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Construction of Racemic and Enantiopure Biaryl Unnatural Amino Acid Derivatives via Pd(II)‐Catalyzed Arylation of Unactivated Csp 3 −H Bonds
Author(s) -
Banga Shefali,
Kaur Ramandeep,
Babu Srinivasarao Arulananda
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100683
Subject(s) - enantiopure drug , chemistry , amino acid , diastereomer , moiety , stereochemistry , norvaline , phthalimide , phenylalanine , enantioselective synthesis , catalysis , leucine , organic chemistry , biochemistry
We report the construction of racemic and enantiopure biaryl unnatural amino acid derivatives via the palladium‐catalyzed stereoselective sp 3 C−H activation and arylation of amino acid derivatives with iodobiaryls. The synthesis of biaryl motif installed (DL‐), L‐ and D‐amino acid derivatives including norvaline, phenylalanine, leucine, norleucine and 2‐aminooctanoic acid with anti stereochemistry is reported. The synthesis of alanine derivatives with two biaryl motifs and aminoalkanoic acids with biaryl motifs is also shown. The C−H arylation of enantiopure carboxamides gave biaryl amino acid derivatives with good enantiopurity. Removal of the directing group 8‐aminoquinoline, deprotection of the phthalimide moiety, and the preparation of biaryl amino acid derivatives containing free amino‐ and carboxylate groups are also reported. The stereochemistry ( anti ) of representative major diastereomers was unequivocally ascertained from X‐ray structure analysis. Biaryl amino acids/peptides are important motifs in medicinal chemistry, and this work therefore represents a contribution towards enriching the library of biaryl amino acids.