Total Synthesis of 2‐(2‐Ketoalkyl)‐piperidine Alkaloids (+)‐ Pelletierine, (+)‐Haloxynine and (‐)‐N‐Methyl‐pelletierine via Regioselective Wacker Oxidation

Abstract

A practical synthesis of naturally occurring piperidine alkaloids (+)‐pelletierine, (+)‐haloxynine and (‐)‐N‐methyl‐pelletierine is described from (‐)‐pipecolinic acid using Wittig reaction and Wacker oxidation as the key steps. The protocol exploits the regioselective oxidation of the internal olefins.

Wacker-type oxidation of styrenes with Markovnikov selectivity using copper as a site-selective sequential photooxidant–photoreductant

“…[1][2][3] The Wacker process achieved the initial breakthrough, 4,5 leveraging the synergistic interplay between copper and palladium to convert alkenes into aldehydes or ketones (Scheme 1A). [6][7][8][9][10][11][12][13][14][15][16] However, besides the reliance on palladium, a significant hurdle is the oxidative C-C cleavage of the olefin, which is especially problematic for styrenes (Scheme 1A). 17,18 The substitution of palladium with an abundant and costeffective metal promises to transform the Wacker-type reaction into a more sustainable and economically viable platform for olefin oxidation.…”

“…1–3 The Wacker process achieved the initial breakthrough, 4,5 leveraging the synergistic interplay between copper and palladium to convert alkenes into aldehydes or ketones (Scheme 1A). 6–16 However, besides the reliance on palladium, a significant hurdle is the oxidative C–C cleavage of the olefin, which is especially problematic for styrenes (Scheme 1A). 17,18…”

An approach towards (+)-allokainic acid via diphenylprolinol-catalyzed direct cross-aldol reaction

“…13 Recently in 2016, Ikemoto's group carried out further detailed investigation on highly stereoselective cross-aldol reaction utilising ethyl glyoxylate (polymeric form) wherein the polymer was directly used without pyrolysis. 14 With our continued interest towards the synthesis of alkaloids, 15 we explored the cross-aldol reaction towards our synthetic approach for (+)-allokainic acid 1 . Herein, we report a unified strategy for the enantioselective synthesis of (+)-allokainic acid which offers an easy access towards C4 functionalization.…”