title: SmI2-mediated radical cross-couplings of α-hydroxylated aza-hemiacetals and N,S-acetals with α,β-unsaturated compounds: asymmetric synthesis of (+)-hyacinthacine A2, (-)-uniflorine A, and (+)-7-epi-casuarine.
abstract: The SmI(2)-mediated radical coupling reactions of β-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with α,β-unsaturated compounds are described. This method allows a rapid access to β-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids hyacinthacine A(2) (2), uniflorine A (3, 6-epi-casuarine), and the unnatural epimer 7-epi-casuarine (37) have been synthesized in four and five steps with overall yields of 34%, 16%, and 13%, respectively. The radical mechanism of the coupling reactions has been confirmed by controlled experiments, which also allowed deducing the anionic mechanism in the coupling between N,S-acetal 6 and carbonyl compounds. This demonstrates that the mechanisms of these SmI(2)-mediated reactions are switchable from Barbier-type anionic to radical by cooperative action of BF(3)·OEt(2) and t-BuOH.
authors.affiliation: Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.
authors.forename: Xue-Kui
authors.initials: XK
authors.lastname: Liu
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Xiang
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Ruan
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Huang
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis*; D001372:Aza Compounds / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006900:Hydroxylation; D007212:Indolizines / Q000138:chemical synthesis*; D007454:Iodides / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis*; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*; D012493:Samarium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D000470:Alkaloids; D001372:Aza Compounds; D005609:Free Radicals; D007212:Indolizines; D007454:Iodides; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; C409108:casuarine; C500284:hyacinthacine A2; C487671:uniflorine A; D012493:Samarium; C409809:samarium diiodide