Despite the apparent similarities to γ-lactam, there is no example of asymmetric α-alkylated six-membered lactams synthesis by enantioselective carbamoylation (Fig. All the above methods could only provide the synthesis of α-alkylated five-membered lactam by the asymmetric 5-exo-trig cyclization. Absolute c 6th edition pdf series#Very recently, a series of asymmetric carbamoylation-initiated difunctionalization of alkenes including borocarbamoylation 29, 30, iodocarbamoylation 31, acylcarbamoylation 32, 33, alkylcarbamoylation 34, 35, 36, 37, 38 and arylcarbamoylation 39, 40 were independently developed by Lautens, Wang, Lin, Ye and our group. The hydrocarbamoylation of alkene was accomplished by Cramer to allow the expedient synthesis of α-methyl pyrrolidinone 28. The seminal Pd-catalyzed asymmetric cyanocarbamoylation of alkenes was developed by Takemoto to access the oxindole 27. This approach allows for the facile synthesis of five-membered lactam, including oxindole and γ-lactam (Fig. The most reliable approaches are the transition metal-catalyzed enantioselective cyclization of carbamoyl electrophile to the pendent alkenes in which the stereogenic center was simultaneously constructed at the α-position of amide functionality with the cyclization to afford the lactam ring. Baudoin group accomplished the only example to construct the β-lactam by palladium-catalyzed desymmetric C(sp 3)‒H carbamoylation (Fig. Recently, several transition metal-catalyzed asymmetric transformations involving carbamoyl electrophiles have emerged as a fascinating tool box for synthesis of chiral lactam moiety 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40. The representative precursor of carbamoylation is formamide and carbamoyl halide, which possess several advantages, including the one-step synthesis from the prevalent secondary amine and exceptional chemo-stable property 24. Nevertheless, this strategy is largely limited to the lactam scope wherein an electron-withdrawing group including ester or aryl group was required at the adjacent position of amide functionality to generate the reactive chiral enolate intermediate 20, 21, 22, 23.Ī strategically distinct approach to forge chiral lactam is the cyclization from the acyclic fragment by the synergistic formation of amide functionality and set-up of a new stereogenic center in the formed lactam ring, namely as asymmetric carbamoylation. Organocatalyst-promoted alkylation and Michael addition were developed to tackle the aforementioned challenge. However, a particular synthetic challenge in this scenario is the enantioselective synthesis of α-alkylated lactam enabled by asymmetric catalysis, likely due to the lack of general asymmetric α-alkylation of simple lactam 16, 17, 18, 19. Owing to these unique pharmacological properties and synthetic utilities, tremendous efforts have been devoted to the development of facile and robust methodologies for stereoselective synthesis of this architecture 7, 8, 9, 10, 11, 12, 13, 14, 15. Amongst these, chiral lactam is recognized as one of the most privileged skeletons 3, 4, 5, 6, which also serves as a valuable subunit for complex molecular synthesis and drug discovery. Nitrogen-containing heterocycles constitute the versatile structure motifs in organic and medicinal chemistry 1, 2. The newly developed chiral 8-Quinox skeleton ligand is the key parameter for this transformation, which significantly enhances the reactivity and enantioselectivity. This protocol features with good functional group tolerance, as well as broad substrate scope. 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. However, despite the extensive efforts, there still remains no protocol to accomplish the related δ-lactam synthesis. 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. Amongst these motifs, the enantioenriched lactams are the ubiquitous scaffolds found in myriad biologically active natural products and drugs. Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |