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A one-pot catalytic synthesis of α-tetrasubstituted amino acid derivatives via in situ generation of N -unsubstituted ketimines is reported. Because of the irreversible formation of N -unsubstituted ketimines, the yields were higher than those generated under the conventional one-pot reaction conditions. This process prevents the need to isolate unstable N -unsubstituted ketimines with alkyl substituents and streamlines the synthesis of highly congested α-amino acid derivatives.

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. [ABSTRACT FROM AUTHOR]

Direct catalytic alkynylation of N-unprotected trifluoromethyl ketimines is reported for the first time. A combination of catalytic amounts of diethylzinc and carboxylic acids promoted the reactions under proton-transfer conditions, allowing an unprecedented direct access to N-unprotected α-tetrasubstituted primary amines without additional deprotection steps. [ABSTRACT FROM AUTHOR]

A green way to amino acids: α‐Tetrasubstituted α‐amino acid derivatives are formed in high yield and enantioselectivity by using a Rh‐catalyzed enantioselective alkynylation of α‐ketiminoesters. This reaction, which involves a proton transfer and can be conducted at room temperature, has high substrate scope (see scheme; Cbz=benzyloxycarbonyl, Fmoc=9‐fluorenylmethyloxycarbonyl). [ABSTRACT FROM AUTHOR]