title: Ligand-controlled C(sp³)-H arylation and olefination in synthesis of unnatural chiral α-amino acids.
abstract: The use of ligands to tune the reactivity and selectivity of transition metal catalysts for C(sp(3))-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp(3))-H arylation using pyridine and quinoline derivatives: The former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of β-Ar-β-Ar'-α-amino acids with excellent levels of diastereoselectivity (diastereomeric ratio > 20:1). Both configurations of the β-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp(3))-H olefination of a protected alanine.
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Suhua
authors.initials: S
authors.lastname: Li
authors.forename: Youqian
authors.initials: Y
authors.lastname: Deng
authors.forename: Haiyan
authors.initials: H
authors.lastname: Fu
authors.forename: Brian N
authors.initials: BN
authors.lastname: Laforteza
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Spangler
authors.forename: Anna
authors.initials: A
authors.lastname: Homs
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000409:Alanine / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006860:Hydrogen Bonding; D008024:Ligands; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000596:Amino Acids; D008024:Ligands; D011725:Pyridines; D011804:Quinolines; D010165:Palladium; D002244:Carbon; D000409:Alanine