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Enantioselective Organocatalytic Cascade Approach to Different Classes of Benzofused Acetals
Author(s) -
Paz Bruno Matos,
Klier Lydia,
Næsborg Line,
Lauridsen Vibeke Henriette,
Jensen Frank,
Jørgensen Karl Anker
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201602992
Subject(s) - stereocenter , iminium , enantioselective synthesis , chemistry , organocatalysis , steric effects , catalysis , substrate (aquarium) , combinatorial chemistry , stereochemistry , amine gas treating , brønsted–lowry acid–base theory , organic chemistry , oceanography , geology
A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ‐keto‐α,β‐unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5‐fused acetals with two stereocenters—the tetrahydrofurobenzofuran scaffolds—proceeds in moderate yields and up to 96 % ee . The other reaction pathway provides 5,6‐bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 % ee . The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25 mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.