cyclopentadienyl complex [16]. In a related study about the same time, Rh 2 (OAc) 4
had been used as racemization catalyst leading to a less efficient DKR [17]
[For a DKR of allylic acetates using a lipase and PdCl 2 (MeCN) 2 , see 18]. Following
these early studies, a great portion of the recent research in alcohol and amine
DKR has focused on catalytic systems that combine heterogeneously immobilized
hydrolases with homogeneous Ru cyclopentadienyl complexes, because of their
high efficiency and broad substrate scope [14, 19–22]. However, with the recent
increasing interest in more green and efficient catalytic processes, there has
been a push to develop fully heterogeneous DKR systems that are easier to
separate and recycle. Thus, significant efforts have lately been dedicated toward
the development of more efficient heterogeneous racemization catalysts [14, 23].
Of the heterogeneous racemization catalysts developed so far, those based on
Pd NPs that operate through a transfer hydrogenation mechanism have been the
most successful, both in terms of efficiency and substrate scope. Following
the seminal discovery by the Reetz group already in 1996 [24], that commercial
Pd/C could be used as a racemization catalyst in a DKR, a number of research
groups started to evaluate and develop different kinds of nanopalladium-based
racemization catalysts. This work has yielded a wide range of Pd-based racemization
catalysts for amine DKR, in which the Pd NPs have been immobilized on different
support materials, such as alkaline earth salts [25, 26], aluminum oxyhydroxide [27–
29], sulfate-anion modified layered double hydroxide [30], and mesoporous silicas
[31–34].
Following the success of these fully heterogeneous DKR systems with separately
immobilized Pd NPs and enzymes, researchers soon became interested in studying if
it was possible to further improve the performance of such DKR systems by bringing
the two catalytic components closer together into so-called nanometal-enzyme
hybrids. The groups of Filice and Palomo were the first to create such a
nanometal-enzyme hybrid for DKR purposes, and they did so by simply mixing
Candida antarctica lipase B (CalB) with Pd(OAc) 2 in an aqueous media [35].
Here, the enzyme worked as the reducing agent for the Pd(II) ions, which mainly
produced small Pd NPs with an average diameter of 1.3 nm. Once formed, these
Pd NPs got entrapped within the enzyme structure, generating a heterogeneous
nanometal-enzyme hybrid composite that could be separated by centrifugation.
This Pd/CalB hybrid allowed for a quite effective DKR of 1-phenylethylamine
with 6 equiv. ethyl acetate as the acyl donor, resulting in 98% yield and >99%
ee of the corresponding (R)-amide within 4 h. Although this DKR was carried out
at a very small scale and under dilute conditions, it constituted the first proof of
concept that a single bifunctional hybrid catalyst could be used to mediate
both reactions of a DKR. Apart from showing the DKR application of this Pd/CalB
hybrid, the authors also demonstrated that it could be used as a catalyst for crosscoupling reactions and an ester hydrolysis/nitro reduction cascade of 4-nitrophenyl
butyrate as well.
A more practical Pd/CalB hybrid was subsequently reported by the group
of Bäckvall, where the Pd NPs and the enzyme were co-immobilized on
the same support material [36]. The Bäckvall group had previously developed
a heterogeneous catalyst based on Pd NPs immobilized on aminopropylNanocatalysis Meets Biology
247
had been used as racemization catalyst leading to a less efficient DKR [17]
[For a DKR of allylic acetates using a lipase and PdCl 2 (MeCN) 2 , see 18]. Following
these early studies, a great portion of the recent research in alcohol and amine
DKR has focused on catalytic systems that combine heterogeneously immobilized
hydrolases with homogeneous Ru cyclopentadienyl complexes, because of their
high efficiency and broad substrate scope [14, 19–22]. However, with the recent
increasing interest in more green and efficient catalytic processes, there has
been a push to develop fully heterogeneous DKR systems that are easier to
separate and recycle. Thus, significant efforts have lately been dedicated toward
the development of more efficient heterogeneous racemization catalysts [14, 23].
Of the heterogeneous racemization catalysts developed so far, those based on
Pd NPs that operate through a transfer hydrogenation mechanism have been the
most successful, both in terms of efficiency and substrate scope. Following
the seminal discovery by the Reetz group already in 1996 [24], that commercial
Pd/C could be used as a racemization catalyst in a DKR, a number of research
groups started to evaluate and develop different kinds of nanopalladium-based
racemization catalysts. This work has yielded a wide range of Pd-based racemization
catalysts for amine DKR, in which the Pd NPs have been immobilized on different
support materials, such as alkaline earth salts [25, 26], aluminum oxyhydroxide [27–
29], sulfate-anion modified layered double hydroxide [30], and mesoporous silicas
[31–34].
Following the success of these fully heterogeneous DKR systems with separately
immobilized Pd NPs and enzymes, researchers soon became interested in studying if
it was possible to further improve the performance of such DKR systems by bringing
the two catalytic components closer together into so-called nanometal-enzyme
hybrids. The groups of Filice and Palomo were the first to create such a
nanometal-enzyme hybrid for DKR purposes, and they did so by simply mixing
Candida antarctica lipase B (CalB) with Pd(OAc) 2 in an aqueous media [35].
Here, the enzyme worked as the reducing agent for the Pd(II) ions, which mainly
produced small Pd NPs with an average diameter of 1.3 nm. Once formed, these
Pd NPs got entrapped within the enzyme structure, generating a heterogeneous
nanometal-enzyme hybrid composite that could be separated by centrifugation.
This Pd/CalB hybrid allowed for a quite effective DKR of 1-phenylethylamine
with 6 equiv. ethyl acetate as the acyl donor, resulting in 98% yield and >99%
ee of the corresponding (R)-amide within 4 h. Although this DKR was carried out
at a very small scale and under dilute conditions, it constituted the first proof of
concept that a single bifunctional hybrid catalyst could be used to mediate
both reactions of a DKR. Apart from showing the DKR application of this Pd/CalB
hybrid, the authors also demonstrated that it could be used as a catalyst for crosscoupling reactions and an ester hydrolysis/nitro reduction cascade of 4-nitrophenyl
butyrate as well.
A more practical Pd/CalB hybrid was subsequently reported by the group
of Bäckvall, where the Pd NPs and the enzyme were co-immobilized on
the same support material [36]. The Bäckvall group had previously developed
a heterogeneous catalyst based on Pd NPs immobilized on aminopropylNanocatalysis Meets Biology
247