Synthesis of Quinolizidinone and Indolizidinone Using N-Acyliminium Ion Cyclization and a One-Pot Procedure for Preparation of Benzoquinolizidinone

Scaffold Diversity from N-Acyliminium Ions

“…Kuntiyong and co-workers reported several examples of the synthesis of tricyclic quinolidizdinone scaffolds. − In an effort to synthesize the tricyclic core of the marine natural products referred to as schulzeines, the tricyclic scaffold of tetrahydroisoquinoline fused with δ-lactam 164 was synthesized from the hydroxylactam 163 in the presence of Lewis acid . Hydroxylactam substrate 165 , readily obtained from DIBAL-H reduction of the corresponding piperidine-2,6-dione substrate, was cyclized to the tricyclic compound 166 using TMSOTf as the acid to form NAIs in situ (Scheme ).…”

Enantiodivergent Synthesis of Benzoquinolizidinones from L-Glutamic Acid

“…Chiral sulfoxide and Oppolzer's sultam were used as a chiral auxiliary for such reaction, as reported by Koomen [15] and Czarnocki [16], respectively, while enantioselective syntheses featuring asymmetric hydrogenation and allylation of dihydroisoquinoline intermediates have also been reported [17]. We have previously reported a diastereoselective synthesis of benzoquinolizidinone and indoloquinolizidinone cores using cyclization of chiral N-acyliminium ion derived from L-glutamic acid and arylethylamine and tryptamine, respectively [18]. The amine was coupled with benzyl N,N-dibenzylglutamate to give the corresponding amide.…”

“…This functionality is suitable for further manipulation to install additional substituents via Michael and hetero-Michael addition. We have previously reported a diastereoselective synthesis of benzoquinolizidinone and indoloquinolizidinone cores using cyclization of chiral N-acyliminium ion derived from L-glutamic acid and arylethylamine and tryptamine, respectively [18]. The amine was coupled with benzyl N,N-dibenzylglutamate to give the corresponding amide.…”

Diastereoselective Synthesis of Tetrahydrofurano[2,3-g]indolizidines and 8-Aminoindolizidines from l-Asparagine

“…Previously, we reported a synthesis of dibenzylaminoindolizidine 13 from N-(3-buteny)succinimide 11. 17 Reduction of the succinimide with LAH resulted in the corresponding hydroxylactam. The reduction occurred exclusively at the less hindered carbonyl.…”

“…Previously, we reported a synthesis of the (dibenzylamine)indolizidine 13 from the N -(but-3-en-1-yl)succinimide 11 (Scheme 1 ; bottom). 17 Reduction of succinimide 11 with LAH gave the corresponding γ-hydroxy lactam, with the reduction occurring exclusively at the less-hindered carbonyl group. 18 The hydroxy lactam underwent N -acyliminium ion cyclization to give the indolizidinone 13 as a single product.…”