Carbocyclic Amino Ketones by Bredt's Rule-Arrested Kulinkovich-de Meijere Reaction

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 7; pp. 2536 - 2539
• Main Authors: Finn, Paul B., Derstine, Brenden P., Sieburth, Scott McN
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 12.02.2016; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; Amides; amino ketones; Arrests; Bredt's rule; Carbon; Chemistry; Chemistry, Multidisciplinary; Forming; Ketones; Kulinkovich reaction; Mannich reaction; Physical Sciences; Science & Technology; titanium; Bredt's rule; amino ketones; Mannich reaction; titanium; STRATEGY; ESTERS; Kulinkovich reaction; CYCLOPROPYLAMINES; CHEMISTRY; CARBOXYLIC-ACIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201509983

The TiII‐mediated formation of cyclopropylamines from alkenes and amides, the Kulinkovich–de Meijere reaction, involves two carbon–carbon bond‐forming steps. Strategic use of a tricyclic intermediate can arrest the process if the second step requires formation of a bridgehead double bond. Use of this Bredt's rule constraint results in the production of carbocyclic amino ketones, key alkaloid building blocks. Frustrated by Bredt's rule: An inability to consummate a Kulinkovich–de Meijere cyclopropanation that would involve a bridgehead double bond transforms the reaction into a transannular cyclization of an unsaturated lactam yielding an amino ketone product with potential for alkaloid synthesis.