Open AccessProgress toward a Convergent, Asymmetric Synthesis of Jervine
Author(s) -
Blane P. Zavesky,
Pedro de Jesús Cruz,
Jeffrey S. Johnson
Publication year - 2020
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.0c00972
Subject(s) - chemistry , desymmetrization , enantioselective synthesis , stereochemistry , tetrahydrofuran , amine gas treating , diol , convergent synthesis , asymmetric carbon , claisen rearrangement , reagent , combinatorial chemistry , organic chemistry , catalysis , optically active , solvent
Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland-Claisen rearrangement to establish the necessary cis- relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.