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. 2017 Jun 28;139(25):8428-8431.
doi: 10.1021/jacs.7b04816. Epub 2017 Jun 15.

CuH-Catalyzed Regioselective Intramolecular Hydroamination for the Synthesis of Alkyl-Substituted Chiral Aziridines

Haoxuan Wang  1 , Jeffrey C Yang  1 , Stephen L Buchwald  1
Affiliations

CuH-Catalyzed Regioselective Intramolecular Hydroamination for the Synthesis of Alkyl-Substituted Chiral Aziridines

Haoxuan Wang et al. J Am Chem Soc. .

Abstract

This report details a general and enantioselective means for the synthesis of alkyl-substituted aziridines. This protocol offers 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. The utility of the products derived from this method is further demonstrated through derivatization of the chiral aziridine products to obtain a diverse array of functionalized enantioenriched amines.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Lindsley’s approach for the synthesis of chiral N-alkyl aziridines and the development of our strategy.
Scheme 1
Scheme 1
N-alkyl aziridine derivatizationa and X-ray crystallographic structure of 10 aReaction conditions: a) TMSN3 (5 equiv), AcOH (5 equiv), MeCN, rt. b) Pd/C (10 mol %), H2 (1 atm), MeOH, rt. c) AcOH (5 equiv), CH2Cl2, rt. d) LiI (1 equiv), CO2 (1 atm), 40 °C. e) PPTS (1.5 equiv), CH2Cl2, rt.
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