Synthesis of Arylglycines by Reaction of Diethyl N-Boc-iminomalonate with Organomagnesium Reagents
Patrizia Calí, Mikael Begtrup*
*Department of Medicinal Chemistry, Royal Danish School of Pharmacy,
Universitetsparken 2, 2100 Copenhagen, Denmark, Email: mb
dfuni.dk
P. Cali, M. Begtrup, Synthesis, 2002, 63-64.
DOI: 10.1055/s-2002-19301
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Abstract
Diethyl N-Boc-iminomalonate, prepared on multi-gram scale, served as a stable and highly reactive electrophilic glycine equivalent which reacted with organomagnesium compounds affording substituted aryl N-Boc-aminomalonates. Subsequent hydrolysis produced arylglycines.
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reactions
Details
The document details the synthesis of arylglycines through the reaction of diethyl N-Boc-iminomalonate with organomagnesium reagents. Diethyl N-Boc-iminomalonate, prepared on a multi-gram scale, serves as a stable and highly reactive electrophilic glycine equivalent. It reacts with Grignard reagents to form substituted aryl N-Boc-aminomalonates, which upon hydrolysis yield arylglycines. The process involves the preparation of N-Boc-triphenyliminophosphorane, which reacts with diethyl mesoxalate to form diethyl N-Boc-iminomalonate. This compound is then reacted with various aryl and heteroaryl iodides, converted to organomagnesium compounds via halogen-metal exchange, to produce the desired adducts. The N-Boc group is removed under mild conditions, and the resulting aminomalonate derivatives are hydrolyzed to obtain arylglycines. The method is advantageous due to the stability and reactivity of diethyl N-Boc-iminomalonate, the commercial availability of starting materials, and the mild deprotection conditions. The document also provides detailed experimental procedures and yields for various arylglycine derivatives, highlighting the efficiency and versatility of this synthetic route.
Key Words
amino acids, arylaminomalonates, arylglycines, imino esters, Grignard reaction, tert-butyl carbamates, decarboxylation
ID: J66-Y2002-1430
