Synthetic approaches to 9-arylated Cinchona alkaloids: stereoselective addition of Grignard reagents to cinchonanones and hydroxylation of 9-phenylcinchonanes

Diastereoselective Corey–Chaykovsky 9-Epoxymethylation of Cinchona Alkaloids: Access to Chiral Scaffolds with Diverse Functionalities

“…Similar facial selectivity was previously reported for the addition of TMS-CF 3 to qunidinone . Conversely, addition at the opposite face occurred in cases where metal chelates were involved, like in the addition of Grignard reagents, and lithium aluminum hydride reduction …”

“…High resolution mass spectra (TOF) were obtained in electrospray ionization mode. All reagents were purchased from commercial suppliers and used as received, CN-1 , and QD-1 were prepared according to literature procedures. , DHCN-1 was prepared following the literature procedure used for CN-1 from 10,11-dihydrocinchonidine and recrystallized from Et 2 O in 62% yield.…”

“…In a 100 mL round-bottom flask were placed recrystallized cinchoninone (11.9g, 40.8 mmol), trimethylsulfonium iodide (8.67 g, 42.4 mmol, 1.04 equiv), and DMSO (64 g). The suspension was stirred for 5 min, and potassium hydroxide (flakes 90%, 2.65 g, 41.8 mmol, 1.03 equiv) was added.…”

“…Nevertheless, there have been relatively few successful modifications to the alkaloid carbon skeleton at the C-9 center. Few examples include the introduction of additional CF 3 , simple alkyl, aryl and vinyl groups, and the corresponding ring rearrangements . An attractive approach to the extension of carbon framework is offered by the Corey–Chaykovsky reaction of sulfur ylides with the respective 9-carbonyl compounds.…”