Computational Ligand Descriptors for Catalyst Design

Ligands, especially phosphines and carbenes, can play a key role in modifying and controlling homogeneous organometallic catalysts, and they often provide a convenient approach to fine-tuning the performance of known catalysts. The measurable outcomes of such catalyst modifications (yields, rates, selectivity) can be set into context by establishing their relationship to steric and electronic descriptors of ligand properties, and such models can guide the discovery, optimization, and design of catalysts. In this review we present a survey of calculated ligand descriptors, with a particular focus on homogeneous organometallic catalysis. A range of different approaches to calculating steric and electronic parameters are set out and compared, and we have collected descriptors for a range of representative ligand sets, including 30 monodentate phosphorus­(III) donor ligands, 23 bidentate P,P-donor ligands, and 30 carbenes, with a view to providing a useful resource for analysis to practitioners. In addition, several case studies of applications of such descriptors, covering both maps and models, have been reviewed, illustrating how descriptor-led studies of catalysis can inform experiments and highlighting good practice for model comparison and evaluation

Iron Catalyzed Double Bond Isomerization:Evidence for an FeI/FeIII Catalytic Cycle

Iron‐catalyzed isomerization of alkenes is reported using an iron(II) β‐diketiminate pre‐catalyst. The reaction proceeds with a catalytic amount of a hydride source, such as pinacol borane (HBpin) or ammonia borane (H3N⋅BH3). Reactivity with both allyl arenes and aliphatic alkenes has been studied. The catalytic mechanism was investigated by a variety of means, including deuteration studies, Density Functional Theory (DFT) and Electron Paramagnetic Resonance (EPR) spectroscopy. The data obtained support a pre‐catalyst activation step that gives access to an η2‐coordinated alkene FeI complex, followed by oxidative addition of the alkene to give an FeIII intermediate, which then undergoes reductive elimination to allow release of the isomerization product

Visible Light-Driven Strain-Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

There are a limited number of ring‐contraction methodologies which convert readily available five‐membered rings into strained four‐membered rings. Here we report a photo‐induced radical‐mediated ring contraction of five‐membered‐ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron‐rich alkenyl boronate complex, leading to an α‐boryl radical. Upon one‐electron oxidation, ring‐contractive 1,2‐metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups

Expansion of the ligand knowledge base for chelating P,P-donor ligands (LKB-PP)

[Image: see text] We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe(8)). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate ligand space, which better captures ligand variation and has been used for the analysis of ligand properties

Cooperative Lewis pairs based on late transition metals: activation of small molecules by platinum(0) and B(C6F5)3

A Lewis basic platinum(0)–CO complex supported by a diphosphine ligand and B(C6F5)3 act cooperatively, in a manner reminiscent of a frustrated Lewis pair, to activate small molecules such as hydrogen, CO2, and ethene. This cooperative Lewis pair facilitates the coupling of CO and ethene in a new way

Catalytic mechanism of the colistin resistance protein MCR-1

The mcr-1 gene encodes a membrane-bound Zn2+-metalloenzyme, MCR-1, which catalyses phosphoethanolamine transfer onto bacterial lipid A, making bacteria resistant to colistin, a last-resort antibiotic. Mechanistic understanding of this process remains incomplete. Here, we investigate possible catalytic pathways using DFT and ab initio calculations on cluster models and identify a complete two-step reaction mechanism. The first step, formation of a covalent phosphointermediate via transfer of phosphoethanolamine from a membrane phospholipid donor to the acceptor Thr285, is rate-limiting and proceeds with a single Zn2+ ion. The second step, transfer of the phosphoethanolamine group to lipid A, requires an additional Zn2+. The calculations suggest the involvement of the Zn2+ orbitals directly in the reaction is limited, with the second Zn2+ acting to bind incoming lipid A and direct phosphoethanolamine addition. The new level of mechanistic detail obtained here, which distinguishes these enzymes from other phosphotransferases, will aid in the development of inhibitors specific to MCR-1 and related bacterial phosphoethanolamine transferases.Royal Society of Chemistry (Reino Unido)Biotechnology and Biological Sciences Research Council (Reino Unido)Engineering and Physical Sciences Research Council (Reino Unido)Medical Research Council (Reino Unido)Depto. de Química FísicaFac. de Ciencias QuímicasTRUEpu