Alkene Difunctionalization Directed by Free Amines: Diamine Synthesis via Nickel-Catalyzed 1,2-Carboamination

Abstract

A versatile method to access differentially substituted 1,3- and 1,4-diamines via nickel-catalyzed three-component 1,2-carboamination of alkenyl amines with aryl/alkenylboronic ester nucleophiles and N–O electrophiles is reported. The reaction proceeds efficiently with free primary and secondary amines without needing a directing auxiliary or protecting group and is enabled by fine-tuning the leaving group on the N–O reagent. The transformation is highly regioselective and compatible with a wide range of coupling partners and alkenyl amine substrates, all performed at room temperature. A series of kinetic studies support a mechanism in which alkene coordination to the nickel catalyst is turnover-limiting.

Electrophilic Sulfur Reagent Design Enables Directed syn-Carbosulfenylation of Unactivated Alkenes

“…The other two components, [ArB­(nep)] and [NaOH], were zero-order. Collectively, the data are consistent with the Ni I /Ni III cycle shown in Scheme E, involving a sequence of transmetalation, migratory insertion, N–S oxidative addition, and C–S reductive elimination. , The kinetic data indicate that the turnover-limiting step at a standard or an elevated alkene concentration is N–S oxidative addition, whereas at a low alkene concentration, an earlier step becomes turnover-limiting, namely alkene coordination or irreversible migratory insertion following reversible alkene binding.…”

“…A Ni(0)/Ni­(II) cycle occurs by an oxidative-addition-first pathway, where the electrophile is incorporated distal to the directing group . Meanwhile, a Ni­(I)/Ni­(III) cycle involving a transmetalation-first mechanism typically manifests in reversed regioselectivity . In both cases, syn -selectivity is dictated by inner-sphere migratory insertion.…”

Catalytic Arylalkylation of Alkenyl Amines at Remote Sites via Directed Nickel Catalysis

“…Among the various synthetic methods, metal‐catalyzed difunctionalization of alkenyl amines has emerged as a powerful strategy for the efficient construction of value‐added complex alkylamines from easily accessible starting materials. [ 3‐11 ] Considering that the structure of alkyl groups appended to the nitrogen atom would influence the physical properties and control the biological interactions, [ 12‐13 ] difunctionalization of alkenyl amines at various sites would be highly desirable to prepare new aliphatic amines, especially those that are difficult to access using traditional methods.…”

Intermolecular Redox-Neutral Carboamination of C–C Multiple Bonds Initiated by Transition-Metal-Catalyzed C–H Activation

“…To address this limitation, an umpolung amination strategy − with N–LG (LG = leaving group)-type electrophilic amination reagents has recently been introduced and its combination with a suitable nucleophilic carbon source would also allow for carboamination of C–C multiple bonds. For instance, organometallic reagents (C–m) undergo facile transmetalation and succeeding syn -specific migratory insertion into π-bonds. − Upon electrophilic amination, syn -carboamination products are obtained. Considering that many organometallic reactants are sensitive to moisture and air and often originate from aromatic or aliphatic hydrocarbons through the intermediacy of organic halides, the direct use of C–H substrates as an alternative carbon nucleophile would arguably be the most desirable method for this transformation (Scheme , lower left).…”