Synthesis of Lactones via C–H Functionalization of Nonactivated C(sp³)–H Bonds

Abstract

An electron-deficient amide is utilized as a directing group to functionalize nonactivated C(sp)-H bonds through radical 1,5-hydrogen abstraction. The γ-bromoamides formed are subsequently converted to γ-lactones under mild conditions. The method described is not limited to tertiary and secondary positions but also allows functionalization of primary nonactivated sp-hybridized positions in a one-pot sequence. In addition, the broad functional group tolerance renders this method suitable for the late-stage introduction of γ-lactones into complex carbon frameworks.

Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues

“…Additionally, amide derivatives of ester 15 were investigated (Scheme ). After saponification, the amide group was introduced by coupling with 3‐(ethyl‐iminomethyleneamino)‐ N , N ‐dimethylpropan‐1‐amine (EDC). Again, the alkene could be epoxidized under mild conditions using DMDO.…”

ATP Regeneration System in Chemoenzymatic Amide Bond Formation with Thermophilic CoA Ligase

“…Standard amide 4 was synthesized according to a similar procedure as described. [20] To a solution of butyric acid (1) (2.00 mmol, 176.6 mg) in dried dichloromethane (DCM) (7 mL) was added 4-dimethylaminopyridine (DMAP) (0.41 mmol, 0.2 equiv., 50.5 mg) followed by N-ethyl-N'-(3dimethylaminopropyl) carbodiimide HCl (EDC.HCl) (2.24 mmol, 1.1 equiv., 462.4 mg), methylamine HCl (2.42 mmol, 1.2 equiv., 163.2 mg) and trimethylamine (5.00 mmol, 2.5 equiv., 506 mg) at 0°C. The mixture was stirred under inert atmosphere at room temperature for 24 h and then quenched with 20 mL saturated ammonium chloride solution.…”

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

“…Moderate isolated yields of lactone 3 were obtained due to the high volatility of these compounds,resulting in significant losses upon purification. [43] However,i ng eneral, the NMR spectroscopic data of the crude mixture show aclean reaction, suggesting that pursuing further synthetic steps without purification is feasible.…”