Bäckvall for their first hybrid catalyst, the authors started from a pre-synthesized
Pd nanocatalyst to which the enzyme was incorporated in the final step of the
synthetic sequence. However, in this system the CalB was not covalently
attached, but directly absorbed on the outer surface of the support particles. In DKR
experiments with 2 equiv. ethyl methoxy acetate as the acyl donor, this catalyst
showed good activity and enantioselectivity, although the chemoselectivity toward
the desired product was modest (98% conv, 63% yield, >99% ee after 8 h at 70
C
under 1 atm H 2 ). Also, the recyclability of this hybrid was found to be limited, which
was most likely due to the non-covalent enzyme immobilization method used.
A series of Pd/CalB-CLEA hybrids with a remarkably high activity in the DKR
of amines was also very recently described by Li et al. [49]. These hybrids were
prepared in analogous manner to the Pd/CalB-CLEA developed by the group
of Bäckvall, but instead of glutaraldehyde as the cross-linking agent, the authors
of this study used the aldehyde-functionalized triblock polymer of propylene
oxide to covalently link CalB together. The protein-polymer conjugate that
formed was then treated with different amounts of Pd(OAc) 2 and reduced, to give
Pd/CalB hybrids of varying Pd loadings and NP sizes. These hybrids allowed for
a highly efficient DKR of three benzylic amines at 55–65
C with 3 equiv. ethyl
acetate as the acyl donor, furnishing the corresponding (R)-amides in 60–99% yield
and in perfect ee. A noteworthy feature of this Pd/CalB hybrid catalyst was
that it enabled the racemization of amines in the absence of a H 2 atmosphere.
Furthermore, it exhibited a remarkable recyclability and allowed for the DKR of
1-phenylethylamine to be carried out ten times, giving >80% yield and 99% ee in
each cycle.
A conceptually different bifunctional hybrid catalyst for the DKR of amines
and alcohols was also recently described by the group of Chen [50]. This hybrid
catalyst was obtained by co-encapsulating Shvo’s dimeric Ru complex and CalB
into a soft nanocomposite consisting of 2-methylimidazole, Co ions, and the
biosurfactant sodium deoxycholate. Shvo’s dimeric Ru complex is a commonly
employed transfer hydrogen catalyst that has been used for a wide range of
oxidation and reduction reactions in organic synthesis [51], and in this hybrid
this complex was responsible for racemizing the alcohol and amine substrates.
Although this hybrid catalyst showed modest performance in the DKR of
1-phenylethylamine, the DKR of 1-phenylethanol worked fairly well and gave the
corresponding (R)-acetate product in 98% yield and 99% ee after 4 h at 70
C.
However, the recyclability of this Ru/CalB DKR hybrid catalyst was modest, and
over five cycles it was found to continuously lose activity.
2.2 The Application of Nanometal-Enzyme Hybrids for Other
Organic Transformations
Nanometal-enzyme hybrids have not only been applied for DKR reactions,
but they have also been used as catalysts for other organic transformations as
250
O. Verho and J.-E. Bäckvall
Pd nanocatalyst to which the enzyme was incorporated in the final step of the
synthetic sequence. However, in this system the CalB was not covalently
attached, but directly absorbed on the outer surface of the support particles. In DKR
experiments with 2 equiv. ethyl methoxy acetate as the acyl donor, this catalyst
showed good activity and enantioselectivity, although the chemoselectivity toward
the desired product was modest (98% conv, 63% yield, >99% ee after 8 h at 70
C
under 1 atm H 2 ). Also, the recyclability of this hybrid was found to be limited, which
was most likely due to the non-covalent enzyme immobilization method used.
A series of Pd/CalB-CLEA hybrids with a remarkably high activity in the DKR
of amines was also very recently described by Li et al. [49]. These hybrids were
prepared in analogous manner to the Pd/CalB-CLEA developed by the group
of Bäckvall, but instead of glutaraldehyde as the cross-linking agent, the authors
of this study used the aldehyde-functionalized triblock polymer of propylene
oxide to covalently link CalB together. The protein-polymer conjugate that
formed was then treated with different amounts of Pd(OAc) 2 and reduced, to give
Pd/CalB hybrids of varying Pd loadings and NP sizes. These hybrids allowed for
a highly efficient DKR of three benzylic amines at 55–65
C with 3 equiv. ethyl
acetate as the acyl donor, furnishing the corresponding (R)-amides in 60–99% yield
and in perfect ee. A noteworthy feature of this Pd/CalB hybrid catalyst was
that it enabled the racemization of amines in the absence of a H 2 atmosphere.
Furthermore, it exhibited a remarkable recyclability and allowed for the DKR of
1-phenylethylamine to be carried out ten times, giving >80% yield and 99% ee in
each cycle.
A conceptually different bifunctional hybrid catalyst for the DKR of amines
and alcohols was also recently described by the group of Chen [50]. This hybrid
catalyst was obtained by co-encapsulating Shvo’s dimeric Ru complex and CalB
into a soft nanocomposite consisting of 2-methylimidazole, Co ions, and the
biosurfactant sodium deoxycholate. Shvo’s dimeric Ru complex is a commonly
employed transfer hydrogen catalyst that has been used for a wide range of
oxidation and reduction reactions in organic synthesis [51], and in this hybrid
this complex was responsible for racemizing the alcohol and amine substrates.
Although this hybrid catalyst showed modest performance in the DKR of
1-phenylethylamine, the DKR of 1-phenylethanol worked fairly well and gave the
corresponding (R)-acetate product in 98% yield and 99% ee after 4 h at 70
C.
However, the recyclability of this Ru/CalB DKR hybrid catalyst was modest, and
over five cycles it was found to continuously lose activity.
2.2 The Application of Nanometal-Enzyme Hybrids for Other
Organic Transformations
Nanometal-enzyme hybrids have not only been applied for DKR reactions,
but they have also been used as catalysts for other organic transformations as
250
O. Verho and J.-E. Bäckvall