Concise, Atom-Economical, and Enantiodivergent Total Synthesis of β-Lycorane via Organocatalyzed [4+2] Cycloaddition Reaction.

We report an enantiodivergent total synthesis of β-lycorane, accomplished in three steps, achieving an overall yield of 28% and an atom economy of 78% via cycloaddition catalyzed by a chiral cis-2,5-disubstituted pyrrolidine organocatalyst. Following successful reaction optimization, a broad substrate scope was explored, affording the corresponding cycloadducts in up to 80% yield, 15:1 dr, and 94% ee. This scalable methodology is also compatible with the branched 2,4-dienals. Importantly, the 5-substituent on the organocatalyst plays a pivotal role in controlling the regioselectivity, effectively suppressing the undesired α- and γ-reactivity.