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Geometry‐Retentive C‐Alkenylation of Lithiated α‐Aminonitriles: Quaternary α‐Alkenyl Amino Acids and Hydantoins
Author(s) -
MasRoselló Josep,
Hachisu Shuji,
Clayden Jonathan
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201704908
Subject(s) - alkene , chemistry , regioselectivity , intramolecular force , isomerization , hydrolysis , nucleophile , urea , medicinal chemistry , amino acid , nucleophilic substitution , yield (engineering) , carbon atom , stereochemistry , organic chemistry , catalysis , ring (chemistry) , biochemistry , materials science , metallurgy
α‐Amino nitriles tethered to alkenes through a urea linkage undergo intramolecular C‐alkenylation on treatment with base by attack of the lithionitrile derivatives on the N′‐alkenyl group. A geometry‐retentive alkene shift affords stereospecifically the E or Z isomer of the 5‐alkenyl‐4‐iminohydantoin products from the corresponding starting E ‐ or Z ‐ N ′‐alkenyl urea, each of which may be formed from the same N ‐allyl precursor by stereodivergent alkene isomerization. The reaction, formally a nucleophilic substitution at an sp 2 carbon atom, allows the direct regioselective incorporation of mono‐, di‐, tri‐, and tetrasubstituted olefins at the α‐carbon of amino acid derivatives. The initially formed 5‐alkenyl iminohydantoins may be hydrolyzed and oxidatively deprotected to yield hydantoins and unsaturated α‐quaternary amino acids.