Highly Regioselective Nickel-Catalyzed Cross-Coupling ofN-Tosylaziridines and Alkylzinc Reagents

Abstract

Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with aliphatic organozinc reagents. The reaction protocol displays complete regioselectivity for reaction at the less hindered C-N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. Moreover, we have developed an air-stable nickel(II) chloride/ligand precatalyst that can be handled and stored outside a glovebox. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni(cod)2 is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetalation (retention), and reductive elimination (retention).

Chelation‐Assisted Nickel‐Catalyzed Oxidative Annulation via Double C−H Activation/Alkyne Insertion Reaction

“…Interestingly,w hen ad imethylamino group is www.chemeurj.org present in the substrate, the expected product 2i was accompanied by as mall amount (2 %) of the side reaction product 2a.I nt he case of 3-(2-tolyloxy)-and 3-benzyloxy-substituted benzamides, 2j (82 %) and 2k (81 %) were obtained in good yields, alongw ith as mall amount of 2a.T he formation of 2a providedaclue that aN i 0 species is involved in the catalytic cycle, because aN i 0 species is known to activates uch types of "hard" bonds. [22][23][24] Surprisingly,w ith the 3-SMe-substituted amide 1p,t he product 2p was obtained in 65 %y ield, and no side product 2a was detected, although there are some examples of Ni 0 -catalyzed CÀSa ctivation reactions in the literature. [25] This reaction is also applicable to the condensed ring system in compounds with more than one aromatic ring, as in 2s, 2t,a nd 2u.T he reactiono f1a with bis(4-methoxyphenyl)ethyne and bis(4-(trifluoromethyl)phenyl)ethyne gave the corresponding naphthalene products 2v and 2w in 87 and 63 %, respectively.…”

Regiodivergent and Stereospecific Aziridine Opening by Copper‐Catalyzed Addition of Silicon Grignard Reagents

“…Ring‐opening and ring‐expansion reactions of aziridines catalyzed by Lewis acids or Lewis bases are driven by release of its ring strain and serve as powerful methods for the synthesis of ubiquitous β‐amino‐functionalized molecules . Over the past few years, numerous advances have been made in transition‐metal‐catalyzed ring‐opening/cross‐coupling reactions of aziridines . Relevant to the present work, Takeda and co‐workers have disclosed a palladium‐catalyzed regioselective borylation of 2‐aryl‐substituted aziridines to yield β‐borylated amines .…”

“…[2] Over the past few years, numerousa dvances have been made in transition-metal-catalyzed ring-opening/cross-coupling reactions of aziridines. [3][4][5][6][7] Relevant to the present work, Ta keda and co-workersh ave disclosed ap alladium-catalyzed regioselective borylation of 2-aryl-substituted aziridines to yield b-borylated amines. [8] To further expand the utility of this type of aziridine chemistry,t he use of new heteroatom nucleophiles is desirable.…”

Nickel Catalysis: Synergy between Method Development and Total Synthesis

“…31 Furthermore, we developed an air-stable nickel(II)chloride/ligand precatalyst that can be handled and stored outside a glovebox, thus avoiding the use of air-sensitive Ni(cod) 2 . Finally, through examination of catalytic intermediates for competency and deuterium-labeling studies, we were able to devise a likely mechanism for this transformation.…”