The <i>in, out</i> Asymmetric Pseudo-Triple Helical Form of a <i>D</i>₃<i>_h</i> Diaza-Macropentacycle

A sterically encumbered [N2S6] macropentacycle (5) related to diazamacrobicycles and cryptands has been synthesized in 53% yield by the [1+1] condensation reaction between functionalized macrocyclic and macrotricyclic precursors. A macrononacycle (18) resulting from the corresponding [2+2] condensation was isolated in 7% yield from the reaction mixture. Both compounds showed broad features in their room-temperature 1H NMR spectra, but their maximal average symmetry (D3h and D2h, respectively) was achieved at high temperature (380 K). At low temperature (200 K, CD2Cl2 solution), the macropentacycle is “frozen” to a single asymmetric (C1) conformation on the 1H NMR time scale, which has also the molecular structure observed in the solid state by X-ray crystallography: pseudo-triple helical (≠C3) shape, io (in, out) form resulting from the endo/exo configuration at the nitrogen bridgehead atoms, and similar orientations of the tosyl substituents. The solution dynamics of the molecule can be described by coupled bridgehead nitrogen inversion, triple helix symmetrization, and reversal of triple helix handedness, with ΔGc⧧ = 54.2 kJ mol-1 in CD2Cl2 at 300 K. Adoption of the io form by macropentacycle 5 in the crystal and in solution at low-temperature most probably results from the steric crowding and strain introduced by the [15]ane-N2S2 macrocyclic bridging subunits.一种与二氮杂大环双环化合物（diazamacrobicycles）及穴状配体（cryptands）相关的位阻型[N2S6]大五环（5），通过功能化大环与大三环前驱体间的[1+1]缩合反应，以53%的产率合成得到。由对应[2+2]缩合反应生成的大九环（18），则从反应混合物中以7%的产率分离获得。两种化合物在室温氢核磁共振（1H NMR）谱中均呈现宽峰特征，但其最高平均对称点群分别为D3h和D2h，仅在高温（380 K）下可实现该对称状态。在低温（200 K，氘代二氯甲烷（CD2Cl2）溶液）条件下，该大五环在氢核磁共振时间尺度上"冻结"为单一不对称（C1）构象，该构象同样为其固态X射线晶体学观测到的分子结构：呈假三重螺旋（≠C3）构型，桥头氮原子的内/外（endo/exo）构型形成io（in, out）型，且对甲苯磺酰基取代基取向一致。该分子的溶液动态行为可通过协同桥头氮翻转、三重螺旋对称化及三重螺旋手性反转来描述，在300 K的氘代二氯甲烷溶液中，其吉布斯自由能活化能垒ΔGc⧧为54.2 kJ·mol⁻¹。大五环5在晶体及低温溶液中均采取io型构象，这一现象大概率源于[15]ane-N2S2型大环桥联亚基所引入的空间位阻与分子张力。