A modular design of ruthenium catalysts with diamine and BINOL-derived phosphinite ligands that are enantiomerically-matched for the effective asymmetric transfer hydrogenation of simple ketones

Article abstract of DOI:10.1039/b502123e

A method is reported for making a potentially very wide series of ruthenium hydrido chloro complexes with diamine and readily-prepared diphosphinite ligand modules as precatalysts for the asymmetric transfer hydrogenation of simple ketones to give chiral alcohols in good yield and enantioselectivity. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b502123e

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COMMUNICATION
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A modular design of ruthenium catalysts with diamine and BINOL-
derived phosphinite ligands that are enantiomerically-matched for the
effective asymmetric transfer hydrogenation of simple ketones{
Rongwei Guo, Christian Elpelt, Xuanhua Chen, Datong Song and Robert H. Morris*
Received (in Berkeley, CA, USA) 14th February 2005, Accepted 14th April 2005
First published as an Advance Article on the web 6th May 2005
DOI: 10.1039/b502123e
A method is reported for making a potentially very wide series
of ruthenium hydrido chloro complexes with diamine and
readily-prepared diphosphinite ligand modules as precatalysts
for the asymmetric transfer hydrogenation of simple ketones to
give chiral alcohols in good yield and enantioselectivity.
allows the opportunity for rapid tuning of the catalyst structure
due to the modular nature of the ligands and precatalysts.
A wide variety of catalyst structures are readily constructed
from three modules A–C. First BINOL (A, (R) or (S)) and
diarylchlorophosphine (B, Ar 5 Ph or 3,5-Me C H (xyl)) are
2
6
3
combined to give the phosphinite ligand. Then this is reacted with
RuHCl(PPh3)3 to produce an intermediate complex
Chiral alcohols are very important building blocks and synthetic
intermediates in organic synthesis and the pharmaceutical
RuHCl(diphosphinite)(PPh ) that is reacted in situ with a diamine
3
1,2
industry. The reduction of prochiral ketones to give chiral
alcohols is among the most fundamental subjects in modern
synthetic chemistry. Noyori and co-workers provided an
C (in this case (R,R)- or (S,S)-DPEN) to produce the desired trans-
RuHCl(diphosphinite)(diamine) complexes in yields of up to 88%
(Scheme 1).
elegant solution for the asymmetric catalytic H
3–6
of simple aryl ketones.
2
-hydrogenation
Complexes of the type trans-
The yellow solid product usually consists of two diastereomers
in the ratio of 2:1 for 1 and 3 and 9:1 for 2 and only one for 4.
Their structures depend on the placement of the trans hydride and
chloride groups relative to the folded backbone of the dipho-
sphinite ligand. The minor isomer slowly changes to the major
isomer as the product crystallizes from solution over the course of
two days. The major isomer also can partly isomerize to the minor
isomer when it stays in solution for more than 24 h.
RuCl (diamine)(diphosphine) with matching configurations of
2
the chiral diphosphine and diamine, e.g. (S)-BINAP/
(S,S)-DPEN, show high reactivity and enantioselectivity. The use
of organometallic complexes as catalysts for asymmetric transfer
hydrogenation from a suitable donor (usually 2-propanol or
formic acid) has been the subject of ongoing research for some
decades. Efficient catalysts for the asymmetric transfer hydrogena-
tion of ketones include Evans’ samarium complexes with chiral
The structure of 3 (Fig. 1){ is similar to that of trans-
18a
RuHCl((R)-BINAP)((R,R)-DPEN) with the PPNN atoms in
the equatorial plane of a slightly distorted octahedron and with the
Ru–Cl bond leaning toward the NN side. The BINOP ligand is
folded over the hydride ligand. Structure determinations of
BINOP-like complexes are scarce but these also have folded
7
amino alcohol ligands and Noyori’s ruthenium complexes
containing arene and N-(p-toluenesulfonyl)-1,2-diphenylethylene-
8
diamine (TsDPEN) ligands. Many other useful catalysts have
1a,9–12
been reported.
Chiral diphosphinite ligands derived from the
19
reaction of 1,19-bi-2-naphthol (BINOL) with chlorodiarylpho-
sphine are easily synthesized and modified and they are widely
used as chiral auxiliaries in rhodium, iridium and palladium
diphosphinite ligands.
A comparison of complexes 1–4 as precatalysts for the
asymmetric transfer hydrogenation of acetophenone by 2-propa-
t
nol in the presence of KO Bu is summarized in Table 1. These
13–16
asymmetric catalytic reactions.
No Ru/diphosphinite/diamine
complexes have been investigated for the transfer hydrogenation of
prochiral ketones although such complexes with monodentate
complexes show slightly higher activity than Noyori’s system
i
RuCl ((R)-BINAP)((R,R)-DPEN)/base/ PrOH in the transfer
2
8,20
hydrogenation of ketones.
21
The TOF is more than 30 h at
phosphinite ligands have been used recently for such H -
2
1
7
hydrogenations. Our group previously reported that ruthenium
phosphine diamine hydrido complexes are effective precatalysts for
the H
ketones and imines to give optically active alcohols and amines.
Herein, we report the convenient, modular synthesis and
characterization of complexes of the type trans-
2
-hydrogenation and transfer hydrogenation of prochiral
18
RuHCl(diphosphinite)(diamine) and their application in the
asymmetric transfer hydrogenation of ketones. This approach
{ Electronic supplementary information (ESI) available: Synthesis and
characterization of 1–4 and the details of a typical catalytic reaction. See
http://www.rsc.org/suppdata/cc/b5/b502123e/
*rmorris@chem.utoronto.ca
Scheme 1 Synthesis of trans-RuHCl(diphosphinite)(diamine) complexes.
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050 | Chem. Commun., 2005, 3050–3052

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a
Table 2 Transfer hydrogenation of ketones catalyzed by complex 3
Entry
R
Conc./M
Time/h
Conv. (%)
ee (%)
1
2
3
4
H
H
H
H
H
H
2.4
0.7
0.1
0.05
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
6
6
3
48
65
94
96
95
95
90
78
95
98
72
96
99
98
22 (R)
63 (R)
92 (R)
93 (R)
89 (R)
87 (R)
85 (R)
88 (R)
92 (R)
88 (R)
80 (R)
90 (R)
90 (R)
92 (R)
3
b
5
6
18
30
3
8
3
3
3
3
3
c
7
8
9
49-Me
49-MeO
49-Br
49-Cl
29-Cl
39-MeO
39-Br
39-Cl
10
11
12
13
14
a
3
Fig. 1 Structure of trans-RuHCl((R)-xylBINOP)((R,R)-DPEN) 3.
All the reactions were carried out in a glove-box under Ar at 20 uC
b
with ketone/cat. 5 100. Ketone/cat. 5 500. Ketone/Cat. 5 1000.
c
Table 1 Transfer hydrogenation of acetophenone with 2-propanol
catalyzed by trans-RuHCl(diphospinite)(diamine) complexes
These observations have also been reported for Noyori’s transfer
8
hydrogenation catalysts.
In conclusion, we have developed an effective, modular catalytic
system for the asymmetric transfer hydrogenation of ketones. The
trans-RuHCl(phosphinite)(diamine) complexes are made in a
Catalyst
Conv. (%)
ee (%)
‘
‘one-pot’’ procedure in high yield. The enantioselectivity of the
RuHCl((R)-BINOP)((R,R)-DPEN) 1
RuHCl((R)-BINOP)((S,S)-DPEN) 2
RuHCl((R)-xylBINOP)((R,R)-DPEN) 3
RuHCl((R)-xylBINOP)((S,S)-DPEN) 4
a
96
95
97
96
79 (R)
47 (R)
92 (R)
63 (R)
catalyst can be tuned by modifying the diphosphinite ligand.
Studies are currently underway to compare the H -hydrogenation
2
and transfer hydrogenation of ketones catalyzed by these kinds of
complexes.
The reactions were carried out in a glove-box under Ar at 20 uC
for 3 h; substrate/cat. 5 100; [acetophenone] 5 0.1 M.
R. H. M. thanks NSERC and the PRF as administered by the
American Chemical Society, for research grants.
2
0 uC (Table 1, entries 1–4) while Noyori’s catalyst has a TOF of
Rongwei Guo, Christian Elpelt, Xuanhua Chen, Datong Song and
Robert H. Morris*
Department of Chemistry, University of Toronto, Ontario, Canada.
E-mail: rmorris@chem.utoronto.ca; Fax: 1-416-978 6962;
Tel: 1-416-978 6962
21 1c
1
0 h at 28 uC. Complex 3 with the more rigid and crowded
phosphinite ligand (R)-xylBINOP and matching diamine
R,R)-DPEN gives the best enantioselectivity (up to 92% ee) with
(
the product in the R configuration (Table 1, entry 3). Complex 4
with (R)-xylBINOP and mismatched (S,S)-DPEN gives a lower
enantioselectivity (Table 1, entry 4).
Notes and references
The scope of the reaction with catalyst 3 was investigated by the
use of aryl methyl ketones. Most of the reactions were carried out
under Ar at 20 uC and reached the maximum conversion allowed
for the particular equilibrium within 3 h (Table 2).
{ Crystal data for 3: C78
H
77ClN
2
O
2
P
2
Ru, M
r
5 1272.87, T 5 293 K,
˚
l 5 0.71073 A, monoclinic, P2
1
, a 5 11.735(2), b 5 17.146(3), c 5
3
23
,
˚
˚
1
7.634(4) A, b 5 105.44(3)u, V 5 3420(1) A , Z 5 2, D
c
5 1.236 Mg m
m 5 0.362 mm , data/restraints/parameters 5 14081/1/719, R
wR (all) 5 0.1548. CCDC reference number 263842. See http://
21
1
5 0.0610,
2
The results show that the ee values and conversions are
significantly affected by the substrate concentration. A lower
concentration gives a higher conversion and enantiomeric excess of
the (R)-alcohol (Table 2, entries 1–4). The ratio of the substrate to
catalyst has less effect on the enantioselectivity (Table 2, entries 3, 5
and 6). The rate and enantioselectivity are also affected by the
electronic properties of the substituent on the phenyl rings. An
acetophenone substituted in the para position with an electron-
releasing group, such as 49-methyl and 49-methoxyl, is reduced
more slowly than acetophenone and is converted to an alcohol of
lower ee (Table 2, entries 7 and 8). The ortho-substituted
acetophenone, 29-chloroacetophenone, is reduced slowly and
shows a significantly lower enantioselectivity (entry 11, Table 2).
www.rsc.org/suppdata/cc/b5/b502123e/ for crystallographic data in CIF
or other electronic format.
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