Highly efficient synthesis of azabicyclo[x.y.0]alkane amino acids and congeners by means of Rh-catalyzed cyclohydrocarbonylation
Highly efficient synthesis of azabicyclo[x.y.0]alkane amino acids and congeners by means of Rh-catalyzed cyclohydrocarbonylation
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DOI：
10.1021/jo061692y
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发表时间：
2007-03-16
影响因子：
3.6
通讯作者：
Ojima, Iwao
中科院分区：
文献类型：
--
作者：
Chiou, Wen-Hua;Mizutani, Nobihiro;Ojima, Iwao
本发明描述了一种通过极高区域选择性的环氢羰基化（CHC）来高效合成1-氮杂双环[x.y.0]烷烃氨基酸衍生物及其同系物的方法。Rh-BIPHEPHOS络合物在温和条件下催化CHC反应。这些CHC反应过程涉及（i）脱氢二肽底物的末端烯烃部分的极线性选择性加氢，（ii）分子内缩合以形成环状N-酰基环己基关键中间体，和（iii）通过杂原子亲核试剂与环状N-酰基环己基部分的分子内亲核加成的第二环化以提供相应的1-氮杂双环[x.y.0]系统。这种连续的双环化过程在大多数情况下以极高的非对映选择性进行。该方法已成功地应用于1-氮杂双环[4.4.0]、-[5.4.0]和-[4.3.0]体系的合成。反应的机制和观察到的极高的非对映选择性的理由。这种Rh催化的CHC过程将作为一种高效和通用的方法，用于合成各种构象受限的二肽，肽模拟物，生物碱，和其他生物活性的天然或非天然产物。
A highly efficient method for the synthesis of 1-azabicyclo[x.y.0]alkane amino acid derivatives and their congeners by means of extremely regioselective cyclohydrocarbonylation (CHC) is described. The CHC reactions are catalyzed by Rh-BIPHEPHOS complex under mild conditions. These CHC reaction processes involve (i) an extremely linear-selective hydroformylation of the terminal alkene moiety of a dehydrodipeptide substrate, (ii) intramolecular condensation to form cyclic N-acyliminium key intermediate, and (iii) the second cyclization through intramolecular nucleophilic addition of a heteoatom nucleophile to the cyclic N-acyliminium moiety to afford the corresponding 1-azabicyclo[x.y.0] system. This consecutive double cyclization process proceeds with extremely high diastereoselectivity in most cases. This method has been successfully applied to the syntheses of 1-azabicyclo[4.4.0], -[5.4.0], and -[4.3.0] systems. The mechanisms of the reactions and the rationale for the observed extremely high diastereoselectivity are presented. This Rh-catalyzed CHC process would serve as a highly efficient and versatile method for the syntheses of a variety of conformationally restrained dipeptides, peptidomimetics, alkaloids, and other biologically active natural or unnatural products.