Catalytic Enantioselective Aminative Difunctionalization of Alkenes

Abstract

Enantioselective difunctionalization of alkenes offers a straightforward means for the rapid construction of enantioenriched complex molecules. Despite the tremendous efforts devoted to this field, enantioselective aminative difunctionalization remains a challenge, particularly through an electrophilic addition fashion. Herein, we report an unprecedented approach for the enantioselective aminative difunctionalization of alkenes via copper-catalyzed electrophilic addition with external azo compounds as nitrogen sources. A series of valuable cyclic hydrazine derivatives via either [3 + 2] cycloaddition or intramolecular cyclization have been achieved in high chemo-, regio-, enantio-, and diastereoselectivities. In this transformation, a wide range of functional groups, such as carboxylic acid, hydroxy, amide, sulfonamide, and aryl groups, could serve as nucleophiles. Importantly, a new cyano oxazoline chiral ligand was found to play a crucial role in the control of enantioselectivity.

Catalytic Asymmetric Aza-Electrophilic Additions of 1,1-Disubstituted Styrenes

“…Although conceptually reasonable, enantioselective versions of this transformation remained elusive due to the lack of efficient catalytic systems . Of particular note, during the preparation of this manuscript, Zhao and his co-workers reported Cu(II)-catalyzed formal [3 + 2] cycloadditions between styrenes and diisopropyl azodicarboxylate (DIAD) (Scheme D) . This catalytic system could also be applied to nucleophile-tethered alkenes to achieve intramolecular endo hydrazinative cyclization with good enantioselectivities.…”

“…However, only 1,2-disubstituted and 1,1,2-trisubstituted substrates were utilized, and 1,1-disubstituted styrenes were not compatible in these reactions. Within above reaction modes, the enantioselectivity was determined in the electrophilic attack step, in which a key enantioenriched aziridium-ion intermediate was proposed to be generated …”

Electrochemical Cyclization of o-Aminyl Azobenzenes: Roles of Aldehydes in N–N Bond Cleavage

“…Azobenzenes play an irreplaceable role in many materials, such as textiles, food, cosmetics, drugs, and photonic materials, supporting their great value for human life . Given the unique properties of these compounds, increasing the diversity of azobenzenes through functionalization has always attracted interest in fundamental research. − However, the direct functionalization of azobezenes remains a long-standing challenge due to their stable conjugated structures . The transformation of classic azobenzenes often involves azo units to enable the generation of hydroazobenzenes, without allowing easy access to arylamines. , Furthermore, these early findings do not show the inherent value of azobenzene in synthetic chemistry.…”

“…Despite advances in azobenzene functionalization, this process is limited by N–N cleavage, which is an essential step. − Some strategies, including azo-directing group-assisted inert C­(sp 2 )–H activation, , aryne insertion, and some others, , can achieve azobenzene functionalization by breaking the NN bond, which yields N-heterocycles that are structurally valuable in synthetic chemistry (Scheme a). In recent years, advances in organic electrochemistry have stimulated the development of synthetic chemistry due to oxidation and reduction processes, which do not require common chemical oxidants or reductants .…”