Simple Catalytic Mechanism for the Direct Coupling of α‑Carbonyls with Functionalized Amines: A One-Step Synthesis of Plavix

The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper­(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone

Direct, Redox-Neutral Prenylation and Geranylation of Secondary Carbinol C–H Bonds: C4-Regioselectivity in Ruthenium-Catalyzed C–C Couplings of Dienes to α‑Hydroxy Esters

The ruthenium catalyst generated <i>in situ</i> from Ru₃(CO)₁₂ and tricyclohexylphosphine, PCy₃, promotes the redox-neutral C–C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C–H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C–C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene–carbonyl oxidative coupling

Amphiphilic π‑Allyliridium <i>C</i>,<i>O</i>‑Benzoates Enable Regio- and Enantioselective Amination of Branched Allylic Acetates Bearing Linear Alkyl Groups

The first examples of amphiphilic reactivity in the context of enantio­selective catalysis are described. Commercially available π-allyliridium <i>C</i>,<i>O</i>-benzoates, which are stable to air, water and SiO₂ chromatography, and are well-known to catalyze allyl acetate-mediated carbonyl allylation, are now shown to catalyze highly chemo-, regio- and enantio­selective substitutions of branched allylic acetates bearing linear alkyl groups with primary amines

Hydroamination versus Allylic Amination in Iridium-Catalyzed Reactions of Allylic Acetates with Amines: 1,3-Aminoalcohols via Ester-Directed Regioselectivity

In the presence of a neutral dppf-modified iridium catalyst and Cs₂CO₃, linear allylic acetates react with primary amines to form products of hydroamination with complete 1,3-regioselectivity. The collective data, including deuterium labeling studies, corroborate a catalytic mechanism involving rapid, reversible acetate-directed aminoiridation with inner-sphere/outer-sphere crossover followed by turnover-limiting proto-demetalation mediated by amine