Synthesis of γ-Butyrolactams by Photoinduced PhSe Group Transfer Radical Cyclization and Formal Synthesis of (±)-Isocynometrine with Diphenyldiselenide as Promoter

Abstract

We have developed a strategy for constructing nitrogen heterocycles by photoinduced PhSe group transfer radical cyclization. trans-Alpha,beta-disubstituted gamma-butyrolactams (2-pyrrolidinones) were prepared in good yields (38-73%) with high regioselectivity and stereoselectivity from N-alkenyl alpha-PhSe beta-keto amides. Reaction outcomes were modulated by the steric effect of the substituents on the nitrogen atom of the cyclization precursors and the stereoelectronic effect of the substrates. Diphenyldiselenide, as an additive, was found to promote ring closure. The advantage of this strategy in natural product synthesis is demonstrated by a formal synthesis of (+/-)-isocynometrine.

Selective Approach toward Multifunctionalized Lactams by Lewis Acid Promoted PhSe Group Transfer Radical Cyclization

“…A PhSe group transfer radical cyclization precursor, amido ester 1a , was synthesized as shown in Scheme . Since the steric bulkiness of substituents on the nitrogen atom of the tertiary amides significantly affects the cyclization efficiency, , bulky tert -butyl group was selected as the substituent on the nitrogen atom of the substrates. On one hand, the tert -butyl group locks the substrate in a conformation prone to cyclization; on the other hand, it can be readily removed by treatment with Lewis acid Sc(OTf) 3 , which is advantageous in syntheses of various substituted heterocycles.…”

“…In previous studies, we have demonstrated the possibility of enantioselective synthesis of carbocycles by bromo atom or PhSe group transfer radical cyclization of unsaturated β-keto esters catalyzed by chiral Lewis acids . Very recently, we reported a photoinduced PhSe group transfer radical cyclization of N -alkenyl β-keto amides and its application in the formal synthesis of (±)-isocynometrine . We report herein regiospecific and stereoselective synthesis of highly functionalized γ- and δ-lactams by exploiting Lewis acid promoted PhSe group transfer radical cyclization with amido esters as precursors.…”

Photochemical Synthesis of Azaheterocycles

“…Butyrolactams were also prepared photochemically by Yang et al 8 Starting with the α-seleno-β-keto amide 3 (Scheme 10), photoexcitation initiated a PhSe group transfer radical cyclization that generated a mixture of the desired product and the selenated intermediate 4. Subsequent treatment with H 2 O 2 resulted in oxidative elimination of the PhSe group to give the corresponding olefin.…”

Enantioselective synthesis of seven-membered carbo- and heterocyles by organocatalyzed intramolecular Michael addition

“…14 Keto ester 2a and diketo olens 2b-e were obtained by alkylation of the corresponding dianions derived from benzyl acetoacetate 1a or b-diketones 1b-e with 5-bromo-1-pentene. 15 Amide 2f was synthesized by aminolysis 16 of ethyl acetoacetate with benzyl 4-pentenyl amine 1f, whereas 2g was prepared by trans-esterication 17 of ethyl benzoylacetate with 4-penten-1-ol (Scheme 1).…”