An efficient and expeditious DABCO-mediated synthesis of functionalized enamides from alkenes is delineated. The reaction proceeds through an unprecedented cascade involving an Aza-Michael addition/α-bromination/elimination and a Morita-Baylis-Hillman type reaction to generate functionalized enamides in a regio- & stereoselective fashion.
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http://dx.doi.org/10.1039/c3ob41847b | DOI Listing |
Acc Chem Res
January 2025
Department of Chemistry and Chemistry Institution for Functional Materials, Pusan National University, Busan 46241, Republic of Korea.
ConspectusControlling selectivity through manipulation of reaction intermediates remains one of the most enduring challenges in organic chemistry, providing novel solutions for selective C-C π-bond functionalization. This approach, guided by activation principles, provides an effective method for selective functional group installation, enabling direct synthesis of organic molecules that are inaccessible through conventional pathways. In particular, the selective functionalization of N-conjugated allenes and alkynes has emerged as a promising research focus, driven by advances in controlling reactive intermediates and activation strategies.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Laboratory of Catalysis and Organic Synthesis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.
The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical-polar crossover strategy. A broad range of alkenes, including vinyl arenes, enamides, enol ethers, vinyl sulfides, and dehydroamino esters, were regioselectively functionalized with an azide and nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric acids, oximes, and phenols. The method led to a more efficient synthesis of 1,2-azidofunctionalized pharmaceutical intermediates when compared to previous approaches, resulting in both reduction of step count and increase in overall yield.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Technical Institute of Fluorochemistry, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, China.
Introducing distinctive functional groups to expand the structural diversity and improve the intrinsic properties of parent molecules has been an essential pursuit in organic chemistry. By using perfluoroalkyl halide (PFAH) as a nontraditional, readily available, ideal 1,2-difluoroalkenyl coupling partner, a defluorinative cyclization reaction of enamides for the construction of fluoroalkenyl oxazoles is first developed. The selective and controllable two-fold cleavage of vicinal C(sp)─F bonds in PFAH not only enables the introduction of a specific 1,2-difluoroalkenyl moiety with ease but also results in the functionalization of two C(sp)─H bonds of enamides without the need for metal catalyst, photocatalyst, oxidant, or light.
View Article and Find Full Text PDFOrg Lett
December 2024
College of Chemistry and Molecular Engineering, Qingdao University of Science & Technology, Qingdao, 266042, China.
The site-selective functionalization of cyclic amides provides an attractive protocol for the synthesis of valuable molecules. We report herein an electrochemical desaturation and β-thiocyanation of cyclic amides under external oxidant-free conditions. This method exhibits broad functional group tolerance, excellent selectivity, mild reaction conditions and can be applied for late-stage functionalization of bioactive molecules.
View Article and Find Full Text PDFOrg Biomol Chem
December 2024
School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, China.
Herein, we report an enantioselective Pd/Cu-catalyzed sequential Heck/Sonogashira coupling reaction of electron-rich enamides with terminal alkynes as substrates. This transformation proceeds smoothly to afford 3-propargyl isoindolinone derivatives bearing quaternary stereogenic centers in moderate to good yields (43-77% yield) and good to excellent enantioselectivity (up to 93% ee). Functional groups such as halogen atoms (F, Cl, and Br), thienyl, and silyl moieties are tolerated well.
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