Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams

Abstract

Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals. Amongst these motifs, the enantioenriched lactams are the ubiquitous scaffolds found in myriad biologically active natural products and drugs. Recently, the transition metal-catalyzed asymmetric carbamoylation has been widely employed as a straightforward arsenal for chiral lactam architecture synthesis, including β-lactam and γ-lactam. However, despite the extensive efforts, there still remains no protocol to accomplish the related δ-lactam synthesis. In this manuscript, the Ni-catalyzed enantioselective carbamoylation of unactivated alkenes by the leverage of reductive dicarbofunctionalization strategy allows for the expedient access to two types of mostly common six-membered lactams: 3,4-dihydroquinolinones and 2-piperidinone in high yield and enantioselectivity. This protocol features with good functional group tolerance, as well as broad substrate scope. The newly developed chiral 8-Quinox skeleton ligand is the key parameter for this transformation, which significantly enhances the reactivity and enantioselectivity.

Catalytic Access to Chiral δ‐Lactams via Nucleophilic Dearomatization of Pyridine Derivatives

“…Encouraged by these results, we explored several chiral ligands, L2-L8. The best performing ligand with regard to both substrate conversion and enantioselectivity was L1 (compare entry 5 with entries [6][7][8][9][10][11][12]. Next, we investigated the effect of the solvent and found that in CH 2 Cl 2 , Et 2 O, t BuOMe, toluene, and 2-methyltetrahydrofuran (2-Me-THF) the reaction proceeded with high enantioselectivity (entries 5 and 13-16), while in THF a racemic mixture of 2 a was formed (entry 17).…”

“…The interest in these compounds has prompted the development of various catalytic asymmetric methodologies for the synthesis of δ ‐lactam precursors. In the majority of these methods, which include N ‐heterocyclic carbene (NHC) catalysed cyclisations of α , β ‐unsaturated esters with sulfonylimines (Scheme 1a), [4] artificial metalloenzyme catalysed tandem C−H activation followed by a [4+2] annulation reaction (Scheme 1b) [5] and Ni‐catalysed carbamoylation of alkenes (Scheme 1c), [6] the cyclic structure of δ ‐lactam is assembled from two acyclic reaction partners. Another interesting strategy based on oxidative relay Heck arylation of enelactams was reported as well (Scheme 1d) [7] …”

Ni-Catalyzed Enantioselective Three-Component Reductive Alkylacylation of Enamides

“…A carbamoyl halide-tethered olefin may react with a carbon terminating reagent via cyclization and C-C coupling under redox-neutral or reductive conditions (Scheme 1C). [52][53][54][55][56][57][58][59][60][61] Alternatively, an aryl iodide-tethered olefin may react with an acylating reagent to fulfil the similar type of reaction. 62 More recently, the groups of Chu, 63 Stanley, 64 Wang, 65 Yuan 66 and other [67][68][69][70][71] have developed various methods for fully three-component racemic carboacylation of olefins.…”

Identification ofavaCfrom infant gut microbial isolates that convert 5AVA to 2-piperidone with high efficiency

“…In addition, 2-piperidone is a fundamental scaffold for the synthesis of various chemical products, including high-value nylon-5 and nylon-6,5 (27)(28)(29)(30)(31).…”

“…In addition, 2-piperidone is a fundamental scaffold for the synthesis of various chemical products, including high-value nylon-5 and nylon-6,5 (27–31). 2-piperidone is usually prepared from 5-aminovaleric acid (5AVA) as the substrate in biosynthetic pathways (32).…”