Stereoselective Synthesis of Enantioenriched 2-Chloro-2-aroylaziridines by Cascade Reaction between Aryl Nitriles, Silyldichloromethanes, and tert-Butanesulfinylimines

Abstract

The cascade coupling of aryl nitriles, silyldichloromethanes, and tert-butanesulfinylimines is described, in which silyldichloromethyllithiums, generated from silyldichloromethanes in the presence of lithium diisopropylamide, undergo nucleophilic addition with aryl nitriles and subsequent [1,3]-aza-Brook rearrangement to give dichlorocarbanions bearing α-N-silyl imine (or their 1-azaenolate equivalents), which are then trapped by tert-butanesulfinylimines via an aza-Darzens-type transformation, affording enantioenriched 2-chloro-2-aroylaziridines after acidic hydrolysis of the N-silyl imine group. The stereochemistry of this cascade reaction can be tuned by selecting appropriate silyl groups on the silyldichloromethanes and altering the order of addition of the imines and the hexamethylphosphoramide additive.

P(NMe2)3-Mediated Aziridination of Imines with α-Ketoesters for Synthesis of Aziridine-2-carboxylates

“…We predicted that we could use azomethines to trap the zwitterion intermediates in an aza-Darzens-like transformation of Kukhtin–Ramirez adducts (Scheme d). − Such an approach could provide efficient access to aziridine-2-carboxylates, which are important precursors in the synthesis of useful nitrogen-containing compounds. − …”

3-Arylaziridine-2-carboxylic Acid Derivatives and (3-Arylaziridin-2-yl)ketones: The Aziridination Approaches

“…More complicated cascade reactions (Scheme 17) which allowed stereoselective obtaining of 3-arylated 2-chloro aziridines was demonstrated by Xu and co-authors [71]. This cascade coupling included nucleophilic addition of anion generated from silyldichloromethane 20 and nitriles 19 in presence of LDA and subsequent [1,3] -aza-Brooke rearrangement to give α-N-silyl imines in equilibrium with 1-azaenolate equivalents.…”

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…The reaction of imines 16 with the base LDA and an organosilicon compound TBSCHCl 2 , or TMSCHCl 2 ( 251 ) in the presence of an aryl cyanide 252 , led to the formation of aziridines 253 , which stereochemistry depends on the starting silicon compound (Scheme 107). [145] For Si =TBS, the corresponding aziridines 253 a were obtained, whereas for Si =TMS, the other diastereomers 253 b were the reaction products. Intermediates I → IV are probably involved in the reaction, the step II → III being a [1,3]‐aza‐Brook rearrangement.…”