Xu Shiqing, Lee Ching-Tien, Rao Honghua, Negishi Ei-Ichi
Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Dr., West Lafayette, IN 47907-2084, USA, ;
Adv Synth Catal. 2011 Nov;353(16):2981-2987. doi: 10.1002/adsc.201100420.
()-1-Halo-1-alkenylboranes (), preparable in 82-90% yields as ≥98% isomerically pure compounds via hydroboration of 1-halo-1-alkynes, have been converted to a wide range of trisubstituted alkenes via three different routes in the tail-to-head (-to-) direction, i.e., (i) Palladium-catalyzed Negishi-Suzuki tandem alkenylation, (ii) treatment of with organolithium or Grignard reagents to generate α-bromo-1-alkenylboronate complexes () that can undergo migratory insertion of a carbon group (R) to form ()-alkenylboranes () with inversion of alkene configuration (≥98% inversion), followed by fluoride-promoted Suzuki alkenylation, and (iii) Negishi coupling to generate ()-alkenylboranes () in ≥98% retention of configuration, followed by treatment with organolithium or Grignard reagents to produce trisubstituted alkenes with reversed stereo configurations. The synthetic utility of the present methodology has been demonstrated in the highly selective synthesis of side chain () of scyphostatin in 28% yield over nine steps in the longest linear sequence from allyl alcohol. Thus, this new tandem protocol has been emerged as the most widely applicable and highly selective route to trisubstituted alkenes including those that are otherwise difficult to prepare.
()-1-卤代-1-烯基硼烷（）可通过1-卤代-1-炔烃的硼氢化反应以82 - 90%的产率制备，产物为异构体纯度≥98%的化合物。通过三种不同的路线，可将其在头对头（-到-）方向转化为多种三取代烯烃，即：（i）钯催化的根岸-铃木串联烯基化反应；（ii）用有机锂试剂或格氏试剂处理以生成α-溴-1-烯基硼酸酯配合物（），该配合物可发生碳基团（R）的迁移插入反应，形成（）-烯基硼烷（），同时烯烃构型发生反转（反转率≥98%），随后进行氟化物促进的铃木烯基化反应；（iii）根岸偶联反应以≥98%的构型保留率生成（）-烯基硼烷（），随后用有机锂试剂或格氏试剂处理以制备具有相反立体构型的三取代烯烃。本方法的合成实用性已在水母毒素侧链（）的高选择性合成中得到证明，从烯丙醇出发，在最长线性序列的九步反应中，产率为28%。因此，这种新的串联方案已成为制备三取代烯烃最广泛适用且高度选择性的路线，包括那些难以制备的烯烃。
