General Zinc‐Catalyzed Intermolecular Hydroamination of Terminal Alkynes

Abstract

Catalytic hydroaminations are one of the most sustainable C-N bond-forming processes as a result of 100% atom economy and the availability of substrates. Here, it is shown that the intermolecular hydroamination of terminal alkynes with anilines proceeds smoothly in the presence of catalytic amounts of zinc triflate, an easily available and inexpensive zinc salt. Amination and subsequent reduction with NaBH3CN gives a variety of secondary and tertiary amines in up to 99% yield and with over 99% Markovnikov regioselectivity. Moreover, difficult functional groups such as nitro and cyano substituents are tolerated by the homogeneous catalyst.

A Simple, Multidimensional Approach to High-Throughput Discovery of Catalytic Reactions

“…Although this reaction occurs in the presence of three of the ligands identified in the combinatorial format, the reaction also proceeded rapidly in the absence of a ligand. This copper-catalyzed reaction represents a rare hydroamination of an alkyne catalyzed by a first-row metal (33–35). As shown by data in Table 1, this process occurs under conditions with 25 mole percent of the inexpensive CuCl in good yield.…”

Copper‐Catalyzed Alkylation of Sulfonamides with Alcohols

“…On the basis of previous studies by others and us on the ruthenium-catalyzed alkylation of amines, [3,6] we became interested in environmentally benign alkylation reactions of amides and sulfonamides. [7,8] The resulting products are useful intermediates for the synthesis of pharmaceuticals and agrochemicals.…”

Lewis Acid Activation of Pyridines for Nucleophilic Aromatic Substitution and Conjugate Addition

“…It should be noted that there have been many examples of zinc‐catalyzed hydroaminations in recent literature; however in the majority of these cases the reactions are air and moisture sensitive, and use benzene as a solvent 12–14. Two examples that do not require air‐ and moisture‐free conditions use a zinc triflate Lewis acid; however, they proceed under higher reaction temperatures (120–130 °C),15, 16 and, in one case, yield a combination of Markovnikov and conjugate addition products 14. By comparison, our methodology proceeds using a simpler practical method, with a cheap reagent at lower temperatures and yields purely the conjugate addition products.…”