1592000-36-6Relevant articles and documents
Molecular design exploiting a fluorine gauche effect as a stereoelectronic trigger
Rey, Yannick P.,Zimmer, Lucie E.,Sparr, Christof,Tanzer, Eva-Maria,Schweizer, W. Bernd,Senn, Hans Martin,Lakhdar, Sami,Gilmour, Ryan
, p. 1202 - 1211 (2014)
Acyclic conformational control often relies on destabilising noncovalent interactions to give rise to predictable conformer populations. Pertinent examples of such strategies include allylic strain (A1,2 and A 1,3) and syn-pentane interactions. However, the incorporation of fluorine vicinal to an electron-withdrawing group (F-Cβ-C α-X) can lead to predictable conformations as a consequence of stabilising hyperconjugative and/or electrostatic interactions. Herein, we describe the application of a fluorine gauche effect to predictably control torsional rotation in a class of fluorinated 4-(dimethylamino)pyridine (DMAP) analogues. Intramolecularisation, such as protonation or acylation, generates an electropositive nitrogen centre vicinal to the fluorine atom at a molecular hinge (F-Cβ-Cα-N+); this is the only rotatable sp3-sp3 bond. In so doing, this substrate binding triggers a conformational change akin to the induced fit process inherent to enzymatic systems. Herein, we validate this design approach to control molecular space. A number of X-ray structures are documented that display this gauche preference (φNCCF ≈ 60°). Preliminary catalysis experiments are disclosed together with a kinetic and reactivity analysis. The fluorine gauche effect was used to control torsional rotation in fluorinated dimethylamino pyridine (DMAP) analogues. Upon substrate binding an electropositive nitrogen centre vicinal to the fluorine atom at a molecular hinge (F-Cβ-Cα-N+) triggers a conformational change akin to those induced in enzymatic systems. Catalysis experiments and kinetic and reactivity studies are disclosed. Copyright
