Categories: C-N Bond Formation, Synthesis of cyclic amines >
Synthesis of aziridines
Amino alcohols were converted into their hydrogen sulfates with chlorosulfonic acid. The sulfates were cyclized with sodium hydroxide, and even with non-nucleophilic sodium carbonate. This improved, mild variation of the typical Wenker synthesis is applicable to unstable amino alcohols in hot sulfuric acid and to unstable sulfates which favor elimination and hydroxide displacement in the presence of strong base.
X. Li, N. Chen, J. Xu, Synthesis, 2010, 3423-3428.
Two alternative and complementary one-pot procedures for the direct transformation of 2-amino alcohols to N-tosyl aziridines are presented. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in water/dichloromethane. Higher substituted amino alcohols give better yields using potassium carbonate in acetonitrile.
L. W. Bieber, M. C. F. de Araujo, Molecules, 2002, 7, 902-906.
In a direct route for the synthesis of alkyl-substituted chiral aziridines from achiral starting materials, readily accessed allylic hydroxylamine esters undergo copper hydride-catalyzed intramolecular hydroamination with a high degree of regio- and enantiocontrol to afford the aziridine products in good to excellent yields in highly enantioenriched form.
H. Wang, J. C. Yang, S. L. Buchwald, J. Am. Chem. Soc., 2017, 139, 8428-8431.
A copper-promoted intramolecular C-H oxidative amination reaction between secondary amine (N-H) and C(sp3)-H at the benzylic position of azaarenes or α-position of ketones enables the synthesis of aziridine derivatives in the presence of oxygen as sole oxidant. Moreover, a Yb(OTf)3-CuI relay system catalyzes the aziridination of electron-deficient vinylarenes with unprotected primary alkyl amines.
Y.-D. Du, Z.-J. Xu, C.-Y. Zhou, C.-M. Che, Org. Lett., 2019, 21, 895-899.
An electrochemical oxidative dehydrogenative C(sp3)-H amination reaction for the construction of trans-2,3-disubstituted aziridines avoids the use of external oxidants and generates only hydrogen gas as the byproduct. With KI as the mediator and electrolyte, the desired aziridines were prepared in good yields in an undivided cell at room temperature.
H. Wang, J. Shi, J. Tan, W. Xu, S. Zhang, K. Xu, Org. Lett., 2019, 21, 9430-9433.
tert-Butyl hypoiodite is a mild and powerful reagent for the cyclization of N-alkenylamides leading to various N-heterocycles. N-alkenylsulfonamides gave three- to six-membered saturated N-heterocycles in good yields, whereas alkenylbenzamide derivatives afforded N-, O- or N-, S-heterocycles.
S. Minakata, Y. Morino, Y. Oderaotoshi, M. Komatsu, Org. Lett., 2006, 8, 3335-3337.
Biologically important N-β-hydroxyethylaziridine intermediates were conveniently prepared by regioselective ring-opening reactions of various epoxides with in situ-generated ethyleneimine from β-chloroethylamine under basic conditions in an aqueous environment.
H. Y. Kim, A. Talukdar, M. Cushman, Org. Lett., 2006, 8, 1085-1087.
Vinylaziridines are useful and versatile synthetic intermediates, as the relief of ring-strain provides a driving force for efficient ring-opening or ring-expansion reactions. Furthermore, the vinyl group can be derivatized into interesting functionalities. The ring-closure of vicinal amino alcohols constitutes a straightforward route to aziridines. Several methods exist for this transformation, although many cannot be applied to vinylaziridines due to their acid lability. This comparative study describes the most effective sequences for the formation of N–H vinylaziridines.
B. Olofsson, R. Wijtmans, P. Somfai, Tetrahedron, 2002, 58, 5979-5982.
Reaction of N-(2-chloroethylidene)-tert-butylsulfinamide with Grignard reagents or organoceriums gives terminal N-tert-butylsulfinyl aziridines in good yields and with organoceriums good diastereomeric ratios. Oxidation of terminal N-tert-butylsulfinyl aziridines provides synthetically useful terminal N-Bus (Bus = tert-butylsulfonyl) aziridines.
D. M. Hodgson, J. Kloesges, B. Evans, Synthesis, 2009, 1923-1932.
A diastereoselective addition of carbamoyl anions to azirines affords synthetically useful 2-aziridinyl amide building blocks. A one-pot conversion of a ketoxime to an aziridinyl amide was also demonstrated.
M. J. Kerner, C. A. Kuttruff, M. Chevliakov, F. G. Buono, D. A. Gao, M. Krawiec, C. A. Busacca, C. H. Senanayake, P. Wipf, J. T. Reeves, Org. Lett., 2021, 23, 4396-4399.
N,N-Dialkyl-β-amino alcohols derived from α-amino acids can be rearranged enantiospecifically by using TFAA/Et3N/NaOH to give 1,2-amino alcohols.
T.-X. Métro, J. Appenzeller, D. G. Pardo, J. Cossy, Org. Lett., 2006, 8, 3509-3512.
BH3 complexation of N-alkyl-2-phenylaziridines is able to promote a regioselective β-lithiation. The lithiated intermediates were configurationally stable, allowing an enantioselective preparation of cis-2,3-disubstituted aziridines. The structure and stereochemistry of the synthesized BH3 complexes have been proved with DFT calculations and NMR experiments.
U. Azzena, G. Dettori, L. Pisano, B. Musio, R. Luisi, J. Org. Chem., 2011, 76, 2291-2295.