32286-98-9Relevant academic research and scientific papers
An Overlooked Pathway in 1,3-Dipolar Cycloadditions of Diazoalkanes with Enamines
Li, Le,Mayer, Peter,Stephenson, David S.,Ofial, Armin R.,Mayer, Robert J.,Mayr, Herbert
supporting information, (2022/02/22)
Methyl diazoacetate reacts with 1-(N-pyrrolidino)cycloalkenes to give products of 1,3-dipolar cycloadditions and azo couplings. The kinetics and mechanisms of these reactions were investigated by NMR spectroscopy and DFT calculations. Orthogonal π-systems in the 1,3-dipoles of the propargyl-allenyl type allow for two separate reaction pathways for the (3+2)-cycloadditions. The commonly considered concerted pathway is rationalized by the interaction of the enamine HOMO with LUMO+1, the lowest unoccupied orbital of the heteropropargyl anion fragment of methyl diazoacetate. We show that HOMO/LUMO(π*N=N) interactions between enamines and methyl diazoacetate open a previously unrecognized reaction path for stepwise cycloadditions through zwitterionic intermediates with barriers approximately 40 kJ mol?1 lower in energy in CHCl3 (DFT calculations) than for the concerted path.
Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis
Ruffell, Katie,Smith, Frances R.,Green, Michael T.,Nicolle, Simon M.,Inman, Martyn,Lewis, William,Hayes, Christopher J.,Moody, Christopher J.
supporting information, p. 13703 - 13708 (2021/09/09)
Diazophosphonates, readily prepared from α-ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron-withdrawing groups, and is regiospecific with asymmetrical alkynes. The potential of diazophosphonates for use in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.
Highly regioselective organocatalyzed synthesis of pyrazoles from diazoacetates and carbonyl compounds
Wang, Lei,Huang, Jiayao,Gong, Xiaojie,Wang, Jian
supporting information, p. 7555 - 7560 (2013/07/05)
A general, organocatalytic inverse-electron-demand [3+2] cycloaddition reaction between a range of carbonyl compounds and diazoacetates has been developed. This reaction is catalyzed by secondary amines as a "green promoter" to generate substituted pyrazoles with high levels of regioselectivity. It is noteworthy that this [3+2] cycloaddition reaction proceeds efficiently at room temperature with a simple and inexpensive catalyst. Considering the large variety and ready availability of the starting materials (e.g. ketones, β-ketoesters, β-diketones, and aldehydes), as well as the operational simplicity of this process, a convenient, practical, and highly modular pyrazole synthesis has been developed. We believe that this work will arouse more research interest in the organocatalytic synthesis of other biologically active heterocycles. Such studies are currently underway in our laboratory. Dipoles apart: In situ formed enamines react with diazoacetates under mild conditions to afford the corresponding polysubstituted pyrazoles in good-to-excellent yields through an inverse-electron-demand 1,3-dipolar cycloaddition process (see scheme). Copyright
