Switchable synthesis of 3-aminoindolines and 2'-aminoarylacetic acids using Grignard reagents and
Toshiki Yamashiro1, Takumi Abe1
1Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 7008530, Japan. t-abe@okayama-u.ac.jp.
Abstract:
The switchable synthesis of 3-aminoindolines and 2'-aminoaryl acetic acids from the same substrates, 3-azido-2-hydroxyindolines, was developed through denitrogenative electrophilic amination of Grignard reagents. The key to success is the serendipitous discovery that the reaction conditions, including solvents and reaction temperature, can affect the chemoselectivity. It is noteworthy that isotope-labeling experiments revealed the occurrence of the aziridine intermediate in the production of 2'-aminoaryl acetic acids.
Related Concept Videos
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Acid Halides to Alcohols: Grignard Reaction
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs,...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism


