Refined Synthesis of 2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin, a Deceptively Simple Precursor to Hydroporphyrins.
Refined Synthesis of 2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin, a Deceptively Simple Precursor to Hydroporphyrins.
复制标题
2,3,4,5-四氢-1,3,3-三甲基二吡林（一种看似简单的氢卟啉前体）的精制合成。
DOI：
10.1021/op050087e
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发表时间：
2005
影响因子：
3.4
通讯作者：
Lindsey,JonathanS
中科院分区：
文献类型：
--
作者：
Ptaszek,Marcin;Bhaumik,Jayeeta;Kim,Han-Je;Taniguchi,Masahiko;Lindsey,JonathanS
2，3，4，5-四氢-1，3，3-三甲基二吡咯（1）是合理合成二氢卟酚和氧代二氢卟酚的重要组成部分。现有的由吡咯-2-甲醛（2）合成1的五步反应采用相对简单和众所周知的反应，但存在一些缺点，包括规模有限（每次运行≤0.5 g 1）。已经制定了一个精简的编制办法，其中包括四个步骤：（i）2和硝基甲烷在纯净条件下的硝基羟醛缩合，得到2-（2-硝基乙烯基）吡咯（3），（ii）用NaBH 4还原3，得到2-硝基乙烯基吡咯（3），（2-硝基乙基）吡咯（4），（iii）4与异亚丙基丙酮在纯净条件下或在高浓度下进行Michael加成，得到γ-硝基环己酮-吡咯5，和（iv）用锌/甲酸铵还原环化5得到1。已经建立了几个多步变换，包括2 →1的直接变换。新方法的优点包括（1）步骤更少，（2）避免了几种有问题的试剂，（3）减少了溶剂和试剂的消耗，（4）减少了对色谱的依赖，以及（5）可扩展性。新的程序便于制备1克级。
2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin (1) is a crucial building block in the rational synthesis of chlorins and oxochlorins. The prior five-step synthesis of1from pyrrole-2-carboxaldehyde (2) employed relatively simple and well-known reactions yet suffered from several drawbacks, including limited scale (≤0.5 g of1per run). A streamlined preparation of1has been developed that entails four steps: (i) nitro-aldol condensation of2and nitromethane under neat conditions to give 2-(2-nitrovinyl)pyrrole (3), (ii) reduction of3with NaBH4to give 2-(2-nitroethyl)pyrrole (4), (iii) Michael addition of4with mesityl oxide under neat conditions or at high concentration to give γ-nitrohexanone-pyrrole5, and (iv) reductive cyclization of5with zinc/ammonium formate to give1. Several multistep transformations have been established, including the direct conversion of2→1. The advantages of the new procedures include (1) fewer steps, (2) avoidance of several problematic reagents, (3) diminished consumption of solvents and reagents, (4) lessened reliance on chromatography, and (5) scalability. The new procedures facilitate the preparation of1at the multigram scale.