Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene

Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate. This key step swiftly assembles the azadecalin framework of the natural product, allows for a succinct synthetic endgame, and enables a 12-step total synthesis (longest linear sequence; 0.8% overall yield). These studies demonstrate that strained cyclic allenes are versatile building blocks in chemical synthesis.

Automated summary

Small rings containing allenes are unconventional compounds that have been known since the 1960s. Despite having similar discovery time to benzyne and advantageous features, strained cyclic allenes have been underutilized in chemical synthesis. This study presents a concise total synthesis of lissodendoric acid A, a manzamine alkaloid, through the selective trapping of a short-lived cyclic allene intermediate. This synthetic approach efficiently constructs the azadecalin framework, resulting in a 12-step total synthesis with a 0.8% overall yield.