Diversification of a β-lactam pharmacophore via allylic C–H amination: accelerating effect of Lewis acid co-catalyst

Abstract

This report describes the use of Pd(II)/bis-sulfoxide 1 catalyzed intra-and intermolecular allylic C -H amination reactions to rapidly diversify structures containing a sensitive β-lactam core similar to that found in the monobactam antibiotic Aztreonam. Pharmacologically interesting oxazolidinone, oxazinanone, and linear amine motifs are rapidly installed with predictable and high selectivities under conditions that use limiting amounts of substrate. Additionally, we demonstrate for the first time that intramolecular C-H amination processes may be accelerated using catalytic amounts of a Lewis acid co-catalyst [Cr(III)(salen)Cl 2].

Palladium-Catalyzed Intermolecular Oxidative Amination of Alkenes with Amines, Using Molecular Oxygen as Terminal Oxidant

“…Although significant developments in aza-Wacker-type reactions have been achieved, the existing aza-Wacker process generally requires non-basic nitrogen nucleophiles such as carboxamides, carbamates, and sulfonamides as amination reagents, under relatively high oxygen pressures (4-10 atm.) or in the presence of an external oxidant source such as benzoquinone (BQ), PhBQ, PhI(OAc) 2 , or PhI(OPiv) 2 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. In contrast, the oxidative amination of olefins using more basic, simple amines as substrates has been less explored, and is generally limited to intramolecular reactions [34][35][36][37][38], because of the strong coordination of amines to Pd, which results in catalyst deactivation.…”

Alcohols or Masked Alcohols as Directing Groups for C–H Bond Functionalization

“…White and co-workers further utilized this methodology on β-lactam-containing substrates to generate pharmacologically interesting oxazolidinones and oxazinanones. 11 The same group also disclosed a palladium(II)sulfoxidecatalyzed intramolecular allylic CH oxidation to form anti-1,4-dioxan-2-ones from homoallylic oxygenates. 12 While homoallylic alcohol derivatives were not suitable for the intermolecular allylic CH oxidation, 13 by being tethered with a carboxylic acid substrates 11 can undergo the desired allylic CO bond formation (Scheme 7).…”

Allylic CH Alkylation of Unactivated α‐Olefins: Serial Ligand Catalysis Resumed

“…We postulated that the allylic CÀH alkylation of unactivated a-olefins may be achieved by a serial ligand catalysis [8] mechanism (SLC). [9] Under this scenario, multiple kinetically labile ligands with different electronic properties reversibly coordinate to the metal center and mediate individual steps of the cycle. [10] Specifically, a SLC mechanism for palladiumcatalyzed allylic C À H alkylation may proceed as follows: 1) catalytic palladium(II)/bis(sulfoxide)-promoted CÀH cleavage to furnish a p-allylPd intermediate, 2) stoichiometric DMSO-promoted functionalization through ionization of the p-allylPd intermediate, and 3) re-oxidation of Pd 0 to Pd II with a quinone.…”