Development of an air-stable nickel precatalyst for the amination of aryl chlorides, sulfamates, mesylates, and triflates

Abstract

A new air-stable nickel precatalyst for C-N cross-coupling is reported. The developed catalyst system displays a greatly improved substrate scope for C-N bond formation to include both a wide range of aryl and heteroaryl electrophiles and aryl, heteroaryl, and alkylamines. The catalyst system is also compatible with a weak base, allowing the amination of substrates containing base-sensitive functional groups.

Figure 1

X-ray crystal structure of (dppf)Ni(o-tolyl)Cl (2) (representation from two different angles). THF molecule and hydrogen atoms are omitted for clarity.

Scheme 1

Synthesis of (dppf)Ni(o-tolyl)Cl (2)

Scheme 2

Amination of Aryl Chlorides using LiOtBua ^aReaction conditions: aryl chloride (1.0 mmol), amine (1.5 mmol), LiOtBu (1.5 mmol), 2 (5 mol %), dppf (5 mol %), MeCN (1.0 mmol), CPME (2 mL), 100 °C, 1 h. Yields are of the isolated product, average of two runs. ^bReaction time 16 h. ^c2 (10 mol %) and dppf (10 mol %), 130 °C, 16 h.

Scheme 3

Amination of Aryl Chlorides using K₃PO₄a ^aReaction conditions: aryl chloride (1.0 mmol), amine (1.5 mmol), K₃PO₄ (3 mmol), 2 (5 mol %), dppf (5 mol %), MeCN (1.0 mmol), tBuOH (2 mL), 3 Å MS (300 mg), 110 °C, 16 h. Yields are of the isolated product, average of two runs. ^bIn cases where using the standard conditions do not give full conversion, omission of the 3 Å MS or using 6 mmol of K₃PO₄ were found to allow the reaction to reach completion. ^cK₃PO₄ (6 mmol), Dioxane (4 mL).

Scheme 4

Amination of Aryl Mesylates, Triflates, and Sulfamatesa ^aReaction conditions: aryl chloride (1.0 mmol), amine (1.5 mmol), K₃PO₄ (3 mmol), 2 (5 mol %), dppf (5 mol %), MeCN (1.0 mmol), CPME (4 mL), 3 Å MS (300 mg), 110 °C, 16 h. Yields are of the isolated product, average of two runs. ^bIn cases where using the standard conditions do not give full conversion, using 6 mmol of K₃PO₄ were found to allow the reaction to reach completion. ^c2 (2.5 mol %), dppf (2.5 mol %), 4 h.