Book of Abstracts - Ruhr-Universität Bochum

OP-29
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Peptide-carbenes and peptide-phosphines transition metal catalysts for “Green”
solid phase catalysts.
Morten Meldal, *a Kasper Worm-Leonhard, a and Christian A. Christensen a
a Carlsberg Laboratory, SPOCC-Centre, Gamle Carlsberg Vej 10, 2500 Valby, Denmark,
E-mail: mpm@crc.dk
In Nature metalloproteins play a crucial role in complex biochemical transformations while displaying
exquisite regio- and enantio-selectivity. More importantly the protein framework coordinates the
catalytic metal and ensure substrate match and lower activation energy of the reaction to provide very
high turnovers, which in turn facilitates the efficient biochemical transformation at low concentration
of the catalytic protein.
These properties can advantageously be mimicked in the field peptide and peptide-organic chemistry
to putatively create catalysts for “green” chemistry. By engineering the peptide scaffold with one or
several ideal ligands for a variety of transition metals, e. g. Pd, Zn or Cu. artificial enzyme like
compounds, displaying selectivity and turnover for general organic chemistry transformations may be
obtained.
This presentation describes the synthesis and application of carbene- and phosphine-precursors for
incorporation into peptide frameworks that folds around a transition metal and forms relatively
compact and stable globular structures with an enzyme like binding cavity for substrate binding and
catalysis. The strategy is modular and well suited for a Split/Mix approach where a large number of
catalysts may be generated in a single combinatorial synthesis.
Backbone phosphinylated peptides (1) were synthesized on polar PEGA supports and in solution and
the catalytic activity was compared. The solid supported catalysts were very efficient and could be
recycled at least 5 times without loss of activity. The palladium coordination of the phosphine could
furthermore be combined with folding and complexation with other dedicated functional groups in the
peptide.
Backbone carbenes (2) formed extremely stable palladium-peptido carbene complexes that did not
loose any activity with time or use. These solid phase catalysts could be used in microwave assisted C-
C and C-N couplings in water with good selectivities and quantitative yields.
References
1. (a) C. A. Christensen and M. Meldal. Efficient Solid-Phase Synthesis of Peptide Based
Phosphine Ligands: Towards Combinatorial Libraries of Selective Transition Metal Catalysts.
Chem. Eur. J. 2004, 11, 4121-4131; (b) C. A. Christensen and M. Meldal. Solid-phase
synthesis of a P,S-ligand system designed for generation of combinatorial peptide-based
catalyst libraries. J. Comb. Chem. 2007, 9, 79-85.
2. (a) J. F. Jensen, K. Worm-Leonhard, and M. Meldal. Optically active (peptido-carbene)
palladium complexes: towards true combinatorial solid phase libraries of transition metal
catalysts. Eur. J. Org. Chem. 2008, 3785-3797 (b) K. Worm-Leonhard and M. Meldal. Green
catalysts: Solid-phase peptide carbene ligands in aqueous transition metal catalysis. Eur. J. Org.
Chem. 2008, 5244-5253.
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