Institute for Organic Chemistry, Westfälische Wilhelms-Universität Münster , Corrensstrasse 40, 48149 Münster, Germany.
J Org Chem. 2017 Oct 6;82(19):9955-9977. doi: 10.1021/acs.joc.7b01281. Epub 2017 Jul 17.
Iteratively executed with exquisite spatial and temporal control, the selective isomerization of polarized alkenes underpins a plethora of complex biological processes ranging from natural product biosynthesis through to the mammalian visual cycle. However, nature's proficiency conceals the inherent difficulties in replicating this contra-thermodynamic transformation in the laboratory. Recently, we disclosed the first highly Z-selective isomerization of polarized alkenes, employing the cinnamoyl chromophore as a retinal surrogate under UV-irradiation (402 nm) with (-)-riboflavin (vitamin B) as an inexpensive, organic photocatalyst (J. Am. Chem. Soc. 2015, 137, 11254-11257). This study was inspired by the propensity of crystalline (-)-riboflavin in the eyes of vertebrates to invert the intrinsic directionality of retinal isomerization. Herein, we extend this methodology to include a bioinspired, catalytic E → Z isomerization of α,β-unsaturated nitriles, thereby mimicking the intermediate Opsin-derived, protonated Schiff base in the visual cycle with simple polarized alkenes. Replacement of the iminium motif by a cyano group is well tolerated and gives an additional degree of versatility for postisomerization functionalization. Broad substrate scope is demonstrated (up to 99:1 Z:E) together with evidence of mechanistic dichotomy via both singlet and triplet energy transfer mechanisms. Kinetic studies, temperature dependent photostationary state correlations and investigation of substituent-based electronic perturbation of the alkene identified polarization combined with increased Z-isomer activation barriers as the selectivity governing factors in catalysis. This investigation demonstrates the importance of internal structural preorganization on photostationary composition and explicates the augmented Z-selectivity upon hydrogen-alkyl exchange at the β-position of the alkene.
具有精湛时空控制能力的反复执行，对极化烯烃的选择性异构化支撑着从天然产物生物合成到哺乳动物视觉周期等多种复杂生物过程。然而，自然界的熟练程度掩盖了在实验室中复制这种反热力学转化的固有困难。最近，我们在紫外线照射（402nm）下，使用肉桂酰发色团作为视黄醛替代品，首次实现了极化烯烃的高 Z 选择性异构化，同时使用廉价的有机光催化剂（-）核黄素（维生素 B）（J. Am. Chem. Soc. 2015, 137, 11254-11257）。这项研究的灵感来自脊椎动物眼中结晶（-）核黄素倾向于反转视黄醛异构化的固有方向性。在此，我们将这种方法扩展到包括生物启发的、催化的 E→Z 异构化α,β-不饱和腈，从而用简单的极化烯烃模拟视觉周期中中间的 Opsin 衍生的质子化席夫碱。亚胺基 motif 被氰基取代得到很好的容忍度，并为异构化后功能化提供了额外的多功能性。展示了广泛的底物范围（高达 99:1 Z:E），并通过单重态和三重态能量转移机制证明了机制二分法的证据。动力学研究、温度依赖的光稳定态相关以及对烯烃取代基电子扰动的研究确定了极化和增加的 Z-异构体激活能垒是催化中选择性控制因素。这项研究表明了内部结构预组织对光稳定组成的重要性，并阐明了在烯烃的β位进行氢-烷基交换时增加的 Z 选择性。
