The successful use of dipyrromethanecarbinols in rational routes to porphyrinic macrocycles requires catalysis conditions that enable irreversible condensation, thereby avoiding substituent scrambling and formation of undesired porphyrin products. Previously, successful conditions of trifluoroacetic acid (TFA) (30 mM) in acetonitrile were identified following a lengthy survey of TFA and BF3-etherate catalysis in diverse solvents. In this study, focus was placed on the acid catalyst by examining 17 acids in CH 2 Cl 2, the traditional solvent for two-step, one-flask porphyrin syntheses. In the self-condensation of the carbinol derived from 1-(4-methylbenzoyl)-5-phenyldipyrromethane, porphyrin yields of 9–55% were obtained from the various acids, compared to 20% under TFA catalysis in acetonitrile. A number of catalytic conditions that produce little to no porphyrin in reactions of pyrrole + benzaldehyde afforded good yields of porphyrin and the suppression of scrambling in reactions of dipyrromethanecarbinols. The four best acid catalysts ( InCl 3, Sc ( OTf )3, Yb ( OTf )3, and Dy ( OTf )3) initially identified were then examined with dipyrromethanecarbinols bearing challenging substituents (alkyl, pyridyl, or no substituent). The greatest improvement was obtained with the pyridyl substrates. Selected reactions performed on a preparative scale (115 to 460 mg of isolated porphyrin) verified the results of the analytical-scale experiments and revealed the more facile isolation of the porphyrin from reactions performed in CH 2 Cl 2 rather than acetonitrile. This study provides alternatives to the use of TFA/acetonitrile that offer advantages in terms of yield and isolation of the porphyrin without sacrificing suppression of scrambling. Furthermore, the finding that poor catalysts for the benzaldehyde + pyrrole reaction can be excellent catalysts for dipyrromethanecarbinols provides guidance for the identification of other catalysts for use with reactive precursors in porphyrin-forming reactions.

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二吡咯甲烷甲醇缩合生成内消旋卟啉的酸催化剂研究

在生成卟啉大环化合物的合理途径中成功使用二吡咯甲烷醇需要能够实现不可逆缩合的催化条件，从而避免取代基加扰和不希望的卟啉产物的形成。此前，在对 TFA 和 BF 进行长期调查后，确定了乙腈中三氟乙酸 (TFA) (30 mM) 的成功条件3-在不同溶剂中的醚化催化。在这项研究中，通过检查 CH 中的 17 种酸，将重点放在酸催化剂上2氯2，用于两步一瓶卟啉合成的传统溶剂。在衍生自 1-(4-甲基苯甲酰基)-5-苯基二吡咯甲烷的甲醇的自缩合过程中，各种酸的卟啉产率为 9-55%，而乙腈中 TFA 催化下的卟啉产率为 20%。在吡咯 + 苯甲醛的反应中产生很少或不产生卟啉的许多催化条件提供了良好的卟啉产率并抑制了二吡咯甲烷甲醇反应中的加扰。四种最佳酸催化剂（InCl3, 钪 ( OTf )3, Yb ( OTf )3, 和镝 ( OTf )3) 然后用带有挑战性取代基（烷基、吡啶基或无取代基）的二吡咯甲烷甲醇进行检查。使用吡啶基底物获得了最大的改进。以制备规模进行的选定反应（115 至 460 mg 分离的卟啉）验证了分析规模实验的结果，并揭示了卟啉更容易从 CH 中进行的反应中分离出来2氯2而不是乙腈。该研究提供了使用 TFA/乙腈的替代方案，在不牺牲对加扰的抑制的情况下，在卟啉的产率和分离方面具有优势。此外，苯甲醛+吡咯反应的不良催化剂可以成为二吡咯甲烷甲醇的优良催化剂这一发现为识别其他催化剂与卟啉形成反应中的反应性前体一起使用提供了指导。