Fundamental Aspects of the Chiral Modification of Platinum with Peptides: Asymmetric Induction in Hydrogenation of Activated Ketones

A series of peptides, all containing the natural amino acid tryptophan (Trp), have been used as chiral surface modifiers for asymmetric hydrogenation reactions on alumina supported platinum catalysts. The surface chiral sites have been investigated using density functional theory calculations in order to elucidate the structure of the asymmetric environment produced by the adsorption of the peptides on the metal surface. As a test reaction, ketopantolactone (KPL) has been asymmetrically hydrogenated using the modified catalyst. Catalytic results were tested against a computational model to shed light on the phenomenon of chiral induction, The choice of Trp as the first member of the peptidic chain is due to its structural resemblance to cinchona alkaloids, already successfully used as modifiers for asymmetric hydrogenation reactions, The amino acidic moiety of Trp was elongated by addition of other natural amino acids via a peptidic bond, and the resulting peptides were tested as chiral modifiers. The indole moiety of Trp anchors the peptide by adsorbing parallel to the metal surface, while the amino acidic chain forms the chiral environment that promotes the asymmetric reaction, It is shown that Trp-based peptides greatly extend the class of chiral Surface modifiers for heterogeneous enantioselective hydrogenations. Peptides are in fact in principle simple to prepare, give access to a huge variety of tridimensional structures able to form stable chiral surface sites, and allow introduction of functional groups through peptidic bond elongation. A preliminary screening carried out in this work using a relatively low number of peptides shows enantioselectivities up to 30% for a choice of standard test asymmetric reactions oil platinum catalyst. The main features of the chiral environment created by the peptidic modifiers on the metal surface are described by means of first principle computational modeling. The enantioselectivity is interpreted using a computational docking model of KPL within the chiral site.