Synthesis of (S)-Nyasol through the Copper-catalyzed Propargylic Substitution
Synthesis of (S)-Nyasol through the Copper-catalyzed Propargylic Substitution
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铜催化炔丙取代合成 (S)-Nyasol
DOI：
10.1055/a-1968-2684
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发表时间：
2023
期刊：
影响因子：
2
通讯作者：
Yuichi Kobayashi and Takayuki Hirotsu
中科院分区：
文献类型：
--
作者：
Yuichi Kobayashi and Takayuki Hirotsu
选择(S)-Nyasol作为目标来证明铜催化取代仲丙基磷酸盐的效率。以TBDPSO(CH2)2CO2H为原料，分四步合成了关键磷酸(R)-TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)]OP(O)(OEt)2。在CuBr·Me2S的催化下，4-TBSOC6H4MgBr在THF-DME中取代磷酸盐，在丙炔位置具有立体选择性和区域选择性。将丙炔产物TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)]（C6H4-4-OTBS）中的硅基全部去除，并利用活性Zn还原乙炔键生成烷基烯烃。最后，HO(CH2)2片段转化为CH2=CH，得到(S)-nyasol，其顺性选择性为97%，ee为94.5%,>对映体特异性为99%。同样地，二氢甲酚是通过取代产物加氢，然后构建末端烯烃来合成的。
(S)-Nyasol was selected as a target to demonstrate the efficiency of a copper-catalyzed substitution of secondary propargylic phosphates. The key phosphate (R)-TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)]OP(O)(OEt)2was synthesized from TBDPSO(CH2)2CO2H in four steps. Substitution of the phosphate with 4-TBSOC6H4MgBr in the presence of CuBr·Me2S as a catalyst in THF–DME proceeded with both stereo- and regioselectivity at the propargylic position. All the silyl groups in the propargylic product, TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)](C6H4-4-OTBS) were removed, and the acetylene bond was reduced by using active Zn to produce thecis-olefin. Finally, the HO(CH2)2moiety was converted into CH2=CH, giving (S)-nyasol with 97%cisselectivity, 94.5% ee, and >99% enantiospecificity. Similarly, dihydronyasol was synthesized through hydrogenation of the substitution product, followed by construction of the terminal olefin.