Assembly of 3a-arylperhydroindoles by the intramolecular cycloaddition of 2-azaallyl anions with alkenes.: Total syntheses of (±)-crinine, (±)-6-epicrinine, (-)-amabiline, and (-)-augustamine

The 2-azaallyl anion route to pyrrolidines was used for the concise synthesis of alkaloids featuring the 3a-arylperhydroindole nucleus. The brevity and efficiency of the syntheses described are particularly notable. The key transformations involved the tin-lithium exchange of (2-azaallyl)stannanes to 2-azaallyl anions, which participated in intramolecular [pi 4s + pi 2s] cycloadditions with styrenes to produce the requisite 3a-arylperhydroindoles. (+/-)-Crinine was synthesized in eight steps in 20% overall yield, with the key cycloaddition producing a single stereoisomer of the perhydroindole in 80% yield. (+/-)-6-Epicrinine was an intermediate in this synthesis. The key cycloaddition involved the use of a diene as the anionophile. The first asymmetric syntheses of (-)-amabiline and (-)-augustamine were accomplished in overall yields of 43% (in eight steps) and 42% (in nine steps), respectively, confirming or determining the absolute stereochemistry of the natural products. The key cycloadditions produced the perhydroindoles in 83% and 74% yields, respectively, with reasonable stereocontrol. The highly stereoselective cycloaddition leading to a trans-dialkoxyperhydroindole in 75% yield was consistent with stereochemical predictions. These studies contribute to a growing body of knowledge on the scope and stereochemistry of 2-azaallyl anion cycloadditions.