High Activity and Efficient Turnover by a Simple, Self-Assembled “Artificial Diels–Alderase”

Abstract

The Diels-Alder (DA) reaction is a cornerstone of synthesis, yet Nature does not use catalysts for intermolecular [4+2] cycloadditions. Attempts to create artificial "Diels-Alderases" have also met with limited success, plagued by product inhibition. Using a simple PdL capsule we now show DA catalysis that combines efficient turnover alongside enzyme-like hallmarks. This includes excellent activity (k/k > 10), selective transition-state stabilization comparable to the most proficient DA catalytic antibodies, and control over regio- and chemoselectivity that would otherwise be difficult to achieve using small-molecule catalysts. Unlike other catalytic approaches that use synthetic capsules, this method is not defined by entropic effects; instead multiple H-bonding interactions modulate reactivity, reminiscent of enzymatic action.

A Self‐Assembled Cage with Endohedral Acid Groups both Catalyzes Substitution Reactions and Controls Their Molecularity

“…[12] As olution lies in endohedrally functionalized cage complexes, [13][14][15] which offer many possibilitiesi nc ontrolled biomimetic catalysis, [16,17] abovea nd beyonds imply increasing the effective concentration of bound substrate. The incorporation of active functions in an enclosed space enables reagent-controlled reactions to take place in enclosed cavities, as opposed to cycloadditions [18][19][20] or unimolecular rearrangements, [21,22] which are still the most commonr eactions studied in synthetic hosts. By internalizing reactive functional groups in ac age, the effect of substrate binding on nucleophilic substitution reactionsc an be investigated.…”

Selective Anion Recognition by a Dynamic Quadruple Helicate

“…In particular, cylindrical M 2 L 4 systems have received much attention. These have proven to be relatively easy to prepare in a rational way, and they provide a motif both for the recognition of anions, as might be expected given the positive charge on most cages, but also neutral molecules . Recognition of anions is topical, given that they are ubiquitous in biological systems and also because many are important pollutants in the environment …”

“…In summary,[ anion&Pd 2 (L 1 ) 4 ] 4 + quadrupleh elicates have been shown to bind ar ange of anions, with as electivity for ClO 4 À ,a nd that, by changing the helical pitch, the size of the internal cavity can be changed to match the size of the encapsulatedanion.…”

“…[1] In particular, cylindrical M 2 L 4 [2] systems have received much attention.T hese have provent ob er elativelye asy to preparei narational way, and they provide am otif both for the recognition of anions, [3] as might be expected given the positive chargeo nm ost cages, but also neutral molecules. [4] Recognition of anionsi s topical, given that they are ubiquitous in biological systems and also because many are important pollutantsi nt he environment. [5] In 1998, we reported the first example of aM 2 L 4 quadruple helicate, [6] formed from the reactiono fP d(py) 2 I 2 (py = pyridine) with two equivalents of 1,4-bis(3-pyridyloxy)benzene (L 1 )a nd excess NH 4 PF 6 ,g iving ap alec rystalline solid which was shown to be [PF 6 À &Pd 2 (L 1 ) 4 ](PF 6 ) 3 .A nX -ray crystal structurec onfirmed the helical nature of the host while NMR and Mass Spectrometry studies showed the internal PF 6 À to be effectively trapped within the cavity,s uggesting that some amount of host disassembly might be requiredf or the PF 6 À guest to escape.…”

Reaction Rate Inside the Cavity of [Ga4L6]12− Supramolecular Metallocage is Regulated by the Encapsulated Solvent

“…[9][10][11][12] Metallocages (M x L y )a re synthesized from metal ions and organic ligands( linkers) and offer well defined cavities in size and shape to host molecules and chemical reactions. [13,14] Examples include Raymond's Ga 4 L 6 (L = (L = N,N'bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene), [15] Fujita's Pd 6 L 4 (L = 1,3,5-tris(4-pyridyl)triazine), [16] Nitschke'st erphenyl edged Fe 4 L 6 , [17] Lusby's Pd 2 L 4 (L = 2,6-bis(3-pyridinylethynyl)pyridine), [18] among others. [19,20] The tetrahedron supramolecular metallocage, K 12 [Ga 4 L 6 ]d evelopedb yR aymonda nd co-workers,h as been applied to many reactions as the CÀCr eductive elimination from Au III and Pt IV complexes, [21] the orthoformate hydrolysis, [22] Nazarov cyclization, [23] the hydroalkylation, [24] etc.…”