Chemistry Reference
In-Depth Information
This chapter reviews the up-to-date achievements of homogeneous transition metal-
catalyzed asymmetric hydrogenation. The development of effective catalytic systems and
their applications in the preparation of various chiral compounds are summarized. We
intend to emphasize the applications of this methodology and try to make this chapter
“substrate oriented.” However, due to the word limit and the large volume of publica-
tions, only the most important and representative results are summarized. We hope that
together with other review articles and topics, this chapter can serve as a good reference
for chemists from all levels.
7.2. CHIRAL LIGANDS FOR ASYMMETRIC HYDROGENATION
In addition to a suitable transition metal species, chiral ligands play a crucial role in
asymmetric hydrogenation. The good enantioselectivity and high activity of the catalyst
are often the results of the structurally well-defi ned and electron-donating chiral ligands.
Continuing development of novel ligands and modifi cations of the current ligands are
especially signifi cant for asymmetric hydrogenation.
Similar to other areas of science, the fast development of chiral ligands is often trig-
gered and continuously infl uenced by a few milestone discoveries. The pioneering dis-
coveries of CAMP and DIPAMP by Knowles and Sabacky [4], and DIOP by Kagan
and Dang [5] have prompted the early studies on chiral ligand synthesis. A few important
concepts were also introduced by these pioneering works, such as monodentate phos-
phine ligands, P-chiral ligands, and
C
2
-symmetric ligands. The early study on phosphorus
ligand produced a number of chiral phosphorus ligands such as Bosnich's CHIRAPHOS
[7] and PROPHOS [8] , Rhone Poulenc ' s CBD [9] , Giongo ' s bis(aminophosphine) ligand
PNNP [10], Kumada's ferrocene ligand BPPFA [11] and BPPFOH [12], and Achiwa's
BPPM [13] (Fig. 7.1 ). The fi rst few attempts on the modifi cations of Kagan's DIOP were
also initiated and resulted in a few related ligands, which provided superior performance
in many cases (Fig. 7.2 ) [14] .
A few years later, the discovery of binaphthyl moiety as chiral ligand motifs by Noyori
and others led to the milestone ligand BINAP [15], which soon delivered extraordinary
results in olefi n [16,17] and ketone [18,19] hydrogenation (Fig. 7.3). The great impact of
BINAP on ligand design can be easily recognized from arguably the largest family of
analogous ligands (Figs. 7.4 and 7.5). Modifi cations of BINAP on the P-substituents and/
or the binaphthyl backbone have been studied in great detail. The well tuning of its
electronic and structural properties has expanded the application of these ligands in
almost every type of substrates. For example, partial hydrogenation of the binaphthyl
rings and/or replacement of the aromatic rings with fused heterocycles has resulted in a
few analogous ligands with different electronic properties. The electron-rich H
8
- BINAP
developed by Takaya and others was found to be more effi cient in the hydrogenation
of unsaturated carboxylic acids [20]. SEGPHOS, developed by Takasago International
Corp., was believed to also have a narrower bite angle compared with BINAP. This
ligand was proved to be more selective than BINAP in the Ru-catalyzed asymmetric
hydrogenation of a wide variety of carbonyl compounds [21]. A recent report revealed
that it also delivered good results in imine reductions [22]. To systematically study the
relationship between bite angles and enantioselectivities, the Zhang group has devel-
oped a family of ligands with tunable linkers within biphenyl backbone. It was found
that the favorable bite angle was strongly related to the specifi c type of substrate [23].
For instance, C2-TunePhos was the most effi cient ligand for Ru-catalyzed hydrogenation
