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Synthesis of the Bicyclic Lactone Core of Leonuketal, Enabled by a Telescoped Diels–Alder Reaction Sequence
Author(s) -
Grant Phillip S.,
Brimble Margaret A.,
Furkert Daniel P.
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201800903
Subject(s) - cycloaddition , bicyclic molecule , adduct , natural product , lactone , diels–alder reaction , chemistry , combinatorial chemistry , stereochemistry , intermolecular force , total synthesis , molecule , organic chemistry , catalysis
The Diels–Alder cycloaddition reaction has become established as a fundamental approach for the preparation of complex natural products; however, successful application of the intermolecular Diels–Alder cycloaddition reaction to the synthesis of particularly congested scaffolds remains surprisingly problematic. Inspired by the terpenoid spiroketal natural product leonuketal, a challenging telescoped reaction sequence has been realized to access the core [2.2.2]‐bicyclic lactone ring system and its [3.2.1] isomer. Our four‐step, protecting‐group‐free process required detailed investigation to circumvent the problems of adduct fragmentation and intermediate instability. Successful solution of these practical issues, along with unambiguous structural determination of the target structures, provide useful insights that will facilitate future applications of the Diels–Alder cycloaddition reaction to challenging, highly congested molecular scaffolds and ongoing synthetic efforts towards this natural product.