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Practical Synthesis of anti ‐β‐Hydroxy‐α‐Amino Acids by Pd II ‐Catalyzed Sequential C(sp 3 )H Functionalization
Author(s) -
Chen Kai,
Zhang ShuoQing,
Jiang HuaiZhi,
Xu JingWen,
Shi BingFeng
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201405942
Subject(s) - chemistry , steric effects , intramolecular force , alkylation , amino acid , stereoselectivity , nucleophile , catalysis , stereochemistry , surface modification , medicinal chemistry , organic chemistry , biochemistry
An improved and practical procedure for the stereoselective synthesis of anti ‐β‐hydroxy‐α‐amino acids ( anti‐ βhAAs), by palladium‐catalyzed sequential C(sp 3 )H functionalization directed by 8‐aminoquinoline auxiliary, is described. followed by a previously established monoarylation and/or alkylation of the β‐methyl C(sp 3 )H of alanine derivative, β‐acetoxylation of both alkylic and benzylic methylene C(sp 3 )H bonds affords various anti ‐β‐hydroxy‐α‐amino acid derivatives. As an example, the synthesis of β‐mercapto‐α‐amino acids, which are highly important to the extension of native chemical ligation chemistry beyond cysteine, is described. The synthetic potential of this protocol is further demonstrated by the synthesis of diverse β‐branched α‐amino acids. The observed diastereoselectivities are strongly influenced by electronic effects of aromatic AAs and steric effects of the linear side‐chain AAs, which could be explained by the competition of intramolecular COAc bond reductive elimination from Pd IV intermediates vs. intermolecular attack by an external nucleophile (AcO − ) in an S N 2‐type process.