Enantio- and Regioselective CuH-Catalyzed Hydroamination of Alkenes

Abstract

A highly enantio- and regioselective copper-catalyzed hydroamination reaction of alkenes has been developed using diethoxy(methyl)silane (DEMS) and esters of hydroxylamines. The process tolerates a wide variety of substituted styrenes, including trans-, cis-, and β,β-disubstituted styrenes to yield α–branched amines. In addition, aliphatic alkenes coupled to generate exclusively the anti-Markovnikov hydroamination products.

C═N-Containing Azaarenes as Activating Groups in Enantioselective Catalysis

“…67 In this work, diethoxymethylsilane (DEMS) was used as the hydride source. Notably, one example of using β,β-disubstituted alkenylarene was also described (eq 20).…”

Enantioselective Allylic C−H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis

“…[20] Additionally, we sought to exploit the latent reactivity of the products’ allylically substituted terminal olefin, demonstrating orthogonality to past efforts that have focused on late-stage modifications to the aryl moiety. [18] Isochroman 2a may be diversified into α,ß-unsaturated amide 9 via ruthenium-catalyzed cross-metathesis [21] , into aliphatic amine 10 via copper-catalyzed hydroamination [22] , and also into terminal alcohol 11 via hydroboration oxidation (Figure 2, Section B). Importantly, all of these manipulations proceeded without racemization of the stereocenter.…”

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

“…[9] We felt that this method, when applied to vinylsilane substrates, would allow the generation of a broad range of chiral α-aminosilanes [Eq. (4)].…”

“…[10] The intermolecular hydroamination of vinylsilanes would likely, based on literature precedent, proceed regioselectively to give chiral α-aminosilanes (III), via the α-silylalkylcopper intermediate II (Scheme 3), [11] on reaction with the O-benzoylhydroxylamine electrophile 2. [9] We began our investigation by examining the hydroamination of (E)-vinylsilane 1a using conditions previously developed for the hydroamination of styrene (Table 1). [9] The reaction furnished α-aminosilane 3a regioselectively in quantitative yield with > 99 % ee after 8 h (entry 1).…”

“…[9] We began our investigation by examining the hydroamination of (E)-vinylsilane 1a using conditions previously developed for the hydroamination of styrene (Table 1). [9] The reaction furnished α-aminosilane 3a regioselectively in quantitative yield with > 99 % ee after 8 h (entry 1). Switching the solvent to cyclohexane, diethyl ether, or toluene (entries 2-4) had no effect, but no conversion was seen in dichloromethane (entry 5).…”