SmI2-Mediated Intermolecular Coupling of 纬-Lactam N-伪-Radicals with Activated Alkenes: Asymmetric Synthesis of 11-Hydroxylated Analogues of the Lead Compounds CP-734432 and PF-044752

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• 作者：Kong-Zhen Hu ; Jie Ma ; Shi Qiu ; Xiao Zheng ; Pei-Qiang Huang
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：March 1, 2013
• 年：2013
• 卷：78
• 期：5
• 页码：1790-1801
• 全文大小：561K
• 年卷期：v.78,no.5(March 1, 2013)
• ISSN：1520-6904

文摘

We report, for the first time, the synthesis of 8-aza-analogues of PGE₂. The SmI₂-mediated cross coupling reactions of 纬-lactam-hemiaminal 9, lactam 2-pyridyl sulfide 17, and lactam 2-pyridyl sulfone 18 with activated alkenes/alkyne were first developed, giving the corresponding 纬-lactams in 49鈥?8%, 45鈥?5%, and 75鈥?0%, respectively. The reactions of lactam 2-pyridyl sulfide and 2-pyridyl sulfone proceeded with 鈮?2:1 trans-diastereoselectivities. This represents the first intermolecular coupling reaction of the 纬-lactam N-伪-alkyl radicals of types B, B1, and B2 with activated alkenes. Two radical-based mechanisms were suggested. The asymmetric synthesis of the 11-hydroxylated analogue of the highly selective EP₄ receptor agonist PF-04475270 (30), the 11-hydroxylated analogue of ocular hypotensive CP-734432 (31), compounds 35 and 36 have been achieved on the basis of this method.