Covalent Molecules as Templates

Apart from the cyclization around a metal ion, specific atoms or molecular groups can be construed as temporary, covalently bound templates. There is a fundamental difference between these and supramolecular host-guest systems, in that molecular recognition is not necessary rather, host and guest (here not functioning as such) are joined together by one or more covalent bonds from the outset. 

The stereoselective synthesis of sterically unhindered alkenes takes place according to this principle [29]. 

Acylation of 3,4,7,8-tetramethylglycoluril by the method of Sun and Harrison [34] leads to the monoacyl derivatives, which can be further selectively acylated with lithium diisopropylamide (LDA) and acyl chlorides. The resulting symmetrical or asymmetrical diacyl compounds undergo a base-catalyzed acyl transfer reaction. Consequently, the glycoluril acts as a temporary template that facilitates a condensation between acyl units. The absence of O-acylation products is explained by chelation of the lithium by the intermediate enolate. 

The functionalized phane tetracation 30 was synthesized by Harriman and coworkers [41] in a one-pot cyclization from 2,5-dibromomethylbenzoic acid and 4,4 -bipyridine via a zwitterionic structure. 

---