Enantioselective Synthesis of Arylglycines via Pd-Catalyzed Coupling of Schöllkopf Bis-Lactim Ethers with Aryl Chlorides.

Arylglycines are important pharmacophores present in several top-selling drugs. This compound class has now been made accessible from abundant aryl chlorides by a Pd-catalyzed Schöllkopf-type amino acid synthesis. In the presence of the catalyst methylnaphthyl(XPhos)-palladium bromide, the base lithium 2,2,6,6-tetramethylpyrrolidide and the additive ZnCl2 , tert-leucine-derived bis-lactim ethers were efficiently arylated at room temperature, reaching yields of 95 % and diastereoselectivities of 98 : 2. Hydrolysis gave the corresponding arylglycines in high enantiomeric excess.

Palladium-Catalyzed PIDA-Mediated δ-C(sp3 )-H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination.

The selective δ-C(sp3 )-H acetoxylation of N-(SO2 Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO2 Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C-H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH2 . Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivity.

Selective Pd-Catalyzed Monoarylation of Small Primary Alkyl Amines through Backbone-Modification in Ylide-Functionalized Phosphines (YPhos).

Ylide-substituted phosphines have been shown to be excellent ligands for C-N coupling reactions under mild reaction conditions. Here we report studies on the impact of the steric demand of the substituent in the ylide-backbone on the catalytic activity. Two new YPhos ligands with bulky ortho-tolyl (pinkYPhos) and mesityl (mesYPhos) substituents were synthesized, which are slightly more sterically demanding than their phenyl analogue but considerably less flexible. This change in the ligand design leads to higher selectivities and yields in the arylation of small primary amines compared to previously reported YPhos ligands. Even MeNH2 and EtNH2 could be coupled at room temperature with a series of aryl chlorides in high yields.

Decarboxylative Ketonization of Aliphatic Carboxylic Acids in a Continuous Flow Reactor Catalysed by Manganese Oxide on Silica.

The sustainable synthesis of long carbon chain molecules from carbon dioxide, water and electricity relies on the development of waste-free, highly selective C-C bond forming reactions. An example for such a power-to-chemicals process is the industrial-scale fermentation for the production of hexanoic acid. Herein, we describe how this product is transformed into 6-undecanone via decarboxylative ketonization using a heterogeneous manganese oxide/silica catalyst. The reaction reaches full conversion with near-complete selectivity when carried out in a continuous flow reactor, requires no solvent or carrier gas, and releases carbon dioxide and water as the only by-products. The reactor was operated for several weeks with no loss of reactivity, producing 7 kg of 6-undecanone from 10 g of catalyst and achieving a productivity of 1.135 kg per litre of reactor volume per hour. 6-Undecanone and other long-chain ketones accessible this way can be hydrogenated to industrially meaningful alkanes, or converted into valuable fatty acids via a hydrogenation/elimination/isomerizing hydrocarboxylation sequence.