1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine-bearing stereotriads.
1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine-bearing stereotriads.
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DOI：
10.1021/jo3000282
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发表时间：
2012-03-02
期刊：
影响因子：
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通讯作者：
Schomaker JM
中科院分区：
文献类型：
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作者：
Rigoli JW;Boralsky LA;Hershberger JC;Marston D;Meis AR;Guzei IA;Schomaker JM
含氮立体三单元体存在于许多生物活性化合物中，但获得这些化合物的通用且灵活的方法主要限于手性烯烃的操作。另一种方法是采用高度化学、区域和立体控制的丙二烯氧化，其可以在三个原始丙二烯碳中的每一个上安装新的碳-杂原子键。在本文中，一个分子内/分子间丙二烯双氮丙啶的描述，提供了潜在的作为一个关键步骤的立体三单元体含有邻位二胺基序的建设。所得的1，4-二氮杂螺[2.2]戊烷（DASP）骨架含有两个电子上不同的氮杂环丙烷，其在C1处与各种杂原子亲核试剂进行高度区域选择性开环，得到手性N，N-缩胺。或者，可以诱导相同的DASP中间体在C1和C3处进行双开环反应，以产生对应于在C3处的形式开环的邻位二胺化产物。炔丙醇的手性可以很容易地以良好的保真度转移到DASP上，为构建对映体富集的含氮立体三聚体提供了新的范例。
Nitrogen-containing stereotriads occur in a number of biologically active compounds, but general and flexible methods to access these compounds are limited mainly to the manipulation of chiral olefins. An alternative approach is to employ a highly chemo-, regio-, and stereocontrolled allene oxidation that can install a new carbon–heteroatom bond at each of the three original allene carbons. In this paper, an intramolecular/intermolecular allene bis-aziridination is described that offers the potential to serve as a key step for the construction of stereotriads containing vicinal diaminated motifs. The resultant 1,4-diazaspiro[2.2]pentane (DASP) scaffolds contain two electronically differentiated aziridines that undergo highly regioselective ring-openings at C1 with a variety of heteroatom nucleophiles to give chiral N,N-aminals. Alternatively, the same DASP intermediate can be induced to undergo a double ring opening reaction at both C1 and C3 to yield vicinal diaminated products corresponding to formal ring opening at C3. The chirality of a propargyl alcohol is easily transferred to the DASP with good fidelity, providing a new paradigm for the construction of enantioenriched nitrogen-containing stereotriads.