Inducing Enantioselectivity in a Dynamic Catalyst by Supramolecular Interlocking

Abstract

The design of an ew class of fluxional biphenyl bisphosphinite (BIBIPHOS) ligands decorated with amino acid-based diamide interaction sites is reported that undergo spontaneous desymmetrization. Hydrogenation of prochiral alkenes using Rh-BIBIPHOS results in enantiomeric ratios of up to 96:4 (R/S). This stereoconvergent behavior of the fluxional BIBIPHOS ligand is triggered by pronounced intermolecular interlocking of the recognition sites,l eading to the formation of as upramolecular assembly,w here the axial orientation of the biphenyl ligand backbone is governed by the chirality of the amino acid moieties.S tereoinduction during catalysis is decoupled from this process and occurs as an immediate consequence of the emergent behavior of the ligands.T his supramolecular system is very robust and has the potential to be adopted for other ligand designs in enantioselective catalysis.Enantioselective interactions between molecules play apivotal role in aw ide range of natural processes.W hile this interaction is of non-covalent nature,i ti st he basis for molecular recognition and chirality transfer,p rocesses believed to be deeply rooted in natural chiral replication. [1] Understanding how non-covalent interactions can be used to exert enantiocontrol over chemical reactions promises farreaching possibilities for the future design of chiral catalysts. Therefore,g reat efforts have been made to find ways to enable enantiocontrol at the molecular level.Thec lassical supramolecular approach aims at the stabilization of am olecular skeleton by non-covalent interaction, which ideally results in catalysts with ac ertain selectivity. [2] Much less prevalent are examples where the nature of the chiral element is determined by the interaction itself.Inspired by nature,n ucleobase-derived ligands [3] as well as ligands bearing amino acid-derived interaction sites [4] have been reported, that mimic naturally occurring hydrogen bonding patterns in DNAorinproteins to enantioselectively generate self-assembled ligands with chiral axes.Other examples were reported where chiral molecules were capable of controlling the stereodynamic element of acatalyst [5] such as its helicity [6] or achiral axis [7] through non-covalent bonding.Amore elaborate feature that results from intermolecular interactions between different components of ac atalytic system, that is,d ifferent catalyst molecules,l igands,o r reagents,i st hat formation of aggregates can cause the emergence of nonlinear effects such as the amplification of asymmetric processes. [8] Particularly intriguing are autocatalytic reactions, [9] where this is induced by the product of the catalysis,a sm ost impressively demonstrated by Soai et al.

Enantioselectivity Induced by Stereoselective Interlocking: A Novel Core Motif for Tropos Ligands

“…The syntheses of the corresponding bisphosphinite ligands 9 a and 9 b has been reported by us in an earlier contribution. [19] Commercially available methyl vanillate 6 was dimerized to give compound 7. Subsequent ester cleavage and introduction of the selector units by two-fold amide formation yielded selector-modified biphenols 8 a,b, which were treated with chlorodiphenylphosphine in the final step of the reaction sequence to afford ligands 9 a,b.…”

“…We recently published preceding results of this phenomenon with a set of corresponding bisphosphinites, ligands 9 a and 9 b among them, and their respective biphenol precursors. [19] Herein, we expand by reporting a series of different phosphorous ligands with valine-and phenylalanine-based diamide selectors. Their self-assembling behavior was investigated, and the structure of the dimer was elucidated using singlecrystal X-ray structure analysis and NMR spectroscopy.…”

“…Results for ligands 9 a,b were taken from ref. [19]. Detailed experimental procedures can be found in the Supporting Information.…”

Asymmetric Induction and Amplification in Stereodynamic Catalytic Systems by Noncovalent Interactions

“…The investigated ligand design was found to trigger a process of spontaneous rotamer enrichment of the Ra isomer for all compounds (see Figure 7). [49][50][51][52] Comprehensive structural investigations revealed that the enrichment process is based on intermolecular interlocking of selector groups that entails the formation of highly-ordered ligand dimers. The point chirality of the amino acid-based selector units causes spatial confinement during this interaction, so that only the Ra rotamers can dimerize.…”

Design and synthesis of a stereodynamic catalyst with reversal of selectivity by enantioselective self‐inhibition

“…Earlier studies have shown that stereodynamic 3,3′‐methoxy‐2,2′‐biphenol‐based ligands with ( S )‐amino acid‐derived interaction sites (selectors) in the 5,5′‐position can be aligned by other ( S )‐amino acid‐derived diamides to induce the opposite stereo information during subsequent asymmetric hydrogenation reactions. Diamide selectors were found to interact in a highly enantioselective manner; however, overly efficient binding resulted in the formation of supramolecular ligand adducts and a concurrent loss of ligand's stereo dynamics . As a consequence, ligands with the same biphenyl core, decorated with ( S )‐phenylalanine‐derived amido ester groups, were to be investigated.…”