Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

Abstract

SummaryThe Abramov reaction, a base-catalyzed nucleophilic addition of dialkyl H-phosphonates (phosphites) to carbonyl compounds, was performed with oxidized quinine derivatives as the substrates. Homologous aldehydes obtained from the vinyl group reacted in a typical way which led to α-hydroxyphosphonates, first reported compounds containing a direct P–C bond between the quinine carbon skeleton and a phosphorus atom. For the C9 ketones a phosphonate–phosphate rearrangement, associated with a tandem elimination of the piperidine fragment, was evidenced.

Improved Synthesis of Naldemedine Tosylate and Crystal Structures of Four Related Solid Forms

“…5 One such reagent is dibutyltin dilaurate (DBTL) whose use has only been described in the polymer industry and only a few examples are known to the best of our knowledge. [6][7][8] Replacement of CuCl2 by DBTL (0.07 equiv.) gave 14 in 94% yield.…”