Quinones as Dienophiles in the Diels–Alder Reaction: History and Applications in Total Synthesis

Abstract

In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels–Alder reaction is among the most powerful and well understood. Its ability to rapidly generate molecular complexity through the simultaneous formation of two carboncarbon bonds is almost unrivalled, and this is reflected in the great number of reported applications of this reaction. Historically, the use of quinones as dienophiles is highly significant, being the very first example investigated by Diels and Alder. Herein, we review the application of the Diels–Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward, respectively, through to the present day examples, such as the tetracyclines.

A Dehydrogenative Diels–Alder Reaction of Prenyl Derivatives with 2,3‐Dichloro‐5,6‐dicyanobenzoquinone

“…[8] Inspired by allylic oxidation reactions with DDQ, [7e, 9] we envisage that the oxidation of a prenyl motif by DDQ would generate an allylic carbocation intermediate, then elimination of a proton and rearrangement would form an isoprene motif. [10] Finally, a DA reaction of the isoprene derivative and DDQ would yield a DHDA reaction product.…”

Electrochemical Multiplexing: Control over Surface Functionalization by Combining a Redox‐Sensitive Alkyne Protection Group with “Click”‐Chemistry

“…After unleashing of the hydroxy group, it acts as nucleophile and attacks the silane intramolecularly, liberating the alkyne group. The selected menadione moiety as quinone structure was crucial to prevent side reactions of the highly reactive quinone system such as spontaneous dimerization, Diels-Alder cyclizations [48] and Michael additions, [49] while maintaining its low redox potential (E 0 = 0.71 V vs SCE in acetonitrile for menadione). Upon reduction of the quinone, the hydroxy-group formed attacks the amide carbonyl intramolecularly, forming a 6-membered lactone and releasing the amine group.…”

Quinones

“…This classic cyclization reaction has shown growth in several areas of organic chemistry. Its application to quinone chemistry has been reviewed (140,141). Much of the recent chemistry has been involved as a key step in the synthesis of complex natural products and will be presented in a later section, The present entries deal with studies that center on the reaction itself.…”