Chiral 5-substituted 3-pyrrolin-2-ones

Addition of lithium derivatives of acetylenides (Li—C=C-C02R) to chiral nitrones proceeds with high stereoselectivity, giving a-acetylene substituted hydroxylamines (410a,b) (656). This reaction has been successfully applied to the synthesis of y-hydroxyamino-a, 3-ethylene substituted acids (411a,b), formed in the reduction of (410) with Zn in the presence of acid (657, 658), and to chiral 5-substituted-3-pyrroline-2-ones (412a,b) (Scheme 2.184) (658). 

Oba and coworkers observed racemization when eliminating a mesylate derived from a 4,5-cis-substituted pyrrolidin-2-one en route to a chiral 3-pyrrolin-2-one (2009TL5053). In order to combat this problem, they inverted the stereochemistry of the hydroxy group using a Mitsunobu-like reaction (Scheme 122). Treatment of alcohol 451 with iodine, polymer-supported triphenylphosphine (PS-PPh3), and imidazole gives the 3-pyrrolin-2-one 453 via intermediate iodide 452. 

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