The origin of selectivity in the α-fluorination of cyclic ketones catalyzed by cinchona alkaloid-derived primary amines is determined with density functional calculations. The chair preference of a seven-membered ring at the fluorine transfer transition state is key in determining the sense and level of enantiofacial selectivity.

Boron tris(trifluoroacetate) is identified as the first effective catalyst for the homoallyl- and homocrotylboration of aldehydes by cyclopropylcarbinylboronates. NMR spectroscopic studies and theoretical calculations of key intermediates and transition states both suggest that a ligand-exchange mechanism, akin to our previously reported PhBCl2-promoted homoallylations, is operative. Our experimental and theoretical results also suggest that the catalytic activity of boron tris(trifluoroacetate) might originate from more facile catalytic turnover of the trifluoroacetate ligands (in agreement with DFT calculations) or from a lower propensity for formation of off-pathway reservoir intermediates (as observed by (1)H NMR). This work shows that carboxylates are viable catalytic ligands for homoallyl- and homocrotylations of carbonyl compounds and opens the door to the development of catalytic asymmetric versions of this transformation.

Saturated heterocycles are found in numerous therapeutics and bioactive natural products and are abundant in many medicinal and agrochemical compound libraries. To access new chemical space and function, many methods for functionalization on the periphery of these structures have been developed. Comparatively fewer methods are known for restructuring their core framework. Herein, we describe a visible light-mediated ring contraction of α-acylated saturated heterocycles. This unconventional transformation is orthogonal to traditional ring contractions, challenging the paradigm for diversification of heterocycles including piperidine, morpholine, thiane, tetrahydropyran, and tetrahydroisoquinoline derivatives. The success of this Norrish type II variant rests on reactivity differences between photoreactive ketone groups in specific chemical environments. This strategy was applied to late-stage remodeling of pharmaceutical derivatives, peptides, and sugars.

The construction of complex aza-cycles is of interest to drug discovery due to the prevalence of nitrogen-containing heterocycles in pharmaceutical agents. Herein we report an intramolecular C-H amination approach to afford value-added and complexity-enriched bridged bicyclic amines. Guided by density functional theory and nuclear magnetic resonance investigations, we determined the unique roles of light and heat activation in the bicyclization mechanism. We applied both light and heat activation in a synergistic fashion, achieving gram-scale bridged aza-cycle synthesis.