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. 2015 Sep 7;21(37):12908-13.
doi: 10.1002/chem.201501667. Epub 2015 Jul 28.

Intramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core

Longle Ma  1 , Daniel Seidel  2
Affiliations

Intramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core

Longle Ma et al. Chemistry. .

Abstract

Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-CH bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies.

Keywords: CH functionalization; azomethine ylides; heterocycles; redox chemistry; synthetic methods.

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Figures

Scheme 1
Scheme 1
Reinhoudt vs. Redox-Mannich Reactions.
Scheme 2
Scheme 2
Scope of the Intramolecular Redox-Mannich Reaction with Pyrrolidine.
Scheme 3
Scheme 3
Intramolecular Redox-Mannich Reaction with THIQ and Related Amines.
Scheme 4
Scheme 4
Pyrrolidine β-functionalization.
Scheme 5
Scheme 5
Study of the dealkoxycarbonylation.
Scheme 6
Scheme 6
Mechanistic considerations.
Scheme 7
Scheme 7
Synthetic Applications.
See this image and copyright information in PMC

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