Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins.
Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins.
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DOI：
10.1021/jo025503x
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发表时间：
2002-05
期刊：
影响因子：
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通讯作者：
Zhen-Jiang Xu;M. Kozlowski
中科院分区：
文献类型：
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作者：
Zhen-Jiang Xu;M. Kozlowski
研究了一类新的手性二胺配体1，5-二氮杂-顺式-十氢萘的构象平衡控制。设计了1，5-二氮杂-顺式-十氢化萘的手性2，6-和3，7-取代衍生物以稳定螯合锂所需的构象形式。这些衍生物以光学纯的形式从1，5-二氮杂-顺式-十氢萘开始合成。由于这些化合物的刚性和构象明确的性质，这些化合物作为手性二胺配体的潜力进行了研究。用这些配体进行了N-叔丁氧羰基吡咯烷和N，N-二异丙基邻乙基苯甲酰胺的不对称锂化取代反应，获得了高达60%ee。对于后一种底物，得到的结果跨越32%ee（R）至60%ee（S）的范围（Δ ee = 92%），其中1，5-二氮杂-顺式-十氢化萘配体仅在两个甲基取代基的位置上不同。不像许多其他的二胺已被用于不对称锂化取代反应，有限的构象灵活性的1，5-二氮杂-顺式-十氢化萘是类似于（-）-金鱼草碱，这些结果可能允许建设的结构-活性关系。
Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted derivatives of 1,5-diaza-cis-decalins were designed to stabilize the conformational form needed to chelate a lithium. These derivatives were synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to the rigid and conformationally well-defined nature of these compounds, the potential of these compounds as chiral diamine ligands was investigated. Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N-diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee was obtained. For the latter substrate, results spanning a range from 32% ee (R) to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands differing only in the location of two methyl substituents. Unlike many other diamines that have been employed in asymmetric lithiation-substitution reactions, the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous to (-)-sparteine such that these results may permit the construction of structure-activity relationships.