Synergistic Diastereo‐ and Enantioselective Functionalization of Unactivated Alkyl Quinolines with α,β‐Unsaturated Aldehydes

• Published in: Angewandte Chemie International Edition Vol. 56; no. 6; pp. 1634 - 1638
• Main Authors: Meazza, Marta, Tur, Fernando, Hammer, Niels, Jørgensen, Karl Anker
• Format: Journal Article
• Language: English
• Published: Germany 01.02.2017
• Subjects: asymmetric catalysis; heterocycles; indium; organocatalysis; synergistic catalysis; organocatalysis; indium; synergistic catalysis; asymmetric catalysis; heterocycles
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201611306

A novel alkyl functionalization of unactivated alkyl quinolines has been developed combining InCl3 activation with organocatalytic activation of α,β‐unsaturated aldehydes in a synergistic fashion. The reaction proceeds in a highly stereoselective manner as a sequence involving two consecutive synergistic catalytic cycles (Lewis acid‐ and iminium ion‐catalyzed) and requires neither pre‐activated alkyl quinoline substrates with electron‐withdrawing substituents nor highly activated electrophiles. The reaction provides selectively double‐ or mono‐addition products in good yields and high to excellent stereoselectivities. Furthermore, based on spectroscopic and labelling experiments, the mechanisms for the reactions are discussed. A fruitful partnership: InCl3 activation of unactivated alkyl quinolines has been combined with organocatalytic activation of α,β‐unsaturated aldehydes. The reaction involves two consecutive synergistic catalytic cycles and provides selectively double‐ or mono‐addition products in good yields and high to excellent stereoselectivities. Based on spectroscopic and labeling experiments, the reaction mechanisms are discussed.