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Development of an Efficient Synthesis of rac ‐3‐Demethoxyerythratidinone via a Titanium(III) Catalyzed Imine‐Nitrile Coupling
Author(s) -
Luu HieuTrinh,
Streuff Jan
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801479
Subject(s) - chemistry , umpolung , imine , nitrile , alkene , combinatorial chemistry , natural product , catalysis , organic chemistry , erythrina , yield (engineering) , enantioselective synthesis , aldehyde , total synthesis , organic synthesis , medicine , materials science , metallurgy , nucleophile , traditional medicine
We herein describe the evolution of a rapid, high‐yielding synthesis of the erythrina alkaloid 3‐demethoxyerythratidinone. The natural product is assembled in six steps from commercial precursors in 30–35 % overall yield and with only two chromatographical purification operations. The key step is a titanium(III) catalyzed umpolung reaction in form of a reductive imine–nitrile coupling that can be combined with a subsequent cyclization reaction on a 50 mmol scale. Furthermore, optimized Wacker oxidation conditions enable the selective alkene oxidation in the presence of a tertiary amine functionality, which has been a problem in previous syntheses of erythrina alkaloids. The racemic route can be used to prepare the natural product on gram scale and the results may be useful for the synthesis of related alkaloids.