Functional cavitands: chemical reactivity in structured environments

Abstract

Container-shaped molecules provide structured environments that impart geometric bounds on the motions and conformations of smaller molecular occupants. Moreover, they provide "solvation" that is constrained in time and space. When inwardly directed functional groups are present, they can interact chemically with the occupants. Additionally, the potential for reactivity and catalysis is greatly enhanced. Deep cavitands, derived from resorcinarenes, nearly surround smaller molecules and have been one of the most successful platforms for elaboration with functional groups. Derivatives bearing organic and metal-binding functional groups have been shown to affect recognition properties and selectively accelerate diverse reactions. In this review, we examine recent examples of these systems with an emphasis on how and why ordered nanoenvironments impart changes in the properties and reactivity of their occupants.

Fig. 1.

The synthesis of deep cavitands from a resorcinarene platform. 1, 1,2-difluoro-4,5-dinitrobenzene, Et₃N, DMF, Δ. 2, SnCl₂, HCl, EtOH, Δ; or H₂, Raney Ni, toluene. 3, acyl chloride, K₂CO₃, EtOAc, H₂O; or acyl chloride, Et₃N, toluene. 4, ortho ester, DMF/CH₂Cl₂; or imidate, EtOH; or aldehyde, C₆H₅NO₂. The model structure of 5 has been minimized by using the AMBER force field, whereas that of 4 is truncated from the crystal structure (51). The R groups have been removed or truncated for viewing clarity.

Fig. 2.

Chiral cavitand 6 and its complex with norbornene. The ¹H NMR spectrum shows that norbornene is desymmetrized in this chiral environment. For example, normally equivalent hydrogens 1 and 4 appear as separate resonances.

Fig. 3.

Atwood's anion-capped cavitand 8 shown as a line drawing, and a rendition of the crystal structure of the encapsulated ion pair.

Fig. 4.

Structures of the octanitro and octaamide cavitands 9 and 10.

Fig. 5.

Functionalized cavitands. Parts of structures 12, 17, and 18 have been removed to show the positioning of the functional groups.

Fig. 6.

SDS complexed by water-soluble tetracarboxylic acid cavitand 19. The hydrocarbon tail of SDS coils to fill the space defined by the cavity, with hydrogen atoms deepest in the cavity shifted farthest up-field in the NMR spectrum.

Fig. 7.

Quinuclidine bound by the introverted methyl ester cavitand 20. One cavity wall has been removed, and ethyl groups are shown as methyl groups for clarity. Model structure of the pyridinone cavitand 18 in complex with the tetrahedral intermediate that is the result of the attack of propylamine on PNPCC.

Fig. 8.

Model structure of the zinc-salen cavitand with bound PNPCC and experimental kinetics curves for the hydrolysis reaction with increasing mol % catalyst loading. The water was present as a 0.01% impurity in commercial CH₂Cl₂.