Intramolecular constitutional isomers

Indolizine is an aromatic 1 On-electron system and constitutional isomer of l-H indole and, consequently, has received a considerable theoretical and practical interest [100]. Considering the well-established fluorescence properties of indolizines [101-103] and biindolizines [102], and the steadily increasing importance of fluorophores in biolabeling and environmental trace analysis, we have been seeking for a new, efficient synthesis of fluorescent indolizines. Two general ways of indolizine syntheses have been known so far [100]. The first route is based on the intramolecular formation of the indolizine by cyclocondensation of suitable pyridinium precursors. However, the second approach takes advantage of a [3 + 2]... 

The products of the reaction between alkyldiphenylphosphines and hexachloro-ethane in the presence of a tertiary amine are the ylide (88) and the a-chloro-alkylphosphine (89), which are interchangeable, constitutional isomers that interconvert via an intramolecular reversible 1,2-chlorine shift from phosphorus to carbon. Application of the triphenylphosphine-hexachloroethane reagent for the self-condensation polymerization of / -aminobenzoic acid has been studied in detail. Related reactions between dicarboxylic acids and diamines, conducted in the presence of pyridine, involve the cationic phosphorane (90) as a key intermediate. Replacement of hexachloroethane by hexabromoethane or... 

The prediction of the partition properties of peptide molecules is difficult, owing to their conformational flexibility, and the possible presence of multiple intramolecular hydrogen bonds and ionizable groups. Richards and coworkers (40-42) were the first to consider explicitly the effects of the population of accessible conformational minima in both phases. These types of calculation are, however, computationally intensive. The introduction of the solvent-accessible surface area in the prediction of log Poct for steric isomers (43,44) also constitutes a promising approach. 

Using in situ prepared [AuOTfPPh3] as catalyst and relatively mild conditions, He and Yang obtained the first intramolecular addition to terminal alkenes [54]. Phenols and carboxylates were the nucleophiles chosen and several types of olefins, even unactivated ones, worked well in the reaction. In this study, the aforementioned authors also discovered gold s capacity for the constitutional isomerization of olefins, as demonstrated by the obtainment of the two isomers shown in Equation 8.16. 

The fluorescence quantum yield of 448 is 0.14, a sixfold increase relative to that of the parent. In comparison, the fluorescence quantum yield of 449 (0.01) is comparable to that of the parent compound. The phosphorescence emission quantum yield of 449 is 0.56 in a frozen matrix as expected as a result of the intramolecular heavy atom effect. In contrast, the phosphorescence is effectively shut off in the anti-isomer where the quantum yield is only 0.04. This observation suggests that the electronic excited state structures and nonradiative decay channels very considerably with constitution of the isomers. The optical gap energy was 3.1 (3.3) eV for 448 (449). 

The cooperative nature of two similar or different meta-related DMG enables DoM at the in-between site thus constituting a different route to continuous 1,2,3-substitution patterns (7) [9]. The analogous meta and para-related DMG isomers provide routes, most of which have not been tested, to other patterns which are a function of their relative hierarchy qualitatively established by inter-or intramolecular competition experiments (Scheme 3) [5],... 

Nonsymmetrical coupling reactions have been used extensively by Schafer and coworkers to generate a variety of natural products [1,8-10, 13-17]. A typical procedure calls for the use of a large excess (5-10 equivalents) of one of the acids. In conjunction with a total synthesis of the pheromone brevicomin [8] (21), compounds 24 and 25 (ratio of 5 1) were co-oxidized in methanolic potassium hydroxide to afford ketone 23 in 33% yield. The heterocoupling was complicated by the allylic nature of the radical derived from 24 the undesired coupling isomer constituted 12% of the product. Subsequent treatment of the desired isomer 23 with osmium tetroxide formed diol 22. Acid-catalyzed intramolecular ketalization led to brevicomin (21) in a 42% yield. 

Halophenols constitute the simplest structural model for the analysis of an intramolecular hydrogen bond since the syn-anti isomerization involves only the rotation of the OH proton around the single C—O bond. Furthermore, the two forms coexist in apolar solvents and give two characteristic absorptions in the OH stretching region of the IR spectrum with the notable exception of the fluoro derivative. In a series of papers Okuyama and Ikawa ° "° have re-examined by FTIR the relative stability of the syn-anti isomers by varying the temperature and the pressure. The enthalpies of isomerization are reported in Table 10. 

The cycloadduct 113 was then transformed into y,3-unsaturated cyclohexenone 114, which was subjected to intramolecular [4 + 2] cycloaddition. Upon exposure to pyrrolidine in MeOH at 60°C, enone 114 afforded intramolecular Diels-Alder adduct 116 in 78% yield after chromatography. This seemed to be the result of initial reversible iminium formation via dehydrative condensation of pyrrolidine and enone 114. Under the reaction condition, isomerization of the transient iminium species to several distinct dienamine constitutional and stereoisomeric forms would occur. Among all possible isomers in dynamic equilibration, only dienamine 115 is conducive to a favorable intramolecular Diels-Alder transition state, resulting in ketone 116 after enamine hydrolysis. The final steps of the synthesis involved Wittig methylenation followed by... 

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