Indolizidin-3-one

Crabtree, Johnson, and Tebby55 have studied the reaction of pyridine with methyl propiolate and found that the major product is 31, high-pressure hydrogenation of which resulted in loss of the acrylic ester side chain to give indolizidin-3-one, whereas treatment with piperidine gave a product (32) believed to be the indolizine [Eq. (8)]. 

The reductive cyclization of N-(w-iodoalkyl)succinimides induced by samarium(II) iodide was disclosed by Ha et al. as a novel method for making pyrrolizidines and indoUzidines (Scheme 46). " In the apphcation of the method to the synthesis of (+)-lentiginosine (127), reaction of N-(4-iodo-butyl)tartarimide (+)-335 with samarium(II) iodide in the presence of the iron(III)—tris(dibenzoylmethane) complex as catalyst produced the unsaturated indolizidin-3-one (+)-336 in 82% yield. Reduction of the bridgehead alkene was accomplished with triethylsilane and trifluoroacetic acid via an intermediate acyliminium ion, giving (+)-337 as the sole product in 93% yield. Routine hydrolysis of the silyl ethers produced the known diol (+)-177, after which reduction of the lactam with Hthium aluminum hydride then completed this short synthesis of (+)-127. 

Another route to (+)-lentiginosine (127) employing radical-mediated cyclization was developed by Chen and Tsai, who began by Mitsunobu coupling between the dithioacetal 338 and the 1-tartarimide 339 (Scheme 47) Chemoselective reduction of the product 340 with sodium borohy-dride was followed by conversion of the 5-hydroxypyrrohdin-2-one 341 via the acetate 342 into the 5-phenylthio derivative 343. Hydrolysis of the dithioacetal with iodobenzene bis(trifluoroacetate) then produced the acyl-silane 344. The key radical cyclization was performed with tributyltin hydride and AIBN as initiator to give the indolizidin-3-one 345 as a 4 1... 

---