Recent advancements in the chemistry of Diels–Alder reaction for total synthesis of natural products: a comprehensive review (2020–2023)

Abstract

Despite being discovered nearly a century ago, the Diels–Alder (DA) reaction remains a crucial tool in the total synthesis of natural products. It accommodates a broad range of building blocks with varying complexity and levels of derivatization, allowing the formation of six-membered rings with precise stereochemistry. This, in turn, simplifies the synthesis of core structures found in many natural products. In recent years, modifications to the traditional Diels–Alder reaction have expanded its scope. These modifications include the inverse electron demand Diels–Alder reaction, dehydro Diels–Alder reaction, hetero-Diels–Alder reaction, photoenolization Diels–Alder reaction, asymmetric Diels–Alder reaction, and domino Diels–Alder reaction have been employed to extend the scope of this process in the synthesis of natural products. This review discusses the application of the Diels–Alder reaction in the total synthesis of natural products from 2020 to 2023, along with select methodologies that are inspired by or can be used to synthesize natural products.