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.
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.
复制标题
DOI：
10.1021/jo200600n
复制
发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Xue-Kui Liu;Shi Qiu;Yong-Gang Xiang;Yuanping Ruan;Xiao Zheng;Pei‐Qiang Huang
中科院分区：
文献类型：
--
作者：
Xue-Kui Liu;Shi Qiu;Yong-Gang Xiang;Yuanping Ruan;Xiao Zheng;Pei‐Qiang Huang
本文报道了SmI（2）介导的β-羟基吡咯烷/哌啶氮杂半缩醛8和9及N，S-缩醛6和33与α，β-不饱和化合物的自由基偶联反应。该方法允许快速获得β-羟基化的吡咯烷、哌啶、吡咯烷酮和吲嗪酮。以N，S-缩醛33为起始原料，经中间体27，经四步和五步合成了风信子碱A（2）（2）、单花碱A（3，6-表箭毒碱）和非天然差向异构体7-表箭毒碱（37），总收率分别为34%、16%和13%。通过控制实验证实了偶联反应的自由基机理，并推测了N，S-缩醛6与羰基化合物偶联反应的阴离子机理。这表明SmI（2）介导的反应机理是通过BF（3）·OEt（2）和t-BuOH的协同作用从Barbier型阴离子反应转变为自由基反应。
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.