Addition of Boronic Acids to N‐Unsubstituted Ketimines

Addition of Boronic Acids to N‐Unsubstituted Ketimines

Author: Chemistry – An Asian Journal

The catalytic enantioselective addition of boronic acids to ketimines is useful for synthesizing enantioenriched amines next to tetrasubstituted carbon stereocenters. This reaction has been well-developed for N-substituted ketimines. However, it remains challenging for N-unsubstituted ketimines. Existing approaches for this reaction require preformed boroxines as a boronic-acid equivalent and stoichiometric amounts of a base.

Hiroyuki Morimoto, Takashi Ohshima, Kyushu University, Fukuoka, Japan, Tamio Hayashi, Nanyang Technological University, Singapore, and colleagues have developed a rhodium(I)/chiral-diene-catalyzed enantioselective addition of boronic acids to N-unsubstituted isatin-derived ketimines (pictured). The team used a chiral diene ligand with a secondary amide moiety, catalytic amounts of K2CO3 as a base, and various boronic acids as reactants. They obtained the desired products in high yields and enantioselectivities.

 
A combination of experimental and computational mechanistic studies revealed that a hydrogen-bonding interaction between the amide moiety of the diene ligand and the N-unsubstituted ketimines is crucial for stabilizing the transition state. This effect leads to high reactivity and enantioselectivity.


 

 

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