Regio‐ and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2‐Diamines

Abstract

The asymmetric formal hydroamination of enamines using aC uH catalyst is reported. The method provides as traightforwarda nd efficient approach to the synthesis of chiral 1,2-dialkyl amines in good yields with high levels of enantioselectivities for abroad range of substrates,and should have significant value for the preparation of molecules bearing a1 ,2-diamine motif.

Copper-Catalyzed Asymmetric Hydroamination: A Unified Strategy for the Synthesis of Chiral β-Amino Acid and Its Derivatives

“…Moreover, without any racemization, the chiral center in 5a was observed under harsh conditions [e.g., in the presence of NaOH or trifluoroacetic acid (TFA)], indicating that these types of chiral compounds might have the capacity to transfer into more complicated chiral compounds while maintaining the enantioselectivity. According to previous reports, [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]62,63 a mechanism involving a regio-and enantioselective insertion of CuH into C-C double bond in a Michael acceptor to form benzylcopper intermediate, followed by an amination process with hydroxylamine 4 to provide expected chiral β-amino carbonyls, might be possible. Other mechanisms cannot be excluded, and further studies need to be carried out to illuminate the origin of this unusual regio-and enantionselectivity.…”

“…Transition-metal-catalyzed asymmetric hydroamination of unsaturated hydrocarbons is a straightforward and powerful approach for rapid assembly of a variety of biologically active chiral amines. [36][37][38][39] In this context, asymmetric hydroamination of various alkenes and alkynes [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] with in situ generated CuH catalysts [56][57][58][59][60][61] has attracted much attention since the pioneering reports by Buchwald 62 and Hirano, and Miura in 2013. 63 Besides, an array of electronically matched CuH-catalyzed asymmetric transformations of Michael acceptors, namely undergoing the 1,4-hydrocupration process, have also been disclosed in past decades (Scheme 1b).…”

Earth-Abundant 3d Transition Metal Catalysts for Hydroalkoxylation and Hydroamination of Unactivated Alkenes

“…It is indeed efficient for the regio-and enantiocontrolled hydroamination of vinylsilanes [148], 1,1-disubstitued alkenes [149], symmetric [150] or unsymmetrical (E)-1,2dialkylsubstituted alkenes [151] (including the feedstock olefin, (E)-2-butene [146]), alkenyl 1,8-diaminonaphthyl boronates [152], vinylphosphine boranes [153], 1-trifluoromethylalkenes [154], enamines [155], N-protected γ-substituted allylic amines [156], unprotected allylic alcohols [157] delivering a range of structurally diverse β-chiral, αand β-functionalized tertiary amines in moderate-to-high enantiopurity as privileged building blocks (Figure 25). Although minimal alteration of the initial reaction conditions using the DTBM-SEGPHOS ligand (L 3 ) as privileged ancillary ligand is usually required, structural optimization of the amine transfer agent, hydrosilane, ligand and substrate or use of additional monodentate phosphine ligand (PPh 3 , P(p-tolyl )3 ), proton source (tBuOH) or specific external bases (Li-OtBu, CsOAc) was needed in some cases to broaden the scope to new compound families and/or overall improve the process efficiency.…”

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

“…Notably, 1,2-diamines have widespread applications as core structures in a variety of natural products, pharmaceuticals, and agrochemicals [34][35][36][37][38] and are valuable ligands [39,40] in stereoselective organic synthesis. Despite the availability of a plethora of synthetic methods for 1,2-diamines [41][42][43][44][45], the reported photocatalytic synthetic methods are mainly limited to aniline-based substrates and do not encompass aliphatic amines. We planned the synthesis of 1,2-diamine compounds having an aliphatic amine moiety by the intermolecular coupling of N-benzylidines with aliphatic amines that not only act as coupling partner but also as electron donors in the photoredox cycle, and the results are reported herein.…”