Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Strategic Use of Visible-Light Photoredox Catalysis in Natural Product Synthesis

“…The construction of C–C and C–N σ-bonds by free radical reactions has the important advantage that common polar functional groups such as alcohols, thiols, carboxylic acids, and primary and secondary amines, which are often not compatible with bond constructions that employ basic reagents, are typically tolerated in free-radical reactions. ,,, Recent advances in visible-light photocatalysis have led to new ways to generate carbon- and nitrogen-centered radicals, both from new and well-established precursors. , By using visible-light photocatalysis, it is now possible to generate carbon radicals directly from common functional groups, avoiding extra steps to introduce “radical-generating” derivatives. Exemplified in total syntheses we have discussed is the direct generation of tertiary-carbon radicals from tertiary alcohols, , α-amino radicals from α-amino acids, , ketones, and tertiary carbamates, as well as nitrogen-centered radicals from secondary aryl sulfonamides and benzamides . In this review, numerous examples are seen of C–C bond formations being achieved, or yields being enhanced, in photocatalytic reactions of carbon radicals compared with the same conversion using conventional conditions for radical generation. ,,,,,, Even when yields were comparable, the photocatalytic reactions often avoided the formation of stoichiometric byproducts (e.g., tin residues) and gave reaction mixtures that were easy to purify. , …”

“…A radical cascade initiated by a benzamidyl radical was developed by Rao and co-workers for the synthesis of benzoindolizidines such as (±)-tylophorine ( 268 ) (Scheme ). Of the conditions surveyed, the use of Ir­[(dF­(CF 3 )­ppy) 2 (dF­(CF 3 )­bpy)]­PF 6 ( 4 ) as the PC and a phosphate base were optimal for generation of a benzamidyl radical (e.g., 269 ) by PCET, whereas various stoichiometric oxidants could be used in the final oxidation of intermediate 270 . Using dilauroyl peroxide, the yield of unsubstituted benzoindolizidine 271 , the direct precursor of (±)-tylophorine ( 268 ), was only 5%.…”

A Pd-Catalyzed [4 + 2] Annulation Approach to Fluorinated N-Heterocycles

“…The suitability of our method for accessing useful fluorinated heterocycles suggested that it might be adapted to allow the incorporation of trifluoromethylthio (SCF 3 ) groups. In this regard, and to the best of our knowledge, only two examples of 3-SCF 3 -substituted piperidines have been reported . Due to its electron-withdrawing nature and high lipophilicity, the SCF 3 moiety can significantly modulate the pharmacological properties of bioactive compounds .…”

“…In this regard, and to the best of our knowledge, only two examples of 3-SCF 3 -substituted piperidines have been reported. 18 Due to its electron-withdrawing nature and high lipophilicity, the SCF 3 moiety can significantly modulate the pharmacological properties of bioactive compounds. 19 Nevertheless, the availability of synthetic methods that deliver saturated N -trifluoromethyl-thiolated six-membered heterocycles is scarce, and those that are documented suffer from limited substrate scope.…”

Visible light-induced N-radical 5-exo/6-endo cyclization of alkenyl amides: facile access to isoindolinones/isoquinolinones

“…1a). After that, many research groups have reported N-radical cyclization reactions of different compounds, such as N -alkyl benzamides, 8 alkenyl amides, 9 N -aryl amides, 10 hydrazones 11 and sulfonic amides. 12 Inspired by these studies, as well as our research interest in NCR chemistry, our group attempted to further study the N-radical cyclization reaction of alkenyl amides, aiming at realizing selective regulation of the cyclization mode by changing intramolecular alkenyl substituents (Fig.…”