Highly Diastereo‐ and Enantioselective Aziridination of α,β‐Unsaturated Amides with Diaziridine and Mechanistic Consideration on Its Stereochemistry

Abstract

Dedicated to Prof. Dieter Seebach on the occasion of his 65th birthday During studies of aziridination of a,b-unsaturated amides with diaziridine, we found that we could prepare both the cis-and trans-aziridinecarboxamides by choosing an appropriately substituted diaziridine. While 3-monosubstituted diaziridine 2 was suitable for the trans-selective aziridination, employment of 3,3-dialkyldiaziridine 1 resulted in the formation of cis-aziridine carboxamides, irrespective of the geometry of the substrate (Scheme 1 and Tables 1 and 2). To elucidate the unique nonstereospecificity and to expand these aziridinations to asymmetric ones, several optically active diaziridines were newly prepared. Aziridination with an optically active 3-monosubstituted diaziridine, 3-cyclohexyl-1-[(1R)-1-phenylethyl]diaziridine 16, proceeded smoothly with high trans-selectivity as well as excellent enantioselectivity (up to 98% ee; see Table 3). On the other hand, highly enantioselective cis-aziridination was achieved (> 99% ee) with optically active 3,3-dimethyl-1-[(1R)-1-phenylethyl]diaziridine 15, though the yield was low (4%). This aziridination was considered to proceed stepwise by way of the enolate intermediate (Scheme 2). Careful inspection of the stereochemistry and its solvent-dependence suggested that the diastereoselection of the reaction was kinetically controlled: the 1,4-addition of N-lithiated diaziridine was a crucial step for determination of the stereochemical course of the aziridination (Figs. 2 ± 4).

Organocatalytic nitrenoid transfer: metal-free selective intermolecular C(sp3)–H amination catalyzed by an iminium salt

“…Previous explorations of nitrogen transfer from oxaziridines and related species have demonstrated reactivity towards olefin aziridination 10 and with strong organometallic nucleophiles, 11 but no examples of C–H insertion have been reported. In contrast, the use of iminium salt catalysts offered a different opportunity ( Scheme 2a ).…”

Unnatural amino acids. 3. Aziridinyl ketones from esters and amides of aziridine-2-carboxylic acids

“…The mixture obtained was stirred at room temperature for 48 h under argon. The methanol was evaporated at low pressure and the residue was purified by chromatography on silica gel (eluant 9:1 chloroform-methanol) to give compound 1 (10.0 g, 88%), mp 85-87°C (in [14] compound 1 was prepared by aziridination of the dimethylamide of acrylic acid in 40% yield). 1 H NMR Spectrum, δ, ppm: 1.40 (1H, br.…”

Unprotected Aziridines: A Synthetic Overview

“…Subsequently, the same group reported the synthesis of both cis ‐ and trans ‐aziridines from different diaziridines . They found that, whilst 3‐monosubstituted diaziridine 29 was suitable for the trans ‐selective aziridination reaction to afford compound 30 , 3,3‐disubstituted diaziridine 27 resulted in the formation of cis ‐aziridine carboxamides 28 , irrespective of the geometry of the substrate.…”