Access to Enantioenriched 1,n-Diamines via Ni-Catalyzed Hydroamination of Unactivated Alkenes with Weakly Coordinating Groups

Abstract

Enantioenriched 1,2- and 1,3-diamines with chiral α-branched aliphatic amine motifs are important substructures in bioactive compounds and related molecules and serve as privileged chiral ligands in both organo- and transition-metal-catalysis. However, direct access to such structural motifs remains a formidable challenge. Herein, a straightforward method to access 1,n-diamines (n = 2, 3, 4) containing a chiral α-branched aliphatic amine is achieved by Ni-catalyzed asymmetric hydroamination of unactivated aliphatic alkenes. Facilitated by a remote weakly coordinating group, the reaction is applicable to both terminal and internal unactivated alkenes, delivering enantioenriched 1,2-, 1,3-, and 1,4-diamine precursors in good yields and excellent enantioselectivities with diverse substitution patterns. Unactivated aliphatic alkenes serve as secondary alkyl nucleophile surrogates in the presence of Ni–H, forging the C–N bond enantioselectively with aminating reagents. In addition, the reaction proceeds at room temperature with excellent functional group tolerance.

Recent Advances in the Catalytic Synthesis of 1,3‐Diamines

“…In 2022, Shu et al [19] . developed a nickel‐catalyzed selective hydrogen amination reaction of alkenes to synthesize 1,3‐diamines (Scheme 12a).…”

Ligand-Controlled NiH-Catalyzed Regiodivergent and Enantioselective Hydroamination of Alkenyl Amides

“…Moreover, the enantioselec- tive syntheses of chiral 1,2-diamines and 1,3-diamines have also been established. Very recently, Hong et al 16 and Shu et al 17 reported an enantioselective hydroamination of allylic amines and homoallylic amines without migration. However, the migratory αor β-selective hydroamination and enantioselective migratory β-selective hydroamination have not been reported yet.…”

“…Ether solvents, such as THF, were found to preferably promote the amination at initial olefinic sites (entry 7 vs entry 8). 16,17 Eventually, after extensive studies, we noticed that the addition of 10 mol % coligand PMe 3 further improved the enantioselectivity of 3-β to 93% with moderate yield (entry 9), which was proposed to suppress the background nonasymmetric reaction. 19 Fortu-nately, selective formation of γ-amination has proven to be possible, as the use of chiral dibenzyl-substituted Ph-Box ligand L6 in THF delivered 3-γ in 89% yield with 92% ee (entry 11).…”

Synthesis of (Hetero)aryl/Alkenyl Iodides via Ni-Catalyzed Finkelstein Reaction from Bromides or Chlorides

“…More importantly, aryl and alkenyl chlorides remains an unmet challenge. As our continuous effort on Ni-catalyzed selective transformations, we herein report the rapid synthesis of (hetero)­aryl and vinyl iodides via Ni-catalyzed Finkelstein reaction from (hetero)­aryl and vinyl halides (Scheme c). The use of a bisoxazoline ligand facilitates halogen exchange and reductive elimination, enabling the reaction proceed under mild conditions (mostly at room temperature) with broad functional group tolerance.…”

“…Based on previous literature precedent of nickel or copper-catalyzed halogen exchange reactions, a plausible mechanism is proposed in Scheme . ,, The coordination between ligand and Ni­(COD) 2 would generate L -Ni­(0) complex A . The oxidative addition of 1 to A could form Ni­(II) intermediate B .…”