Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of N-Containing Molecules from Alkenes and Alkynes

Abstract

Nitrogen (N) is ubiquitously found in bioactive molecules, pharmaceutical agents, and organic functional materials. Accordingly, development of new C−N bond-forming catalysis has been one of the long-standing research subjects in synthetic organic chemistry. In this Perspective, recent advances in highly selective amination reactions with electrophilic amination reagents are described: by taking advantage of the concept of nitrogen umpolung, otherwise challenging aminofunctionalizations, such as hydroamination, aminoboration, and carboamination, of readily available feedstock-like alkenes and alkynes are possible, giving densely functionalized complex and often chiral alkylamines with high selectivity. The scope, limitations, and reaction mechanism are briefly summarized.

Metal-Free Photochemical Imino-Alkylation of Alkenes with Bifunctional Oxime Esters

“…Difunctionalization of alkenes offers a straightforward and powerful strategy for constructing structurally complex molecules, installing two chemical bonds across an alkene using readily available feedstocks. Given the most versatile and omnipresent C–C and C–N bonds in pharmaceuticals and bioactive compounds, the alkene carboamination process represents a vibrant area of investigation in organic synthesis, forging both carbon- and nitrogen-based functional units in a single operation (Figure a). − In this context, a wide variety of carboamination strategies have been developed such as classic arylamination, − aminocyanation, − trifluoromethylamination, − and alkylamination − to construct amines; however, these transformations are mainly limited to transition-metal-catalyzed processes. Further, despite significant progress in this arena, traditional alkene difunctionalization methods rely on the use of harsh conditions, organometallic reagents, and expensive catalysts. − , In addition to these issues, another formidable challenge associated with this conventional manifold is the β-hydride elimination of alkylmetal intermediates, particularly for unactivated alkenes, thus limiting the use of C­(sp 3 )-hybridized alkyl groups.…”

“…Further, despite significant progress in this arena, traditional alkene difunctionalization methods rely on the use of harsh conditions, organometallic reagents, and expensive catalysts. [1][2][3][4][5]28 In addition to these issues, another formidable challenge associated with this conventional manifold is the β-hydride elimination of alkylmetal intermediates, particularly for unactivated alkenes, thus limiting the use of C(sp 3 )-hybridized alkyl groups. Despite the increasing interest in C(sp 3 )-rich small organic molecules, 29 remarkable pharmacokinetic (PK) properties, hydrogen bonding capabilities, and enzymatic stability exhibited by molecules possessing C−F bonds.…”

The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines

“…To complement our non-comprehensive article, the readers are referred to excellent reviews on catalytic aminations for extended reading. [11][12][13][14][15][16][17] 2 Introduction of nitrogen through electrophilic reagents…”

“…To complement our non-comprehensive article, the readers are referred to excellent reviews on catalytic aminations for extended reading. 11–17…”

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

“…The dual-catalyzed enantioselective C–N bond formation provides access to N -acyl α-branched aliphatic amines facilitated by a remote directing group. Hydroamination of alkenes has been developed as a powerful tool for the construction of C–N bonds, including metal-hydride-catalyzed hydroamination and the direct addition of the N–H bond across the alkene. , Recent process in metal-hydride-catalyzed asymmetric hydroamination of alkenes offers opportunities for enantioselective C–N bond formation. Pioneered by Buchwald and Miura, CuH-catalyzed enantioselective hydroamination of alkenes to afford enantioenriched amines has been developed. − This strategy could be applied to activated alkenes such as styrenes, , substituted styrenes, , alkenyl dan boronates, 1-trifluoromethylalkenes, and vinylsilanes .…”