Ir(I)-Catalyzed Enantioselective Secondary sp³ C–H Bond Activation of 2-(Alkylamino)pyridines with Alkenes

Abstract

A cationic Ir(I)-tolBINAP complex catalyzed an enantioselective C-C bond formation initiated by secondary sp(3) C-H bond cleavage adjacent to a nitrogen atom. The reaction of 2-(alkylamino)pyridines with various alkenes gave chiral amines in good yields with high enantiomeric excesses.

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…[92][93][94] Indeed, with the exception of the present authors work, [95][96][97][98][99] all other late transition metal catalyzed hydroaminoalkylations require pyridyl directing groups in combination with mono-olefin reactants. [100][101][102][103][104][105][106][107][108] In a significant departure from prior art, it was found that ruthenium catalyzed hydrogen transfer from 4-aminobutanol to 1-substituted-1,3-dienes results in the generation of dihydropyrrole-allylruthenium pairs, which combine to form products of hydroaminoalkylation with good to complete control of anti-diastereoselectivity (Scheme 18). 95 As corroborated by deuterium labeling experiments, kinetically preferred hydrometalation of the terminal olefin of the 1-substituted-1,3-diene delivers a 1,1-disubstituted π-allylruthenium complex that isomerizes to the more stable monosubstituted π-allylruthenium complex.…”

Transition-Metal-Catalyzed Functionalization of C(sp3)&singleBond;H Bonds of Amines

“…[122][123][124][125] Tunable and modular mono(amidate) tantalum and niobium complexes, as well as chiral iridium(I) complexes, have been successfully used as catalysts to achieve the selective synthesis of the branched amines in a diastereo-and enantioselective fashion. [122][123][124][125] Mono(amidate) tantalum complexes 156 with varying degrees of steric bulk are easily available from the reaction of benzamides 155 with pentakis(dimethylamido)tantalum(V) at ambient temperature in hexanes (Scheme 50). [122] Most importantly, complexes 156 allow a-alkylation of N-methylaniline with oct-1-ene at a lower temperature compared to pentakis(dimethylamido)tantalum(V) (Section 40.1.1.5.6.3.1.1.1).…”

“…The C-H functionalization reaction proceeds efficiently in both cases in chlorobenzene to give alkylated products 170 (R 1 = H, Me) in moderate to high yield (Scheme 54). [125] N Me 24 41 [125] The enantioselective hydroaminoalkylation reaction of N-ethylpyridin-2-amine (169, Table 36. The chiral amines 172 are obtained in good yields with enantiomeric excesses of up to 91%.…”

“…The chiral amines 172 are obtained in good yields with enantiomeric excesses of up to 91%. [125] Tol-BINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl the chiral amine (S)-(-)-174 in 81% yield without loss of enantiomeric purity (Scheme 55). [125] Scheme 55 Stereospecific Transformation into a Chiral Amine [125] 1.…”

“…[125] Tol-BINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl the chiral amine (S)-(-)-174 in 81% yield without loss of enantiomeric purity (Scheme 55). [125] Scheme 55 Stereospecific Transformation into a Chiral Amine [125] 1. [N-(2,6-Diisopropylphenyl)pivalamidato]tetrakis(dimethylamido)tantalum(V) (156,R 1 = t-Bu; R 2 = iPr): [122] N-(2,6-Diisopropylphenyl)pivalamide (155,R 1 =t-Bu; R 2 = iPr; 0.325 g, 1.25 mmol) was suspended in hexanes (3 mL).…”