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

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.