ICIQ-Institute of Chemical Research of Catalonia, Tarragona, Spain.
J Am Chem Soc. 2011 Sep 28;133(38):15212-8. doi: 10.1021/ja206517s. Epub 2011 Sep 2.
The Diels-Alder reaction is probably the most powerful technology in the synthetic repertoire for single-step constructions of complex chiral molecules. The synthetic power of this fundamental pericyclic transformation has greatly increased with the emergence of asymmetric catalytic variants, and research aimed at further expanding its potential is still exciting and fascinating the chemical community. Here, we document the first asymmetric catalytic Diels-Alder reaction of in situ generated heterocyclic ortho-quinodimethanes (oQDMs), reactive diene species that have never before succumbed to a catalytic approach. Asymmetric aminocatalysis, that uses chiral amines as catalysts, is the enabling strategy to induce the transient generation of indole-, pyrrole- or furan-based oQDMs from simple starting materials, while directing the pericyclic reactions with nitroolefins and methyleneindolinones toward a highly stereoselective pathway. The approach provides straightforward access to polycyclic heteroaromatic compounds, which would be difficult to synthesize by other catalytic methods, and should open new synthetic pathways to complex chiral molecules using nontraditional disconnections.
Diels-Alder 反应可能是合成复杂手性分子的单步构建中最强大的技术。随着不对称催化变体的出现，这种基本的周环转化的合成能力大大增强，旨在进一步扩大其潜力的研究仍然令化学界兴奋和着迷。在这里，我们记录了首例不对称催化的原位生成的杂环邻醌二甲基（oQDM）的 Diels-Alder 反应，这是一种从未通过催化方法得到的反应性二烯物种。不对称氨基催化使用手性胺作为催化剂，是从简单起始原料诱导瞬态生成吲哚、吡咯或呋喃基 oQDM 的有效策略，同时指导与硝基烯烃和亚甲基茚满酮的周环反应朝着高度立体选择性的途径进行。该方法提供了直接获得多环杂芳族化合物的途径，这些化合物很难通过其他催化方法合成，并且应该为使用非传统的切断法合成复杂手性分子开辟新的合成途径。
