enantioselectivity (up to 91% ee) was observed in the
hydrogenation of 2-phosphonomethylpropenoic acids with
a (R)-Cl-MeO-BIPHEP-Ru catalyst,3 for most substrates, the
enantioselectivities were still less satifactory. Therefore, the
search of a new catalytic system for the enantioselective
hydrogenation of a wider range of 2-phosphonomethylpro-
penoate derivatives is still highly desirable. As a part of our
ongoing efforts in the development of new catalytic hydro-
genation methods for the enantioselective synthesis of chiral
phosphonates,5 herein we report a highly enantioselective
synthesis of chiral 3-phosphono-2-arylmethylpropanoic acid
esters via the rhodium-catalyzed asymmetric hydrogenation
with a new class of chiral diphosphine ligands [(Rc,SFc)-
ImiFerroPhos] based on ferrocenyl and heterocyclic scaffolds.
Rh-catalyzed asymmetric hydrogenation of this challenging
substrate class.
The synthetic route for (Rc,SFc)-ImiFerroPhos 1a-i is
illustrated in Scheme 1.
Scheme 1. Preparation of (Rc,SFc)-ImiFerroPhos 1a-i
In the past few years, many ferrocenyl diphosphine ligands
with subtle structural variations have been developed and
successfully employed in a variety of asymmetric catalyses.6
However, ferrocenyl bisphosphine ligands with a heterocycle
remain less explored.7 These ligands are more amenable to
asymmetric catalysis than many other types of chiral ligands
as a result of their easy accessibility and derivatization as
well as special electronic and steric properties. Indeed, new
chiral ImiFerroPhos ligands, with an imidazole ring, can be
easily prepared from acylferrocenes through a modular
procedure, and they display superior enantioselectivity in the
(1) (a) Bartlett, P. A.; Kezer, W. B. J. Am. Chem. Soc. 1984, 106, 4282.
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The chiral ferrocene-based phosphine-amine compounds
(Rc,SFc)-PPFA-R 2 were used as the starting materials, which
can be readily prepared from acylferrocenes through a three-
step transformation according to the literature procedure.8
Heating (Rc,SFc)-2 with imidazole in AcOH afforded (Rc,SFc)-
3 with complete configurational retention at the central
chirality.9 The treatment of (Rc,SFc)-3 with 1.5 molar equiv
of n-BuLi in Et2O at rt or -78 °C followed by trapping with
1.5 molar equiv of ClPR1 gave the target diphosphine
2
ligands (Rc,SFc)-ImiFerroPhos 1a-g in moderate yields. In
a similar synthetic procedure, ligands (Rc,SFc)-1h-i were
prepared from the corresponding phosphine-amine inter-
mediates in moderate yields. (Rc,SFc)-ImiFerroPhos 1a-i are
air-stable and can be handled in air, which makes the
synthesis, use, and storage of these ligands very convenient.
The structure of (Rc,SFc)-ImiFerroPhos 1c was confirmed
by X-ray crystallography (Figure 1).
With these newly developed diphosphine ligands in hand,
we then examined their efficiency in the Rh-catalyzed
asymmetric hydrogenation of this challenging substrate
class, 2-phosphonomethylpropenoates 4.10 Initially, ethyl 2-
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