Rhodium(II)-Catalyzed Alkynyl Carbene Insertion into N-H Bonds
Akashdeep Sharma, Himani Vaid, Riya Kotwal, Zuhaib N. Mughal, Ramani Gurubrahamam*
*Department of Chemistry, Indian Institute of Technology Jammu, NH-44, PO Nagrota, Jagti, Jammu and Kashmir
181221, India, Email: guru.ramaniiitjammu.ac.in
A. Sharma, H. Vaid, R. Kotwal, Z. N. Mughal, R. Gurubrahamam, Org. Lett., 2024, 26, 4887-4892.
DOI: 10.1021/acs.orglett.4c01345
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Abstract
Alkynyl hydrazone carboxylates can be used as donor-acceptor carbene precursors for Rh-catalyzed insertion into the N-H bonds of various amines, amides, and 1,2-diamines. A wide variety of 3-alkynyl 3,4-dihydroquinoxalin-2(1H)-ones and densely functionalized α-alkynyl α-amino esters are obtained in good yields.
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proposed mechanism
Details
The document discusses the first successful insertion of an alkynyl carbene into N−H bonds using Rhodium(II) catalysis. Alkynyl hydrazone carboxylates serve as carbene precursors, enabling the formation of 3-alkynyl 3,4-dihydroquinoxalin-2(1H)-ones and α-alkynyl α-amino esters in good to excellent yields. This method is significant for synthesizing nitrogen-containing heterocycles, which are prevalent in natural products and biologically active molecules. The study highlights the challenges and optimization of the reaction conditions, including the use of different catalysts and solvents. Rhodium(II) catalysts, particularly Rh2(OAc)4, provided the best yields. The research also explores the substrate scope, demonstrating the method's compatibility with various hydrazones and diamines. Mechanistic studies suggest that the key 1,2-proton transfer occurs through a metal-bound ylide. The protocol's practical utility is exemplified by scaled-up synthesis and various synthetic transformations, including the creation of heterocycles with medicinal and material science applications. The study opens avenues for developing enantioselective protocols with alkynyl diazoacetates, contributing to the field of C−N bond formation reactions.
Key Words
benzo-fused N-heterocycles, PIDA
ID: J54-Y2024