Enantioselective Synthesis of α‐Aminosilanes by Copper‐Catalyzed Hydroamination of Vinylsilanes

Abstract

The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEG-PHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds.

Copper Hydride Catalyzed Hydroamination of Alkenes and Alkynes

“…[29] Due to their potential application as amino acid bioisosteres in medicinal chemistry, there is considerable interest in the enantioselective preparation of these compounds. [30] Using the previously reported DTBM-SEGPHOS-based CuH catalyst system, high enantioselectivities and yields were observed for a series of vinylsilanes and hydroxylamine O -benzoate electrophiles.…”

Copper-Catalyzed Enantioselective Hydroamination of Alkenes

“…Using non-racemic DTBM-SEGPHOS as the supporting ligand, the Markovnikov-selective hydroamination of styrenes can be effected with high enantioselectivity, thus constructing a common α-chiral amine substructure. 4 Likewise, α-aminosilanes 6 and α-aminoboranes, 7 which are also useful fragments in organic synthesis, can be assembled using this strategy from simple olefins. Furthermore, all of the above hydroamination reactions are known to proceed with exclusive syn -diastereoselectivity relative to the olefin.…”

Enantioselective Cu‐Catalyzed Functionalizations of Unactivated Alkenes

“…Buchwald and co‐workers expanded the scope of the hydroamination also to vinylsilanes . This hydroamination provides access to amino acid mimics and other useful chiral organosilicon compounds (Scheme ).…”