Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]‐ and Calix[12]pyrrole Analogues
Chiral Calix[3]pyrrole Derivatives: Synthesis, Racemization Kinetics, and Ring Expansion to Calix[9]‐ and Calix[12]pyrrole Analogues
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手性 Calix[3] 吡咯衍生物：合成、外消旋动力学以及扩环为 Calix[9]- 和 Calix[12] 吡咯类似物
DOI：
10.1002/anie.202301460
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Inokuma Yasuhide
中科院分区：
文献类型：
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作者：
Inaba Yuya;Yang Jian;Kakibayashi Yu;Yoneda Tomoki;Ide Yuki;Hijikata Yuh;Pirillo Jenny;Saha Ranajit;Sessler Jonathan L.;Inokuma Yasuhide
手性吡咯大环化合物继续引起人们的兴趣。然而，它们的分子设计仍然具有挑战性。在这里，我们报告了一个基于杯吡咯的手性大环系统，杯[1]呋喃[1]吡咯[1]噻吩（1），从低聚酮合成。大环1在固态时呈部分锥形构象，并通过环翻转进行外消旋化。分子动力学模拟表明，噻吩的转化是速率决定步骤。吡咯N-甲基化抑制外消旋并允许手性拆分。对映选择性N-甲基化也发生在手性铵盐的存在下，尽管立体选择性是适度的。1的一个独特特征是它作为一种有用的合成前体，产生几种杯[n]呋喃[n]吡咯[n]噻吩产物（n=2-4），包括杯[12]吡咯类似物，据我们所知，该类似物构成了结构表征的最大杯[n]吡咯类物质。
Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole‐based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene (1), synthesized from an oligoketone. Macrocycle1adopts a partial cone conformation in the solid state, and undergoes racemization via ring inversion. Molecular dynamics simulations revealed that inversion of the thiophene is the rate determining step. PyrroleN‐methylation suppressed racemization and permitted chiral resolution. EnantioselectiveN‐methylation also occurred in the presence of a chiral ammonium salt, although the stereoselectivity is modest. A unique feature of1is that it acts as a useful synthetic precursor to yield several calix[n]furan[n]pyrrole[n]thiophene products (n=2–4), including a calix[12]pyrrole analogue that to our knowledge constitutes the largest calix[n]pyrrole‐like species to be structurally characterized.