Synthesis of a new class of chiral 1,5-diphosphanylferrocene ligands and their use in enantioselective hydrogenation

Article abstract of DOI:10.1002/1521-3765(20020215)8:4<843::AID-CHEM843>3.0.CO;2-9

A new family of ferrocenylphosphane ligands has been prepared. Their flexible synthesis allows many structural modifications. The asymmetric induction of these ligands was examined in the hydrogenation of functionalized C=C, C=O, and C=N bonds. The enantioselectivity of the reaction was strongly dependent on the substituent R at the position α to the ferrocene moiety. In many cases, both enantiomeric β-hydroxyesters of the reduction product can be obtained by simply replacing a dimethylamino group in the ligand with a methyl group.

Full text of DOI:10.1002/1521-3765(20020215)8:4<843::AID-CHEM843>3.0.CO;2-9

FULL PAPER
Synthesis of a New Class of Chiral 1,5-Diphosphanylferrocene Ligands and
Their Use in Enantioselective Hydrogenation
[b]
[a]
[c]
[a]
Tania Ireland, Katja Tappe, Gabi Grossheimann, and Paul Knochel*
Abstract: A new family of ferrocenylphosphane ligands has been prepared. Their
flexible synthesis allows many structural modifications. The asymmetric induction of
these ligands was examined in the hydrogenation of functionalized CˆC, CˆO, and
CˆN bonds. The enantioselectivity of the reaction was strongly dependent on the
substituent R at the position a to the ferrocene moiety. In many cases, both
enantiomeric b-hydroxyesters of the reduction product can be obtained by simply
replacing a dimethylamino group in the ligand with a methyl group.
Keywords: asymmetric catalysis ¥
ferrocene ¥ hydrogenation ¥ iron ¥
metallocenes ¥ ligands
Introduction
Although few examples of efficient chiral 1,5-diphosphanes
are known,[ we envisioned that the partial rigidity of the
diphosphane backbone of 1 should allow good transfer of
chiral information. Furthermore, the ligand structure should
be easily optimizable by introducing various R groups at the
a-position of the ferrocene unit or by modifying the electronic
properties of the phosphane moieties. Here we report on the
synthesis of phosphanes 1 and their application in enantiose-
lective hydrogenation.
4]
Asymmetric catalysis is a powerful tool for producing
enantiomerically enriched compounds. In particular, asym-
metric hydrogenations can be conducted on large scale
without producing intrinsic by-products by using hydrogen
as a cheap reducing agent.[ Many chiral phosphanes proved
to give excellent activities and enantioselectivities in several
1]
[1, 2]
metal-catalyzed hydrogenations.
However, since careful
matching of the chiral ligand, the reaction type, the catalyst,
and the substrate is usually necessary, there is still a demand
for easily accessible, air-stable chiral diphosphanes whose
structure allows convenient modification of steric and elec-
tronic properties. Their synthesis must be highly flexible to
allow simple fine-tuning and
Results and Discussion
Ligand design: The phosphanes 1 are readily prepared in five
steps starting from ferrocene (Scheme 1). Friedel ± Crafts
acylation of ferrocene with 2-bromobenzoyl chloride furnish-
ed the ketone 2 in 80% yield. Corey ± Bakshi ± Shibata (CBS)
rapid optimization of ligand ±
substrate matches. We recently
described a new class of chiral
1,5-diphosphanylferrocene li-
gands of type 1 that have these
characteristics.[
3]
[
a] Prof. Dr. P. Knochel, K. Tappe
Department Chemie, Ludwig-Maximilians Universit‰t M¸nchen
Butenandtstrasse 5-13, 81377 M¸nchen (Germany)
Fax : (‡49)89-2180-7680
E-mail: Paul.Knochel@cup.uni-muenchen.de
Scheme 1. Synthesis of the phosphanes 1. a) CBS catalyst (0.3 equiv),
BH ¥ Me S, 0 8C, 2 h; b) Ac O, pyridine, 12 h; c) HNR R , CH CN or THF,
3 2 2 3
[
b] Dr. T. Ireland
1
2
RHODIA Recherches, Centre de Recherche de Lyon
Groupe Catalyse 85
avenue des Fr e¡ res Perret, 69192 Saint Fons (France)
Fax : (‡33)4-72-89-68-90
c] Dr. G. Grossheimann
Bayer AG, IS-SSS-HLS, Geb. 2978
H
ClPR
2
O, 12 h; d) tBuLi (3.5 equiv), À788C to room temperature, 1 h; then
3
2
(2.5 equiv).
[
reduction of the ketone 2 afforded the corresponding alcohol
5]
3
in 95% yield and 96% ee.[ The alcohol 3 was obtained in
5
1368 Leverkusen (Germany)
almost enantiomerically pure form (99.5% ee) after recrys-
tallization from heptane. Acylation of 3 gave quantitatively
the intermediate acetate, which was converted to the corre-
Supporting information for this article (NMR spectra of the ferrocenyl
compounds) is available on the WWW under http//wiley-vch.de/home/
chemistry/ or from the author.
Chem. Eur. J. 2002, 8, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0843 $ 17.50+.50/0
843

P. Knochel et al.
FULL PAPER
sponding ferrocenylamine 4 with retention of configuration
to ferrocene by substituting the amino group with organozinc
reagents. This substitution is known to proceed with retention
of the configuration. Thus, reaction of the ferrocenylamine 5
[6]
by treatment with an amine. Finally, diastereoselective
dilithiation[ of the amine 4 followed by reaction with a
chlorophosphane gave the corresponding diphosphane 1. This
flexible synthetic pathway allowed us to easily introduce
7]
[8]
with Me Zn or iPr Zn in the presence of acetyl chloride as a
2
2
promoter led to the products 7a,b in 70 ± 83% yield with high
retention of configuration (d.r. ˆ 94:6). Finally, double bro-
mine ± lithium exchange by reaction of 6, 7a, and 7b with
nBuLi followed by quenching with ClPPh2 afforded the
phosphanes 1k, 1l, and 1m in 75, 92, and 31% yield,
respectively (Scheme 2). Steric hindrance due to the isopropyl
substituent might explain the low yield of 1m, and mixtures of
monophosphanes were identified as side products.
The highly flexible synthesis of the ferrocenylphosphanes 1
allowed us to rapidly modify the ligand structure. The
influence of substituents on the phosphorus atom and in the
position a to ferrocene on the ligand properties, as well as the
efficiency and selectivity of these ligands were examined in
asymmetric catalysis.
1
2
3
various substituents R , R , and R . Variations of the
phosphorus and nitrogen substituents of the ligands 1 are
summarized in Table 1.
Table 1. Variations of the phosphorus and the nitrogen substituents of the
ligands of type 1.
1
2
R3
Ph
(3,5-xylyl)
Ph
R R N-
2
P-
P-
Product 4 [%] Product 1 Yield [%]
Me
Me
CH
2
2
N-
N-
2
4a
P- 4a
4b
90 1a
90 1b
94 1c
99 1d
77 1e
98 1 f
93 1g
90 1 h
90 1i
88 1j
88
33
64
41
58
41
62
53
46
36
2
(
(
(
2
CH
2
)
2
N-
2
2
2
2
2
2
2
2
P-
P-
P-
P-
P-
P-
P-
P-
R)-PhCH(Me)MeN- Ph
S)-PhCH(Me)MeN- Ph
4c
4d
4e
4 f
Me
Et N-
nPr N-
nBu N-
iBu N-
2
NCH
2
CH
2
MeN- Ph
2
Ph
Ph
Ph
Ph
2
4g
4 h
4i
Enantioselective hydrogenation of CˆC bonds: Rhodium-
catalyzed asymmetric hydrogenation of a-(acylamino)acrylic
2
2
Variation of the phosphorus sub-
3
stituents: Different PR were in-
2
troduced by dilithiation of the
ferrocenylamine 4a followed by
treatment with ClPPh or ClP(3,5-
2
xylyl) to give 1a and 1b in about
2
8
0 and 30% yield, respectively, for
two steps. The moderate yield of
b is probably due to the steric
1
hindrance of the xylyl substituents
on the phosphorus atoms.
Variation of the nitrogen substitu-
1
ents: Different substituents R
2
and R on the nitrogen atom were
introduced by straightforward
substitution of the intermediate
acetate with various amines. Thus,
the diphosphanes 1c ± j bearing
alkyl, cyclic, functionalized, and
chiral amino groups at the posi-
tion a to the ferrocene moiety
Scheme 2. Synthesis of the diphosphanes 1k ± m. a) tBuLi (3.5 equiv), À788C to room temperature, 1 h; then
Cl Br (2.2 equiv), 1 h; b) Et SiH (10 equiv), TFA, room temperature, 72 h; c) CH COCl (2 equiv), R Zn
4
2
C
2
3
3
2
(4 equiv), THF, À788C to room temperature, 12 h; d) nBuLi 2.2 equiv), À788C, 15 min; then ClPPh
2
(2.3 equiv), À788C to room temperature, 1 H. TFA ˆ trifluoroacetic acid.
were prepared in moderate to good yields depending on the
steric bulk of the amine (see Table 1).
acids and esters to produce the corresponding amino acid
derivatives has been extensively studied[ and affords a good
starting point for comparing the effectiveness of a new chiral
ligand.[ Asymmetric hydrogenation of a-acetamidocinnam-
ic acid (8a) and its methyl ester 8b (Scheme 3) was performed
9]
10]
Introduction of hydrogen and alkyl substituents at the
position a to ferrocene: To investigate further the influence
of the stereocenter at the position a to ferrocene on the ligand
properties, the diphosphane 1k bearing no substituent and
1
l,m bearing alkyl substituents were prepared. The amine 4a
was dilithiated in situ with tBuLi and treated with Cl Br C to
4
2
2
give the dibrominated product 5 as a single diastereomer in
0% yield. Reduction of the benzylic amino group of 5 with
8
triethylsilane in trifluoroacetic acid gave the deaminated
product 6 in 57% yield and 97% ee. Starting from the amine
Scheme 3. Rhodium-catalyzed asymmetric hydrogenation of a-acetamido-
cinnamic acid (8a) and its methyl ester 8b with the 1,5-diphosphane ligands
1a ± m. nbd ˆ norbornadiene.
5
, alkyl substituents were readily introduced at the position a
844
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0844 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 4

Chiral Phosphanylferrocenes
843±852
in MeOH or MeOH/toluene (1/1) with 1 mol% of the catalyst
Table 3. Hydrogenation of dimethyl itaconate 10.
Entry Ligand Solvent Pressure Reaction Conversion ee
prepared in situ from [Rh(nbd) ]BF (1 mol%) and the ligand
2
4
[bar]
time [h] [%][
a]
[%][a]
(
1 mol%). The results are summarized in Table 2.
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1 f
1k
1l
MeOH
EtOH
MeOH/Tol
MeOH
MeOH
MeOH
MeOH
MeOH/Tol
MeOH
1
1
1
1
1
1
10
1
1
14
17
14
16
1.5
20
3
quant.
0
quant.
91
quant.
0
quant.
quant.
quant.
91 (S)
±
81 (S)
74 (S)
98.2 (S)
±
75 (S)
19 (R)
97.9 (S)
Table 2. Hydrogenation of a-acetamidocinnamic acid derivatives 8a,b.
Entry Ligand Substrate Solvent
Pressure Reaction Conversion ee
time [h] [%][
a]
[%][a]
[bar]
[
[
[
b]
b]
b]
[c]
1
2
3
4
5
6
7
8
9
0
1
1a
1c
1k
1a
1c
1d
1e
1f
8a
8a
8a
MeOH
MeOH
MeOH
MeOH/Tol. 1
MeOH/Tol. 5
MeOH/Tol. 1
MeOH/Tol. 1
MeOH/Tol. 1
1
1
5
14
21
1
0.5
3
17
83 (R)
rac.
traces
quant.
quant.
quant.
90
quant.
traces
90
1
4
76 (R)
95 (R)
92 (R)
70 (R)
95 (R)
±
77 (R)
52 (S)
96.6 (R)
1m
8b
8b
8b
8b
8b
8b
8b
8b
[
a] Determined by 1H NMR spectroscopy. [b] Determined by HPLC
analysis (Daicel Chiracel OD). [c] No conversion was observed using
bar of hydrogen pressure.
16
1
1.5
20
2.5
0.6
4
1k
1l
1m
MeOH
MeOH
MeOH/Tol. 1
5
1
Enantioselectivities of up to 98.2% (Table 3, entry 5) were
obtained with 1e. The same trend as described above was
observed for the influence of the ligand structure on the
enantioselectivity of the reaction.
1
1
quant.
quant.
[
a] Determined by GC analysis (Chirasil l-Val). [b] The hydrogenation
product 9a was esterified with trimethylsilyldiazomethane before the GC
Enol esters and enamides are interesting substrates for
asymmetric hydrogenation since the reduction products can
be easily converted to optically active alcohols or amines.
Hydrogenation of the enol ester 12 with ligand 1a afforded
the acetate 13 with 72% ee (Scheme 4). Hydrogenation of the
enamide 14 afforded the amide 15 in 68% ee with ligand 1a
and 76% ee with ligand 1c (Scheme 5). Unlike the preceeding
examples, use of the pyrrolidyl-substituted ligand 1c led to
better enantioselectivities than with 1a, and this confirms the
importance of ligand ± substrate matching.
measurements.
Although poor activities and moderate enantioselectivities
were observed for the hydrogenation of the free acid 8a
(
Table 2, entries 1 ± 3), hydrogenation of (Z)-methyl a-
acetamidocinnamate (8b) proceeded smoothly to give reduc-
tion product 9b with enantioselectivities of up to 96.6% with
the isopropyl-substituted ligand 1m (Table 2, entry 11). The
substituent in the position a to the ferrocene moiety appeared
to play an essential role in the efficiency of the ligand and the
enantioselectivity of the reaction. Using the phosphane 1k
without a substituent in the a position gave 9b with only
77% ee, and a hydrogen pressure of 5 bar was necessary
(
Table 2, entry 9), whereas 9b was obtained in 95% ee with
the dimethylamino-substituted ligand 1a (Table 2, entry 4).
Surprisingly, 9b with the opposite configuration was obtained
with the methyl-substituted ligand 1l (Table 2, entry 10).
Replacing the dimethylamino group (1a) by a pyrrolidyl
substituent (1c) led to a slight decrease in the activity and
enantioselectivity of the reaction (Table 2, entry 5). Of special
interest is the marked difference in the enantioselectivity and
reactivity for 1d and 1e (Table 2, entries 6 and 7), which bear
chiral amino substituents with opposite configurations. An
internal cooperativity exists between the stereocenter at the
position a to the ferrocene moiety and that of the N-methyl-
N-phenylethyl substituent, analogous to the principle of
matched and mismatched (external cooperativity) introduced
Scheme 4. Hydrogenation of the enol ester 12 with the ligand 1a.
Scheme 5. Hydrogenation of the enamide 14 with ligands 1a and 1c.
[
11]
by Masamune et al. No hydrogenation occurred with the
ligand 1 f bearing a second coordination site (Table 2,
entry 8). The enantioselectivities obtained for the hydro-
genation of 8b are quite encouraging since they are com-
parable with those described in the literature with known
ligands.[
Enantioselective hydrogenation of CˆO bonds: The ferroce-
nylphosphanes of type 1 are also highly efficient for the
ruthenium-catalyzed asymmetric hydrogenation of various
1,3-ketoesters (Scheme 6).[
1, 10]
All the ruthenium-catalyzed
hydrogenation reactions were performed with 0.5 mol% of
the catalyst formed in situ from [Ru(cod)(C H ) ]/HBr (™Ru∫,
12]
4
7 2
Ligands 1 proved to be also very efficient for the rhodium-
catalyzed hydrogenation of dimethyl itaconate (10). Hydro-
genation of 10 was performed in MeOH or MeOH/toluene (1/
cod ˆ 1,5-cyclooctadiene; 0.5 mol%) and the ligand
(0.5 mol%).[ The results obtained for the hydrogenation
of various 1,3-ketoesters 16 are summarized in Table 4.
Whereas the reduction product 17a was obtained with the
same configuration with 1a, 1k, or 1m, the a-hydroxyester
17a with the opposite configuration was obtained with 1l
13]
1) under 1 bar of hydrogen pressure with 1 mol% of the
catalyst prepared in situ from [Rh(nbd) ]BF (1 mol%) and
2
4
the ligand (1 mol%). The results are summarized in Table 3.
Chem. Eur. J. 2002, 8, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0845 $ 17.50+.50/0
845

P. Knochel et al.
FULL PAPER
Table 4. Hydrogenation of various 1,3-ketoesters.
Entry Substrate[a] Ligand Temp
8C]
50
Time Conversion ee
[h]
[
[%][
b]
[%][c]
1
16a
16a
16a
16a
16b
16b
16b
16b
16b
16b
16b
16b
16b
16b
16c
16c
16c
16c
16d
16d
16e
16e
16 f
16 f
16 f
16 f
1a
1k
1l
14
quant.
quant.
quant.
quant.
quant.
quant.
90
96.3 (R)
78 (R)
86 (S)
93.3 (R)
95.5 (R)
93.4 (R)
84 (R)
2
3
4
5
6
7
8
9
room temperature 10
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
8
9
8
17
9
16
15
19
16
19
6
9
12
9
8
8
9
10
12
10
23[
22
17
8
1m
1a
Scheme 6. Ruthenium-catalyzed asymmetric hydrogenation of the 1,3-
ketoesters 16a ± f.
[d]
1b
1d
1e
1g[
[
d]
quant.
quant.
quant.
quant.
quant.
75
59 (R)
d]
84.6 (R)
76.9 (R)
70.4 (R)
98.6 (S)
69 (S)
[
d]
(
Table 4, entry 3). Similarly, both enantiomers of 17b ± f could
10
11
1 h
1i[
1j[
1l
d]
be obtained by using either 1a or 1l. These results are
consistent with those obtained previously for the hydro-
genation of CˆC bonds. Remarkably, whereas changing the
d]
12
13
14
15
1m
1a
1d
1l
1m
1a
1l
1a
1l
1a
1d
1e
1l
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
quant.
82
95.9 (R)
95.0 (S)
86.0 (S)
93.7 (R)
96.0 (S)
96.5 (R)
92.7 (S)
95.9 (R)
96.5 (S)
75 (S)
substituents on the nitrogen atom from methyl to propyl led to
a decrease in enantioselectivity for the reduction of 16b
16
17
18
19
20
(
Table 4, entries 5, 9 ± 11), ligand 1j bearing a diisobutylamino
group in the position a to ferrocene gave the reduction
product 17b with the opposite configuration and 98.6% ee
(
Table 4, entry 12). Reduction of the chloromethyl-substitut-
21
22
ed a-ketoester 16 f led to the corresponding a-hydroxyester
e]
23
24
25
26
17 f with moderate enantioselectivities (Table 4, entries 23 ±
74 (S)[
d]
quant.
quant.
quant.
26). Lower enantioselectivities for the reduction of 16 f were
79 (S)[
46 (R)
d]
also observed by Burk et al. (76% ee) with the DuPHOS
ligand.[ Higher reaction rates and better enantioselectivities
for the hydrogenation of 16a with ligand 1a were obtained by
increasing the hydrogen pressure from 10 to 100 bar (10 bar:
14]
[
[
a] MeOH was used as a solvent for methylesters and EtOH for ethylester.
b] Determined by H NMR spectroscopy. [c] Determined by HPLC
1
analysis (Daicel Chiracel OD). [d] ™Ru™: 0.8 mol%, ligand 0.9 mol%.
[e] Reaction performed at 908C in CH Cl
16 h, 95.6% ee; 100 bar: 1 h, 96.9% ee). It is noteworthy that
2
2
.
the reduction of 16b could be
performed with a substrate/cat-
alyst ratio of 5000 to give
the a-hydroxyester 17b with
93.2% ee in 62 h.
Hydrogenation was also suc-
cessful for cyclic ketoesters
such as ethyl 2-oxocyclopenta-
necarboxylate (18; Scheme 7
and Table 5) and ethyl 2-oxo-
Scheme 7. Ruthenium-catalyzed hydrogenation of ethyl 2-oxocyclopentanecarboxylate (18) with the 1,5-
diphosphane ligands 1a, 1b, and 1l.
cyclohexanecarboxylate
Scheme 8 and Table 6). De-
pending on the ligand
(20;
1
and the reaction conditions,
high diastereoselectivities and
enantioselectivities were ob-
served for the hydrogenation
of 18 (Table 5, entries 1 and 4).
Although poor diastereoselec-
tivities were observed for the
Scheme 8. Ruthenium-catalyzed hydrogenation of ethyl 2-oxocyclohexanecarboxylate (20).
Table 5. Hydrogenation of ethyl 2-oxocyclopentanecarboxylate 18.
Entry[a]
Ligand
Solvent
Temp.
8C]
Time
[h]
de
[%][
ee
[%]
b,c]
[d]
[
1
2
3
4
1a
1a
1b
1l
EtOH/CH
EtOH
EtOH
2
Cl
2
(1/10)
50
50
50
63
22
16
21
98.2
67
38.3
90.5
90.9 (1R,2R)
[c]
81 (1R,2R)
51.7 (1R,2R)[
91.6 (1S,2S)
c]
EtOH
room temperature
[
[
a] Results determined after complete conversion. [b] The major diastereomer is the anti product. [c] Determined by HPLC analysis (Daicel Chiracel OD).
d] 0.8 mol% ™Ru∫, 0.9 mol% ligand.
846
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0846 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 4

Chiral Phosphanylferrocenes
843±852
Table 6. Hydrogenation of ethyl 2-oxocyclohexanecarboxylate 20.
Entry[a]
Ligand
Time
h]
de
[%][
ee [%][c]
of syn-21
ee [%][c]
of anti-21
b,c]
[
1
2
3
4
5
1a
1b
1d
1e
1l
63
19
24
24
31
11
96.5 (1S,2R)
89.6 (1R,2R)
> 99 (1R,2R)[
c]
c]
c]
84.6
79.7
41.1
6
> 99 (1S,2R)
> 99 (1S,2R)
99.5 (1S,2R)
82.7 (1R,2S)
[
> 99 (1R,2R)
> 99 (1R,2R)[
Scheme 10. Hydrogenation of unsymmetrical 1,3-diketone 26.
50.8 (1R,2R)
[
a] Results determined after complete conversion. [b] In both cases the anti
diastereomer was the major product. [c] Determined by HPLC analysis
Daicel Chiracel OD). [d] 0.8 mol% ™Ru∫, 0.9 mol% ligand.
hydrazones.[16] These substrates have the advantage of pos-
sessing a second coordination site. Hydrogenation of various
(
N-benzoylhydrazones 28a ± c (Scheme 11) was performed in
reduction of 20 with 1a and 1l, the anti product 21 was
obtained with up to 84.6% de and greater than 99% ee with
the bulkier ligands 1b and 1d (Table 6, entries 2 and 3).
Hydrogenation of the a-ketoester 22 with ligand 1a (in
CH Cl for 65 h) or with ligand 1l (in EtOH/CH Cl 10/1 for
2
2
2
2
31 h) led after complete conversion to the a-hydroxyester 23
not only with the opposite topicity but also with the opposite
diastereoselectivity (Scheme 9).
Hydrogenation
of
symmetrical
1,3-diketones
RCˆOCH CˆOR 24 (a: R ˆ Me; b: R ˆ Ph) under the same
2
reaction conditions led to the corresponding diols
RC(OH)CH C(OH)R 25 (a: R ˆ Me; b: R ˆ Ph) with high
2
Scheme 11. Hydrogenation of the N-benzoylhydrazones 30a ± c.
diastereoselectivities in favor of the anti products and with
high enantioselectivities (up to 98.9% de and 98.8% ee;
Table 7, entry 5).
MeOH in the presence of 1 mol% of the catalyst prepared in
High diastereoselectivities and enantioselectivities were
also obtained in the hydrogenation of the unsymmetrical 1,3-
situ from [Rh(nbd) ]BF (1 mol%) and 1 (1 mol%). The
2
4
results are summarized in Table 8.
Moderate
enantioselectivities
were generally observed with all
ligands 1. Surprisingly, the best
enantioselectivity was obtained with
the unsubstituted ligand 1k (Table 8,
entry 9). Furthermore, the methyl-
substituted ligand 1l gave 29a,b with
the same configuration that was
obtained with the other ligands,
and 29c with the opposite configu-
Scheme 9. Hydrogenation of ethyl 2-methyl-3-oxobutyrate (22).
Table 7. Hydrogenation of symmetrical 1,3-diketones of type 24.
Table 8. Hydrogenation of the N-benzoylhydrazones 28a ± c.
Entry
Substrate
Ligand
Time
h]
de
[%][
ee
[%]
Entry
Substrate
Ligand
Pressure
[bar]
Conversion
[%]
ee
[%]
a,b]
[b]
[a]
[
1
2
3
4
5
24a: R ˆ Me
24a
24a
1a
1l
1m
1a
1l
8
8
9
8
95.9
84.0
94.4
98.0
98.9
96.7 (R,R)
78.0 (S,S)
98.6 (R,R)
98.2 (S,S)
98.8 (R,R)
1
2
3
4
5
6
7
8
9
28a
28a
28a
28a
28a
28b
28b
28b
28b
28b
28c
28c
28c
28c
28c
1a
1b
1c
1k
1l
30
30
10
30
30
30
50
10
30
30
50
50
50
30
30
71
quant.
53
quant.
quant.
90
quant.
32
> 95
quant.
53
quant.
59
86
41 (S)
21.7 (S)
36 (S)
53 (S)
43 (S)
57 (S)
28.7 (S)
56 (S)
65 (S)
45 (S)
b
24b: R ˆ Ph
24b
12
1a
1b
[
a] The major diastereomer is the anti product. [b] Determined by GC
[b,c]
(
Chirasil-DexCB) or HPLC analysis (Daicel Chiracel OD).
1c
1k[
1l
1a
1b[
1c
1k
1l
d]
diketone 26 (Scheme 10). Once again, both enantiomers of
the anti-diol 27 could be obtained by using ligands 1a or 1l.
10
[
e]
1
1
1
1
1
2
3
4
65 (À)
b]
[e]
15,2 (À)
[
e]
67 (À)
8 (À)
Enantioselective hydrogenation of CˆN bonds: Preparation
of optically pure amines by catalytic asymmetric hydrogena-
tion of imines is still a challenging task, although promising
methodologies have been developed.[ The efficiency of the
ligands 1 was first examined for the hydrogenation of
[e]
e]
[
15
> 95
17 (‡)
[
0
a] Determined by HPLC analysis (Daicel Chiracel OJ). [b] [Rh(cod)
.8 mol%, ligand 0.8 mol%. [c] 408C, 14 h. [d] EtOH was used as solvent.
[e] The absolute configuration of 29c has not been determined yet.
2 4
]BF
15]
Chem. Eur. J. 2002, 8, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0847 $ 17.50+.50/0
847

P. Knochel et al.
FULL PAPER
ration. The results obtained for the hydrogenation of 28c are
somewhat different. Ligand 1c led to the hydrazine 29c with
the best enantioselectivity (Table 8, entry 13), and 1l gave
hydrazine 29c with the opposite configuration (Table 8,
entry 15). Ligand ± substrate matching appears to be even
more important for the hydrogenation of CˆN bonds than for
CˆO or CˆC bonds.
elemental analysis (%) calcd for C17
found: C 55.12, H 3.77.
H
13BrFeO (369.0): C 55.33, H 3.55;
Synthesis of (R)-(a-hydroxy-o-bromophenylmethyl)ferrocene (3): Ketone
(4.00 g, 10.80 mmol) was dissolved in THF (20 mL) and treated with
BH ¥ SMe (1m in THF, 11 mL, 11 mmol) and CBS catalyst (0.90 g,
2
3
2
3
.25 mmol, 0.3 equiv) in THF (10 mL) according to the procedure
[5a]
described in the literature (addition time: 2 h, reaction time: 30 min).
Chromatography (pentane/MTBE 4/1) of the crude product afforded the
alcohol 2 (3.80 g, 10.26 mmol, 95% yield, 96 ± 97% ee) as an orange solid:
m.p. 718C. Recrystallization from heptane gave the alcohol in enantiomeri-
2
0
cally pure form. [a]ꢀkap†dꢀ=kap† ˆ À159.7 (c ˆ 0.41 in CHCl
heptane/iPrOH 92/8, 0.6 mL/min): t
/min ˆ 15.9 (R), 18.4 (S); H NMR
200 MHz, CDCl
, 258C, TMS): d ˆ 7.65 ± 7.07 (m, 4H), 5.81 (s, 1H), 4.41
(m, 1H), 4.26 (s, 5H), 4.20 (m, 1H), 4.16 (m, 2H), 2.74 (s, 1H); C NMR
50 MHz, CDCl
3
); HPLC (OD,
Conclusion
1
r
(
3
1
3
In summary, we have developed a new family of ferrocenyl
phosphanes 1 whose synthesis is highly flexible and offers
many possibilities for variation. This allowed us to rapidly
modify the structure of phosphanes 1 to optimize ligand ±
substrate matching. Ligands 1 proved to be very efficient
ligands and led to excellent enantioselectivities in the hydro-
genation of various functionalized double bonds and 1,3-
dicarbonyl compounds. Furthermore, the two opposite con-
figurations of the reduced products could be obtained by
merely modifying the substituent in the position a to the
ferrocene moiety.
(
3
, 258C): d ˆ 142.4, 132.5, 128.8, 127.8, 127.4, 122.3, 93.6,
‡ ‡
7
3
5
0.2, 68.4, 68.1, 67.7, 67.5, 66.2; MS: m/z (%): 372 (21) [M‡1] , 371 (4) [M] ,
‡
70 (22) [M À 1] ; elemental analysis (%) calcd for C17
H15BrFeO (371.1): C
5.03, H 4.07; found: C 54.86, H 3.95.
Synthesis of (R)-[a-(N,N-dimethylamino)-o-bromophenylmethyl]ferro-
cene (4a): Alcohol 3 (3.50 g, 9.43 mmol) was treated with acetic anhydride
(2 mL) and pyridine (5 mL), and the solution was stirred for 12 h at room
temperature. Volatile matter was removed in vacuo. The crude acetate was
dissolved in acetonitrile (50 mL) and treated with dimethylamine (40% in
H
2
O, 16 mL) at room temperature overnight. The reaction mixture was
then concentrated and poured into saturated aqueous NH Cl and extracted
with diethyl ether. After conventional workup, the crude product was
purified by chromatography (pentane/Et O 4/1 to pure Et O) to give the
amine 4a (3.56 g, 8.96 mmol, 95% yield) as an orange solid. M.p. 738C;
4
2
2
2
0
1
[
2
a]ꢀkap†dꢀ=kap† ˆ À72.8 (c ˆ 1.02 in CHCl
3 3
); H NMR (300 MHz, CDCl ,
Experimental Section
58C, TMS): d ˆ 7.73 ± 7.70 (m, 1H), 7.64 ± 7.61 (m, 1H), 7.39 ± 7.31 (m, 1H),
7.16 ± 7.06 (m, 1H), 4.47 (s, 1H), 4.25 ± 4.24 (m, 1H), 4.20 ± 4.19 (m, 1H),
General: Melting points are uncorrected. NMR spectra were recorded at
room temperature in CDCl on Bruker ARX 200, AC 300, AM 400 or
3
13
4
.16 ± 4.14 (m, 1H), 4.11 ± 4.09 (m, 1H), 3.76 (s, 5H), 2.07 (s, 6H); C NMR
(
75 MHz, CDCl
3
, 258C): d ˆ 142.9, 132.3, 129.5, 128.1, 127.1, 124.8, 89.7,
‡ ‡
AMX 500 instruments. Chemical shifts are given relative to the residual
solvent peak. Signals of the minor diastereomer that differ from those of
the major isomer are given for sake of comparison. Optical rotations were
measured on a Perkin Elmer 241 polarimeter. IR spectra were recorded on
a Nicolet 510 FT-IR spectrometer. Electron impact (EI) mass spectra were
recorded on a Varian CH 7A. Enantiomeric excesses were determined by
HPLC analysis (Chiralcel OD and OJ columns, Daicel Chemical Industries
with n-heptane/2-propanol as mobile phase and detection by a diode array
UV/Vis detector) or by GC analysis (Chirasil-DEX CB or Chiralsil-l-Val
columns, Chrompak, with hydrogen as carrier gas). Racemic compounds
were used to choose the operating conditions for the resolution of the
enantiomer and diastereomer peaks. Organic layers were dried over
7
3
5
0.6, 68.5, 68.3, 66.1, 44.0; MS: m/z (%): 399 (62) [M‡1] , 398 (15) [M] ,
‡
97 (64) [M À 1] ; elemental analysis (%) calcd for C19
H20BrFeN (398.1): C
7.32, H 5.06, N 3.52; found: C 57.03, H 5.37, N 3.43.
Synthesis of (R)-[a-(1-pyrrolidyl)-o-bromophenylmethyl]ferrocene (4b):
After acetylation of the alcohol 3 (1.20 mmol), the resulting acetate was
treated with pyrrolidine (0.5 mL, 6.0 mmol, 5 equiv) in acetonitrile (15 mL)
and H
Et O 3/1 to pure Et
.13 mmol, 94% yield) was obtained as an orange solid. M.p. 838C;
2
O (2.5 mL) as described above. After chromatography (pentane/
2
2
O) of the crude product, the amine 4b (0.48 g,
1
2
0
1
[
2
a]ꢀkap†dꢀ=kap† ˆ À59.7 (c ˆ 1.03 in CHCl
3 3
); H NMR (300 MHz, CDCl ,
58C, TMS): d ˆ 7.81 ± 7.78 (m, 1H), 7.64 ± 7.61 (m, 1H), 7.38 ± 7.31 (m, 1H),
7.15 ± 7.12 (m, 1H), 4.49 (s, 1H), 4.25 ± 4.23 (m, 2H), 4.16 ± 4.13 (m, 1H),
anhydrous MgSO
6
2
4
. Column chromatography was carried out on silica gel
0 (70 ± 230 mesh, ASTM). Hydrogenations were performed in 100 or
00 mL stainless steel autoclaves or in a Schlenk tube with a hydrogen-
4
.10 ± 4.08 (m,1H), 3.84 (s, 5H), 2.37 ± 2.27 (m, 4H), 1.69 ± 1.65 (m, 4H);
1
3
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 143.8, 132.4, 130.0, 128.1, 127.3,
1
24.1, 90.8, 70.2, 68.6, 68.3, 67.3, 66.08, 66.1, 53.3, 23.2; MS: m/z (%): 425
filled balloon for the reactions under 1 bar pressure.
‡
‡
‡
(
42) [M‡1] , 424 (13) [M] , 423 (45) [M À 1] ; elemental analysis (%)
calcd for C21 22BrFeN (424.2): C 59.47, H 5.23, N 3.30; found: C 59.22, H
.21, N 3.58.
Materials: Tetrahydrofuran (THF), diethyl ether, methyl tert-butyl ether
H
(
MTBE), and toluene were distilled from sodium/benzophenone; CH
2 2
Cl
5
was distilled from CaH ; acetone from CaCl ; and MeOH and iPrOH were
2
2
Synthesis of (R)-[a-{(R)-N-methyl-1-phenylethylamino}-o-bromophenyl-
methyl]ferrocene (4c): After acetylation of the alcohol 3 (1.35 mmol), the
resulting acetate was treated with (R)-N-methyl-1-phenylethylamine
distilled from Mg turnings. Pyridine was dried over KOH. Commercial
reagents were used without further purification. The following starting
materials were prepared according to literature procedures:
[
17]
[2a]
(0.6 mL, 4.1 mmol, 3.0 equiv) in acetonitrile (18 mL) and H O (2.5 mL)
[
{Rh(nbd)Cl}
2
],
[Rh(nbd)
2
]BF
4
,
(S,S)-diphenylprolinolmethyloxaza-
2
[
18]
as described above. After conventional workup and removal of the solvent
and the excess reagents in vacuo, the pure amine 4c (657 mg, 1.35 mmol,
borolidine (CBS catalyst).
Synthesis of o-bromobenzoylferrocene (2): A solution of aluminum(iii)
chloride (7.88 g, 59.10 mmol) and o-bromobenzoyl chloride (12.40 g,
9
9.8% yield) was obtained as an orange oil. Purification of the crude
product by column chromatography on silica gel led to decomposition.
7
.40 mL, 56.51 mmol) in CH
2
Cl
2
(50 mL) was added dropwise to a solution
Cl (50 mL) at 08C. The mixture
2
0
1
[
a]ꢀkap†dꢀ=kap† ˆ ‡227 (c ˆ 0.48 in CHCl
3 3
); H NMR (300 MHz, CDCl , 258C,
of ferrocene (10.00 g, 53.75 mmol) in CH
2
2
TMS): d ˆ 8.21 ± 8.13 (m, 1H), 7.82 ± 7.79 (m, 1H), 7.66 ± 7.26 (m, 7H), 5.13
was warmed to room temperature and stirred for 2 h. Hydrolysis was then
performed at 08C by addition of ice-cold water. The reaction mixture was
diluted with CH Cl and washed twice with saturated aqueous K CO .
2 2 2 3
After conventional workup, the crude product was purified by chromatog-
(
3
s, 1H), 4.45 ± 4.43 (m, 2H), 4.35 ± 4.33 (m, 1H), 4.29 ± 4.28 (m, 1H), 4.02 ±
1
3
.94 (m, 6H), 1.94 (s, 3H), 1.51 (d, J ˆ 6.8 Hz, 3H); C NMR (75 MHz,
, 258C): d ˆ 144.2, 143.9, 132.5, 129.9, 128.3, 127.7, 127.5, 126.2, 124.9,
0.5, 71.1, 68.7, 68.7, 68.5, 66.4, 66.1, 64.1, 56.4, 32.8, 10.2; MS: m/z (%): 489
CDCl
3
9
raphy (pentane/MTBE 4/1) to give the ketone 2 (16.09 g, 43.60 mmol, 81%
‡
‡
‡
1
(29) [M‡1] , 488 (10) [M] , 487 (30) [M À 1] .
yield) as a dark red solid. M.p. 1028C; H NMR (300 MHz, CDCl
3
, 258C,
TMS): d ˆ 7.64 ± 7.61 (m, 1H), 7.52 ± 7.45 (m, 1H), 7.42 ± 7.26 (m, 2H), 4.73 ±
Synthesis of (R)-[a-{(S)-N-methyl-1-phenylethylamino}-o-bromophenyl-
methyl]ferrocene (4d): After acetylation of the alcohol 3 (1.48 mmol), the
resulting acetate was treated with (S)-N-methyl-1-phenylethylamine
1
3
4
.71 (m, 2H), 4.59 ± 4.58 (m, 2H), 4.29 (s, 5H); C NMR (75 MHz, CDCl
3
,
2
58C): d ˆ 199.4, 141.3, 133.4, 130.8, 128.7, 126.7, 119.5, 78.2, 72.9, 71.1, 70.1;
‡
‡
‡
MS: m/z (%): 370 (100) [M‡1] , 369 (56) [M] , 368 (98) [M À 1] ;
(0.65 mL, 4.50 mmol, 3 equiv) in acetonitrile (20 mL) and H
2
O (2.7 mL)
848
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 0947-6539/02/0804-0848 $ 17.50+.50/0 Chem. Eur. J. 2002, 8, No. 4

Chiral Phosphanylferrocenes
843±852
as described above. Filtration of the reaction mixture and drying of the
precipitate afforded the amine 4d (558 mg, 1.43 mmol, 77% yield) as an
orange solid. Purification of the crude product by column chromatography
elemental analysis (%) calcd for C25
2.90, Br 16.57; found: C 62.34, H 6.69, N 2.87, Br 16.46.
H
32BrFeN (482.3): C 62.26, H 6.69, N
Synthesis of (R)-[a-(N,N-diisobutylamino)-o-bromophenylmethyl]ferro-
cene (4i): After acetylation of the alcohol 3 (2.70 mmol), the resulting
2
0
on silica gel led to decomposition. M.p. 1358C; [a]ꢀkap†dꢀ=kap† ˆ À39.8 (c ˆ
1
0
7
1
.47 in CHCl
3
); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.78 (dd, J ˆ
acetate was dissolved in THF (10 mL) and H
diisobutylamine (2.36 mL, 13.52 mmol, 5 equiv) as described above. After
chromatography (pentane/Et O 4/1) of the crude product, the amine 4i
1.15 g, 2.38 mmol, 88% yield) was obtained as an orange solid. M.p. 77 ±
2
O (10 mL) and treated with
.8, 1.7 Hz, 1H), 7.56 (dd, J ˆ 8.0, 1.0 Hz, 1H), 7.37 ± 7.03 (m, 7H), 4.84 (s,
H), 4.19 ± 4.17 (m, 2H), 4.07 ± 4.06 (m, 1H), 4.02 ± 4.01 (m, 1H), 3.80 (q,
2
1
3
J ˆ 6.8 Hz, 1H), 3.68 (s, 5H), 1.70 (s, 3H), 1.12 (d, J ˆ 6.8 Hz, 3H); C NMR
75 MHz, CDCl
, 258C): d ˆ 144.0, 143.9, 132.6, 130.0, 128.2, 127.9, 127.7,
27.4, 126.2, 125.1, 90.5, 70.6, 68.7, 68.5, 66.5, 66.2, 64.4, 55.7, 33.2, 11.8; MS:
(
7
(
1
3
20
1
88C; [a]ꢀkap†dꢀ=kap† ˆ À10.1 (c ˆ 1.11 in CHCl
, 258C, TMS): d ˆ 7.56 (dd, J ˆ 8.0, 1.2 Hz, 1H), 7.38 (dd, J ˆ 7.7,
.7 Hz, 1H), 7.22 (td, J ˆ 7.5, 1.0 Hz, 1H), 7.04 (td, J ˆ 7.6, 1.5 Hz, 1H), 5.41
s, 1H), 4.45 ± 4.44 (m, 1H), 4.06 ± 4.05 (m, 1H), 3.98 ± 3.97 (m, 1H), 3.94 (s,
3
); H NMR (300 MHz,
CDCl
1
(
3
‡
‡
‡
m/z (%): 489 (43) [M‡1] , 488 (30) [M] , 487 (45) [M À 1] ; elemental
analysis (%) calcd for C26
C 63.90, H 5.46, N 2.83.
H26BrFeN (488.2): C 64.06, H 5.38, N 2.88; found:
5
0
H), 3.84 ± 3.83 (m, 1H), 2.01 ± 1.98 (m, 4H), 1.65 (sept, J ˆ 6.7 Hz, 2H),
13
.79 (d, J ˆ 6.5 Hz, 6H), 0.69 (d, J ˆ 6.6 Hz, 6H); C NMR (75 MHz,
, 258C): d ˆ 140.5, 133.1, 131.7, 128.7, 126.7, 89.8, 71.1, 69.1, 69.0, 67.6,
Synthesis of (R)-[a-{N-methyl(2-N ,' N'-dimethylamino)ethylamino}-o-bro-
mophenylmethyl]ferrocene (4e): After acetylation of the alcohol
1.35 mmol), the resulting acetate was treated with N,N,N'-trimethylethy-
lenediamine (0.77 mL, 6.73 mmol, 5 equiv) in acetonitrile (18 mL) and
CDCl
4.2, 60.2, 27.5, 21.4, 21.1; MS: m/z (%): 483 (14) [M‡1] , 481 (16) [M À 1] ;
elemental analysis (%) calcd for C25 32BrFeN (482.3): C 62.26, H 6.69, N
.90, Br 16.57; found: C 62.26, H 6.65, N 2.84, Br 16.18.
3
3
‡
‡
6
(
H
2
H
1
2
O (2.5 mL) as described above. After chromatography (pentane/Et
2
O 3/
to Et O with 2% NEt ) of the crude product, the amine 4e (601 mg,
2
3
Synthesis of 1-(S )-diphenylphosphanyl-2-[(R)-a-(N,N-dimethylamino)-o-
Fc
2
0
1
(
7
.32 mmol, 98% yield) was obtained as an orange oil. [a]ꢀkap†dꢀ=kap† ˆ À33.4
c ˆ 1.07 in CHCl ); H NMR (300 MHz, CDCl , 258C, TMS): d ˆ 7.62 ±
.53 (m, 2H), 7.32 ± 7.23 (m, 1H), 7.10 ± 7.00 (m, 1H), 4.70 (s, 1H), 4.21 ± 4.20
m, 1H), 4.07 ± 4.02 (m, 3H), 3.74 (s, 5H), 2.37 ± 2.16 (m, 4H), 2.02 (s, 6H),
, 258C): d ˆ 142.6, 132.5, 129.9,
28.2, 127.1, 125.2, 89.6, 70.7, 68.6, 68.2, 67.3, 66.8, 66.5, 57.3, 52.5, 45.7, 40.1;
diphenylphosphanylphenylmethyl]ferrocene (1a): The amine 4a (502 mg,
1
3
3
1.26 mmol) was dissolved in Et O (5 mL) under argon and cooled to
2
À788C. Then tBuLi (1.45m in pentane, 3.05 mL, 4.41 mmol, 3.5 equiv) was
(
1
added dropwise. The mixture was warmed to room temperature and stirred
.98 (s, 3H); 13C NMR (75 MHz, CDCl
for 1 h at room temperature. ClPPh (0.58 mL, 3.15 mmol, 2.5 equiv) was
3
2
1
then added dropwise at À788C, and the mixture was stirred for 1 h at room
‡
‡
‡
MS: m/z (%): 456 (10) [M‡1] , 455 (10) [M] , 454 (9) [M À 1] ; elemental
temperature. After hydrolysis and conventional workup, the crude product
analysis (%) calcd for C22
H
27BrFeN
2
(455.2): C 58.05, H 5.98, N 6.15; found:
was purified by flash chromatography (pentane/Et O 5/1) to give the
2
C 57.81, H 5.88, N 6.27.
phosphane 4a (763 mg, 1.11 mmol, 88% yield) as an orange solid. M.p.
2
0
1
8
2
1
2
1
4
48C; [a]ꢀkap†dꢀ=kap† ˆ ‡297 (c ˆ 1.06 in CHCl
3 3
); H NMR (300 MHz, CDCl ,
58C, TMS): d ˆ 7.52 ± 7.42 (m, 2H), 7.32 ± 6.66 (m, 22H), 6.00 (d, J ˆ
Synthesis of (R)-[a-(N,N-diethylamino)-o-bromophenylmethyl]ferrocene
4 f): After acetylation of the alcohol 3 (2.60 mmol), the resulting acetate
was dissolved in THF (10 mL) and H O (8 mL) and treated with N,N-
diethylamine (1.4 mL, 13.2 mmol, 5 equiv) as described above. After
chromatography (pentane/Et O 4/1) of the crude product, the amine 4 f
1.00 g, 2.50 mmol, 93% yield) was obtained as an orange oil.
(
0.1 Hz, 1H), 4.54 (s, 1H), 4.28 ± 4.26 (m, 1H), 3.87 (s, 1H), 3.82 (s, 5H),
2
1
3
.02 (s, 6H); C NMR (75 MHz, CDCl
3
, 258C): d ˆ 146.93 (d, J ˆ 24.3 Hz),
39.46 ± 126.42 (m), 98.47 (d, J ˆ 24.7 Hz), 73.21 (d, J ˆ 14 Hz), 71.46 (d, J ˆ
2
3
1
.5 Hz), 71.17 (d, J ˆ 5.4 Hz), 70.14, 68.63, 64.55 ± 64.07 (m), 43.17;
P
(
NMR (81 MHz, CDCl
3
, 258C): d ˆ À16.7 (d, J ˆ 19.1 Hz), À23.2 (d, J ˆ
2
0
); 1H NMR (300 MHz, CDCl
[
2
a]ꢀkap†dꢀ=kap† ˆ À24.9 (c ˆ 1.51 in CHCl
3
3
,
‡
1
9.1 Hz); MS: m/z (%): 687 (37) [M] ; elemental analysis (%) calcd for
58C, TMS): d ˆ 7.63 (d, J ˆ 7.5 Hz, 1H), 7.54 (dd, J ˆ 8.0, 1.2 Hz, 1H), 7.28
43 2
C H39FeNP (687.6): C 75.11, H 5.72, N 2.04; found: C 74.87, H 5.64, N 1.97.
(
t, J ˆ 7.3 Hz, 1H), 7.05 (td, J ˆ 7.6, 1.5 Hz, 1H), 4.92 (s, 1H), 4.21 ± 4.20 (m,
Synthesis of 1-(SFc)-bis(3,5-xylyl)phosphanyl-2-[(R)-a-(N,N-dimethylami-
no)-o-bis(3,5-xylyl)phosphanylphenylmethyl]ferrocene (1b): The amine
1
H), 4.07 ± 4.02 (m, 3H), 3.71 (s, 5H), 2.35 (q, J ˆ 7.0 Hz, 4H), 0.80 (t, J ˆ
.1 Hz, 6H); 1 C NMR (75 MHz, CDCl
3
7
1
3
, 258C): d ˆ 144.2, 132.9, 130.6,
4
a (1.00 g, 2.50 mmol) in Et
pentane, 7.4 mL, 12.6 mmol, 3.5 equiv) and ClP(3,5-xylyl)2 (2.42 g,
.73 mmol, 2.5 equiv) according to the procedure described for 1a. After
flash chromatography (pentane/Et O 4/1), the diphosphane 1b (0.65 g,
.82 mmol, 33% yield) was obtained as an orange solid. M.p. 84 ± 858C;
2
O (12 mL) was treated with tBuLi (1.5m in
28.5, 127.6, 125.6, 91.0, 71.0, 69.1, 68.5, 67.3, 66.6, 63.7, 43.2, 11.7; MS: m/z
‡
‡
(
%): 427 (31) [M‡1] , 425 (34) [M À 1] ; elemental analysis (%) calcd for
8
21
C H
24BrFeN (426.2): C 59.18, H 5.68, N 3.29; found: C 59.00, H 5.69, N
3
.13.
2
0
Synthesis of (R)-[a-(N,N-di-n-propylamino)-o-bromophenylmethyl]ferro-
cene (4g): After acetylation of the alcohol 3 (3.20 mmol), the resulting
20
1
[
2
5
a]ꢀkap†dꢀ=kap† ˆ ‡208.8 (c ˆ 1.09 in CHCl
3 3
); H NMR (300 MHz, CDCl ,
58C, TMS): d ˆ 7.35 ± 6.45 (m, 12H), 6.38 (s, 1H), 6.18 ± 6.16 (m, 2H),
acetate was dissolved in THF (11 mL) and H
n-propylamine (2.2 mL, 16.04 mmol, 5 equiv) as described above. After
chromatography (pentane/Et O 4/1) of the crude product, the amine 4g
1.29 g, 2.84 mmol, 90% yield) was obtained as an orange oil.
2
O (9 mL) and treated with di-
.81 ± 5.78 (m, 1H), 4.30 (s, 1H), 4.08 (s, 1H), 3.72 (s, 1H), 3.65 (s, 5H), 2.06
13
(
s, 7H), 1.99 (s, 12H), 1.86 (s, 5H), 1.79 (s, 6H); C NMR (75 MHz, CDCl
3
,
2
2
1
1
58C): d ˆ 137.7 (d, J ˆ 7.3 Hz), 137.4 (d, J ˆ 8.7 Hz), 136.8 (d, J ˆ 12.7 Hz),
36.7 (d, J ˆ 7.3 Hz), 135.2, 133.4 (d, J ˆ 24.6 Hz), 132.3 (d, J ˆ 3.7 Hz),
32.1 (d, J ˆ 3.7 Hz), 131.9 (d, J ˆ 20.9 Hz), 130.9 ± 130.1 (m), 129.2, 74.7 (d,
(
2
0
1
[
2
a]ꢀkap†dꢀ=kap† ˆ À6.9 (c ˆ 1.54 in CHCl
3 3
); H NMR (300 MHz, CDCl ,
58C, TMS): d ˆ 7.55 ± 7.51 (m, 2H), 7.25 (t, J ˆ 7.4 Hz, 1H), 7.08 ± 7.02
31
J ˆ 15.1 Hz), 72.1, 71.4, 70.5, 43.6, 21.8, 21.5; P NMR (81 MHz, CDCl
3
,
(
m, 1H), 5.11 (s, 1H), 4.27 (s, 1H), 4.03 (s, 2H), 3.97 (s, 1H), 3.80 (s, 5H),
2
58C): d ˆ À16.9 (d, J ˆ 16.6 Hz), À23.7 (d, J ˆ 16.6 Hz); MS: m/z (%): 799
‡
1
3
2
2
6
1
.36 ± 2.19 (m, 4H), 0.66 (t, J ˆ 7.4 Hz, 6H); C NMR (75 MHz, CDCl
3
,
(
34) [M] ; elemental analysis (%) calcd for C51
2
H54FeNP (798.8): C 76.98,
58C): d ˆ 143.2, 132.9, 131.0, 128.5, 127.2, 125.9, 90.7, 70.9, 69.1, 68.2, 67.9,
H 6.84, N 1.80; found: C 77.17, H 7.16, N 1.62.
‡
6.9, 64.1, 52.1, 20.6, 12.2; MS: m/z (%): 455 (71) [M‡1] , 453 (78) [M À
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-(1-pyrrolidyl)-o-diphe-
nylphosphanylphenyl)methyl]ferrocene (1c): The amine 4b (335 mg,
‡
] ; elemental analysis (%) calcd for C23
H
28BrFeN (454.2): C 60.82, H 6.21,
N 3.08, Br 17.59; found: C 60.91, H 6.25, N 3.02, Br 17.28.
0
.81 mmol) in Et
1.96 mL, 2.84 mmol, 3.5 equiv) and ClPPh
according to the procedure described for 1a. After flash chromatography
(pentane/Et O 5/1), the diphosphane 1c (370 mg, 0.52 mmol, 64% yield)
2
O (15 mL) was treated with tBuLi (1.45m in pentane,
Synthesis of (R)-[a-(N,N-di-n-butylamino)-o-bromophenylmethyl]ferro-
cene (4h): After acetylation of the alcohol 3 (4.06 mmol), the resulting
2
(0.37 mL, 2.02 mmol, 2.5 equiv)
acetate was dissolved in THF (14 mL) and H
di-n-butylamine (3.4 mL, 20.3 mmol, 5 equiv) as described above. After
chromatography (pentane/Et O 4/1) of the crude product, the amine 4h
1.76 g, 3.65 mmol, 90% yield) was obtained as an orange oil.
2
O (11 mL) and treated with
2
2
0
was obtained as an orange solid. M.p. 948C; [a]ꢀkap†dꢀ=kap† ˆ ‡232 (c ˆ 1.14 in
1
2
CHCl
3
); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.72 ± 7.64 (m, 1H),
(
7.59 ± 7.52 (m, 2H), 7.37 ± 6.76 (m, 21H), 6.10 ± 5.84 (m, 1H), 4.62 ± 4.52 (m,
1H), 4.30 (s, 1H), 3.92 (s, 1H), 3.78 (s, 5H), 2.50 ± 2.32 (m, 4H), 1.38 ± 1.10
(m, 4H); C NMR (75 MHz, CDCl
2
0
); 1H NMR (300 MHz, CDCl
[
2
a]ꢀkap†dꢀ=kap† ˆ À14.2 (c ˆ 1.47 in CHCl
3
3
,
1
3
58C, TMS): d ˆ 7.53 (d, J ˆ 8.0 Hz, 2H), 7.25 (t, J ˆ 7.6 Hz, 1H), 7.07 ± 7.01
3
, 258C): d ˆ 148.6 (d, J ˆ 25 Hz),
(
m, 1H), 5.06 (s, 1H), 4.25 ± 4.24 (m, 1H), 4.03 ± 4.02 (m, 2H), 3.99 (s, 1H),
139.4 ± 126.1 (m), 99.3 (d, J ˆ 23 Hz), 76.4, 72.4 (d, J ˆ 14.9 Hz), 71.1 (d, J ˆ
3
1
3
0
1
2
.78 (s, 5H), 2.28 ± 2.21 (m, 4H), 1.27 ± 1.20 (m, 4H), 1.14 ± 1.03 (m, 4H),
3
4.5 Hz), 69.7, 68.1, 62.5 (m), 51.5, 22.9; P NMR (81 MHz, CDCl , 258C):
1
3
.73 (t, J ˆ 7.2 Hz, 6 H) ; C NMR (75 MHz, CDCl
3
, 258C): d ˆ 143.4, 132.9,
d ˆ À17.1 (d, J ˆ 20.3 Hz), À22.4 (d, J ˆ 20.3 Hz); MS: m/z (%): 713 (62)
‡
30.9, 128.5, 127.3, 125.8, 111.2, 90.8, 71.0, 69.1, 68.3, 67.8, 66.8, 64.1, 50.1,
[M] ; elemental analysis (%) calcd for C45
H
41FeNP
2
(713.6): C 75.74, H
‡
‡
9.4, 20.9, 17.9, 14.5; MS: m/z (%): 483 (52) [M‡1] , 481 (56) [M À 1] ;
5.79, N 1.96; found: C 75.61, H 5.97, N 1.68.
Chem. Eur. J. 2002, 8, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0849 $ 17.50+.50/0
849

P. Knochel et al.
FULL PAPER
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-{N-(R)-methyl-1-phe-
nylethylamino}-o-diphenylphosphanylphenylmethyl]ferrocene (1d): The
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-(N,N-di-n-propylami-
no)-o-diphenylphosphanylphenylmethyl]ferrocene (1h): The amine 4g
amine 4c (500 mg, 1.02 mmol) in Et
(
2
2
O (10 mL) was treated with tBuLi
1.35m in pentane, 2.60 mL, 3.57 mmol, 3.5 equiv) and ClPPh (0.47 mL,
.55 mmol, 2.5 equiv) according to the procedure described for 1a. After
(706 mg, 1.55 mmol) in Et
pentane, 3.6 mL, 5.4 mmol, 3.4 equiv) and ClPPh
2.2 equiv) according to the procedure described for 1a. After flash
chromatography (pentane/Et O 4/1 and pentane/Et
O ˆ 20/1), the diphos-
2
O (10 mL) was treated with tBuLi (1.5m in
2
2
(0.61 mL, 3.42 mmol,
flash chromatography (pentane/Et
2
O 25/1 with 2% Et
3
N), the diphosphane
2
2
1
1
d (325 mg, 0.48 mmol, 41% yield) was obtained as an orange solid. M.p.
phane 1h (375 mg, 0.83 mmol, 53% yield) was obtained as a bright orange
058C; [a]ꢀ2 k0 ap†dꢀ=kap† ˆ ‡227 (c ˆ 0.48 in CHCl
); H NMR (300 MHz,
1
solid. M.p. 159 ± 1608C; [a]ꢀkap†dꢀ=kap† ˆ ‡315.3 (c ˆ 1.15 in CHCl
20
1
3
3
); H NMR
CDCl
3
, 258C, TMS): d ˆ 8.09 ± 7.91 (m, 1H), 7.60 ± 7.45 (m, 2H), 7.40 ± 6.75
(300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.45 ± 7.41 (m, 2H), 7.30 ± 7.17 (m,
(
m, 26H), 6.19 (d, J ˆ 10.6 Hz, 1H), 4.48 ± 4.47 (m, 1H), 4.24 ± 4.22 (m, 1H),
.03 ± 3.93 (m, 2H), 3.56 (s, 5H), 1.75 (s, 3H), 0.80 (d, J ˆ 6.6 Hz, 3H);
3
13H), 6.95 ± 6.85 (m, 4H), 6.74 (t, J ˆ 6.9 Hz, 3H), 6.62 (td, J ˆ 7.4, 1.0 Hz,
1H), 6.52 (d, J ˆ 11.0 Hz, 1H), 6.44 (t, J ˆ 7.0 Hz, 1H), 4.66 (s, 1H), 4.31 ±
4.29 (m, 1H), 3.95 (s, 1H), 3.84 (s, 5H), 2.46 ± 2.39 (m, 2H), 2.34 ± 2.25 (m,
4
1
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 150.2 (d, J ˆ 27.1 Hz), 144.3, 135.5 ±
1
6
26.0 (m), 101.5 (d, J ˆ 26.1 Hz), 72.6 (d, J ˆ 15.9 Hz), 71.9 ± 71.7 (m), 69.9,
2H), 1.23 ± 1.19 (m, 2H), 1.07 ± 1.00 (m, 2H), 0.59 (t, J ˆ 7.3 Hz, 6H);
3
1
13
8.6, 63.1 (d, J ˆ 23.8 Hz), 56.4, 35.7 (d, J ˆ 1.5 Hz), 16.1 (d, J ˆ 5.4 Hz);
, 258C): d ˆ À18.0 (d, J ˆ 17.8 Hz), À23.4 (d, J ˆ
7.8 Hz); elemental analysis (%) calcd for C50 45FeNP (777.7): C 77.22, H
.83, N 1.80; found: C 76.87, H 5.74, N 1.60.
P
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 148.2 (d, J ˆ 28.9 Hz), 140.4 (d, J ˆ
NMR (81 MHz, CDCl
1
5
3
12.9 Hz), 139.7 (d, J ˆ 11.7 Hz), 138.2 (d, J ˆ 11.1 Hz), 136.0 ± 132.7 (m),
H
2
129.1, 128.5 ± 126.6 (m), 99.8 (d, J ˆ 24.7 Hz), 73.0 (d, J ˆ 14.5 Hz), 72.2 ±
3
1
72.0 (m), 70.4, 68.8, 54.4, 22.8, 12.1; P NMR (81 MHz, CDCl
3
, 258C): d ˆ
‡
À17.0 (d, J ˆ 17.4 Hz), À25.1 (d, J ˆ 17.4 Hz); MS: m/z (%): 743 (10) [M] ;
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-{N-(S)-methyl-1-phenyl-
ethylamino}-o-diphenylphosphanylphenylmethyl]ferrocene (1e): The
elemental analysis (%) calcd for C47
.88; found: C 75.63, H 6.40, N 1.82.
2
H47FeNP (743.7): C 75.91, H 6.37, N
1
amine 4d (1.20 g, 2.46 mmol) in Et
(
5
2
O (15 mL) was treated with tBuLi
1.57m in pentane, 5.0 mL, 7.8 mmol, 3.2 equiv) and ClPPh (1.0 mL,
.4 mmol, 2.2 equiv) according to the procedure described for 1a. After
O 25/1 with 2% Et N), the diphosphane
2
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-(N,N-di-n-butylamino)-
o-diphenylphosphanylphenyl)methyl]ferrocene (1i): The amine 4h
flash chromatography (pentane/Et
2
3
(687 mg, 1.42 mmol) in Et
pentane, 3.3 mL, 5.0 mmol, 3.6 equiv) and ClPPh
2.2 equiv) according to the procedure described for 1a. After flash
chromatography (pentane/Et 20/1), the diphosphane 1i (509 mg,
0.66 mmol, 46% yield) was obtained as a bright orange solid. M.p. 68 ±
2
O (10 mL) was treated with tBuLi (1.5m in
1
1
e (1.11 g, 1.43 mmol, 58% yield) was obtained as an orange solid. M.p.
2
(0.56 mL, 3.13 mmol,
04 ± 1088C; [a]ꢀ2 k0 ap†dꢀ=kap† ˆ ‡261 (c ˆ 0.5 in CHCl
1
3
); H NMR (300 MHz,
CDCl
3
, 258C, TMS): d ˆ 7.46 ± 7.45 (m, 2H), 7.32 ± 6.92 (m, 20H), 6.90 ± 6.61
2
O
(
(
m, 6H), 6.58 ± 6.49 (m, 2H), 5.27 ± 5.06 (m, 1H), 4.82 (brs, 1H), 4.39 ± 4.38
2
0
1
m, 1H), 4.00 (s, 1H), 3.74 (s, 5H), 1.59 (s, 3H), 1.41 (d, J ˆ 6.6 Hz, 3H);
698C; [a]ꢀkap†dꢀ=kap† ˆ ‡300.1 (c ˆ 1.23 in CHCl
3
); H NMR (300 MHz,
1
3
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 148.6 (d, J ˆ 26.1 Hz), 145.9, 139.9 ±
CDCl
3
, 258C, TMS): d ˆ 7.48 ± 7.39 (m, 4H), 7.30 ± 7.17 (m, 11H), 6.95 ± 6.85
1
7
2
25.9 (m), 97.9 (d, J ˆ 26.4 Hz), 72.7 (d, J ˆ 16.0 Hz), 71.4 (d, J ˆ 4.0 Hz),
(m, 4H), 6.79 ± 6.74 (m, 3H), 6.62 (td, J ˆ 7.4, 1.2 Hz, 1H), 6.51 ± 6.44 (m,
2H), 4.63 (s, 1H), 4.30 ± 4.29 (m, 1H), 3.95 (s, 1H), 3.82 (s, 5H), 2.53 ± 2.43
(m, 2H), 2.36 ± 2.28 (m, 2H), 1.18 ± 0.9 (m, 8H), 0.69 (t, J ˆ 7.0 Hz, 6H);
3
1
3
1.0 (br), 70.1, 69.1, 60.7 (br), 59.6, 33.5, 19.9; P NMR (81 MHz, CDCl ,
58C): d ˆ À18.3 (d, J ˆ 31.2 Hz), À23.3 (d, J ˆ 31.2 Hz); elemental
1
3
analysis (%) calcd for C50
C 76.91, H 6.29, N 1.97.
H
45FeNP
2
(777.7): C 77.22, H 5.83, N 1.80; found:
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 148.4 (d, J ˆ 28.8 Hz), 140.4 (d, J ˆ
12.9 Hz), 139.7 (d, J ˆ 10.3 Hz), 138.0 ± 133.9 (m), 132.8 (d, J ˆ 19.4 Hz),
1
6
31.1, 129.0 ± 126.6 (m), 73.0 (d, J ˆ 14.4 Hz), 72.1 (d, J ˆ 4.7 Hz), 70.4,
31
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-{N-methyl(2-N ,' N'-dime-
thylamino)ethylamino}-o-diphenylphosphanylphenylmethyl]ferrocene
3.2 ± 62.8 (m), 52.3, 32.0, 20.9, 14.6; P NMR (81 MHz, CDCl
3
, 258C): d ˆ
‡
À17.0 (d, J ˆ 16.8 Hz), À25.0 (d, J ˆ 16.8 Hz); MS: m/z (%): 771 (11) [M] ;
(
1 f): The amine 4e (170 mg, 0.37 mmol) in Et
tBuLi (1.56m in pentane, 0.8 mL, 1.3 mmol, 3.5 equiv) and ClPPh
.9 mmol, 2.5 equiv) according to the procedure described for 1a. After
2
O (2 mL) was treated with
elemental analysis (%) calcd for C49
2
H51FeNP (771.7): C 76.26, H 6.66, N
2
(0.2 mL,
1.81; found: C 75.68, H 6.60, N 1.63.
0
flash chromatography (Et
2
O with 3% Et
3
N), the diphosphane 1 f (132 mg,
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-(N,N-diisobutylamino)-
o-diphenylphosphanylphenylmethyl]ferrocene (1j): The amine 4i (603 mg,
2
0
0
.18 mmol, 48% yield) was isolated as an orange solid. [a]ꢀkap†dꢀ=kap†
ˆ
1
‡
232.4 (c ˆ 0.45 in CHCl
3
); H NMR (300 MHz, CDCl
3
, 258C, TMS):
1.25 mmol) in Et
2.9 mL, 4.4 mmol, 3.5 equiv) and ClPPh
according to the procedure described for 1a. After flash chromatography
2
O (10 mL) was treated with tBuLi (1.5m in pentane,
d ˆ 7.55 ± 7.44 (m, 2H), 7.35 ± 7.18 (m, 12H), 7.00 ± 6.58 (m, 10H), 6.29 (d,
2
(0.49 mL, 2.75 mmol, 2.2 equiv)
J ˆ 10.6 Hz, 1H), 4.51 (brs, 1H), 4.32 (brs, 1H), 3.95 (brs, 1H), 3.86 (s, 5H),
2
.62 ± 2.57, (m, 2H), 2.27 (s, 3H), 2.09 ± 1.93 (m, 7H), 1.74 ± 1.62 (m, 1H);
C NMR (75 MHz, CDCl
(pentane/Et
2
O 20/1), the diphosphane 1j (346 mg, 0.45 mmol, 36% yield)
1
3
20
3
, 258C): d ˆ 147.5 (d, J ˆ 26.5 Hz), 139.9 ± 126.3
was obtained as a bright orange solid. M.p. 84 ± 858C; [a]ꢀkap†dꢀ=kap† ˆ ‡366.3
1
(
(
(
m), 98.6 (d, J ˆ 25.2 Hz), 73.2 (d, J ˆ 14.2 Hz), 71.5 (d, J ˆ 4.8 Hz), 71.2
(c ˆ 1.05 in CHCl
3
); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.69 ±
3
1
m), 70.1, 68.6, 64.7 (dd, J ˆ 24.5 and 6.8 Hz), 58.2, 52.9, 45.7, 39.9; P NMR
81 MHz, CDCl
, 258C): d ˆ À16.8 (d, J ˆ 14.0 Hz), À24.0 (d, J ˆ 14.0 Hz);
(744.7): C 74.19, H 6.23, N
.76; found: C 73.84, H 6.10, N 3.56, HRMS: calcd 744.2485; found
44.2496.
7.63 (m, 2H), 7.33 ± 7.17 (m, 13H), 7.02 ± 6.87 (m, 4H), 6.72 ± 6.50 (m, 5H),
6.23 (t, J ˆ 7.0 Hz, 1H), 5.03 (s, 1H), 4.30 (s, 1H), 3.93 ± 3.92 (m, 1H), 3.82
(s, 5H), 2.25 ± 2.09 (m, 4H), 1.75 ± 1.70 (m, 2H), 0.88 (d, J ˆ 6.5 Hz, 6H),
3
2 2
elemental analysis (%) calcd for C46H46FeN P
3
7
1
3
0.55 (d, J ˆ 6.5 Hz, 6H); C NMR (75 MHz, CDCl , 258C): d ˆ 46.7 (d, J ˆ
3
27.1 Hz), 140.2 ± 138.9 (m), 136.0 ± 134.7 (m), 134.0 (d, J ˆ 17.9 Hz), 132.8 (d,
J ˆ 18.9 Hz), 132.1, 128.6 ± 126.7 (m), 99.1 (d, J ˆ 25.8 Hz), 72.9 ± 72.4 (m),
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[(R)-a-(N,N-diethylamino)-o-
diphenylphosphanylphenylmethyl]ferrocene (1g): The amine 4 f (685 mg,
3
1
7
0.5, 68.7, 62.9 (d, J ˆ 30.2 Hz), 60.6, 27.7, 21.5 (d, J ˆ 15.1 Hz); P NMR
(
81 MHz, CDCl
3
, 258C): d ˆ À16.6 (d, J ˆ 14.1 Hz), À26.6 (d, J ˆ 14.2 Hz);
1
3
.61 mmol) in Et
.8 mL, 5.6 mmol, 3.5 equiv) and ClPPh
according to the procedure described for 1a. After flash chromatography
pentane/Et O 4/1), the diphosphane 1g (0.71 g, 0.99 mmol, 62% yield) was
2
O (10 mL) was treated with tBuLi (1.5m in pentane,
‡
MS: m/z (%): 771 (10) [M] ; elemental analysis (%) calcd for C49
H
51FeNP
2
2
(0.63 mL, 3.5 mmol, 2.2 equiv)
(
771.7): C 76.26, H 6.66, N 1.81; found: C 75.77, H 6.76, N 1.72.
Synthesis of 1-(SFc)-bromo-2-[(R)-a-(N,N-dimethylamino)-o-bromophe-
nylmethyl]ferrocene (5): The amine 4a (270 mg, 0.68 mmol) in Et
(3 mL) was treated with tBuLi (1.45m in pentane, 1.65 mL, 2.39 mmol,
3.5 equiv) and C Br Cl (487 mg, 1.49 mmol, 2.2 equiv) in Et O (2 mL)
according to the procedure described for 1a. After flash chromatography
(
2
2
0
obtained as an orange solid. M.p. 206 ± 2078C; [a]ꢀkap†dꢀ=kap† ˆ ‡296.3 (c ˆ
2
O
1
1.21 in CHCl
3
); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.50 ± 7.47 (m,
2
H), 7.35 ± 7.18 (m, 13H), 6.95 ± 6.86 (m, 5H), 6.81 ± 6.75 (m, 2H), 6.66 (td,
2
2
4
2
J ˆ 7.4, 1.4 Hz, 1H), 6.59 ± 6.54 (m, 1H), 6.45 (d, J ˆ 10.6 Hz, 1H), 4.56 (s,
1
H), 4.31 ± 4.29 (m, 1H), 3.95 (s, 1H), 3.80 (s, 5H), 2.65 ± 2.54 (m, 2H),
(pentane/Et
2
O 5/1), the amine 4a (260 mg, 0.54 mmol, 80% yield, 97.5%
1
3
20
2
2
1
3
.41 ± 2.29 (m, 2H), 0.68 (t, J ˆ 7.0 Hz, 6H); C NMR (75 MHz, CDCl
3
,
ee) was obtained as an orange solid. M.p. 848C; [a]ꢀkap†dꢀ=kap† ˆ ‡125.5 (c ˆ
58C): d ˆ 148.7 (d, J ˆ 27.1 Hz), 140.4 ± 139.6 (m), 138.0 (d, J ˆ 12.1 Hz),
36.2 ± 135.7 (m), 134.4 (d, J ˆ 19.5 Hz), 134.1 (d, J ˆ 4.2 Hz), 133.9 (d, J ˆ
.9 Hz), 132.8 (d, J ˆ 18.9 Hz), 131.2, 129.1 128.6 ± 127.4 (m), 126.6, 100.0 (d,
0.71 in CHCl
3
); HPLC (OJ, heptane/iPrOH 95/5, 0.6 mL/min): t
r
/min ˆ 7.11
1
(1SFc, aR), 10.65 (1RFc, aS); H NMR (300 MHz, CDCl
7.56 ± 7.54 (m, 1H), 7.20 ± 7.18 (m, 2H), 7.07 ± 7.00 (m, 1H), 5.06 (s, 1H),
4.47 ± 4.46 (m, 1H), 4.37 ± 4.36 (m, 1H), 4.18 ± 4.13 (m, 1H), 4.12 (s, 5H),
2.43 (s, 6H); C NMR (75 MHz, CDCl
128.2, 127.1, 126.2, 90.2, 77.3, 71.7, 70.0, 67.5, 67.2, 65.3, 44.4; MS: m/z (%):
3
, 258C, TMS): d ˆ
3
1
J ˆ 25.8 Hz), 73.2 (d, J ˆ 14.5 Hz), 72.1 ± 71.8 (m), 70.4, 68.9, 45.3, 14.9;
P
1
3
NMR (81 MHz, CDCl
3
, 258C): d ˆ À17.04 (d, J ˆ 17.3 Hz), À24.61 (d, J ˆ
3
, 258C): d ˆ 141.0, 132.4, 131.0,
‡
1
C
7.3 Hz); MS: m/z (%): 715 (11) [M‡1] ; elemental analysis (%) calcd for
43FeNP (715.6): C 75.53, H 6.06, N 1.96; found: C 75.29, H 6.10, N 1.87.
‡
‡
‡
45
H
2
479 (30) [M‡2] , 477 (61) [M] , 475 (33) [M À 2] ; elemental analysis (%)
850
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 0947-6539/02/0804-0850 $ 17.50+.50/0 Chem. Eur. J. 2002, 8, No. 4

Chiral Phosphanylferrocenes
843±852
calcd for C19
H
19Br
2
FeN (477.0): C 47.84, H 4.01, N 2.94; found: C 47.72, H
NMR (81 MHz, CDCl
5.7 Hz); MS: m/z (%): 644 (56) [M] ; HRMS calcd for C41
3
, 258C): d ˆ À13.6 (d, J ˆ 5.7 Hz), À21.9 (d, J ˆ
‡
3
.94, N 2.79.
H
34FeP
2
:
6
44.1485; found: 644.1478.
Synthesis of 1-(SFc)-bromo-2-(o-bromophenylmethyl)ferrocene (6): The
amine 5 (295 mg, 0.62 mmol) was dissolved in trifluoroacetic acid (2 mL),
Synthesis of 1-(S )-diphenylphosphanyl-2-[1'-(R)-(o-diphenylphosphanyl-
Fc
and Et
stirred for 72 h at room temperature and then extracted with Et
organic layer was washed with saturated K CO solution and brine and
dried over MgSO . After removal of the solvent, the crude product was
3
SiH (1 mL, 6.20 mmol, 10 equiv) was added. The mixture was
phenyl)ethyl]ferrocene (1l): Compound 7a (285 mg, 0.63 mmol) in dry
THF (4 mL) was treated with nBuLi (1.6m in hexane, 0.87 mL, 1.40 mmol,
2.2 equiv) and ClPPh2 (0.30 mL, 1.52 mmol, 2.4 equiv) according to the
2
O. The
2
3
4
procedure described for 1k. After flash chromatography (pentane/Et O 20/
2
purified by flash chromatography (pentane/Et
0
2
O 20/1) to give 6 (152 mg,
1), the diphosphane 1l (384 mg, 0.58 mmol, 92.6% yield, d.r. ˆ 96/4) was
.35 mmol, 57% yield, 97% ee) as an orange oil. [a]ꢀ2 k0 ap†dꢀ=kap† ˆ À28.5 (c ˆ
20
obtained as an orange solid. [a]
ꢀ
kap†dꢀ=kap†
ˆ ‡354.5 (c ˆ 0.55 in CHCl );
3
1
1
.04 in CHCl
3
); HPLC (OJ, heptane/iPrOH 98/2, 0.6 mL/min): t
r
/min ˆ
H NMR (300 MHz, CDCl , 258C, TMS): d ˆ 7.58 ± 7.50 (m, 2H), 7.38 ± 6.96
3
1
1
2.78 (SFc), 15.66 (RFc); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.56 ±
(m, 21H), 6.84 ± 6.81 (m, 1H), 4.95 ± 4.88 (m, 1H), 4.24 ± 4.22 (m, 1H),
7
5
2
6
.53 (m, 1H), 7.21 ± 7.16 (m, 1H), 7.11 ± 7.04 (m, 2H), 4.45 (m, 1H), 4.20 (s,
H), 4.15 (m, 1H), 4.09 (m, 1H), 3.93 (m, 2H); C NMR (75 MHz, CDCl
4.13 ± 4.12 (m, 1H), 3.95 (s, minor diastereomer), 3.69 ± 3.68 (m, 6H), 1.24
1
3
13
3
,
(d, J ˆ 7.1 Hz, minor diastereomer), 0.85 (d, J ˆ 7.1 Hz, 3H); C NMR
58C): d ˆ 14.0, 132.5, 130.1, 127.8, 127.3, 124.2, 85.2, 80.3, 71.3, 69.8, 67.7,
(75 MHz, CDCl , 258C): d ˆ 151.1 (d, J ˆ 23.5 Hz), 140.7 ± 127.6 (m), 126.2,
3
‡
‡
‡
6.0, 34.5; MS: m/z (%): 436 (24) [M‡2] , 434 (44) [M] , 432 (25) [M À 2] ;
99.7 (d, J ˆ 25.4 Hz), 75.9 (d, J ˆ 12.1 Hz), 70.8 (d, J ˆ 4.3 Hz), 69.7, 69.7,
3
1
elemental analysis (%) calcd for C17
found: C 47.31, H 3.45.
H
14Br
2
Fe (434.0): C 47.05, H 3.25;
69.5, 69.4 (m), 36.3 (dd, J ˆ 25.0, 9.7 Hz), 25.2 (d, J ˆ 5.4 Hz); P NMR
(81 MHz, CDCl , 258C): d ˆ À12.9 (d, J ˆ 18.4 Hz), À22.4 (d, J ˆ 18.4 Hz);
3
minor diastereomer, separate signals: À18.3 (d, J ˆ 33.0 Hz), À21.7 (d, J ˆ
Synthesis of 1-(SFc)-bromo-2-[1'-(R)-o-bromophenylethyl]ferrocene (7a):
Me Zn (2m in THF, 1.7 mL, 4.2 mmol) was added to a solution of the amine
(400 mg, 1.05 mmol) in dry THF (6 mL) under argon at À788C, followed
by CH COCl (0.12 mL, 1.68 mmol). The reaction mixture was allowed to
‡
3
6
5
3.0 Hz); MS: m/z (%): 658 (43) [M] ; HRMS calcd: 658.1642; found:
2
58.1636; elemental analysis (%) calcd for C42
2
H36FeP (658.5): C 76.60, H
5
.51; found: C 76.41, H 5.42.
3
warm to room temperature overnight. After hydrolysis and conventional
workup, the crude product was purified by flash chromatography (pentane/
Synthesis of 1-(SFc)-diphenylphosphanyl-2-[1'-(R)-(o-diphenylphosphanyl-
phenyl)-2'-methylpropyl]ferrocene (1m): Compound 7b (190 mg,
0.40 mmol) in dry THF (2 mL) was treated with nBuLi (1.6m in hexane,
Et
2
O 50/1) to give 7a (330 mg, 0.73 mmol, 70% yield, d.r. ˆ 95/5, 98.5% ee)
20
as a sticky orange solid. [a]ꢀkap†dꢀ=kap† ˆ ‡78.9 (c ˆ 0.45 in CHCl
3
); HPLC
0.55 mL, 0.88 mmol, 2.2 equiv) and ClPPh (0.18 mL, 0.96 mmol, 2.4 equiv)
2
(
OD, 99.7% heptane/0.3% iPrOH, 0.6 mL/min): t
r
/min ˆ 12.97 (1RFc, 1'S),
according to the procedure described for 1k. After flash chromatography
(pentane), the diphosphane 1m (85 mg, 0.12 mmol, 31% yield, d.r. ˆ 95/5)
1
1
6.88 (1SFc, 1'R); H NMR (300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.57 ± 7.54
2
0
(
m, 1H), 7.41 ± 7.48 (m, 1H), 7.35 ± 7.31 (m, 1H), 7.05 ± 7.00 (m, 1H), 4.52 (q,
J ˆ 7.1 Hz, 1H), 4.33 ± 4.32 (m, 1H), 4.14 (s, minor diastereomer), 3.97 ±
.96 (m, 1H), 3.94 ± 3.83 (m, 6H), 1.50 (d, J ˆ 7.1 Hz, minor diastereomer),
was obtained as an orange solid. M.p. 988C; [a]
ˆ ‡315.5 (c ˆ 0.45
ꢀ
kap†dꢀ=kap†
1
in CHCl ); H NMR (300 MHz, CDCl , 258C, TMS): d ˆ 7.57 ± 7.46 (m,
3
3
3
2H), 7.38 ± 7.11 (m, 17H), 6.96 ± 6.82 (m, 3H), 6.75 ± 6.62 (m, 2H), 5.24 ±
5.19 (m, 1H), 4.55 (brs, 1H), 4.84 ± 3.69 (m, minor diastereomer), 4.28 ±
4.26 (m, 1H), 3.68 (s, 5H), 3.14 (s, minor diastereomer), 2.49 ± 2.48 (m, 1H),
0.75 (d, J ˆ 6.7 Hz, 3H), 0.51 (d, J ˆ 6.7 Hz, 3H), 0.26 (d, J ˆ 6.6 Hz, minor
1
3
1
1
.39 (d, J ˆ 7.1 Hz, 3H); C NMR (75 MHz, CDCl
32.90, 129.0, 127.9, 127.4, 124.2, 91.4, 79.2, 71.0, 69.8, 66.0, 64.7, 23.8; minor
diastereomer, separate signals: 132.4, 128.1, 127.5, 71.3, 70.3, 65.5, 65.4, 38.2,
3
, 258C): d ˆ 144.9,
‡
‡
‡
13
2
0.6; MS: m/z (%): 450 (59) [M‡2] , 448 (100) [M] , 446 (70) [M À 2] ;
diastereomer); C NMR (75 MHz, CDCl , 258C): d ˆ 150.9 (d, J ˆ
3
elemental analysis (%) calcd for C18
found: C 48.01, H 3.62.
H
16Br
2
Fe (448.0): C 48.26, H 3.60;
27.5 Hz), 139.8 ± 126. 8 (m), 125.4, 101.4 (d, J ˆ 27.1 Hz), 74.0 (d, J ˆ
16.6 Hz), 71.6 (d, J ˆ 4.4 Hz), 69.8, 69.6, 68.8, 47.6 (d, J ˆ 20.4 Hz), 33.4,
3
1
2
3.5, 21.5; P NMR (81 MHz, CDCl
3
, 258C): d ˆ À17.8 (d, J ˆ 26.7 Hz),
Synthesis of 1-(SFc)-bromo-2-[1'-(R)-o-bromphenyl-2'-methylpropyl]ferro-
cene (7b): The amine 5 (230 mg, 0.48 mmol) in dry THF (3 mL) was treated
À22.8 (d, J ˆ 26.7 Hz); minor diastereomer, separate signals: À17.6 (d),
‡
À25.8 (d, J ˆ 44.5 Hz); MS: m/z (%): 686 (11) [M] ; HRMS calcd for
with iPr
.00 mmol) according to the procedure described for 7a. The crude product
was purified by flash chromatography (pentane/Et O 50/1) to give 7b
2 3
Zn (2m in THF, 1.0 mL, 2.00 mmol) and CH COCl (0.07 mL,
44 2
C H40FeP : 686.1950; found: 686.1955.
1
2
Asymmetric hydrogenation: general procedure: In situ preparation of
rhodium catalyst: The rhodium complex (0.01 mmol) and the ligand 1
(1.05 ± 1.1 equiv) were placed in a dried Schlenk tube under an argon
atmosphere and the indicated solvent (4 mL) was added. The mixture was
then stirred for 10 ± 20 min at room temperature.
(
190 mg, 0.40 mmol, 83% yield, d.r. ˆ 95/5, 98.5% ee) as an orange oil.
20
[
a]ꢀkap†dꢀ=kap† ˆ ‡119 (c ˆ 0.51 in CHCl
3
); HPLC (OD, 99.5% heptane/0.5%
1
iPrOH, 0.6 mL/min): t
r
/min ˆ 8.61 (1SFc, 1'R), 9.66 (1RFc, 1'S); H NMR
(
300 MHz, CDCl
3
, 258C, TMS): d ˆ 7.70 ± 7.66 (m, minor diastereomer),
7
1
2
.54 ± 7.51 (m, 1H), 7.16 ± 7.10 (m, 1H), 7.01 ± 6.95 (m, 2H), 4.39 ± 4.35 (m,
In situ preparation of ruthenium catalyst:[12] [Ru(cod)(2-methallyl)
0.01 mmol) and the ligand 1 (1.05 ± 1.1 equiv) were placed in a dried
2
]
H), 4.33 ± 4.30 (m, 1H), 4.13 ± 4.09 (m, 6H), 3.71 (s, minor diastereomer),
.52 ± 2.41 (m, 1H), 2.04 ± 1.90 (m, minor diastereomer), 1.25 (d, 3H, J ˆ
(
Schlenk tube under an argon atmosphere and acetone (2 mL) was added. A
solution of HBr in MeOH (0.1 mL, 0.3m) was added dropwise to this
solution. An orange precipitate formed. After 10 ± 20 min of stirring, the
solvent was removed under vacuum, and the indicated solvent (4 mL) was
added.
7
0
2
4
1
.5 Hz), 0.83 (d, 3H, J ˆ 6.8 Hz), 0.79 (d, J ˆ 6.6 Hz, minor diastereomer),
1
3
.75 (d, J ˆ 6.6 Hz, minor diastereomer); C NMR (75 MHz, CDCl
3
,
58C): d ˆ 143.6, 132.3, 130.4, 127.2, 127.0, 91.6, 78.9, 71.5, 70.2, 67.1, 65.2,
8.9, 32.5, 23.1, 20.8; minor diastereomer, separate signals: 128.5, 127.5,
‡
‡
26.5, 71.0, 55.8, 21.5; MS: m/z (%): 478 (64) [M‡2] , 476 (100) [M] , 474
‡
Hydrogenation in Schlenk tubes: The catalyst solution was added to the
substrate under an argon atmosphere. The Schlenk tube was then briefly
connected to vacuo and purged with hydrogen from a balloon.
(
64) [M À 2] , 433 (40), 215 (80), 152 (82); elemental analysis (%) calcd for
20 2
C H20Br Fe (476.0): C 50.46, H 4.23; found: C 50.26, H 4.23.
Synthesis of 1-(SFc)-diphenylphosphanyl-2-(o-diphenylphosphanylphenyl-
methyl)ferrocene (1k): nBuLi (1.6m in hexane, 0.37 mL, 0.59 mmol,
Hydrogenation in an autoclave: The substrate was placed in a glass tube
equipped with a stirring bar in the autoclave. After three cycles of
vacuum ± argon, the catalyst solution was added to the substrate by syringe
under an argon stream. Volatile substrates were added directly to the
catalyst solution before introduction to the autoclave under argon. The
autoclave was then purged three times with hydrogen, heated to the desired
2
.2 equiv) was added dropwise to a solution of the ferrocenyl compound
6
(120 mg, 0.27 mmol) in dry THF (2 mL), at À788C. The mixture was
2
stirred for 15 min and then ClPPh (0.12 mL, 0.66 mmol, 2.4 equiv) was
added. The solution was then warmed to room temperature and stirred for
h. After hydrolysis and conventional workup, the crude product was
purified by flash chromatography (pentane/Et O 20/1) to give 1k (130 mg,
.20 mmol, 75% yield) as an orange solid. M.p. 828C; [a]ꢀkap†dꢀ=kap† ˆ ‡46.4
c ˆ 0.59 in CHCl ); H NMR (300 MHz, CDCl , 258C, TMS): d? ˆ 7.66 ±
1
2
temperature, and placed under the indicated H pressure.
2
2
0
0
(
Hydrogenation products: determination of enantiomeric excess: The
substrates used for hydrogenation are commercially available or were
prepared according to literature procedures. Most of the hydrogenation
1
3
3
7.56 (m, 2H), 7.45 ± 7.15 (m, 18H), 7.02 ± 6.91 (m, 3H), 6.84 ± 6.74 (m, 1H),
4
.35 ± 4.31 (m, 1H), 4.27 ± 4.17 (m, 3H), 3.94 (s, 5H), 3.79 ± 3.78 (m, 1H);
products have been previously described. N-acetylphenylalanine methyl
1
3
[2d]
C NMR (75 MHz, CDCl
3
, 258C): d ˆ 145.5 (d, J ˆ 25.1 Hz), 139.4 (d, J ˆ
ester (9b): GC (Chiralsil L-Val) 1408C isotherm: t
r
/min ˆ 10.1 (R), 11.7
(S); dimethyl 2-methylsuccinate (11):[ HPLC (OJ, 208C, 5% iPrOH in
2e]
1
7
0.0 Hz), 137.8 ± 127.6 (m), 126.0, 93.2 (d, J ˆ 27.6 Hz), 75.7 (d, J ˆ 1.9 Hz),
3
1
2.7 ± 72.5 (m), 70.7 (d, J ˆ 4.1 Hz), 69.8, 68.9, 33.0 (dd, J ˆ 23.1, 9.9 Hz);
P
heptane, 0.6 mL/min): t
r
/min ˆ 9.9 (R), 15.2 (S); methyl 2-acetoxypropa-
Chem. Eur. J. 2002, 8, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0851 $ 17.50+.50/0
851

P. Knochel et al.
FULL PAPER
noate (13):[19] HPLC (OD, 208C, 1% iPrOH in heptane, 0.6 mL/min): t
/
[3] a) T. Ireland, G. Grossheimann, C. Wieser-Jeunesse, P. Knochel,
Angew. Chem. 1999, 111, 3397; Angew. Chem, Int. Ed. 1999, 38, 3212;
b) Degussa-Huels: Patent application WO/0037478.
[4] G. Descotes, D. Lafont, D. Sinou, J. Organomet. Chem. 1978, 150 (1),
C14 ± C16.
r
[
20]
min ˆ 13.4 (S), 15.6 (R); acetyl 1-phenylbutylamide (15): GC (Chiralsil
L-Val) 1158C isotherm: 23.5 (R), 24.9 (S); methyl 3-hydroxybutanoate
[
21]
(
9
17a): HPLC (OD, 208C, 5% iPrOH in heptane, 0.9 mL/min): t
r
/min ˆ
[
21]
.2 (R), 13.3 (S); ethyl 3-hydroxybutanoate (17b): HPLC (OD, 208C, 5%
iPrOH in heptane, 0.9 mL/min): t
r
/min ˆ 7.3 (R), 10.2 (S); ethyl 3-hydroxy-
[5] a) L. Schwink, P. Knochel, Chem. Eur. J. 1998, 4, 95; b) J. Wright, L.
Framkes, P. Reeves, J. Organomet. Chem. 1994, 476, 215; c) E. J.
Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. 1987, 109, 7925.
[6] I. K. Ugi, D. Marquarding, G. W. Gokel, J. Org. Chem. 1972, 37, 3052.
[7] I. K. Ugi, L. F. Batelle, R. Bau, G. W. Gokel, J. Am. Chem. Soc. 1973,
95, 482.
-phenylpropanoate (17c):[ HPLC (OD, 308C, 5% iPrOH in heptane,
21]
3
0
[
21]
.9 mL/min): t
r
/min ˆ 11.3 (S), 15.9 (R); ethyl 3-hydroxyhexanoate (17d):
/min ˆ 12.0 (R),
6.4 (S); ethyl 3-hydroxy-4-methylpentanoate (17e):[21] HPLC (OD, 208C,
HPLC (OD, 208C, 5% iPrOH in heptane, 0.5 mL/min): t
r
1
5
3
% iPrOH in heptane, 0.5 mL/min): t
r
/min ˆ 10.8 (R), 15.9 (S); ethyl
-hydroxy-4-chlorobutanoate (17 f):[ HPLC (OD, 308C, 2% iPrOH in
21]
[8] M. Lotz, T. Ireland, J. J. Almena, P. Knochel, Tetrahedron: Asymmetry
1999, 10, 1839.
heptane, 0.6 mL/min): t
r
/min ˆ 10.6 (S), 15.6 (R); ethyl 2-hydroxycyclopen-
[21]
tane carboxylate (19):
.32 mL/min):
/min ˆ 19.7 (1R,2S), 25.7 (1S,2R), 27.4 (1R,2R), 31.1
1S,2S); ethyl 2-hydroxycyclohexane carboxylate (21):
58C, 2% iPrOH in heptane, 0.3 mL/min): t
/min ˆ 18.0 (1R,2S), 19.3
1S,2R), 23.0 (1S,2S), 23.8 (1R,2R); ethyl 2-methyl-3-hydroxybutanoate
HPLC (OD, 408C, 2% iPrOH in heptane,
[9] a) T. V. RajanBabu, T. A. Ayers, A. L. Casalnuovo, J. Am. Chem. Soc.
1994, 116, 4101; b) C. R. Landis, J. Halpern, J. Am. Chem. Soc. 1987,
109, 1746; c) W. S. Knowles, Acc. Chem. Res. 1983, 16, 106; d) A. S. C.
Chan, J. J. Pluth, J. Halpern, J. Am. Chem. Soc. 1980, 102, 5952;
e) J. M. Brown, Chem. Soc. Rev. 1993, 25; f) M. J. Burk, J. E. Feaster,
W. A. Nugent, R. L. Harlow, J. Am. Chem. Soc. 1993, 115, 10125.
[10] For reviews, see: a) K. E. Koenig in Asymmetric Synthesis (Ed.: J. D.
Morrison), Academic Press, Orlando, FL, 1985, p. 71; b) H. Takaya, T.
Ohta, R. Noyori in Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
VCH, New York, 1993, p. 1; c) R. Noyori, Asymmetric Catalysis in
Organic Synthesis, Wiley, New York, 1994, p. 16.
[11] S. Masamune, W. Choy, J. S. Petersen, L. R. Sita, Angew. Chem. 1985,
97, 1; Angew. Chem. Int. Ed. Engl. 1985, 24, 1.
[12] J. J. Almena Perea, A. Bˆrner, P. Knochel, Tetrahedron Lett. 1998, 39,
8073, and references therein.
[13] a) J. P. Gen e√ t, C. Pinel, S. Mallart, S. Jug e¬ , S.Thorimbert, J. Laffitte, A.
Tetrahedron: Asymmetry 1991, 2, 555; b) J. P. Gen e√ t, C.Pinel, V.
Ratovelomanana-Vidal, S. Mallart, X. Pfister, L. Bischoff, S. Darses,
C. Galopin, J. A. Laffitte, Tetrahedron: Asymmetry 1994, 5, 675.
0
t
r
[
21]
(
3
HPLC (OD,
r
(
(
(
[
21]
23): GC (Chiralsil L-Val) 748C isotherm: 14.4 (2S,3S), 15.2 (2R,3S), 15.7
[
21]
2S,3R), 16.4 (2R,3R); 2,4-pentanediol (24a): GC (Chiralsil L-Val) 888C
isotherm: 5.3 (S,S), 6.2 (R,R), 8.6 (R,S); 1,3-diphenyl-1,3-propanediol
[
21]
(
1
3
24b): HPLC (OD, 308C, 10% iPrOH in heptane, 0.6 mL/min): t
r
/min ˆ
6.5 (S,S), 19.2 (R,R), 23.3 (S,R); 1-phenyl-1,3-butanediol (27): HPLC (OD,
08C, 5% iPrOH in heptane, 0.7 mL/min): t
/min ˆ 22.0 (1S,3R), 25.2
r
[
16b]
(
1S,3S), 32.8 (1R,3R); 1-phenyl-1-(2-benzoylhydrazino)ethane (29a):
HPLC (OJ, 308C, 10% iPrOH in heptane, 0,6 mL/min): t
r
/min ˆ 14.3 (R),
[16b]
1
(
1
9.9 (S); 1-(2-naphthyl)-1-(2-benzoylhydrazino)ethane (29b):
OJ, 408C, 10% iPrOH in heptane, 0.8 mL/min): t
/min ˆ 20.6 (R), 23.0 (S);
-(2-benzoylhydrazino)tetralone (29c): HPLC (OD, 408C, 10% iPrOH in
/min ˆ 16.9 (‡), 22.5 (À).
HPLC
r
heptane, 0.6 mL/min): t
r
[
14] M. J. Burk, M. F. Gross, T. G. Harper, P. C. S. Kalberg, J. R. Lee, J. P.
Martinez, Pure Appl. Chem. 1996, 68, 37.
Acknowledgements
[
[
15] Recent review: S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99, 1069.
16] a) M. J. Burk, J. E. Feaster, J. Am. Chem. Soc. 1992, 114, 6266; b) M. J.
Burk, J. P. Martinez, J. E. Feaster, Tetrahedron 1994, 50, 4399.
17] E. W. Abel, M. A. Bennett, G. Wilkinson, J. Chem. Soc. 1959, 3178.
18] D. J. Mathre, T. K. Jones, L. C. Xavier, T. J. Blackblock, R. A.
Reamer, J. J. Mohan, T. T. Jones, K. Hoogsteen, M. W. Baum, E. J. J.
Grabowski, J. Org. Chem. 1991, 56, 751.
We thank the DFG (SFB 260, Graduiertenkolleg Marburg, Leibniz-
Programm) and the Fonds der Chemischen Industrie for financial support.
We thank Degussa-H¸ls for the generous donation of chemicals.
[
[
[
[
1] a) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994; b) Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH,
Weinheim, 1993.
2] a) M. D. Fryzuk, B. Bosnich, J. Am. Chem. Soc. 1977, 99, 6262; b) W. S.
Knowles, Acc. Chem. Res. 1983, 16, 106; c) R. Noyori, H. Takaya, Acc.
Chem. Res. 1990, 23, 345; d) M. J. Burk, J. E. Feaster, W. A. Nugent,
R. L. Harlow, J. Am. Chem. Soc. 1993, 115, 10125; e) A. Togni, C.
Breutel, A. Schnyder, F. Spindler, H. Landert, T. Tijani, J. Am. Chem.
Soc. 1994, 116, 4062.
[19] M. J. Burk, C. S. Kalberg, A. Pizzano, J. Am. Chem. Soc. 1998, 120,
4345.
[20] M. J. Burk, Y. M. Wang, J. R. Lee, J. Am. Chem. Soc. 1996, 118, 5142.
[21] K. Mashima, K. H. Kusano, N. Sato, Y. Matsumura, K. Nozaki, H.
Kumobayashi, N. Sayo, Y. Hori, T. Ishizaki, S. Akutagawa, H. Takaya,
J. Org. Chem. 1994, 59, 3064.
Received: May 21, 2001 [F3276]
852
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0804-0852 $ 17.50+.50/0
Chem. Eur. J. 2002, 8, No. 4