One‐Pot Synthesis of Chiral N‐Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N‐Arylation

Abstract

The combination of biocatalysis and chemo‐catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral‐amine‐producing biocatalysts with a Buchwald–Hartwig cross‐coupling reaction, affording a variety of α‐chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual‐enzyme biocatalytic hydrogen‐borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.

Chemoenzymatic Synthesis of Sterically Hindered Biaryls by Suzuki Coupling and Vanadium Chloroperoxidase Catalyzed Halogenations

“…Therefore, minimal concentrations of Na 2 CO 3 (100 mM) and 4 (5 mM) were kept in the second chemoenzymatic step of the one‐pot reaction, on the condition that the coupling reaction still performed well. Other investigations of adding a surfactant in an attempt to accelerate the rate in aqueous phase, [19c] and screening of other Pd catalysts [19e] did not lead to significant improvements (Table S2).…”

Polydopamine‐Encapsulated Dendritic Organosilica Nanoparticles as Amphiphilic Platforms for Highly Efficient Heterogeneous Catalysis in Water

“…The chemoenzymatic reactions, which merge the advantages of chemo‐ and bio‐catalysis, are becoming a popular trend in various fields, especially the cascade counterparts, due to the appealing features in eliminating the purification of intermediates, reducing the operating time, and achieving the cooperative effects of multiple catalysts. [ 40‐45 ] In this regard, the integration of Pd‐catalyzed Suzuki cross‐coupling and ADH‐catalyzed asymmetric reduction was explored to realize the chemoenzymatic cascade synthesis of enantioenriched biaryl alcohols (Scheme 3a). The Suzuki coupling catalyzed by DON@Pd@PDA was performed at 70 o C in alkaline water solution.…”

Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

“…Buchwald–Hartwig cross‐coupling consists of the reaction between amines and aryl bromides in the presence of Pd catalysts [24] . The first time that it was combined with a biotransformation was the asymmetric reductive amination of different ketones using a chimeric amine dehydrogenase (ChiAmDH) followed by reaction of so‐obtained chiral amines with the corresponding aryl bromides, [Pd(allyl)Cl] 2 , t BuXPhos as ligand, NaOH, and a degassed aqueous solution of surfactant TPGS‐750‐M (Scheme 5A) [25] . Thus, ( R )‐N‐substituted amines were obtained in 49–83 % conv.…”

“…Thus, several enantiopure alcohols were synthesized. This strategy, [25, 70] has also been successfully implemented to a one‐pot sequence Suzuki–Miyaura cross‐coupling followed by an alkene bioreduction [84] …”