The following double cyclization was used to generate the ring system of the lycoanitine alkaloids in 2005. Demonstrate your understanding of this C−C bond-forming process by providing a mechanistic rationale (using arrows that represent electron movement) for the boxed reaction.

Double cyclization reaction scheme

From what I know in my current synthetic organic chemistry class, this question appears to me like a Paal–Knorr reaction, but the product isn't a pyrrole. I don't even know where to start, and I'm not entirely certain how and where the Lewis acid interacts.

Ignore the boxed part, that's for me to do; I'm just curious to know how the carbons attached to the methoxy group on the tertiary amine are able to bond with the C2 carbons on the 1,4-diketone.


1 Answer 1


This is a variant of the Mannich reaction. The methoxymethyl groups on the amine are a form of captured Mannich intermediates or masked formaldehyde equivalents. The Lewis acid unmasks them by binding to the oxygen of the methoxy group, creating the functional equivalent of H2C=N+. These are reactive electrophiles which react with the active methylenes of the B-ketoester to give the alkaloid.

More on the Mannich reaction here


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.