Ring-constrained derivatives

Molecular models reveal that the five-membered ring constrains the azepine nucleus in a near planar conformation with the result that the oxazoloazepine (232 n = 1), unlike most other Af-acyl-1//-azepines, is unstable and dimerizes spontaneously in a highly selective [6+4] manner (see Section 5.16.3.2.3). In contrast, the oxazinoazepine (232 n= 2) formed in 26% yield by FVP of phenethyl azidoformate is less strained and is stable as the monomer (8ICC 1087). Likewise, the benzoxazinoazepine (233), derived from biphenyl-2-yl azidoformate, is thermally quite stable, but in acid rearranges to 2-(o-hydroxyphenyl)-3/7-azepine (81CC241). 

Aldehydes and phosphole-derived nonstabilized ylides react with a kinetic preference for the ( )-alkene (Table 13). Since the phosphole ring constrains bond angles for two of the three phosphorus ligands, ylide 125 will preferentially react via the TS geometry 126 (Scheme 18 similar to 119 or 120). The role of... 

Table 1. Ring-constrained cycloaddition of chloroacetylated alkynes 2b-e derived from alkylamines.W...

The hemispherands, spherands, calixarenes, and related derivatives. A number of hosts for which the pre-organization criterion is half met (the hemispherands) (Cram et al., 1982) or fully met (the spherands) (Cram, Kaneda, Helgeson Lein, 1979) have been synthesized. An example of each of these is given by (251) and (252), respectively. In (251), the three methoxyl groups are conformationally constrained whereas the remaining ether donors are not fixed but can either point in or out of the ring. This system binds well to alkali metal ions such as sodium and potassium as well as to alkylammonium ions. The crystal structure of the 1 1 adduct with the f-butyl ammonium cation indicates that two linear +N-H - 0... 

The most common bicyclic 5-6 system with one bridgehead N-O and one extra heteroatom described in the period covered in this chapter has been the diketopiperazine derived from proline as it is present in natural products, in biologically active synthetic molecules, and has been used as starting material for the preparation of conformationally constrained peptidomimetics. The classical approach to this class of molecule is the ring closing of the dipeptide derived from proline and another amino acid via nucleophilic attack of the NH2 to the activated carboxylic group. This method has been applied several times to prepare different diketopiperazines for different uses. 

Cyclization of parts of the PAF molecular backbone produces the second family of PAF-related antagonists, those with a constrained framework. For example, insertion of a tetrahydrofuran ring has led to derivatives such as SRI 63-072 (8), SRI 63-441 (9a), SRI 63-675 (9b) and BN 55009 (10). The... 

Polynitro derivatives of pentacyclo[5.4.0.0 .0 °.0 ]undecane have attracted interest as potential high-energy explosives. Molecular strain in this caged system could arise from both the constrained norbomyl moiety and the cyclobutane ring. Additional strain would be expected from nonbonding interactions if the S-endo and 1 l-endo positions were substituted with gm-dinitro groups. 

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