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Pyrone Diels–Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ 7 ‐Mesembrenone
Author(s) -
Gan Pei,
Smith Myles W.,
Braffman Nathaniel R.,
Snyder Scott A.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201510520
Subject(s) - total synthesis , diels–alder reaction , simple (philosophy) , modular design , combinatorial chemistry , chemistry , organic chemistry , computer science , programming language , catalysis , philosophy , epistemology
Abstract Although the Diels–Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6‐dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these—the complex amaryllidaceae alkaloid gracilamine—affording the shortest route to date in terms of linear step count.