Hemicryptophane

Keywords Phosphorylated hosts Cavitands Hemicryptophanes Complexation ... 

Fig. 14 Stereoview of the molecular structure of the hemicryptophane complex 22-toluene (hydrogen atoms have been omitted for clarity)...

Two isomers were expected according to the outside or inside orientation of the thiophosphoryl group. Only one isomer was characterized showing the P=S bond directed outside. The new hemicryptophane 22 presents a molecular cavity large enough to complex a toluene molecule as shown in the solid state structure depicted in Fig. 14. The toluene complex is stabilized through Van der Waals and specific r-interactions. 

Figure 6.46 The four isolated isomers of hemicryptophane 6.94 showing the two pairs of enantiomers along with their respective circular dichroism spectra (reprinted with permission from [66] 1996 American Chemical Society).

Gautier, A., Mulatier, J. C., Crassous, J., Dutasta, J. P., Chiral trialkanolamine-based hemicryptophanes Synthesis and oxovanadium complex. Org. Lett. 2005, 7, 1207-1210. 

An impressive threefold Ugi reaction using carefully designed trifunctional building blocks has been subsequently developed by Wessjohann (Scheme 22). This reaction unified eight components (74, 75, three equivalents each of formaldehyde and isopropylamine) via twelve reactions including two macrocyclization steps in a one-pot fashion to produce hemicryptophane 76 in 44% yield [99, 100]. 

Scheme 2.18 Scheme 2.18 Synthesis of the hemicryptophane 2.130. The X-ray crystal structure shows a toluene solvent molecule encapsulated within the host.

Fnnctionalizing the internal space of cryptophanes increases the range of applications that cryptophanes may have. For example, internal carboxylic acid groups allow the binding of metal cations. This, again, points to the development of more sophisticated hosts with nano-reactor capabilities, snch as the hemicryptophane able to act as a supramolecnlar catalyst throngh an internal vanatrane unit. 

This review is dedicated to the synthesis of water-soluble cryptophanes and of the closely related hemicryptophane derivatives that were developed more recently. The study of their binding properties with different species and some peculiar properties related to their chiral structure are also described. A particular attention is given to xenon-cryptophane complexes since, as above mentioned, these complexes have played a major role in the development of water-soluble cryptophane derivatives. We describe in a concise manner the different approaches, which have been reported in the literature to introduce hydrophilic moieties onto the cryptophane structure. Finally, we report some physical properties of the water-soluble cryptophane complexes. This mainly concerns the study of their binding properties with neutral molecules or charged species. The preparation of enantiopure cryptophanes has also contributed to the development of this field. Indeed, it was stressed that cryptophanes exhibit remarkable chiroptical and binding properties in water [11]. These properties are also described. The last part of this review is devoted to hemicryptophane derivatives, which are closely related to the cryptophane structure and which allow the functionalization of the inner space of the molecular cavity. These show a renewed interest in their applications in chiral recognition and supramolecular catalysis. 

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