Enantioselective Catalyzed Synthesis of Amino Derivatives Using Electrophilic Open‐Chain N‐Activated Ketimines

Abstract

N‐Activated ketimines are characterized by the presence of acyl, sulfonyl, and phosphinoyl groups linked to the nitrogen atom of the azomethine system. These electron‐withdrawing groups enhance the electrophilic character of the imino moiety allowing the addition of even weak nucleophilic reagents. The presence of the oxygen atoms in these activating groups with its coordinating and Lewis or Brønsted properties is of paramount importance in asymmetric catalyzed reactions. This review collects the results that have appeared in the literature during the last two decades on the utilization of open‐chain N‐activated ketimines for the synthesis of optically active α‐disubstituted and α‐trisubstituted amino derivatives including nitrogen‐containing heterocyclic compounds.

Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism

“…In particular, we decided to examine the use of tertiary α-halonitriles as electrophiles so as to produce α-disubstituted α-aminonitriles. Whereas catalytic enantioselective Strecker reactions of aldimines provide a versatile approach to the synthesis of enantioenriched α-monosubstituted α-aminonitriles, , the corresponding reactions of ketimines to afford α-disubstituted α-aminonitriles are less well-developed. − …”

Diastereo‐ and Enantioselective Reductive Mannich‐type Reaction of α,β‐Unsaturated Carboxylic Acids to Ketimines: A Direct Entry to Unprotected β2,3,3‐Amino Acids

“…Moreover, despite the importance of sterically diverse β‐ amino acid synthesis, there is no precedent for using ketimines as imine substrates in (Mukaiyama) Mannich‐type reactions of unprotected carboxylic acids. This is because the relatively similar sizes of the non‐hydrogen substituents must be distinguished, and the poor electrophilic nature of ketimines needs to be overcome [7d,e] . Herein, we report a single‐step, highly diastereo‐ and enantioselective reductive Mannich‐type reaction of unprotected acrylic acids with ketimines that yields sterically congested β 2,3,3 ‐amino acids with vicinal stereogenic centers (Scheme 1c) [14]…”

“…This is because the relatively similar sizes of the non‐hydrogen substituents must be distinguished, and the poor electrophilic nature of ketimines needs to be overcome. [ 7d , 7e ] Herein, we report a single‐step, highly diastereo‐ and enantioselective reductive Mannich‐type reaction of unprotected acrylic acids with ketimines that yields sterically congested β 2,3,3 ‐amino acids with vicinal stereogenic centers (Scheme 1 c). [14]…”

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

“…Direct catalytic enantioselective addition to ketimines is an effective method for producing chiral amines with a tetrasubstituted carbon stereocenter under proton-transfer conditions. − The majority of the reactions use N -substituted ketimines, and the substituent on the nitrogen atom can tune reactivity and selectivity . 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.…”

“…1−4 The majority of the reactions use N-substituted ketimines, and the substituent on the nitrogen atom can tune reactivity and selectivity. 5 However, these reactions require the protection and deprotection of the substituent to obtain Nunprotected 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, 6−13 although the scope is yet limited to certain types of reactions.…”