An Efficient Synthesis of 2- and 2,6-Substituted Piperidines Using PdII-Catalyzed 1,3-Chirality Transfer Reaction
An Efficient Synthesis of 2- and 2,6-Substituted Piperidines Using PdII-Catalyzed 1,3-Chirality Transfer Reaction
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DOI：
10.1021/jo801926g
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发表时间：
2009-01-02
影响因子：
3.6
通讯作者：
Uenishi, Jun'ichi
中科院分区：
文献类型：
--
作者：
Hande, Sudhir M.;Kawai, Nobuyuki;Uenishi, Jun'ichi
发展了一种利用Pd Ⅱ催化的1，3-手性转移反应合成2-和2，6-取代哌啶的高效通用方法。各种N-保护的ζ-氨基烯丙醇在PdCl_2（CH_3CN）（2）存在下环化，得到具有高立体选择性的取代哌啶。以光学纯的烯丙醇（S）-14 c和（R）-14 c为原料，经3步反应合成了（S）-（+）-和（R）-（-）-毒芹碱。虽然在CH 2Cl 2中反应速率显著加快，但THF具有最高的立体选择性。PdCl_2（CH_3CN）（2）是该转化反应的最佳催化剂。提出了一个合理的反应途径，包括由手性仲烯丙醇指导的Pd π-络合物的形成，然后进行顺式氮杂钯化，随后进行顺式消除PdCl（OH）。
An efficient and general method for 2- and 2,6-substituted piperidine syntheses using Pd-II-catalyzed 1,3-chirality transfer reaction has been developed. The various N-protected zeta-amino allylic alcohols cyclize in the presence of PdCl2(CH3CN)(2) to give substituted piperidines with high stereoselectivities. The syntheses of (S)-(+)- and (R)-(-)-coniine were achieved in 3 steps from the optically pure allylic alcohols (S)-14c and (R)-14c, respectively. Although the rates of reactions were significantly accelerated in CH2Cl2, THF gave the highest stereoselectivity. PdCl2(CH3CN)(2) was found to be the best catalyst for this transformation. A plausible reaction pathway involving the formation of the Pd pi-complex directed by the chiral secondary allylic alcohol followed by syn-azapalladation, and subsequent syn-elimination of PdCl(OH) is proposed.