RESUMO
Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)-H fluorinations using Selectfluor® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H-TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3x higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.
RESUMO
The control of molecular motions is a central topic of molecular machine research. Molecular brakes are fundamental building blocks towards such goal as they allow deliberately decelerating specific motions after an outside stimulus is applied. Here we present azotriptycenes as structural framework for light-controlled molecular brakes. The intrinsic kinetics and their changes upon azotriptycene isomerization are scrutinized comprehensively by a mixed theoretical and variable temperature NMR approach. With azotriptycenes C-N bond rotation rates can be decelerated or accelerated reversibly by up to five orders of magnitude. Rate change effects are highly localized and are strongest for the C-N bond connecting a triptycene rotor fragment to the central diazo group. The detailed mechanistic insights provide a solid basis for further conscious design and applications in the future.
RESUMO
Imidazolidinone-based α,ß-unsaturated iminium ions are the reactive species within countless synthetic protocols in asymmetric organocatalysis. However, (E,Z) and (Z,Z) imidazolidinone iminium ions, i.e. (Z)-CîC configurations, have been elusive so far. Herein we describe how in situ photoisomerization enables the observation and assignment of high energetic (Z)-configured intermediates below the detection limit of NMR spectroscopy for (E,Z) and (Z,Z) iminium perchlorate complexes derived from MacMillan's 1st generation catalyst and cinnamaldehyde. Traces of (E,Z) could even be detected under synthetic conditions at 25 °C in MeCN. Using back isomerization studies and diffusion ordered spectroscopy, conditions were found to stabilize the (E,Z) and (Z,Z) isomers for several hours via ion pair aggregation. Thus, at least (E,Z) should be considered for future investigations in asymmetric iminium ion catalysis.
RESUMO
Of the methods for direct fluorination of unactivated C(sp3)-H bonds, photosensitization of SelectFluor is a promising approach. Although many substrates can be activated with photosensitizing catalysts, issues remain that hamper fluorination of complex molecules. Alcohol- or amine-containing functional groups are not tolerated, fluorination regioselectivity follows factors endogenous to the substrate and cannot be influenced by the catalyst, and reactions are highly air-sensitive. We report that benzoyl groups serve as highly efficient photosensitizers which, in combination with SelectFluor, enable visible light-powered direct fluorination of unactivated C(sp3)-H bonds. Compared to previous photosensitizer architectures, the benzoyls have versatility to function both (i) as a photosensitizing catalyst for simple substrate fluorinations and (ii) as photosensitizing auxiliaries for complex molecule fluorinations that are easily installed and removed without compromising yield. Our auxiliary approach (i) substantially decreases the reaction's induction period, (ii) enables C(sp3)-H fluorination of many substrates that fail under catalytic conditions, (iii) increases kinetic reproducibility, and (iv) promotes reactions to higher yields, in shorter times, on multigram scales, and even under air. Observations and mechanistic studies suggest an intimate 'assembly' of auxiliary and SelectFluor prior/after photoexcitation. The auxiliary allows other EnT photochemistry under air. Examples show how auxiliary placement proximally directs regioselectivity, where previous methods are substrate-directed.
