Bypassing the abnormal Chichibabin reaction dead-end provides a biomimetic access to pre-haouamine

Haouamines are highly constrained marine alkaloids possessing a unique in nature skeleton. The high degree of complexity of such alkaloids raises questions about their chemical assembly. This is addressed in this paper in which we propose a biomimetic scenario corroborated experimentally by a fine study of the classical Chichibabin pyridine synthesis, especially in its “abnormal” oxidative version. Finely tuned reductive conditions and mechanistic investigations permit the concise obtention of an advanced and challenging intermediate that we coined “pre-haouamine”.