Categories: C=N Bond Formation >
Synthesis of α-Diazoketones
An improved Arndt-Eistert synthesis to obtain α-diazoketones allows the efficient transformation of acid halides using a stoichiometric amount of diazomethane in the presence of calcium oxide, without concomitant ketene or haloketone formation. The obtained α'-brominated-α-diazoketones were employed for the synthesis of interesting α-arylamino-α′-halomethylketones.
V. Pace, G. Verniest, J.-V. Sinisterra, A. R. Alcántara, N. De Kimpe, J. Org. Chem., 2010, 75, 5760-5763.
The chain extension of carboxylic acids developed by Arndt and Eistert was applied to the construction of peptides containing β-amino acids. The method may be used for the generation of new types of peptide-containing combinatorial libraries.
J. Podlech, D. Seebach, Angew. Chem. Int. Ed., 1995, 34, 471-472.
Reaction of trimethylsilyldiazomethane with a mixed anhydride derived from a carboxylic acid and ethyl chloroformate yields the corresponding diazoketone in high yield. Subsequent Wolff rearrangement of the diazoketone leads to the homologated ester. Reactions of trimethylsilyldiazomethane with convenient active esters are described.
J. Cesar, M. Sollner Dolenc, Tetrahedron Lett., 2001, 42, 7099-7102.
The reaction of 1,3-diketones, TsN3, and MeNH2 in EtOH enables a highly efficient synthesis of α-diazoketone via a tandem reaction including a novel primary amine-catalyzed Regitz diazo transfer of 1,3-diketones and a novel primary amine-mediated C-C bond cleavage of 2-diazo-1,3-diketones.
J. Zhang, W. Chen, D. Huang, X. Zeng, X. Wang, Y. Hu, J. Org. Chem., 2017, 82, 9171-9174.
Sonication of diazo ketones derived from Fmoc-protected amino acids in dioxane in the presence of silver benzoate and water results in clean formation of the corresponding β-amino acid derivatives. The degree of racemization was examined using capillary zone electrophoresis. No substantial epimerization occured except for phenylglycine.
A. Müller, C. Vogt, N. Sewald, Synlett, 2006, 837-841.
α-Aryl-α-diazo ketones derived from direct diazo transfer with α-aryl ketones cyclize efficiently in the presence of Rh catalysts to give the corresponding α-aryl cyclopentanones.
D. F. Taber, W. Tian, J. Org. Chem., 2007, 72, 3207-3210.
Various diazoacetates were synthesized from the corresponding bromoacetates by treatment with N,N'-ditosylhydrazine in moderate to high yields. Ease of operation with the stable crystalline reagent as well as a short reaction time offer a useful alternative to the conventional methods.
T. Toma, J. Shimokawa, T. Fukuyama, Org. Lett., 2007, 9, 3195-3197.
2-Azido-4,6-dimethoxy-1,3,5-triazine (ADT) as an intrinsically safe, highly efficient, and shelf-stable diazo-transfer reagent. ADT is very stable upon >1 year storage under air at room temperature. Diazo-transfer reactions based on ADT give diazo compounds in excellent yields within several minutes at room temperature.
S. Xie, Z. Yan, Y. Li, Q. Song, M. Ma, J. Org. Chem., 2018, 83, 10916-10921.
2-Azido-1,3-dimethylimidazolinium chloride (ADMC) can be prepared by N-nitrosation of N-aminoguanidine or by the reaction of 2-chloro-1,3-dimethylimidazolinium chloride and sodium azide. The corresponding crystalline phosphate salt (ADMP) is a stable and safe reagent. Both ADMC and ADMP reacted with 1,3-dicarbonyl compounds under mild conditions to give 2-diazo-1,3-dicarbonyl compounds in high yields.
M. Kitamura, N. Tashiro, S. Miyagawa, T. Okauchi, Synthesis, 2011, 1037-1044.
Diazo transfer from 2-azido-1,3-dimethylimidazolinium chloride to 1,3-dicarbonyl compounds proceeds under mild conditions to give 2-diazo-1,3-dicarbonyl compounds in high yields, which are easily isolated because the by-products are highly soluble in water.
M. Kitamura, N. Tashiro, T. Okauchi, Synlett, 2009, 2931-2934.
Diazo-transfer reactions with tosyl azide followed by efficient chromatographic purifications on silica gel and/or alumina enable a practical protocol for the large-scale preparation of 2-diazo-1,3-dicarbonyl compounds.
M. Presset, D. Mailhol, Y. Coquerel, J. Rodriguez, Synthesis, 2011, 2549-2552.