Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross Couplings via C–N Bond Activation

Abstract

We developed a strategy to harness alkyl amines as alkylating agents via C–N bond activation. This Suzuki–Miyaura cross coupling of alkyl pyridinium salts, readily formed from primary amines, is the first example of a metal-catalyzed cross coupling via C–N bond activation of an amine with an unactivated alkyl group. This reaction enjoys broad scope and functional group tolerance. Primary and secondary alkyl groups can be installed. Preliminary studies suggest a NiI/NiIII catalytic cycle.

Deaminative Strategy for the Visible‐Light‐Mediated Generation of Alkyl Radicals

“…[7] Primary amines also feature prominently in numerous biologically active natural products [8] and drug molecules, [9] and as such, arange of methods exist for their synthesis. [12] While this cross-coupling reaction is presumed to proceed via the formation of an alkyl radical species,t he open-shell intermediate is inaccessible for direct functionalization as it is immediately captured by the nickel catalyst in af ormal oxidative addition process (II!IV). [12] While this cross-coupling reaction is presumed to proceed via the formation of an alkyl radical species,t he open-shell intermediate is inaccessible for direct functionalization as it is immediately captured by the nickel catalyst in af ormal oxidative addition process (II!IV).…”

Transition‐Metal‐Free Deaminative Vinylation of Alkylamines

“…Tremendous progress has been made in the development of transition metal-mediated/catalysed cross coupling reactions via the cleavage of C(sp 2 )À N bonds in recent years. In 2017, the Watson [11] and Glorius [12] groups reported that Katritzky salts can act as alkylating agents in radical-induced deaminative arylation by using metal catalysts. The chemical bond energy of inert C(sp 3 )À N could be effectively reduced by the conversion of primary alkyl amines into pyridinium salts, known as "Katritzky salts".…”

Catalyst‐Free Deaminative Functionalizations of Primary Amines by Photoinduced Single‐Electron Transfer

“…[11] We sought an alternative functional group that could act as av ersatile photoactive handle for catalyst-free generation of non-stabilized carbon-centered radicals.O ne possibility was Katritzky N-alkylpyridinium salts 1,w hich are easily prepared from primary amines 2 by reaction with 2,4,6-triphenylpyrylium 3,a re air and moisture stable,a nd allow selective deaminative transformations of abundant amino groups (Scheme 1A). [13,14] We recently reported ac atalyst-free deaminative borylation reaction that proceeds through EDAcomplex formation between 1 and bis(catecholato)diboron (B 2 cat 2 )( Scheme 1B). [13,14] We recently reported ac atalyst-free deaminative borylation reaction that proceeds through EDAcomplex formation between 1 and bis(catecholato)diboron (B 2 cat 2 )( Scheme 1B).…”

“…[17] Given the overall transformation is reductive,astoichiometric reductant was required. Aldehydes were tolerated (12)(13)(14), although the substituted enals methacrolein (13)a nd tiglic aldehyde (14)r equired higher temperatures for successful reaction. [10c,d] Gratifyingly,i rradiation (l max = 450 nm) of am ixture of 4-aminopiperidinederived pyridinium 1a,Hantzsch ester,and methyl acrylate in DMA yielded the desired Giese adduct 6 in 77 %y ield ( Table 1).…”