Synthesis of the verapamil intermediate through the quaternary carbon-constructing allylic substitution
Synthesis of the verapamil intermediate through the quaternary carbon-constructing allylic substitution
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通过季碳烯丙基取代合成维拉帕米中间体
DOI：
10.1055/s-0036-1588518
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发表时间：
2017
期刊：
影响因子：
2
通讯作者：
Keita Nishimura
中科院分区：
文献类型：
--
作者：
Yuichi Kobayashi;Ryohei Saeki;Yutaro Nanba;Yuta Suganuma;Masao Morita;Keita Nishimura
以（R，Z）-4-碘-5-甲基己-3-烯-2-醇的TBS醚为原料，在Pd（PPh 3）4催化下与烯丙基溴化镁偶联，合成了关键的吡啶甲酸仲烯丙酯。由3，4-（MeO）2C 6 H3 MgBr和Cu（acac）2按2：1的比例合成的铜试剂与吡啶甲酸酯发生烯丙基取代反应，得到手性完全转移的反式SN 2 ′产物，区域选择性为91%。烯烃部分的合成操作导致腈基，产生用于合成（S）-维拉帕米的中间体。
In the present study, the key secondary allylic picolinate was synthesized via Pd(PPh3)4-catalyzed coupling of the TBS ether of (R,Z)-4-iodo-5-methylhex-3-en-2-ol with allyl-MgBr. Allylic substitution of the picolinate with the copper reagent derived from 3,4-(MeO)2C6H3MgBr and Cu(acac)2in a 2:1 ratio afforded the anti SN2′ product with complete chirality transfer and 91% regioselectivity. Synthetic manipulation of the olefin moiety led to the nitrile group, generating the intermediate for the synthesis of (S)-verapamil.