Novel monodentate spiro phosphorus ligands for rhodium-catalyzed
hydrogenation reactions
Yu Fu, Jian-Hua Xie, Ai-Guo Hu, Hai Zhou, Li-Xin Wang and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, 94 Weijin Rd.,
Tianjin 300071, China. E-mail: qlzhou@public.tpt.tj.cn
Received (in Cambridge, UK) 2nd November 2001, Accepted 22nd January 2002
First published as an Advance Article on the web 7th February 2002
Novel monodentate phosphorus ligands containing the 1,1A-
spirobiindane backbone have been synthesized and applied
in the asymmetric rhodium-catalyzed hydrogenation of
functionalized olefins, providing excellent enantioselectiv-
ities (up to 99.3% ee).
genation of methyl 2-acetamidocinnamate was performed at
room temperature under ambient H2 pressure in the presence of
1 mol% catalyst formed in situ from [Rh(COD)2BF4] and the
phosphoramidite ligand (S)-1 (1+2.1). Excellent enantiose-
lectivities (95.6–97.4% ee) were achieved in nonprotic solvents
such as CH2Cl2, toluene, EtOAc, THF and acetone, although the
reaction in methanol gave a slightly lower enantioselectivity
(93.9% ee). The pre-generation of the active catalyst was found
to be unnecessary.
The influence of H2 pressure and the Rh+substrate ratio on
the rate and enantioselectivity in the hydrogenation of methyl
2-acetamidocinnamate was examined in CH2Cl2. A higher
pressure of H2 accelerated the hydrogenation reaction, but gave
almost no difference in the enantiomeric excess compared with
the reaction under ambient H2 pressure (Table 1, entry 1–3).
When the Rh+substrate ratio was changed from 1+20 to 1+200,
the change in catalyst amount had no obvious effect on the level
of enantio-control, although the hydrogenation with less
catalyst needed a longer reaction time (Table 1, entry 3–5).
However, when the Rh+substrate ratio was decreased to 1+1000
the reaction conversion was only 25% after 48 h under 20 atm
H2 pressure. A slightly higher enantioselectivity was obtained
when the hydrogenation reaction was carried out at 0 °C (Table
1, entry 6).
The homogeneous catalytic asymmetric hydrogenation of
functionalized prochiral olefins is one of the most developed
and most useful transition metal-catalyzed reactions. In the
rhodium-catalyzed asymmetric hydrogenation of prochiral
enamines, the use of chiral phosphorus ligands has been found
to be extremely successful and those that are bidentate have
been the most effective.1–3 However, the development of
monodentate chiral phosphorus ligands for asymmetric hydro-
genation has been less successful even though the earliest chiral
ligand used by Knowles and Sabacky in this reaction was
monodentate phosphine.4 Very recently, chiral monodentate
phosphines, phosphonites, phosphites and phosporamidites
have been reported to be excellent ligands in the rhodium-
catalyzed asymmetric hydrogenation of dehydroamino acid and
itaconic acid derivatives.5–9 It is noteworthy that all the reported
monodentate ligands that induced high enantioselectivity are
phosphorus derivatives of binaphthol.10
In the ligand design for asymmetric synthesis, C2-symmetric
biaryls, like 1,1A-binaphthalene derivatives, occupy a prominent
position. By contrast, spiranes, another class of C2-symmteric
molecules which also possess axial chirality, have received
much less attention. The rigidity of the spirocyclic framework
should decrease the flexibility of these ligands and their related
complexes and consequently benefit selectivity in asymmetric
catalysis. The chiral spiro compounds which have been
employed in asymmetric synthesis include spiro bis(phosphi-
nite) and spiro bis(isoxazoline).11,12 Both of them are bidentate
ligands. In this paper, we report the synthesis of novel and
highly effective chiral monodentate phosphoramidite ligands
containing a 1,1A-spirobiindane backbone and their application
in the rhodium-catalyzed asymmetric hydrogenation of func-
tionalized olefins, which provides the first example of mono-
dentate chiral ligands with a spiro structure in asymmetric
catalysis.
The asymmetric hydrogenation of various dehydroamido
acid derivatives [eqn. (1)] was investigated in CH2Cl2 at room
(1)
temperature under ambient H2 pressure and the results are
summarized in Table 2. For all the methyl esters, the
conversions are quantitative and the enantioselectivities
(95.6–99.3% ee) are higher than or comparable to those
achieved with other monodentate phosphorus ligands and
bidentate phosphorus ligands (e.g. DIOP 64–84%,1 BINAP
67–100%,2 DuPHOS 99–99.4%,3 MonoPHOS, 93.2–99.8%.8)
Under similar conditions, the asymmetric hydrogenation
reactions of itaconic acid derivatives 4 were also performed and
The chiral spiro phosphoramidite ligands 1 (SIPHOS) were
conveniently synthesized in high yields from enantiomerically
pure (S)- and (R)-1A1-spirobiindane-7,7A-diol13 and hexamethyl
phosphoramide (HMPT). Compounds 1 have been charac-
Table 1 Asymmetric hydrogenation of methyl 2-acetamidocinnamate with
different catalyst loading and H2 pressurea
1
terized by elemental analysis, H and 31P NMR spectroscopy.
They are white solids and are very stable in the atmosphere.14
Entry
pH2/atm
Rh+substrate 1
Time/hb
% eec
1
2
3
4
5
6d
20
5
1
1
1
1+100
1+100
1+100
1+20
1
4
10
4
16
20
96.2
96.7
96.6
97.1
96.4
97.8
1+200
1
1+100
a The reaction was performed at room temperature with 0.5 mmol of
substrate and 1 mol% of catalyst {[Rh(COD)2BF4]+(S)-1 = 1+2.1} in 5 mL
of solvent unless stated otherwise. b Time taken for 100% conversion of
substrate. c Determined by chiral HPLC using a CHIRACEL-OJ column.
The configurations of product are S. d Reaction temperature was 0 °C.
Ligands 1 were found to be highly efficient in the rhodium-
catalyzed hydrogenation of dehydroamino esters. The hydro-
480
CHEM. COMMUN., 2002, 480–481
This journal is © The Royal Society of Chemistry 2002