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

Abstract

Enantioenriched α-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize α-aminoboronates via CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio-and enantioselectivity. Alkenes and alkynes are ideal starting materials in organic synthesis due to the fact that they can be readily prepared using a variety of convenient synthetic methods and are widely available from commercial suppliers. Catalytic functionalization of the π-bonds in these substrates leads to a valuable array of building blocks and in the case of alkenes offers a Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Primary trifluoroborate-iminiums enable facile access to chiral α-aminoboronic acids via Ru-catalyzed asymmetric hydrogenation and simple hydrolysis of the trifluoroborate moiety

“…The study of ruthenium catalysts revealed that Ru-(p-cymene)-phosphine ligand complexes showed very low activity and no enantioselectivity in the hydrogenation of substrate 2a (Table S3, entries 2-14). The RuOAc 2 -phosphine complexes showed limited enantioselecivity and also low conversions (Table S3, entries 15, 16), while the RuCl-diphosphine-diamine complexes performed slightly better in terms of enantioselecivity, but with similarly meagre conversions (Table S3, entries [17][18][19][20][21][22][23][24]. The dimethylamine adducts of RuCl-phosphine complexes were slightly more active but gave low enantioselectivity (Table S3, entries [25][26][27].…”

Cobalt‐Catalyzed One‐Pot Asymmetric Difunctionalization of Alkynes to Access Chiral gem‐(Borylsilyl)alkanes

“…In 2019, the Engle group developed an asymmetric Cu‐catalyzed cascade hydroboration/hydroamination of alkynes to synthesize chiral α‐amino organoboronates (Scheme 1 A). [7a] In 2020, Hirano and Miura reported a Cu‐catalyzed hydrosilylation/hydroamination sequence of alkynes to prepare chiral α‐amino organosilanes (Scheme 1 A). [7b] Inspired by these two seminal reports, we envisioned that asymmetric one‐pot hydrosilylation/hydroboration of alkynes would provide the most straightforward and convenient protocol to synthesize chiral gem ‐(borylsilyl)alkanes.…”

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

“…Recently, the challenge of α‐aminoboronic acid synthesis was tackled by reductive amination of acylboranes (Scheme 1, entries 1 and 2), [10,11] borylation of amides, [12–14] hydroboration of enamides, [15] electrophilic amination of gem ‐diborylalkanes (Scheme 1, entry 3), [16] a cascade copper‐catalyzed aminoboration of alkynes, [17] and also an interesting one‐pot borono‐Strecker reaction [18] . Two complementary rhodium‐catalyzed approaches were disclosed independently by two research groups, successfully hydrogenating α‐boryl enamides (Scheme 1, entry 4) [19,20] .…”