Carbamoyl Anion Addition to Azirines

Michael J. Kerner, Christian A. Kuttruff, Maxim Chevliakov, Frederic G. Buono, Donghong A. Gao, Mariusz Krawiec, Carl A. Busacca, Chris H. Senanayake, Peter Wipf and Jonathan T. Reeves*

*Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877, United States, Email: jonathan.reevesboehringer-ingelheim.com

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.

DOI: 10.1021/acs.orglett.1c01334

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Abstract

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.

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one-pot conversion of a ketoxime to an aziridinyl amide

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Addition of Carbamoyl Anions to Azirines. General procedure:

A reaction flask equipped with a magnetic stir bar was charged with azirine (2.59 mmol), N,N-dialkylformamide (5.44 mmol) and anhydrous THF (5.5 mL) and the resultant solution was cooled to -78°C. Then LDA solution (2.60 mL, 5.20 mmol, 2.0 M solution in THF/heptane/ethylbenzene) was added dropwise. After 30 min, the reaction mixture was quenched with water and allowed to warm to rt. The reaction was diluted with MTBE (12 mL) and washed with water (2 x 12 mL). The organic layer was dried over Na₂SO₄, filtered, and concentrated in vacuo. The crude product was purified by chromatography on SiO₂ (25% MTBE/hexanes).

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Key Words

Aziridines, α-Amino Acid Derivatives

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ID: J54-Y2021