Pyrroline-3-ones

Pyrrolin-3-ones alkylation, 4, 301 oxidative dimerization, 4, 304 synthesis, 4, 365... 

A-Acyliminium precursors in tetracarbonyliron-mediated stereoselective alkylations of 5-(R)-isopropoxy-3-pyrrolin-3-ones 98EJ01729. 

FIGURE 14.28 The vinylogous relationship between the carbonyl and the amino group in pyrroline-3-ones gives them the reactivity of secondary amidesd ... 

Pyrroline-3-ones were used as peptidic bond surrogates by Hirsehmann et al. In sueh compounds (Figure 14.28), thanks to vinylogy, the earbonyl and the amino group show the same chemieal reaetivity to that of a secondary amide. 

More unusual isosteric replacements for the pwptidic bond were recently proposed (Fig. 13.18). Among them hydroxyethylureas served in the design of a novel class of potent HTV-1 protease inhibitors, diacylcyclopropanes in the design of novel renin inhibitors, and pyrroline-3-ones for various proteolytic enzyme inhibitors. Vinyl fluorides can probably be considered as representing the closest possible bioisosteres of the peptide bond. The synthetic methods available allow, by an appropriate selection of... 

Hydrolysis of the trifluoroacetyl-derivative (153) produces a mixture of the pyrrolin-2-ones (154) and (155) the latter is unstable, and gradually isomerizes to the former." Whereas the 7V-benzyl- and N-phenyl-pyrrolin-3-ones (156 R = CH2Ph or Ph) exist in the keto form shown, the iV-methyl derivative forms an equilibrium mixture of keto (156 R = Me) and enol tautomers (157)." The reaction of the pyrrolinone (158) with p-nitrobenzaldehyde unexpectedly yields compound (159)." The product of the action of thiobenzoic acid on (160) is the spiro-pyrrolinone (161), contrary to a previous report." Treatment of p-hydroxyphenylacetic acid with di-isopropylcarbodi-imide gives the imino-pyrrolinone (162), which rearranges to the bridged spiro-compound (163) in the presence of boron trifluoride etherate." ... 

In the similar iodocyclization of a-amino ynones 41 (Scheme 24), PEG MOO was a less effective solvent and better yields of 42 were obtained at room temperature with acetonitrile as a solvent [47]. However, the a-amino ynones 41 underwent 5-endo-dig cycloisomerization in PEG 3400 rmder microwave irradiation in the presence of platinmn(ll) chloride affording pyrrolin-3-ones 43 [48]. In the presence of potassium carbonate, the reaction proceeded without substantial epimerization of the products 43. The recyclability of tiie catalytic system and PEG 3400 was also investigated. 

---