Rh₂(II)-Catalyzed Intermolecular N-Aryl Aziridination of Olefins Using Nonactivated N Atom Precursors

Abstract

The development of the first intermolecular Rh2(II)-catalyzed aziridination of olefins using anilines as nonactivated N atom precursors and an iodine­(III) reagent as the stoichiometric oxidant is reported. This reaction requires the transfer of an N-aryl nitrene fragment from the iminoiodinane intermediate to a Rh2(II) carboxylate catalyst; in the absence of a catalyst only diaryldiazene formation was observed. This N-aryl aziridination is general and can be successfully realized by using as little as 1 equiv of the olefin. Di-, tri-, and tetrasubstituted cyclic or acylic olefins can be employed as substrates, and a range of aniline and heteroarylamine N atom precursors are tolerated. The Rh2(II)-catalyzed N atom transfer to the olefin is stereospecific as well as chemo- and diastereoselective to produce the N-aryl aziridine as the only amination product. Because the chemistry of nonactivated N-aryl aziridines is underexplored, the reactivity of N-aryl aziridines was explored toward a range of nucleophiles to stereoselectively access privileged 1,2-stereodiads unavailable from epoxides, and removal of the N-2,4-dinitrophenyl group was demonstrated to show that functionalized primary amines can be constructed.

N-Aminopyridinium reagents as traceless activating groups in the synthesis of N-Aryl aziridines

“…The developed cross-coupling conditions enable cross-coupling with simple arylboronic acids substituted in the 4-position ( 5a – 5j ) and in the 3-position ( 5k ), but substitution in the 2-position ( 5l ) and alkyl boronic acids (i.e., n -butylboronic acid) were not tolerated. Notably, electron-neutral and electron-rich aryl groups can be incorporated in the N -arylaziridine efficiently, which represent specific challenges in direct nitrene transfer strategies 11 , 15 . Similarly, various substitutions of the pyridinium aziridine coupling partner were also tolerated ( 5m – 5s ).…”

“…1a ) 8 – 10 . Metal-catalyzed nitrene transfer catalysis typically requires electron-withdrawing groups, such as N -sulfonyl substituents, to activate the nitrogen equivalent for transfer 11 – 13 ; there are limited reports of metal-catalyzed nitrene transfer from aryl azide precursors 14 , 15 . The resulting N -protected aziridines can be challenging to utilize in downstream N -functionalization chemistry.…”

Theoretical Study on Ir-Catalyzed α-Amidation of 2-Acylimidazoles: Mechanism and Insertion Selectivity

“…Transition-metal-catalyzed carbene/nitrene transfer reactions to synthesize divergent products have attracted great research attention due to their step- and atom-economy. − In particular, nitrene transfer reaction has become a powerful tool for constructing the C–N bond. − For example, metal-nitrene can transfer directly into various bonds such as C–H, CC, CC, and metal–C bonds, realizing amination, aziridination, annulation, and cascade reactions, which have been considered as robust methods to prepare synthetically useful N-containing compounds. − Dioxazolones are a class of prepared conveniently and highly efficient acyl nitrene transfer reagents by which amidation products can be successfully obtained. , …”

Stereospecific Synthesis of Unprotected, α,β-Disubstituted Tryptamines and Phenethylamines from 1,2-Disubstituted Alkenes via a One-Pot Reaction Sequence

“…A ziridines are readily prepared from alkene feedstocks and have considerable potential as intermediates for the convergent synthesis of pharmaceutically relevant aminecontaining compounds. 1 In particular, the Friedel−Crafts addition of electron-rich (hetero)arenes to protected aziridines is an efficient approach for the synthesis of biomedically relevant tryptamines and phenethylamines (Scheme 1a), 2,3 although additional steps are required for aziridine synthesis and protecting group removal. In a conceptually related work, we recently described a HFIP-mediated, 4 metal-free three-component synthesis of alkyl trifluoromethyl sulfides (Y = SCF 3 ) that proceeded via in situ formation of a threemembered thiiranium salt, followed by Friedel−Crafts addition (Scheme 1b).…”