Nickel-Catalyzed Amination of α-Aryl Methyl Ethers

Abstract

α-Aryl amines are prevalent in pharmaceutically active compounds and natural products. Herein, we describe a Ni-catalyzed protocol for their synthesis from readily available α-aryl ethers. While α-aryl ethers have been used as electrophiles in Ni-catalyzed C–C bond formations, their use in C–heteroatom bond formation is much less prevalent. Preliminary mechanistic insight suggests that oxidative addition is facilitated by an anionic ligand and that reductive elimination is a reversible process.

Nickel-Catalyzed Reductive Alkyne Hydrocyanation Enabled by Malononitrile and a Formaldehyde Additive

“…The addition of formaldehyde to the reaction mixture led to the observation of des -cyano-MPMN/formaldehyde adduct 27 by GC–MS (Scheme , Hypothesis D). We have previously reported that α-CN anion 25 can be detrimental to catalysis. , Thus, we hypothesized that formaldehyde may be necessary to trap 25 and generate an innocuous metal alkoxide adduct to enable efficient catalysis.…”

“…We have previously reported that α-CN anion 25 can be detrimental to catalysis. 72,73 Thus, we hypothesized that formaldehyde may be necessary to trap 25 and generate an innocuous metal alkoxide adduct to enable efficient catalysis.…”

Overcoming the Naphthyl Requirement in Stereospecific Cross-Couplings to Form Quaternary Stereocenters

“…10e Under these optimized conditions, we observed high yields and stereochemical fidelity across a range of pivalates (Scheme 2). Substrates with both electron-rich (4, 5) and electron-poor (7) aryl groups were tolerated. The electron-poor examples were particularly noteworthy, as they do not benefit from the lower dearomatization energies that electron-donating substituents can provide.…”

“…Alcohols and their derivatives are attractive substrates because of the high incidence of C–O bonds and alcohols in natural products and pharmaceuticals as well as simple starting materials . Indeed, C­(sp 3 ) cross-coupling through C–O bond cleavage has been demonstrated to forge various bonds, including C–C, C–B, C–N, and C–P . Among these, stereospecific cross-couplings using enantioenriched alcohol derivatives offer a potentially powerful method for asymmetric synthesis because the alcohol precursors are easily accessible in high enantiopurity, the reactions often proceed with high stereochemical fidelity, and many of the products are otherwise challenging to synthesize asymmetrically …”