Conformationally rigid heterocycles

Besides the synthetic route depicted in 5.5. the seven membered central heterocyclic ring of iboga alkaloids was also accessed by the palladium mediated closure of the indole derivative bearing a pendant double bond shown in 5.21. The reaction is believed to be initiated by the palladation of indole in the 2-position followed by insertion of the double bond. Since fi-hydride elimination from the formed intermediate is blocked by the conformational rigidity of the system, the reaction stops at this stage and the addition of a reducing agent is required to remove the palladium and obtain the product.21... 

A new bis (sulfoxide) with conformational rigidity, 2,6-dithiaspiro[3.3] heptane 2,6-dioxide 51, which has axial asymmetry due to two puckered thietane ring systems, has been designed (13TA781).The four-membered heterocycle 52 is an isolable intermediate of the rhodium-catalyzed coupling of arenes with aziridines (13AGE2577). 

Enhanced conformational rigidity can be achieved by incorporation of the phosphorus atom in heterocycles, as shown with the achiral (1) [88] and a helical phosphite (2) (Figure 2.22) [46]. Incompletely condensed silsesquioxanes can likewise be used as a backbone for monophosphites 3 (POSSphites = polyhedral oligosilsesquioxanes phosphites) [86]. 

Thus, aside from furan-2-carboxaldehyde, where the equilibrium between conformers is rather sensitive to external effects, the 2-formyl derivatives of five-membered heterocycles are rather rigid from a conformational point of view. 

The bridged biphenyl (472) (67ZN(B)1296> has a rigid twist-boat-chair conformation in the crystal (72CC985) and is an eight-membered heterocycle with two torsional constraints in a 1,3 relationship. It has been resolved by chromatography on cellulose acetate, and AG for racemization is 120 kJ mol-1 (67M1323). 

An analysis of conformational flexibility of imidazole rings in guanine and adenine indicates that these heterocycles are much more rigid (Table 21.4). 

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