Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, Wisconsin 53706, USA.
J Org Chem. 2012 Mar 2;77(5):2446-55. doi: 10.1021/jo3000282. Epub 2012 Feb 14.
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.
含氮立体三联体存在于许多生物活性化合物中，但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反应，该反应可以在三个原始丙二烯碳原子中的每一个上安装新的碳杂原子键。本文描述了一种分子内/分子间丙二烯双氮丙啶化反应，它有可能作为构建含有相邻二氨基化模体的立体三联体的关键步骤。所得的 1,4-二氮杂螺[2.2]戊烷（DASP）支架含有两个电子差异的氮丙啶，它们在 C1 处与各种杂原子亲核试剂进行高度区域选择性环开环反应，得到手性 N,N-亚胺。或者，相同的 DASP 中间体可以诱导在 C1 和 C3 处进行双重环开环反应，生成相应于 C3 处的形式环开环的相邻二氨基化产物。炔丙醇的手性很容易以良好的保真度转移到 DASP 中，为构建手性含氮立体三联体提供了新的范例。
