Directed, Nickel-Catalyzed Umpolung 1,2-Carboamination of Alkenyl Carbonyl Compounds

Abstract

We report a regioselective, nickel-catalyzed syn-1,2-carboamination of non-conjugated alkenyl carbonyl compounds with O-benzoyl hydroxylamine (N-O) electrophiles and aryl/alkylzinc nucleophiles to afford β-and γ-amino acid derivatives. This method enables preparation of products containing structurally diverse tertiary amine motifs, including heterocycles, and can also be used to form quaternary carbon centers. The reaction takes advantage of a tethered 8-aminoquinoline directing group to control the regiochemical outcome and suppress two-component coupling between the N-O electrophile and organozinc nucleophile. File list (4) download file view on ChemRxiv Manuscript.pdf (544.78 KiB) download file view on ChemRxiv Supporting Info.pdf (40.39 MiB) download file view on ChemRxiv 3a.cif (379.57 KiB) download file view on ChemRxiv 4a.cif (835.

Nickel-Catalyzed 1,2-Diarylation of Simple Alkenyl Amides

“…Our inspiration for this approach originated from a series of seminal publications by Fu and coworkers, in which simple amides and other carbonyl-containing compounds were used to effectively direct C–X oxidative addition and stabilize the resulting intermediate for a variety of enantioselective cross-coupling reactions under nickel catalysis. 9 Given our group’s interest in nickel-catalyzed alkene difunctionalization, 10 we wondered if previously employed, strongly coordinating directing groups such as 8-aminoquinoline (AQ) could be replaced with simple amides. Practically speaking, this advance would be advantageous in that it would allow use of diverse amide directing groups, including those that are readily cleavable as well as those that are native to the target compound of interest.…”

Recent developments in nickel-catalyzed intermolecular dicarbofunctionalization of alkenes

“…This SET mode of nickel catalysis using AQ-bound substrates was later extended to a complementary 1,2-carboamination system. 28 Very recently, the Lin and Yao groups applied this AQ-directed system toward a reductive 1,2-dialkynylation of non-conjugated alkenes. 29 In 2018, the Zhao group reported a series of 1,2-and 1,3dicarbofunctionalization reactions using a 2-aminopyrimidine directing group derived from allyl amine with C(sp)/C(sp 2 )-X electrophiles and C(sp 2 )-boronic acids as nucleophiles (Fig.…”

Design and Scalable Synthesis of N‐Alkylhydroxylamine Reagents for the Direct Iron‐Catalyzed Installation of Medicinally Relevant Amines**

“…[2] However, the majority of the reported aminofunctionalizations introduce the amine in ap rotected form (e.g.t osyl, nosyl) because these methods often require an electron-deficient nitrogen to enhance the electrophilicity of the aminating species involved. [3] In contrast, and despite their synthetic utility,e lectron-rich alkylamino sources are mostly unreactive in those cases,o ften preventing the development of efficient and useful intermolecular aminofunctionalization reactions.Inanotable exception, an umpolung approach which features migratory insertion of alkenes into M À Xbonds (M = Cu, Ni, Zr;X= B, C, H), followed by an ucleophilic attack of this alkyl-metal species on ahydroxylamine derivative,has led to synthetically attractive examples of intermolecular aminoboration, [4] hydroamination [5] and carboamination [6] of unactivated olefins (Scheme 1b). Given the synthetic relevance of alkylamines in medicinal chemistry, [7] the installation of further functionalities via intermolecular aminofunctionalization reactions remains ac entral goal in synthetic chemistry.…”