New strategy for the synthesis of proaporphine and homoproaporphine-type alkaloids from a common intermediate

Recent Advances in the Total Synthesis of the Tetrahydroisoquinoline Alkaloids (2002–2020)

“…Alternatively, Magnus and co-workers demonstrated that the spirocyclization could be achieved through an intramolecular displacement of a mesylate derivative 102 using CsF in NMP at 150 °C to deliver stepharine 100 as well (Scheme 14B). 41 Takao and co-workers reported the enantioselective synthesis of a distinct proaporphine alkaloid (−)-misramine 110 utilizing their previously developed enantioselective Friedel− Crafts 1,4-addition of enones. 42,43 From phenethyl enone 103, their key enantioselective intramolecular 1,4-addition was accomplished by using epi-cinchonine amine C1 as a catalyst (Scheme 15).…”

“…N -Methylation of 100 further delivered pronuciferine 101 . Alternatively, Magnus and co-workers demonstrated that the spirocyclization could be achieved through an intramolecular displacement of a mesylate derivative 102 using CsF in NMP at 150 °C to deliver stepharine 100 as well (Scheme B) …”

A Concise Total Synthesis of (±)-Stepharine and (±)-Pronuciferine

“…6 Then, 3 can be obtained through an Au-catalyzed 6-exo-dig cyclization of 2′-alkynylaryl-2ethylamine 4. Lastly, the key intermediate 4 can be quickly synthesized from aryl iodide 5, aziridine 6, and (triisopropylsilyl)acetylene (7) via a Catellani reaction. 9 We started our synthesis with the preparation of building block 5 to investigate the key three-component Catellani reaction.…”

Enantioselective Total Synthesis of (−)-Misramine

“…2 In recent examples, Honda and Shigehisa reported the total synthesis of (±)-1 by aromatic oxidation of an isoquinoline− phenol derivative, 3 and Magnus and co-workers established a new strategy for the synthesis of (±)-1 based on intramolecular C-alkylation of the phenolate generated in situ. 4 Although various routes to proaporphines have been developed, all of them are racemic syntheses. The asymmetric synthesis remains a challenging and important research goal for proaporphines in synthetic chemistry.…”

“…Because of this synthetically challenging structure, proaporphines have attracted attention from synthetic chemists for half a century . In recent examples, Honda and Shigehisa reported the total synthesis of (±) -1 by aromatic oxidation of an isoquinoline–phenol derivative, and Magnus and co-workers established a new strategy for the synthesis of (±) -1 based on intramolecular C -alkylation of the phenolate generated in situ . Although various routes to proaporphines have been developed, all of them are racemic syntheses.…”