Laboratory for Organic Chemistry, Swiss Federal Institute of Technology (ETH) Zürich, 8093 Zürich, Switzerland.
Chemistry. 2012 Feb 13;18(7):2006-13. doi: 10.1002/chem.201102859. Epub 2012 Jan 16.
The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8-C9 (τ(1)) and C9-C4' (τ(2)) bonds giving rise to four low energy conformers (1; anti-closed, anti-open, syn-closed, and syn-open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine-ammonium ion gauche effect (σ(C-H) → σ(C-F)*; F(δ-)⋅⋅⋅N(+)) encodes for two out of the four possible conformers (2). This constitutes a partial solution to the long-standing problem of governing internal rotations in cinchonium-based catalysts relying solely on a fluorine conformational effect.
奎宁生物碱的 C9 位起到分子铰链的作用，C8-C9（τ(1)）和 C9-C4'（τ(2)）键的内旋转导致四个低能量构象（1；反闭、反开、顺闭和顺开）。通过用构型定义的氟取代基取代 C9 手性中心，氟-铵离子 gauche 效应（σ(C-H) → σ(C-F)*；F(δ-)⋅⋅⋅N(+)) 可以编码四个构象中的两个（2）。这为仅依靠氟构象效应来控制基于 cinchonium 的催化剂中内部旋转的长期问题提供了部分解决方案。
