reflux, 14 h,
quant.
Ligands of type 19a or 19b are of interest for hydrofor- ited set of hydrogenation results and also recent results ob-
mylation reactions and initial results for the hydrofor- tained with another substrate class clearly show the poten-
mylation of vinyl acetate and styrene look promising.[26]
tial of these novel ligands.[29]
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Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis
FULL PAPER
Table 1. Hydrogenation of enamide derivatives with [(COD)Rh(ligand)]BF4 precatalysts in methanol. All reactions proceeded with com-
plete conversion of the substrate.
Substrate
R1, R2, R3
R4
Cat. [mol-%] p(H2) [bar]
Temp. [°C]
Ligand
ee [%]
20a
20a
20b
20b
20c
20d
20d
20d
20d
20e
20f
Ph, H, COOMe
Ph, H, COOMe
H, H, COOH
Ac
Ac
Ac
Ac
CBz
Ac
Ac
Ac
Ac
Ac
Ac
Ac
0.5
0.5
0.5
0.5
0.1
1.0
1.0
1.0
1.0
1.0
0.5
1.0
1
5
1
5
10
5
5
5
5
25
35
25
35
35
35
35
35
35
25
25
25
13
94.4 R
94.9 R
98.7 R
98.2 R
98.7 R
87.6
93.0
90.0
86.8
98.0
13
13
H, H, COOH
13
p-NO2Ph, H, COOMe
H, H, m-BnOPh
H, H, m-BnOPh
H, H, m-BnOPh
H, H, m-BnOPh
H, COOMe, Et
H, COOMe, i-Bu
COOMe, H, Me
14
13
21a[a]
14
21b[a]
13
5
14
5
14
13
87.0
90.0
20g
[a] 21a: MeDuPHOS; 21b: EtDuPHOS.
NMR Discussion
HMBC spectra. The assignments made for 13 are depicted
in Figure 1.
The lack of C2 symmetry in these ligands results in rela-
tively complex NMR spectra, but this allows the assign-
ment of all signals in the spectra in a relatively straightfor-
ward manner. For example, the assignment of the signals in
the spectra of ligand 13 starts with the observation of an
NOE signal between one aromatic proton and several ali-
phatic protons. Clearly, the aromatic proton must be 7-H,
whereas the aliphatic protons must belong to the phos-
pholane group attached to the C-3 atom. Following from
this, a series of 1D TOCSY experiments allowed the set
of protons belonging to either phospholane moiety to be
identified. It is well established that the coupling of the
methyl groups syn to the lone electron pair of the phospho-
rus is large (ca. 30 Hz) and small (ca. 0–5 Hz) for the methyl
group anti to the lone pair.[30] Together with the C,H corre-
lation obtained from an HSQC experiment this allowed the
identification of the corresponding methyl groups in either
phospholane moiety. The assignment of the other signals of
the phospholanes as well as of the aromatic part of the li-
gand was derived from the COSY spectrum and the assign-
ment of the phosphorus signals of either phospholane moi-
X-ray Structures
Ligand 14 is a crystalline solid and crystals suitable for
X-ray structural analysis were obtained from an ethanolic
solution. Interestingly, the angles of the P–C bonds relative
to the thiophene ring are quite irregular (Figure 2) and de-
viate strongly from the (theoretical) value calculated for a
regular pentagon (which would be 126°). This is also true
for the rhodium complex [(14)Rh(COD)]BF4 (Figure 3),
which was also crystallized from an ethanolic solution. The
coordination of the phosphorus atoms to rhodium leads to
some compression of the P1–C1–C2 and P2–C2–C1 angles
relative to the free ligand (121.7° vs. 126.2° and 114.6° vs.
116.5°, respectively). Contrary to our expectations, the bite
angle P–Rh–P (85.2°) is almost identical to the bite angle
in [Rh(MeDuPHOS)(COD)]SbF6.[5b] A comparison of the
bite angles of all known X-ray structures of DuPHOS-type
1
ety was based on the observation of crosspeaks in a H/31P
HETCOR experiment between the phosphorus atoms and
the proton signals of the methyl groups and also of the CH
protons that are syn to the lone pair of the phosphorus.
The signals of the quaternary carbon atoms are very weak
when directly observed but can be easily derived from the
Figure 2. Displacement ellipsoid plot (PLATON)[31] of 14. Ellip-
soids are at the 30% probability level; all hydrogen atoms and the
BF4– anion have been omitted for clarity. Selected bond angles: P2–
C2–C8: 131.6°; P2–C2–C1: 116.5°; C2–C1–P1: 126.2°; P1–C1–S:
121.2°.
1
Figure 1. H and 13C NMR chemical shifts (ppm) for ligand 13.
Eur. J. Org. Chem. 2006, 2100–2109
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U. Berens, U. Englert, S. Geyser, J. Runsink, A. Salzer
FULL PAPER
under argon. The mixture was cooled in an ice bath and bromine
(246 g, 3.1 mol) in chloroform (200 mL) was added dropwise. The
solvent was concentrated and the residue extracted with water and
a 0.1  sodium hydroxide solution. Evaporation of the solvent in
vacuo gave the crude product. The product was further purified
by vacuum distillation. Yield: 136.6 g (46%). 1H NMR (CD2Cl2,
500 MHz): δ = 7.40–7.50 (m, 1 H), 7.50–7.60 (m, 2 H), 7.70–7.80
(m, 2 H) ppm. 13C NMR (CD2Cl2, 125 MHz): δ = 107.81 (1 C),
123.03, 124.02, 125.34, 125.60, 126.16 (5 C), 137.74, 138.87 (2
C) ppm.
rhodium complexes has been carried out and shows a mean
value for the P–Rh–P angle of 84.7°.[11a] For the MalPHOS
ligand, based on a maleinic anhydride scaffold, a value of
86.1° has been calculated by DFT methods,[12d] while the
same angle for UlluPHOS, based on a 3,4-substituted thio-
phene, is 85.86°.[12f] These values suggest that the bite angle
at rhodium is quite insensitive to the nature of the ligand
backbone. No correlation is seen between the bite angle and
the enantioselectivities obtained in asymmetric hydrogena-
tion reactions[9a] and no attempt has yet been made to the
best of our knowledge to correlate catalytic activities with
crystallographic parameters. The X-ray determination of
another rhodium complex of the methyl derivative 13 has
been reported.[11b]
Chlorobis(dimethylamino)phosphane (6): A 250-mL Schlenk flask
was charged under argon with phosphorus trichloride (60 g,
0.44 mol). The flask was cooled to 0 °C and tris(dimethylamino)
phosphane (142.9 g, 0.88 mol) was added under permanent cool-
ing. The product was collected without purification as a light yel-
low liquid. Yield: 203 g (100%). 31P NMR (CDCl3, 121 MHz): δ =
164.15 ppm.
3-[Bis(dimethylamino)phosphanyl]benzo[b]thiophene (7): A 2-L flask
fitted with a mechanical stirrer was charged with magnesium turn-
ings (41.0 g, 1.69 mol) and THF (200 mL). Under an inert atmo-
sphere a solution of 3-bromobenzo[b]thiophene (173 g, 0.81 mol)
and chlorobis(dimethylamino)phosphane (145 g, 0.94 mol) in THF
(300 mL) was added dropwise to the magnesium turnings over a
period of 2½ h. The reaction mixture started to reflux and after
the addition of the reagents had been completed, the mixture was
maintained at reflux for another 1½ h. Then the mixture was co-
oled to ambient temperature and decanted from the magnesium
turnings into a 2-L flask. After removal of the solvent on a rota-
vapor, the residue was extracted with hexane three times. The com-
bined hexane extracts were concentrated to give a brown oil. The
residue was extracted a further three times with ethyl acetate. Re-
moval of the ethyl acetate from the combined extracts left an oil
which by 1H NMR was almost identical to the product from the
hexane extractions. Distillation of the combined oils over a Vigreux
column in vacuo gave the product as a pale yellow oil; b.p. 120 °C/
0.018 mbar, yield = 136.5 g (66.7% based on 3-bromobenzo[b]thio-
Figure 3. Displacement ellipsoid plot (PLATON)[31] of [(14)-
Rh(COD)]BF4. Ellipsoids are at the 30% probability level; all hy-
drogen atoms have been omitted for clarity. Selected bond angles:
P2–C2–C8: 132.8°; P2–C2–C1: 114.5°; C2–C1–P1: 121.7°; P1–C1–
S: 125.3°.
1
3
phene). H NMR (CDCl3, 300 MHz): δ = 2.88 (d, JH,P = 9.4 Hz,
12 H, NCH3), 7.37–7.46 (m, 2 H, 5-H, 6-H), 7.50 (d, J = 1.2 Hz,
1 H, 2-H), 7.94 (d, J = 6.7 Hz, 1 H, 7-H/8-H), 7.99 (d, J = 7.6 Hz,
1 H, 7-H/8-H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 41.99 [d,
2JC,P = 15.8 Hz, 4 C, NCH3], 122.45, 124.17 (d, J = 8.2 Hz), 124.24,
124.43, 129.96 (d, J = 9.8 Hz) (5 C, CH-Ar), 136.00 (d, J = 2.9 Hz),
140.26 (d, J = 18.9 Hz), 142.13 (d, J = 5.2 Hz) (3 C, C-Ar) ppm.
31P NMR (CDCl3, 121 MHz): δ = 93.80 ppm.
Summary and Conclusions
A new and very flexible strategy for the synthesis of vari-
ous families of mono- and bidentate ligands has been pre-
sented. Initial results on selected applications of catalysts
derived from these ligands show promising results and some
ligands of this class are already commercially available from
Solvias AG under the name of ButiPhane®.
2,3-Bis[bis(dimethylamino)phosphanyl]benzo[b]thiophene (9): A 1-L
flask was charged under argon with 3-[bis(dimethylamino)phos-
phanyl]benzo[b]thiophene (17.5 g, 69 mmol), TMEDA (10.5 g,
90 mmol) and 500 mL toluene. The mixture was cooled to 0 °C and
then nBuLi (26.6 mL, 2.7 , 69 mmol) was added dropwise over a
period of 45 min while the temperature was held at around 5 °C.
The reaction mixture was warmed to room temperature and stirred
for 1 h. It was then cooled again to 5 °C and chlorobis(dimethyl-
amino)phosphane (10.7 g, 69 mmol) was added over a period of
1 h. The flask was slowly warmed to room temperature and stirred
for another 2 h. The product can be purified by evaporation of the
Experimental Section
All reactions were carried out under nitrogen using Schlenk tech-
niques. Solvents were dried and deoxygenated by standard pro-
cedures. NMR spectra were recorded with a Varian Mercury 300
(1H: 300 MHz; 13C: 75 MHz; 31P: 121 MHz) and a Varian Unity
500 (1H: 500 MHz; 13C: 125 MHz; 31P: 202 MHz) at ambient tem-
perature. IR spectra were recorded with a Perkin–Elmer FT-IR
model 1720 X spectrometer. Mass spectra were obtained with a
Finnigan MAT 95 spectrometer using CI (isobutane as reactand
gas) and SIMS recording techniques.
solvent and vacuum distillation, but purification normally is not
3
necessary. 1H NMR (CDCl3, 300 MHz): δ = 2.80 (d, JH,P
=
9.0 Hz, 24 H, NCH3), 7.22–7.37 (m, 2 H, 5-H, 6-H), 7.87 (d, J =
7.6 Hz, 1 H, 7-H/8-H), 8.23 (d, J = 8.2 Hz, 2 H, 7-H/8-H) ppm.
3
13C NMR (CDCl3, 75 MHz): δ = 41.92 (d, JH,P = 19.0 Hz), 41.95
3
3
3
3-Bromobenzo[b]thiophene (5): A 2-L flask was charged with a solu-
tion of benzo[b]thiophene (187 g, 1.4 mol) in chloroform (500 mL)
(d, JH,P = 19.0 Hz), 42.66 (d, JH,P = 17.0 Hz), 42.71 (d, JH,P
=
16.7 Hz) (4 C, NCH3), 121.98, 123.63, 123.87, 125.06 (4 C, CH-
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Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis
FULL PAPER
Ar), 136.73 (dd, J = 11.2, 15.6 Hz, 1 C, C-2), 143.30 (dd, J = 1.5,
3.3 Hz, 1 C, C-4/C-9), 143.62 (d, J = 8.4 Hz, 1 C, C-4/C-9), 152.92 A solution of the cyclic sulfate derived from (2R,5RS)-octane-2,5-
(dd,
22.3, 33.2 Hz, 1C, C-3) ppm. 31P NMR (CDCl3,
2,3-Bis[(2S,5S)-2,5-(diethylphospholan-1-yl)]benzo[b]thiophene (14):
J
=
diol (4.4 g, 21 mmol) in THF (250 mL) was degassed by bubbling
argon through the solution at 0 °C for 1 h. 2,3-Bis(phosphanyl)
benzothiophene (2.0 g, 10 mmol) was then added to the degassed
solution and vigorously stirred before being added dropwise to a
solution of LDA (50 mmol, 22.5 mL of a 2.2  solution). When
the addition was complete, the mixture was warmed to ambient
temperature. The solvent was then removed on the rotavapor and
water (ca. 100 mL) was added to the residue. The product was ex-
tracted with pentane (100 mL) and obtained as a white solid by
removal of the solvent from the dried (Na2SO4) extract. Yield: 2.0 g
(47%). 1H NMR (CD2Cl2, 500 MHz): δ = 0.82 (t, J = 7.3 Hz, 3 H,
CH3), 0.90 (t, J = 7.3 Hz, 3 H, CH3), 0.92 (t, J = 7.3 Hz, 3 H,
CH3), 0.97 (t, J = 7.3 Hz, 3 H, CH3), 1.28–1.37, 1.39–1.49, 1.54–
1.67, 1.68–1.74, 1.77–1.87 (m, 10 H, CH2), 2.00–2.22 (m, 3 H, CH,
CH2), 2.28–2.38 (m, 3 H, CH2), 2.46–2.56 (m, 1 H, CH2), 2.59–
2.67, 3.17–3.24 (m, 2 H, CH) ppm. 13C NMR (CD2Cl2, 125 MHz):
δ = 14.05 (1 C, CH3), 14.44 (2 C, CH3), 14.72 (1 C, CH3), 24.90,
25.22, 29.37, 27.78, 34.29, 34.43, 34.73, 37.12 (8 C, CH2), 39.97,
43.62, 44.15, 47.55 (4 C, CH), 122.47, 124.15, 124.36, 125.32 (4 C,
CH-Ar), 140.48, 143.09, 143.43, 153.07 (4 C, C-Ar) ppm. 31P NMR
(CD2Cl2, 202 MHz): δ = –12.10 (d, JP,P = 158. 2 Hz), –10.90 (d,
JP,P = 155.7 Hz) ppm.
121 MHz): δ = 97.37, 99.52 (AB, J = 28 Hz) ppm.
2,3-Bis(dichlorophosphanyl)benzo[b]thiophene (10): HCl gas was
passed through the reaction mixture from the preparation of 2,3-
bis[bis(dimethylamino)phosphanyl]benzo[b]thiophene. The reac-
tion was monitored by 31P NMR spectroscopy. After the starting
material was no longer visible, the addition of HCl was continued
for another 15 min. The precipitate was filtered off and washed
with diethyl ether. The solvent from the combined organic phases
was evaporated and the product collected as an orange-yellow so-
lid. Yield: 14.6 g (63%). Purification by extraction of the solid with
pentane in a Soxhlet extractor gave pale yellow crystals; m.p. 96 °C.
1H NMR (CDCl3, 300 MHz): δ = 7.51–7.60 (m, 2 H, 5-H, 6-H),
7.93–7.97 (m, 1 H, 4-H/7-H), 8.62–8.68 (m, 1 H, 7-H/4-H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 123.38 (1 C, C-7), 126.04 (1 C,
C-6), 126.74 (1 C, C-4), 128.04 (1 C, C-5), 138.52, 144.22 (2 C, C-
8, C-9), 142.77 (dd, J = 11, 50 Hz), 156.66 (dd, J = 24.9, 25 Hz) (2
C, C-2, C-3) ppm. 31P NMR (CDCl3, 121 MHz): δ = 133.99, 138.01
(AB, J = 450 Hz) ppm.
2,3-Bis(phosphanyl)benzo[b]thiophene (12): A 1-L three-necked flask
was charged under argon with LiAlH4 (2.7 g, 72.0 mmol) and THF
(100 mL). Under reflux, 2,3-bis(dichlorophosphanyl)benzo[b]thio-
phene (8.0 g, 24 mmol) in diethyl ether (100 mL) was added. After
the addition was complete, the reaction mixture was heated for an-
other 1 h. The reaction mixture was cooled to room temperature
and hydrolysed by careful addition of water. The solution was sepa-
rated and the residue was extracted three times with pentane. The
solvent was evaporated from the combined organic layers and the
product purified by vacuum distillation. Yield: 3.0 g (63%); b.p.
{2,3-Bis[(2S,5S)-2,5-diethylphospholan-1-yl]benzo[b]thiophene}(1,5-
cyclooctadiene)rhodium(I) Tetrafluoroborate, [Rh(COD)(S)-EtButi-
Phane][BF4]: A 50-mL Schlenk flask was charged with [Rh(COD)-
acac] (0.861 g, 2.77 mmol) and THF (5 mL). A solution of the li-
gand (1.0 g, 2.77 mmol) and HBF4·OEt2 (0.450 g, 2.77 mmol),
which had been diluted to 5 mL with THF, was added dropwise to
2
the vigorously stirred solution at 65 °C. After about ⁄3 of the li-
gand/acid solution had been added, the catalyst started to precipi-
tate. The crystallisation of the product went to completion when
TBME (ca. 7 mL) was added very slowly to the reaction mixture.
After cooling to ambient temperature, the catalyst was filtered off
using a Schlenk filter and washed with a mixture of THF/MTBE
(10 mL, 4:6, v/v). Drying in vacuo gave 1.018 g of orange crystals
1
91 °C/0.09 mbar. H NMR (CDCl3, 300 MHz): δ = 3.77 (dm, JP,H
= 205 Hz, 2 H, PH2), 4.02 (dm, JP,H = 207 Hz, 2 H, PH2), 7.26–
7.40 (m, 2 H, 5-H, 6-H), 7.68 (d, 1 H, J = 7.3 Hz, 7-H), 7.76 (d, 1
H, J = 7.8 Hz, 4-H) ppm. 31P NMR (CDCl3, 121 MHz): δ =
–167.1, –150.8 (AB, JP,P = 65 Hz) ppm.
1
(55.6% yield). H NMR (CDCl3, 300 MHz): δ = 0.87, 1.00, 1.01,
1.14 (4 t, J = 7.3 Hz, 3 H each, 4 CH3), 1.27–1.43 (m, 2 H), 1.43–
1.67 (m, 4 H), 1.78–2.17 (m, 7 H), 2.30–2.73 (m, 14 H), 2.99–3.17
(m, 1 H, CHP), 4.73–4.83, 5.02–5.13, 5.45–5.53, 5.66–5.76 (4 m, 1
H each, COD-CH), 7.46–7.58 (m, 2 H, 5-H, 6-H), 7.90, 7.96 (2 d,
J = 8.1 Hz each, 1 H each, 4-H, 7-H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 14.61 (dd, J = 2.6, 5.9 Hz), 14.69 (dd, J = 2.1,
5.1 Hz), 15.74 (dd, J = 3.1, 8.4 Hz), 16.25 (dd, J = 3.4, 8.7 Hz) (4
CH3), 22.84 (s), 23.90 (s), 26.46 (d), 27.55 (d) (4 CH2CH3), 28.72
(s), 28.81 (s), 32.96 (s), 33.02 (s) (4 COD-CH2), 33.46 (s), 34.54 (d),
34.69 (s), 34.88 (s) (4 phospholane CH2), 44.29 (m), 45.18 (m),
46.77 (m), 53.50 (m) (4 ABX CHP), 91.24 (m), 93.99 (m), 104.13
(m), 108.45 (m) (4 ABX COD-CH), 124.85 (s), 124.87 (s) (C-4, C-
7), 126.31 (s), 127.04 (s) (C-5, C-6), 135.66 (m), 143.21 (m), 150.47
(d), 152.90 (m) (C-2, C-3, C-8, C-9) ppm. 31P NMR (CDCl3,
121 MHz): δ = 56.16 (AB, JP,P = 23, JP-1,Rh = 145.7 Hz), 56.28 (AB,
JP-2,Rh = 147.7 Hz) ppm.
2,3-Bis[(2R,5R)-2,5-(dimethylphospholan-1-yl)]benzo[b]thiophene
(13): A solution of the cyclic sulfate derived from (2S,5S)-hexane-
2,5-diol (3.96 g, 22 mmol) in THF (250 mL) was degassed by bub-
bling argon through the solution at 0 °C for 1 h. 2,3-Bis(phos-
phanyl)benzo[b]thiophene (1.98 g, 10 mmol) was added to the de-
gassed solution and under continuous cooling and vigorous stirring
a solution of LDA [45 mmol, 22.3 mL of a 2  solution in methyl
tert-butyl ether (MTBE)] was added slowly. When the addition was
complete, the mixture was warmed to ambient temperature. The
solvent was removed on the rotavapor and water (ca. 100 mL) was
added to the residue. The product was extracted with MTBE
(100 mL) and obtained as a pale yellow oil by removal of the sol-
vent from the dried (Na2SO4) extract. Yield: 1.91 g (53%). 1H
NMR (CDCl3, 500 MHz): δ = 0.74 (dd, J = 7.0, 10.2 Hz, 3 H,
CH3), 0.85 (dd, J = 7.0, 10.4 Hz, 3 H, CH3), 1.11 (dd, J = 7.2,
19.1 Hz, 3 H, CH3), 1.19 (dd, J = 6.9, 19.4 Hz, 3 H, CH3), 1.21,
1.34, 1.56, 1.71, 1.93, 2.13, 2.14, 2.27 (m, 4 CH2), 2.24, 2.40, 2.69, 2,3-Bis[(2S,5S)-2,5-diisopropylphospholan-1-yl]benzo[b]thiophene
3.25 (m, 4 CH), 7.17, 7.23 (2 “t”, Ar-CH), 7.72, 7.90 (2 “d”, Ar-
CH) ppm. 13C NMR (CDCl3, 125 MHz): δ = 16.55 (s, CH3), 16.89
(d, CH3), 20.89, 21.33 (2 m, 2 CH3), 32.07 (m, CH), 35.32 (m, CH),
(14a): A solution of the cyclic sulfate derived from (3R,6R)-2,7-
dimethyloctane-3,6-diol (12.2 g, 52 mmol) in THF (100 mL) was
degassed by bubbling argon through the solution at 0 °C for 1 h.
36.16 (m, CH), 36.66 (s, CH2), 37.27 (d, CH2), 37.66 (t, CH2), 38.17 2,3-Bis(phosphanyl)benzothiophene (4.9 g, 25 mmol) was then
(m, CH), 39.49 (d, CH2), 122.29 (s, Ar-CH), 123.92 (s, Ar-CH), added to the degassed solution and to the vigorously stirred solu-
124.02 (s, Ar-CH), 124.29 (s, Ar-CH), 124.64 (t, Ar-CH), 139.44,
142.85, 151.96 (Ar-C) ppm. 31P NMR-(CDCl3, 202 MHz): δ =
–5.59 (d, JP,P = 158.5 Hz), –4.39 (d, JP,P = 158.9 Hz) ppm.
tion was then added dropwise a solution of LDA (120 mmol,
60 mL of a 2  solution in THF). When the addition was complete,
the mixture was warmed to ambient temperature. The solvent was
Eur. J. Org. Chem. 2006, 2100–2109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2105

U. Berens, U. Englert, S. Geyser, J. Runsink, A. Salzer
FULL PAPER
then removed and water (ca. 150 mL) was added to the residue.
The product was extracted with MTBE (100 mL), the extracts dried
with Na2SO4 and the solvent evaporated to yield 8.5 g (73%) of a
pale yellow oil. 1H NMR (CDCl3, 300 MHz): δ = 0.68–1.14 (m, 24
H), 1.18–2.43 (m, 14 H), 2.56 (m, 1 H), 3.17 (m, 1 H), 7.28 (m, 2
ArH), 7.80 (m, 1 ArH), 8.10 (d, J = 7.9 Hz, 1 ArH) ppm. 31P NMR
(CDCl3, 121.5 MHz): δ = –16 (br.) ppm.
6), 134.54 (d, J = 35 Hz, C-2), 140.75 (d, J = 2.6 Hz, C-8), 142.22
(d, J = 2 Hz, C-9) ppm. 31P{1H}NMR (C6D6, 121 MHz): δ =
163.1 ppm.
3-[(2S,5S)-2,5-Dimethylphospholan-1-yl]benzo[b]thiophene (17): A
1-L flask was charged with degassed THF (100 mL) and 3-phos-
phanylbenzo[b]thiophene (5.44 g, 32.7 mmol). A solution of
KOtBu (4.03 g, 36 mmol) in THF (20 mL) was added to this solu-
tion. The resulting red solution was transferred to a cooled (0 °C)
degassed solution of the cyclic sulfate derived from (2R,5R)-hex-
ane-2,5-diol (6.2 g, 34.4 mmol) in THF (40 mL). The resulting mix-
ture was stirred for 2 h and the colour gradually turned pale yellow.
More KOtBu (4.03 g, 36 mmol) dissolved in THF (20 mL) was
added and the mixture was stirred for another 2 h. Water (100 mL)
and diethyl ether (100 mL) were then added and the organic layer
was removed using a double-ended needle. The reaction mixture
was extracted with a further diethyl ether (50 mL) and the organic
layer was removed as described above. The combined organic layers
were dried (sodium sulfate). Evaporation of the solvent gave a pale
yellow oil, which was crystallized from ethanol (10 mL) at –20 °C.
The crystals were removed by filtration through a Schlenk filter
and dried to give 5.23 g (64.4%) of colourless crystals; m.p. 58 °C.
1H NMR (CDCl3, 300 MHz): δ = 0.85 (dd, J = 6.7, 10.8 Hz, 3 H,
CH3), 1.40 (m, 1 H, 1 CH2 at δC = 37.07), 1.41 (dd, J = 7.7,
19.9 Hz, 3 H, CH3), 1.61 (dddd, J = 3.3, 6.0, 12.0, 18.3 Hz, 1 H, 1
{2,3-Bis[(2S,5S)-2,5-diisopropylphospholan-1-yl]benzo[b]thiophene}-
(1,5-cyclooctadiene)rhodium(I) Tetrafluoroborate, [Rh(COD)(S)-
iPrButiPhane]BF4: A 250-mL Schlenk flask was charged with
[Rh(COD)]BF4 (8.55 g, 21 mmol) and THF (45 mL). A solution of
the ligand (10 g, 21 mmol) in THF (40 mL) was added dropwise to
2
the vigorously stirred solution at 65 °C. After about ⁄3 of the li-
gand solution had been added, the catalyst started to precipitate.
When MTBE (ca. 45 mL) was added very slowly to the reaction
mixture, the crystallisation of the product went to completion. Af-
ter cooling to ambient temperature the catalyst was filtered off and
washed with a mixture of THF/MTBE (100 mL, 1:1 v/v). Drying
in a vacuum gave 10 g of orange crystals (60% yield). 1H NMR
(CDCl3, 300 MHz): δ = 0.63 (d, J = 9.3 Hz, 3 H, CH3), 0.80, 0.85,
0.87 (3 d, J = 9.3 Hz, 9 H, CH3), 1.07, 1.15, 1.18 (3 d, J = 9.3 Hz,
9 H, CH3), 1.26 (d, J = 9.3 Hz, 3 H, CH3), 1.53–2.66 (m, 23 H),
3.05 (m, 1 H), 4.97, 5.06, 5.55, 5.70 (4 m, 4 H, COD), 7.55 (m, 2
H, ArH), 7.90 (m, 2 H, ArH), 8.00 (d, J = 10.1 Hz) ppm. 31P NMR
(CDCl3, 121.5 MHz): δ = 50 (dd), 51 (dd) ppm.
CH2 at δC = 37.35), 2.07 (ddm, J = 2, 5.9 Hz, 1 H, 1 CH2 at δC
=
37.35), 2.29 (m, 1 H, CH at δC = 35.09), 2.37 (m, 1 H, 1 CH2 at
δC = 37.07), 2.83 (m, 1 H, CH at δC = 36.18), 7.38 (“t”, J = 7.0 Hz,
1 H, CH at δC = 124.66), 7.41 (d, J = 1.7 Hz, 1 H, 2-H), 7.44 (“t”,
J = 7 Hz, 1 H, CH at δC = 124.30), 7.92 (“d”, J = 8.1, 1 H, CH at
δC= 122.76), 8.22 (“d”, 1 H, CH at δC = 124.04) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 15.83 (CH3), 21.83 (d, J = 33.9 Hz, CH3),
35.09 (d, J = 7.3 Hz, CH), 36.18 (d, J = 10.6 Hz, CH), 37.07 (CH2),
37.35 (d, J = 4.0 Hz, CH2), 122.76 (CH), 124.04 (CH), 124.23 (br.
s, CH), 124.66 (br. s, CH), 129.17 (d, J = 6.7 Hz, C-2), 131.90 (d,
J = 32.7 Hz, C-3), 140.89 (d, J = 4.6 Hz), 143.53 (d, J = 24.7 Hz)
(C-8, C-9) ppm. 31P NMR (CDCl3, 121 MHz): δ = –8.59 ppm.
3-(Dichlorophosphanyl)benzo[b]thiophene (15): A stream of gaseous
HCl was passed through a solution of 3-[bis(dimethylamino)phos-
phanyl]benzo[b]thiophene (32.5 g, 129 mmol) in diethyl ether
(250 mL) until no more HCl gas was absorbed and a sample
showed complete conversion of the starting material by 31P NMR
spectroscopy. The colourless emulsion obtained was concentrated
at normal pressure to give a light-brown crystalline residue. This
was triturated three times with MTBE (ca. 50 mL each). Removal
of the solvent from the combined extracts and distillation (107–
112 °C at 0.1 mbar) gave the product (19.09 g, 63%) as a colourless
1
liquid. H NMR (CDCl3, 300 MHz): δ = 7.48 (t, J = 7 Hz, 1 H, 6-
2-[Bis(dimethylamino)phosphanyl]-3-[(2S,5S)-dimethylphospholan-1-
yl]benzo[b]thiophene (18): A 100-mL Schlenk flask was charged un-
der argon with 3-[(2S,5S)-dimethylphospholan-1-yl]benzo[b]thio-
phene (4.2 g, 16.9 mmol) and TMEDA (2.0 g, 17 mmol). After the
addition of anhydrous diethyl ether (30 mL), a solution of nBuLi
(10.6 mL of a 1.6  solution, 16.9 mmol) in hexanes was added.
The mixture was stirred at ambient temperature overnight and then
a solution of chlorobis(dimethylamino)phosphane (2.62 g,
H), 7.54 (t, J = 7.5 Hz, 1 H, 5-H), 7.94 (dm, J = 7.8 Hz, 1 H, 7-
H), 8.14 (d, JP,H = 8.1 Hz, 1 H, 2-H), 8.46 (d, J = 8.1 Hz, 1 H, 4-
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 123.39 (C-7), 124.43 (d,
1
3JP,C = 4.4 Hz, C-4), 125.36 (C-5), 125.92 (C-6), 134.82 (d, JP,C
=
62.3 Hz, C-3), 137.10 (d, 2JP,C = 52.1 Hz, C-2), 137.33 (C-8), 141.77
(d, JP,C = 1.9 Hz, C-9) ppm. 31P NMR (CDCl3, 121 MHz): δ =
3
148.5 ppm.
3-Phosphanylbenzo[b]thiophene (16): Under nitrogen, a three- 17 mmol) in diethyl ether (10 mL) was added dropwise through a
necked 1-L flask was charged with diethyl ether (200 mL) and a
solution of LiAlH4 in THF (58 mL of a 1  solution, 58 mmol)
was added. A solution of 3-(dichlorophosphanyl)benzo[b]thio-
phene (18.24 g, 77.6 mmol) in diethyl ether (ca. 40 mL) was added
dropwise over about 30 min. An exothermic reaction took place
and a solid formed. The excess LiAlH4 was hydrolysed by the drop-
wise addition of NaOH (15 mL of a 4  solution), which led to
the formation of a colourless solid which precipitated readily. The
supernatant liquid was removed using a cannula and the solid was
extracted with further diethyl ether (20 mL). Evaporation of the
solvent in vacuo gave the crude phosphane as a mobile oil which
was further purified by vacuum distillation. Yield: 11.31 g (87%);
syringe. When the exothermic reaction had subsided the solvent
was removed in vacuo and the residue was redissolved in pentane
(30 mL). The LiCl was removed by filtration through a Schlenk
filter and the solvent was removed again from the filtrate in vacuo.
The residue was redissolved in pentane and the last traces of LiCl
were filtered off as described above. Removal of the solvent from
the filtrate in vacuo gave the product as yellow oil. 1H NMR
(CDCl3, 300 MHz): δ = 0.91 (dd, J = 7.3, 9.5 Hz, 3 H, CH3 at δC
= 16.61), 1.27 (dd, J = 6.9, 19.2 Hz, 3 H, CH3 at δC = 21.55), 1.48,
2.37 (2 m, 1 H each, CH2 at δC = 37.61), 1.92, 2.29 (2 m, 1 H each,
CH2 at δC = 39.37), 2.54 (m, 1 H, CH at δC = 35.19), 2.75 [d, J =
9.6 Hz, N(CH3)2, 12 H], 3.33 (m, 1 H, CH at δC = 32.62), 7.23–
b.p. 93 °C/0.036 mbar. 1H NMR (C6D6, 300 MHz): δ = 3.59 (dd, 7.38 (m, 2 H, 5-H, 6-H), 7.85 (d, J = 7.4 Hz, 1 H, CH at δC
=
4
1JP,H = 200.5, J = 1.2 Hz, 2 H, PH2), 7.10 (“t”, J = 7.4 Hz, 1 H,
6-H), 7.19 (“dt”, 2JH,P = 7.5, 4J = 1.2 Hz, 2-H), 7.20 (t, J = 7.4 Hz,
1 H, 5-H), 7.57 (d, J = 7.5 Hz, 1 H, 7-H), 7.70 (d, J = 7.5 Hz, 1
H, 4-H) ppm. 13C NMR (C6D6, 75 MHz): δ = 122.06 (d, J =
16.1 Hz, C-2), 122.693 (C-7), 123.72 (C-4), 124.60, 124.63 (C-5, C-
122.63), 8.02 (d, J = 7.9 Hz, 1 H, CH at δC = 124.84) ppm. 13C
NMR (CDCl3, 75 MHz): δ = 16.61 (d, J = 2.0 Hz, CH3), 21.55 (d,
J = 36.0 Hz, CH3), 32.62 (dd, J = 6.5, 8.6 Hz, CH), 35.19 (dd, J =
1.6, 11.7 Hz, CH), 37.61 (d, J = 4.1 Hz, CH2), 39.337 (br. s, CH2),
41.65 (d, J = 17.9 Hz), 41.94 (dd, J = 2.2, 17.8 Hz) [N(CH3)2],
2106
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2100–2109

Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis
FULL PAPER
1
122.63 (CH), 123.68, 123.75 (C-5, C-6), 124.84 (CH), 134.03 (dd, give the product mixture which was assayed for conversion by H
J = 20.1, 41.3 Hz), 143.16 (s), 143.80 (d, J = 3.4 Hz), 159.31 (dd,
J = 32.5, 37.5 Hz) ppm. 31P NMR (CDCl3, 121 MHz): δ = –3.51
(d, J = 119 Hz, P-3), 93.12 {d, P[N(CH3)2]2} ppm.
NMR spectroscopy and for ee by chiral HPLC.
Hydrogenation of 20a: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel OD (0.46×25 cm), hex-
ane(95)/EtOH(5), flow 1.0 mLmin, T = 25 °C, t (1st enantiomer)
= 12.54 min, t (2nd enantiomer) = 14.12 min.
(S,S)-4-{3-[(2S,5S)-Dimethylphospholan-1-yl]benzo[b]thiophen-2-
yl}-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-aЈ]dinaphthalene (19a):
A 50-mL Schlenk flask was charged with a solution of 2-[bis(dime-
thylamino)phosphanyl]-3-[(2S,5S)-dimethylphospholan-1-yl]-
benzo[b]thiophene (1.23 g, 33.5 mmol) in toluene (5 mL) under ar-
gon. (S,S)-Binaphthol (0.96 g, 33.5 mmol) was added to this solu-
tion and the mixture was heated at 110 °C overnight. The conver-
sion was monitored by 31P NMR spectroscopy and was completed
within this time. The solvent was removed in vacuo and the residue
was redissolved in CH2Cl2 (ca. 5 mL). The solvent was removed
again and this was repeated once more in order to remove the last
traces of toluene and dimethylamine. The product was formed as
a colourless foam in quantitative yield. 1H NMR/13C HSQC:
(CDCl3, 500 MHz): δ = 1.05 (dd, J = 7.0, 10.0 Hz, 3 H, CH3 at δC
= 16.37), 1.47 (dd, J = 7.0, 19.5 Hz Hz, 3 H, CH3 at δC = 20.97),
1.59 (m, 1 H, H at δC = 37.94), 2.04, 2.41 (2 m, 2×1 H, CH2 at δC
= 39.70), 2.41 (m, 1 H, H at δC = 37.94), 2.67 (m, 1 H, CHP at δC
= 35.55), 3.43 (m, 1 H, CHP at δC = 34.11), 6.84 (d, J = 9 Hz, H
at δC = 121.68), 7.31 (H at δC = 126.47), 7.34 (H at δC = 126.29),
Hydrogenation of 20b: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel AD (0.46×25 cm), hex-
ane(90)/EtOH(10), flow 1.0 mLmin, T = 25 °C, t (1st enantiomer)
= 7.49 min, t (2nd enantiomer) = 12.03 min.
Hydrogenation of 20c: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel OD (0.46×25 cm), hex-
ane(90)/EtOH(10), flow 1.0 mLmin, T = 25 °C, t (1st enantiomer)
= 19.93 min, t (2nd enantiomer) = 23.58 min.
Hydrogenation of 20d: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel OJ (0.46×25 cm), hex-
ane(80)/iPrOH(20), flow 0.8 mLmin, T = 25 °C, t (1st enantiomer)
= 13.4 min, t (2nd enantiomer) = 16.4 min.
Hydrogenation of 20e: Determination of conversion and ee by GC:
LIPODEX E (0.25 mm×50 m), T = 145 °C isothermic, gas: H2
(195 kPa), t (20e) = 3.6 min, t (1st enantiomer) = 6.9 min, t (2nd
enantiomer) = 7.2 min.
7.36 (H at δC = 125.54), 7.40 (H at δC = 127.22), 7.43 (H at δC
=
124.21), 7.45 (H at δC = 125.00), 7.48 (H at δC = 127.22), 7.49 (H
at δC = 125.24), 7.65 (d, 2×J = 9.0 Hz, 2×1 H, H at δC = 121.68,
H at δC = 129.99), 7.69 (d, J = 8.0 Hz, H at δC = 123.29), 7.86 (d,
Hydrogenation of 20f: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel OD (0.46×25 cm), hex-
ane(98)/EtOH(2), flow 1.0 mLmin, T = 25 °C, t (1st enantiomer)
= 12.16 min, t (2nd enantiomer) = 13.45 min.
J = 8.5 Hz, H at δC = 128.59), 7.99 (d, J = 9.0 Hz, H at δC
=
128.66), 8.06 (d, J = 9.0 Hz, H at δC = 130.85), 8.17 (d, J = 9.0 Hz,
H at δC = 125.71) ppm. 13C NMR (CDCl3, 125 MHz), additional
quaternary C’s: d 124.50, 125.00, 127.71, 131.31, 131.92, 132.89,
133.20, 141.35, 142.24, 144.13, 149.12, 150,28 ppm. 31P NMR
(CDCl3, 121 MHz): δ = –5.85 (d, JP,P = 195.5 Hz, P-3), 166.85 (P-
2) ppm.
Hydrogenation of 20g: Determination of conversion by 1H NMR
spectroscopy and ee by HPLC: Chiralcel AD (0.46×25 cm), hex-
Table 2. Crystallographic data for compounds 14 and [(14)-
Rh(COD)]BF4.
(R,R)-4-{3-[(2S,5S)-Dimethylphospholan-1-yl]benzo[b]thiophen-2-
yl}-3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-aЈ]dinaphthalene (19b):
This compound was prepared in exactly the same way as described
for compound 19 using (R,R)-binaphthol. 31P NMR (CDCl3,
121 MHz): δ = –2.83 (d, JP,P = 194.3 Hz, P-3), 166.23 (P-2) ppm.
Complex
14
[(14)Rh(COD)BF4]
Empirical formula
Formula weight
Crystal size [mm]
Crystal habit
Crystal system
Space group
a [Å]
C24H36P2S
418.53
0.8×0.4×0.4
fragment of rod
orthorhombic
P212121
9.1657(16)
11.778(2)
21.711(4)
2343.8(7)
1.186
C32H48BF4P2RhS
716.46
0.60×0.15×0.15
trigonal prism
trigonal
Hydrogenation Reactions: Substrates 20a, 20b, 22 and 24 were ob-
tained from commercial sources and used as received. Substrates
20e, 20f,[28c] 20g[32] and 23[33] were prepared as previously reported.
Substrate 20c was obtained by the Wittig–Horner olefination[34a]
of p-nitrobenzaldehyde with N-(benzyloxycarbonyl)trimethylphos-
phonoglycine[34b] in 75% yield. Substrate 20d was obtained follow-
ing a reported procedure[35a] from the ketone oxime and its spectral
properties were as reported.[35b]
P32
10.3398(12)
b [Å]
c [Å]
26.290(3)
2434.1(5)
1.47
V [Å3]
D [gcm–1
]
Z
4
3
Diffractometer
T [K]
Bruker APEX CCD
183
NONIUS CAD4
223
Typical Procedure: A 10-mL Schlenk flask with a magnetic stirring
bar was charged with the respective catalyst. The Schlenk flask was
evacuated and flushed with argon three times. Then the degassed
solvent (3 mL) was added and the catalyst dissolved. Substrate 20
was transferred into a 25 mL Schlenk flask, which was purged by
three cycles vacuum/argon flushing, and then dissolved in the sol-
vent (3 mL). The catalyst and substrate solutions were transferred
sequentially into a thermostatted stainless-steel autoclave (50 mL)
equipped with a magnetic stirring bar under argon. The autoclave
was submitted to a hydrogen pressure (10 bar) and the pressure
released. After three cycles, the pressure and temperature were set
to the described level and 20 min later magnetic stirring was
started. After 17 h the autoclave was cooled to ambient tempera-
ture and the pressure released. The resulting solution was evapo-
rated under reduced pressure (rotavapor, max. bath temp. 40 °C) to
Wavelength [Å]
µ(Mo-Kα) [mm–1
θ range [°]
0.71073
0.282
2.4–28.3
0.71073
0.734
2.3–26.0
]
Index range (h, k, l)
Refl. collected
Rint
Unique refl. in refin.
Refl. with I Ͼ 2σ(I)
Param. refined
–12/12, –15/15, –28/27 –11/12, –12/2, –32/32
28259
0.0319
5822
5595
248
12526
0.1202
6356
5388
374
R1 [refl. with I Ͼ 2σ(I)] 0.0290
0.0393
0.0759
0.0952
–0.01(3)
1.045
R1 (all data)
0.0305
wR2 (all data)
Flack param.
0.0728
–0.04(5)
1.072
Goodness of fit
Diff. peak/hole [eÅ–3
]
–0.19/0.32
–1.43/1.35
Eur. J. Org. Chem. 2006, 2100–2109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2107

U. Berens, U. Englert, S. Geyser, J. Runsink, A. Salzer
FULL PAPER
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22.5 min
[9]
Hydrogenation of 24: Determination of conversion and ee by
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Acknowledgments
The authors wish to gratefully acknowledge financial support from
the Deutsche Forschungsgemeinschaft DFG within the Collabora-
tive Research Centre (SFB, 380): “Asymmetric Synthesis with
Chemical and Biological Methods”. We also wish to thank Daniel
Sprenger and Oliver Dosenbach from Ciba for their skilful support,
Dr. Martin Kesselgruber and Reto Kellerhals (Solvias) for commu-
nicating preparative details of ligand 14a and Dr. Felix Spindler
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2108
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2100–2109

Bidentate P,P Ligands as Highly Efficient Ligands for Asymmetric Catalysis
FULL PAPER
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Eur. J. Org. Chem. 2006, 2100–2109
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2109