10.1002/ejoc.201800319
European Journal of Organic Chemistry
COMMUNICATION
Proline-rich short peptides with photocatalytic activity for the
nucleophilic addition of methanol to phenylethylenes
Sergej Hermann,[a] Daniel Sack,[a] and Hans-Achim Wagenknecht*[a]
Abstract: Short proline-rich peptides were synthesized and modified
with 1-(N,N-dimethylamino)pyrene by copper(I)-catalyzed
350 kJ/mol. Photoredox catalysis was developed as an important
method to overcome this principal problem.[5-14] It applies
photoinduced electron transfer processes instead of sensitization
in order to generate reactive radicals and radical ions. After
chemical transformation of those reactive intermediates to the
desired products, back electron transfer closes the photoredox
catalytic cycle. Transition metal complexes, mainly [Ru(bpy)3]Cl2,
are broadly applied photoredox catalysts.[11] Most recently,
organic dyes, in particular eosin Y,[12] 9-mesityl-10-methyl-
acridiniumperchlorat[13] and rhodamine 6G[14] are used to enhance
the sustainability and to broaden the substrate and reaction
scopes. We used 1-(N,N-dimethylamino)pyrene and 1,7-dicyano-
perylene-3,4:9,10-tetracarboxylic acid bisimide as photoredox
catalysts for the nucleophilic addition of alcohols to 1,1-
diphenylethylene (1) and other styrene derivatives to products
with Markovnikov-[15] and anti-Markovnikov orientation,[16]
respectively. These photocatalytic reactions, however, required
triethylamine and thiophenol, respectively, as additives to
enhance the photocatalytic efficiency by shuttling forward and
backward electron and proton transfers. Herein, we report short
proline-rich peptides modified with 1-(N,N-dimethylamino)pyrene
(Py) that not only allow to avoid triethylamine during photoredox
catalysis, but additionally give a closer look on their photocatalytic
activity by means of nucleophilic additions of MeOH to 1,1-
diphenylethylene derivatives 1a-1c into products 2a-2c with
Markovnikov orientation (Scheme 1). Especially the influence of
the secondary structure induced by proline residues on the
photocatalytic activity of the peptides was investigated.
cycloaddition. They perform photoredox catalysis of the nucleophilic
addition of methanol to 1,1-diphenylethylene derivatives into products
with Markovnikov orientation. The common additive triethylamine is
avoided because forward and backward electron transfer is controlled
by substrate binding. A free carboxylic function in the substrate allows
more precise substrate binding and defines the electron transfer path
better than the unspecific exciplex formation with the substrate
bearing a carboxylic ester. A proline-type turn is an advantage for
photoredox catalysis, but a proline-induced helix is not required. This
is the first successful example for introducing secondarily structured
peptides to photoredox catalysis.
Over the last ten years, peptides were developed as efficient
catalysts for a variety of important classes of organic reactions,
including acylations, epoxidations and C-C bond formation, in
particular aldol-like reactions. Especially the pioneering work by
Miller et al.[1] and Wennemers et al.[2] evidenced the huge
potential of small peptides as organocatalysts. On the one hand
they pointed out that short peptides consisting of less than 10
amino acids show astonishing catalytic activities, excellent
enantioselectivities and broad substrate scopes despite their
lower structural complexity compared to larger proteins or real
enzymes. On the other hand, short peptides are synthetically well
accessible, thus can be simply varied by their structure, and allow
chemical transformations in a variety of both organic and aqueous
solvents. However, short peptides with photoredox catalytic
activity are rarely found in literature. Early examples are peptides
as models for DNA photolyase that cleave thymidine-thymidine
dimers by photoinduced electron transfer processes.[3] Recently,
we published the synthesis of first peptide-based photoredox
catalysts for the nucleophilic addition of methanol to styrene
derivatives.[4]
Visible light provided by sunlight is an unlimited and thereby
“green” natural energy source. In the laboratory, LEDs are cheap
and energy-saving light sources for reproducible photocatalysis.
However, visible light does not provide enough energy to perform
important transformations in organic chemistry regarding carbon
bond energies. For instance, blue light (=440 nm) has an energy
of 270 kJ/mol that is not sufficient to cleave a typical C-C bond of
Scheme 1. Photocatalytic Markovnikov-type nucleophilic addition of MeOH to
substrates 1a-1c and proposed photocatalytic mechanism for the conversion to
products 2a-2c using Py-containing peptides as photoredox catalysts.
[a]
Dipl.-Chem. Sergej Hermann, Prof. Hans-Achim Wagenknecht
Institute of Organic Chemistry
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
E-mail: Wagenknecht@kit.edu
Supporting information for this article is given via a link at the end of
the document.
By excitation at approximately 400 nm, a singlet energy of
E00= 3.1 V adds to the oxidation potential of 1-(N,N-
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