Asymmetric Synthesis of α-Aminoboronic Acid Derivatives by Copper-Catalyzed Enantioselective Hydroamination

Abstract

A copper-catalyzed regio- and enantioselective hydroamination of alkenyl dan boronates (dan =1,8-diaminonaphthyl) with hydrosilanes and hydroxylamines proceeds to deliver the chiral α-aminoboronic acids in good yields with high enantiomeric ratios. The key to success is the introduction of an umpolung, electrophilic amination strategy. The copper catalysis can provide an unprecedented catalytic asymmetric approach to alkyl-substituted chiral α-aminoboronic acid derivatives of great potential in the fields of organic synthesis and medicinal chemistry.

Mechanism-based enhancement of scope and enantioselectivity for reactions involving a copper-substituted stereogenic carbon centre

“…With dihydronaphthalene 6 , increasing the hydroxyamine concentration led to improvement in enantioselectivity ( 11 from 80% to 92% e.e. ); similarly, in the reaction with alkenyl–B(dan) 3 there was significant increase in e.e. when larger electrophile amounts were present (from 76% to 92% e.e.).…”

“…Generally, additions to aliphatic olefins are less efficient but aryl and heteroaryl olefins or alkenyl boronates and silanes are suitable, and Cu–C and/or C–B(pin) bonds can be further functionalized. Reactions that begin with enantioselective Cu–H addition (via iii ) 3 are a notable subset.…”

Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

“…By employing a class of electrophilic aminating reagents established by Johnson (17) to intercept these organometallic intermediates, our laboratory (18) and Miura and Hirano (19–21) have independently developed a CuH-catalyzed approach for the enantioselective hydroamination of olefins (22). Based on these studies and notable contributions from other groups in the area of copper-catalyzed enantioselective reductive aldol reactions (6,7, 23–26), we envisioned the development of CuH chemistry as a general platform for the use of simple olefins as latent carbon nucleophiles in carbonyl addition (Fig.…”

Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration

“…By capturing the catalytically generated organocopper species with electrophilic aminating reagents, our laboratory 10 and Hirano and Miura 11 have independently developed a new approach for the enantioselective hydroamination of olefins. More recently, we have also demonstrated the feasibility of engaging organocopper intermediates in carbon–carbon bond-forming processes.…”