Enantioselective Synthesis of α-Amidoboronates Catalyzed by Planar-Chiral NHC-Cu(I) Complexes

Abstract

The first highly selective catalytic hydroboration of alkyl-substituted aldimines to provide medicinally relevant α-amidoboronates is disclosed. The Cu(I)-catalyzed borylation proceeds with excellent facial selectivity when a set of planar-chiral N-heterocyclic carbenes (NHCs) were employed as ligands. Density functional theory computations suggest that interactions between BPin and the planar-chiral catalyst are responsible for the observed stereoselectivity. Important pharmacophores, such as the boronate analogue of isoleucine, can be prepared using a chromatography-free protocol starting from commercially available reagents. The application of these NHC ligands in these Cu(I)-catalyzed processes offers a significant contribution to existing strategies for laboratory-scale preparation of enantioenriched α-amidoboronates.

Multilayer 3D Chirality and Its Synthetic Assembly

“…Even though multilayer chirality has existed in nature from the beginning of the living world, a strategy to mimic this functionality by using planar chirality has not been established yet to the best of our knowledge. So far, planar chirality has only been focused on two-layer arrangement which has been applied to a series of asymmetric reactions [25][26][27][28][29][30][31][32][33][34]. For example, Lautens and coworkers established a bulky and electron rich Qphos ligand for Pd-catalyzed cycloisomerization (carbohalogenation) reaction for the formation of versatile heterocycles in which the carbon iodine bond was regenerated at the end of the catalytic cycle [27][28][29][30].…”

“…For example, Lautens and coworkers established a bulky and electron rich Qphos ligand for Pd-catalyzed cycloisomerization (carbohalogenation) reaction for the formation of versatile heterocycles in which the carbon iodine bond was regenerated at the end of the catalytic cycle [27][28][29][30]. Scheidt's group deployed planar-chiral NHC copper complexes for highly selective control of the delivery of the boron nucleophile to in situ formed imines to give medicinally relevant -amidoboronates [31]. It is interesting that, during this work, the synthesis of both -tosyl benzamide and enantioenriched potassium -amido trifluoroborates would be regarded as GAP (Group-Assisted Purification) since their special functional groups enabled their purification to be performed simply by washing.…”

Cascade CuH-catalysed conversion of alkynes into enantioenriched 1,1-disubstituted products

“…Herein, we report an efficient strategy to synthesize enantioenriched α-aminoboronates via a cascade process in which a single CuH catalyst mediates sequential hydroboration and hydroamination of readily available alkyne substrates. The transformation offers practical value in streamlining access to the important aminoboronates substructure in a manner that complements existing methods [25][26][27][28][29][30][31][32][33][34] . This system takes advantage on in situ formation of the key terminal alkenylBdan intermediate, a process that had only been described for aliphatic alkynes with HBpin (pin = pinacolato) using a Cu•NHC catalyst (NHC = N-heterocyclic carbene) prior to this work [35][36][37] .…”

Catalytic Approach to Diverse α‐Aminoboronic Acid Derivatives by Iridium‐Catalyzed Hydrogenation of Trifluoroborate‐Iminiums

“…Reduction of TIMs with KBH 4 led to stable and isolable trifluoroborate‐ammoniums (TAMs) [11] . TAMs proved to be easy to use and more convenient intermediates than the corresponding boronic ester counterparts in several reports (Scheme 1, entry 3) [16,19,23] . Bode et al.…”