Rhodium(I)/Chiral Diene‐Catalyzed Enantioselective Addition of Boronic Acids to N‐Unsubstituted Isatin‐Derived Ketimines

Abstract

Enantioselective addition of boronic acids to N‐unsubstituted isatin‐derived ketimines was realized using rhodium(I)/chiral diene catalysts. The reactions can be performed in the presence of catalytic amounts of a base to give adducts in high yield with high enantioselectivity. Preliminary mechanistic information including a computational model to explain the observed enantioselectivity is also provided.

Recent Progress on Catalytic Addition Reactions toN-Unsubstituted Imines

“…Very recently Morimoto, Hayashi, Ohshima, and co-workers reported Rh/chiral diene catalyzed enantioselective addition of boronic acids 92 to N-unsubstituted isatin-derived ketimines 91 (Scheme 18a). 50 The use of Rh/diene catalysis allowed the use of readily available boronic acids as the nucleophile with a catalytic amount of a base. They performed several preliminary mechanistic studies and found that the N−H moiety of the amide in the diene ligand 94 was crucial for promoting the reaction.…”

“…Very recently Morimoto, Hayashi, Ohshima, and co-workers reported Rh/chiral diene catalyzed enantioselective addition of boronic acids 92 to N -unsubstituted isatin-derived ketimines 91 (Scheme a) . The use of Rh/diene catalysis allowed the use of readily available boronic acids as the nucleophile with a catalytic amount of a base.…”

Organocatalytic Direct Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines for the Synthesis of α-Aminophosphonates

“…However, these reactions require the protection and deprotection of the substituent to obtain N -unprotected amines, resulting in longer reaction steps and unwanted chemical waste formation. A greener process can be realized by using N -unsubstituted ketimines that directly afford N -unprotected amines with a tetrasubstituted carbon stereocenter without protection/deprotection steps, − although the scope is yet limited to certain types of reactions.…”

Direct Catalytic Enantioselective Hydrophosphonylation of N-Unsubstituted Ketimines

“…Hydrophosphonylation of Ketimines N-Unsubstituted ketimines are attractive substrates because they directly afford N-unprotected α-tetrasubstituted α-aminophosphonates without protection/deprotection steps. [7][8][9][10][11][12][13][14] Despite several reports of hydrophosphonylation reactions that directly affording N-unprotected products have been reported in a racemic form (eq 2), [15][16][17][18] the use of N-unsubstituted ketimines in catalytic enantioselective hydrophosphonylation has not, to the best of our knowledge, been reported. 19 Herein we report the first direct catalytic enantioselective hydrophosphonylation of N-unsubstituted ketimines (eq 3).…”