Diels–Alder Cascades in Natural Product Total Synthesis

Natural product total synthesis continues to be one of the most challenging endeavors for synthetic chemists. Two powerful concepts for rapidly accessing molecular complexity, the Diels-Alder reaction and cascade sequences, have long been applied in total synthesis work. This chapter presents a contemporary review of the Diels-Alder cascades as a transformative concept in natural product syntheses as reported over the last 20 years. The Diels-Alder reaction is the prototypical cycloaddition reaction, uniting a diene with a dienophile to form a cyclohexene ring, generally with high regioselectivity and diastereoselectivity. The design of Diels-Alder cascades to provide requisite architectures of substantial structural and stereochemical intricacy found in nature represents a formidable intellectual challenge for synthetic chemists. These cascades represent not only extraordinary feats of synthetic efficiency, but also elevate the art and science of total synthesis due to their aesthetic appeal.