Iodine-mediated direct α-amination of dimethyl methylmalonate using non-protected amines

In this study, direct CAN bond formation was achieved via the reaction of a dimethyl methylmalonate with various amines in the presence of molecular iodine to produce alpha-aminocarbonyl compounds. This versatile methodology of the alpha-amination of a carbonyl-containing compound involves the in situ iodination of the dimethyl methylmalonate, thus promoting the formation of its enolate isomer, which then facilitates its nucleophilic substitution reaction with an amine. This strategy is highly practical and can be used in industry due to its requirement of only readily available reagents without any pre-preparation of the amines and other substrates. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

This study presents a versatile methodology for the synthesis of alpha-aminocarbonyl compounds via direct CAN bond formation by reacting dimethyl methylmalonate with various amines in the presence of molecular iodine. The strategy involves in situ iodination of the dimethyl methylmalonate, promoting its enolate isomer formation for nucleophilic substitution with an amine. The practical approach is industry-friendly as it uses readily available reagents without the need for pre-preparation of amines and other substrates.