DOI: 10.1002/cplu.201200203
Manganese Salen Compounds Embedded within Cross-Linked Chiral
Polyethylenimine: Asymmetric Epoxidation in an Aqueous Biphasic
Medium
Noam Levi and Ronny Neumann*[a]
Polyethylenimine and derivative polymers have been used as
enzyme mimics or surrogates, also called synzymes.[1] By at-
taching catalytic pyridoxamine and thiazolium moieties to the
polymer backbone they have also been used to mimic
enzyme-catalyzed transamination, and benzoin condensation
reactions.[2] In the past our research group has embedded
polyoxometalates and nanoparticles within alkylated polyethy-
lenimine derivatives to catalyze aqueous biphasic epoxidation
or carbon–carbon bond cleavage of alkenes, chemoselective
hydrogenation of alkenes, and lipophiloselective oxidation of
secondary alcohols.[3]
can also be augmented by template effects.[8] In addition, the
hydrophilic surface of the constructs enables reactions in an
aqueous biphasic mode, akin to a reaction catalyzed by
a water-soluble enzyme with its inherent advantages,[9] obviat-
ing the need for an organic solvent.
The synthetic pathway for the preparation of amphiphilic
cross-linked chiral polyethylenimines is presented in Scheme 1.
Short polyamino acids were prepared by the N-carboxyanhy-
dride (NCA) technique using a primary amine as a polymeri-
zation initiator.[10] The N-carboxy anhydrides of l-leucine (Leu)
and l-phenylalanine (Phe) were polymerized in the presence of
2-aminoacetonitrile to yield polyLeu and polyPhe terminated
by a cyanomethyl group. Simultaneous reduction of both the
amide and nitrile units with BH3 yielded a primary amine-termi-
nated, chiral linear polyethylenimine with non-polar side
chains, 1Leu and 1Phe. Cross-linked chiral linear polyethyleni-
mines with hydrophilic units were then prepared in two ways.
In method A, compound 1Leu was cross-linked at the primary
amine terminus with terephthaldehyde. The resulting Schiff
base was reduced with NaBH4 and then alkylated with 2-bro-
methanol to yield 2Leu. The MnIIIsalen catalyst, 4, was intro-
duced after formation of 2Leu to yield the MnSalen-2Leu cata-
lytic construct. Alternatively, in method B a cross-linker, 5, was
prepared by the reaction of 2-aminoethanol with two equiva-
lents of epichlorohydrin that was then reacted with com-
pounds 1 at the primary amine terminus in the presence of 4
to yield MnSalen-3Leu and MnSalen-3Phe.
Polymerization of the N-carboxyanhydride units of Leu and
Phe at a 6:1 ratio per 2-aminoacetonitrile yielded polyLeu and
polyPhe each terminated with one cyanomethyl group that
was then reduced to give 1Leu and 1Phe as determined by
ESI-MS (Figure 1). The spectrum of 1Leu is easy to decipher
with molecular peaks at m/z 458, 557, 656, 755, and 854 amu
for four to eight repeating units. Fragments for the molecular
peak minus the iso-butyl side chain were identified at m/z 500,
599, 698, and 797 amu. The spectrum of 1Phe shows consider-
able fragmentation. Molecular peaks were observed at 726 and
859 amu for five and six repeating units. Fragments of the mo-
lecular peaks minus the benzyl side chain were observed at
635 and 768 amu and fragments for the molecular peaks
minus the chain terminator NH2CH2CH2 were obtained at 684
and 817 amu. Other fragments including molecular peaks plus
Na+ were also observed. It would appear from the ESI-MS that
1Leu has a broader range of molecular weights (n=4–8) rela-
tive to 1Phe where mostly polymers of five and six repeating
units were obtained.
Conceptually our approach is based on a bottom-up prepa-
ration of an enzyme mimic with a metal-based active site. The
first step is the synthesis of an alkylated polyethylenimine that
assembles in water as globules with a hydrophilic surface and
a hydrophobic core. Such globules, which incorporate known
catalysts, can be considered primitive mimics of water-soluble
metalloenzymes. Importantly, the catalysts or guests are not
covalently attached to the polyethylenimine host, thus the ap-
proach is a general one, not requiring specific design of syn-
thetic procedures for the preparation of each catalyst system.[3-
a,b]
Similarly, more difficult to synthesize dendrimers and hyper-
branched polymers have been used as vehicles for the incor-
poration of catalysts into their cores.[4] Chiral dendrimers have
also been used in this context.[5] Because enzymes are often
cross-linked by cysteine, the second step imparts some rigidity
to the alkylated polyethylenimine constructs by the introduc-
tion of cross-linking moieties to yield hydrogel-like materials.[3c]
Herein, we proceeded to a third step through the relatively
simple preparation of chiral polyethylenimine polymers[6] that
can be cross-linked and then used to incorporate a MnIIIsalen
moiety as an active catalytic site.[7] In addition, we wished to
test the hypothesis that a chiral polyethylenimine globule with
a hydrophobic core can induce stereoselectivity to a catalytic
center by weak van der Waals, hydrogen bonding, and/or p–p
stacking interactions to lead to an enantioselective transforma-
tion. This is an approach that contrasts the one commonly
used in asymmetric catalysis, where a chiral ligand is com-
plexed to a catalytic center by strong interactions, such as co-
valent or coordination bonds, in order to give stereocontrolled
access to the active catalytic site, and where stereoselectivity
[a] Dr. N. Levi, Prof. R. Neumann
Department of Organic Chemistry
Weizmann Institute of Science
Rehovot, 76100 (Israel)
Constructs, such as MnSalen-3Leu containing 6.8 wt%
MnSalen are not freely soluble in water, but form a rather
Supporting information for this article is available on the WWW under
ChemPlusChem 2012, 00, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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