Divergent Total Syntheses of Six Crinipellin‐Type Diterpenoids through Tandem 4π‐Electrocyclization/Dicycloexpansion

Abstract Crinipellins are a significant class of naturally occurring highly congested tetraquinane diterpenoids, with many members exhibiting bio‐important antibacterial and anticancer activities. However, their complex structures, particularly their dense 5/5/5/5 tetracyclic frameworks, have made efficient synthesis challenging, leading chemists to attempt to create highly efficient and divergent routes. This study presents a concise, divergent synthesis of six crinipellins, completed in just 9–11 steps using commercially available materials. Particular highlights include: (1) a vital one‐step 4π‐electrocyclization/dicycloexpansion cascade that rapidly constructs the angular/fused tetraquinane scaffold with two contiguous quaternary carbons, and (2) strategic functionalizations through iso ‐propylation, methylation, and Wacker oxidation/dehydrogenation, enabling the divergent syntheses of the six crinipellin members without using protecting groups. This approach provides a versatile platform for accessing additional crinipellin derivatives, which we believe will benefit medicinal and biological research.