A Rapid, Solvent‐Free Phase‐Transfer Catalysis Procedure for N‐Alkylation of Dihydropyridones and Construction of the Indolizidine, Quinolizidine and Pyridoazepine Structures

Abstract

We have developed a solvent‐free phase‐transfer catalysis (PTC) method for the N‐alkylation of sulfur‐substituted dihydropyridone 4a to give products 5 with varying side‐chains and functional groups. Treatment of the chlorides 5a and 5c with NaI in acetone at reflux gave high yields of the iodides 6a and 6b. The reaction of iodides 7a and 7b with t‐BuLi at low temperature, followed by sequential treatment with HOAc and NaBH4, resulted in the formation of quinolizidine 8a and pyridoazepine 8b, respectively. Similar reaction of bromide 5j with t‐BuLi gave indolizidine 11.

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

“…Imino-Diels-Alder reactions are very useful for the synthesis of tetrahydropyridines [17][18][19]. We have previously developed a new imino-Diels-Alder reaction of thio-substituted 3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) to synthesize piperidine derivatives [20,21], and have used this method to prepare some indolizidines and quinolizidines [22][23][24][25][26][27][28][29][30][31][32]. We have recently reported the use of cross metathesis (CM) to transform the terminal alkenes 1a-c into the α,β-unsaturated esters 2a-c, and after detosylation the resulting amides 3a-c…”