Molecular Capsule Catalysis: Ready to Address Current Challenges in Synthetic Organic Chemistry?

Abstract

Self-assembled molecular capsules, host structures that form spontaneously when their building blocks are mixed, have been known since the 1990s. They share some basic similarities with enzyme pockets, as they feature defined hydrophobic binding pockets that are able to bind molecules of appropriate size and shape. The potential to utilize such host structures for catalysis has been explored since their discovery; however, applications that solve current challenges in synthetic organic chemistry have remained limited. In this short article, we discuss the challenges associated with the use of molecular capsules as catalysts, and highlight some recent applications of supramolecular capsules to overcome challenges in synthetic organic chemistry.

Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables β-selective O-glycosylations

“…It has been demonstrated that the entrapment inside capsules and cages can lead to different reactivities and selectivities compared to regular solution chemistry. 5,7,[10][11][12][13][14][15][16][17][18][19][20][21][22][23] One fascinating facet of substrate activation inside enzyme pockets, which has not been mimicked with man-made catalysts so far, involves proton wires. Proton wires enable the facile transfer of protons over long distances via hydrogen bonds.…”

Anion-Based Self-assembly of Resorcin[4]arenes and Pyrogallol[4]arenes

“…Hexameric capsules ( R4C ) 6 (H 2 O) 8 and ( P 4 C ) 6 (Figure a,b) are one of the largest and, at the same time, the easiest to obtain artificial capsules based on hydrogen bonds. , They spontaneously form by interactions between polyphenolic macrocycles [C-alkyl resorcin[4]­arenes ( R 4 C ) or C-alkyl progallol[4]­arenes ( P 4 C ) Figure a,b], enclosing >1000 Å 3 of the internal space. These hexameric capsules (found in the solid state , and low-polarity solvents) have unique encapsulation properties, exhibit high-fidelity self-sorting, and amazing enzyme-like catalytic activity. − They are nowadays considered the classics of supramolecular chemistry. ,− After many years of extensive studies, it seems that these macrocycles carry no mysteries. However, our recent studies performed for related compounds ([5]­arenes) demonstrated a new interaction model that has not been known before for polyphenolic macrocycles.…”

Optimized iminium-catalysed 1,4-reductions inside the resorcinarene capsule: achieving >90% ee with proline as catalyst

“…[2][3][4][5][6][7][9][10][11][12][13][14][15] More recently, this container has started being explored as a container for other catalysts 16 or as a catalyst itself. 17,18 The eld has been reviewed, [19][20][21][22][23] and novel applications have been found very recently. [24][25][26][27] In 2016, our group reported that iminium-catalysis can be performed inside capsule I (Fig.…”