Asymmetric Inverse-Electron-Demand Diels–Alder Reactions of 2-Pyrones by Lewis Acid Catalysis

Abstract

Diels-Alder reactions of 2-pyrones with alkenes could provide highly functionalized [2,2,2]-bicyclic lactones under mild reaction conditions. The synthetic utilizations have been well demonstrated in natural product synthesis. Although several catalytic asymmetric strategies have been realized, current research in this area is still largely underdeveloped. Herein, the recent advancement of enantioselective inverse-electron-demand Diels-Alder reactions by Lewis acid catalysis are reviewed.

Pd-Catalyzed Formal [3 + 3] Heteroannulation of Allylic gem-Diacetates: Synthesis of Chromene-Based Natural Products and Exploration of Photochromic Properties

“…To construct six-membered carbo- and heterocycles, the [4 + 2] cycloaddition is by far the best known and most widely applied strategy among others . The [3 + 3] cycloaddition, although symmetry-forbidden to be a concerted process, is a potential alternative to synthesize such systems but is less known under metal catalysis .…”

Nickel(II)-Catalyzed Asymmetric Inverse-Electron-Demand Diels–Alder Reaction of 2-Pyrones with Styrenes and Indenes

“…Since the pioneering work of Posner at al . and Markó et al, catalytic asymmetric IEDDA reactions of 2-pyrone with electron-rich alkenes have attracted increasing interest owing to the synthetic value of the resulting bridged bicyclic lactones and their derivatives . In 2021, Cai et al pioneered the catalytic asymmetric IEDDA reaction of 2-pyrones with indenes using a Cu­(OTf) 2 - SaBox complex as the catalyst (Scheme b) .…”

Gram-Scale Enantioselective Synthesis of (+)-Lucidumone

“…An enantioselective synthesis would be allowed by enantioselectively obtaining fragment 5, for which we envisaged an inverse-electrondemand Diels−Alder (IEDDA) reaction involving a 2-pyrone 6 and an enol ether 7. 10,11 The introduction of the methyl ketone moiety can be envisaged either in the early steps of the synthesis or in the endgame. This approach presents three key steps/challenges: (i) It is unclear whether the electron-demand in the late-stage IMDA reaction will be favorable or not, given the presence of an electron-donating group at C 7 ′ (supposed to meet the electron-deficient site of the diene C 6 ′) and an electron-withdrawing group at C 2 ′ (supposed to meet the electron-enriched site C 3 ′).…”