Effective differentiation of prochiral carbon–hydrogen (C–H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C–H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of β-methylene C–H bonds in aliphatic amides. Using bidentate ligands to accelerate C–H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C–H activation is also demonstrated by enantioselective β-C–H arylation of simple carboxylic acids without installing directing groups.

Ligand-accelerated enantioselective methylene C(sp3)–H bond activation

A convenient synthesis of flindersine, atanine and their analogues

2.08 – Pyridines and their Benzo Derivatives: (v) Synthesis

Publisher Summary This chapter discusses 1-, 2-, and 3-Benzazepines. Ring closure with the formation of a carbon-nitrogen bond, of the types A-E shown in the chapter, has been used to synthesize derivatives of 1-, 2-, and 3-benzazepines, with aminocarboxylic acids, amino halides, dihalides, dinitriles, dicarboxylic acids, and carboxylic acid diamides as starting materials. The yields are generally fair to good. In some cases, preferential formation of a five- or six-membered ring is observed. The formation of a carbon-carbon bond to construct the seven-membered ring of the benzazepines has been achieved by ring closures of the types F-L. The Friedel-Crafts reaction (limited in the 1-benzazepine series), Dieckmann, acyloin, and aldol condensations, Bischler-Napieralski, Vilsmeyer, and Pictet-Spengler-type reactions, and phenolic oxidative coupling have been used in the synthesis of the isomeric benzazepines. The Friedel-Crafts intramolecular acylation, so often used in the formation of six-membered heterocyclics, proved to be of less value in the synthesis of 1-benzazepines.

A. K. Cho

Papers

Rearrangement of Methyl 3-Azabenzocycloheptene-4,7-dione-6-carboxylate to 2,4-Dihydroxyquinoline-3-acetic Acid in Acid and Base