Periodic Reporting for period 3 - Met_Cav (Metal-Functionalized Cavitands for a Site-Selective C-H hydroxylation of Aliphatic Compounds)
Okres sprawozdawczy: 2022-11-01 do 2024-04-30
One of the major constituents of petroleum, alkanes, are mostly considered as synthetic dead ends. This is because of the inertness of their C-H bonds and therefore 90% of them are just burnt as fuel. Currently, the only available industrial process for the conversion of alkanes into feedstocks chemicals is oil cracking, which is a major ecological concern all over the world. Therefore, activation of C-H bonds is one of the greatest challenges in modern chemistry and specifically their hydroxylation. This is because not only the resulting alcohols are valuable chemical products by themselves, but the hydroxyl moieties can easily be interconverted into nearly any other functional group. Such an effective and environmentally friendly process will open the doors for the fabrication of large-scale production of commodity chemicals from a natural feedstock.
In Nature, selective hydroxylation of C-H bonds is performed under mild conditions by metalloenzymes. Hypervalent transition metal-oxo cores were found to be the key reactive intermediates in these processes. The aim of this project is to develop artificial catalytic systems for C-H hydroxylation based on cavitands which are small (compered to enzymes) organic molecules containing an internal cavity. By embedding an active metal center capable of forming the reactive metal-oxo species at the bottom of their cavity, we hope to mimic the reactivity and the selectivity of the active site of natural metalloenzymes involved in C-H hydroxylation processes.
In Nature, selective hydroxylation of C-H bonds is performed under mild conditions by metalloenzymes. Hypervalent transition metal-oxo cores were found to be the key reactive intermediates in these processes. The aim of this project is to develop artificial catalytic systems for C-H hydroxylation based on cavitands which are small (compered to enzymes) organic molecules containing an internal cavity. By embedding an active metal center capable of forming the reactive metal-oxo species at the bottom of their cavity, we hope to mimic the reactivity and the selectivity of the active site of natural metalloenzymes involved in C-H hydroxylation processes.
During the first stage of our research all our efforts were dedicated to developing the synthesis of novel metallocavitands described in our proposal. These are bowl-shaped molecules functionalized with an active metal site at the bottom of their inner cavity. Preparation of such functional molecules requires a multi-step synthetic protocol. This synthesis starts with the construction of a lower rim of the "bowl" containing two nitrogen atoms positioned opposite to each other across the central pore. The nitrogen atoms are then used as joints for connecting this rim with the bottom part of the cavitand.
We developed a reliable synthesis of this key intermediate in order to be used as a starting material in all subsequent syntheses. We then prepared different linkers aimed to bridge two nitrogen atoms at the opposite position of the ring effectively forming the bottom part of this "bowl". By reaction with the rim which we performed, each of the linkers created a different kind of metal binding site at the bottom of the "bowl".
At this point, as a proof of concept we decided to study the coordination ability of these incomplete cavitands and reacted them with various Fe, Mn, and Co precursors. To our great satisfaction, formation of 1:1 complexes between the incomplete cavitand and those metals was confirmed by high-resolution mass spectroscopy, and in case of Fe(III), we were even able to obtained single crystals suitable for X-Ray diffractometry. The obtained molecular structure demonstrated that Fe(III) center was indeed bound at the designated position at the bottom of those incomplete cavitands. Most importantly, the orientation of a solvent molecule (toluene or acetonitrile) trapped within their shallow cavity was such that one of its C-H was closely approaching the metal center. However, instead of the anticipated square-pyramidal geometry the metal ion adopted a trigonal bipyramidal geometry with no free coordination site available for the envisaged formation of the metal-oxo. We believe that an additional stiffening of the scaffold by introduction of "bowl walls" is required in order to enforce the desired square-pyramidal geometry of the metal coordination sphere. We therefore are now working on constructing the "bowl walls" in order to complete the structures of metallocavitands envisaged in our proposal.
We developed a reliable synthesis of this key intermediate in order to be used as a starting material in all subsequent syntheses. We then prepared different linkers aimed to bridge two nitrogen atoms at the opposite position of the ring effectively forming the bottom part of this "bowl". By reaction with the rim which we performed, each of the linkers created a different kind of metal binding site at the bottom of the "bowl".
At this point, as a proof of concept we decided to study the coordination ability of these incomplete cavitands and reacted them with various Fe, Mn, and Co precursors. To our great satisfaction, formation of 1:1 complexes between the incomplete cavitand and those metals was confirmed by high-resolution mass spectroscopy, and in case of Fe(III), we were even able to obtained single crystals suitable for X-Ray diffractometry. The obtained molecular structure demonstrated that Fe(III) center was indeed bound at the designated position at the bottom of those incomplete cavitands. Most importantly, the orientation of a solvent molecule (toluene or acetonitrile) trapped within their shallow cavity was such that one of its C-H was closely approaching the metal center. However, instead of the anticipated square-pyramidal geometry the metal ion adopted a trigonal bipyramidal geometry with no free coordination site available for the envisaged formation of the metal-oxo. We believe that an additional stiffening of the scaffold by introduction of "bowl walls" is required in order to enforce the desired square-pyramidal geometry of the metal coordination sphere. We therefore are now working on constructing the "bowl walls" in order to complete the structures of metallocavitands envisaged in our proposal.