2017/09/26 by Masanao Sawa, Kazuhiro Morisaki, Yuta Kondo +2 · 4 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Fluorine in Organic Chemistry #Asymmetric Synthesis and Catalysis #Synthesis and Catalytic Reactions
paper · doi:10.1002/chem.201703516
openalex publication_date 2017/09/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/13
Direct catalytic C-C bond-forming addition to N-unprotected ketimines is an efficient and straightforward method of synthesizing N-unprotected tetrasubstituted amines that eliminates prior protection/deprotection steps and allows facile transformation of the products. Despite its advantages, however, N-unprotected ketimines have difficulties in C-C bond-forming reactions, and only a limited number of reactions and substrates are reported compared with their N-protected counterparts. Herein we report that N-unprotected trifluoromethyl ketimines are effective for C-C bond-forming reactions using Mannich-type reactions as a model case. We demonstrate that Lewis acid catalysis was effective for promoting reactions with various N-unprotected trifluoromethyl ketimines, and thiourea organocatalysis was effective for promoting highly enantioselective reactions with various carbonyl nucleophiles, providing direct access to various N-unprotected α- and/or β-tetrasubstituted amino acid esters. Furthermore, direct construction of vicinal tetrasubstituted chiral carbon stereocenters was achieved for the first time in a highly enantio- and diastereoselective manner. These results demonstrate the potential of N-unprotected ketimines as substrates applicable to many other addition reactions.