Nickel-catalyzed, base-mediated amination/hydroamination reaction sequence for a modular synthesis of indoles

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Ackermann published a series of papers exploring Pd and Ni complexes for the tandem reaction to prepare a variety of variously substituted indoles via an N-arylation-hydroamination sequence. By using a Pd-carbene complex [342,343], bulky substituents could be incorporated as the N-substituent, while Ni did not allow for this same flexibility for the incorporation of sterically demanding substituents (Scheme 15.108) [344]. By exploiting the known formation of indole from σ-ethynylaniline, Okuma was able to realize this Lewis-acid-mediated transformation with simple Zn 2+ salts (Scheme 15.109).…”

Cationic [(Iminophosphine)Nickel(Allyl)]+ Complexes as the First Example of Nickel Catalysts for Direct Hydroamination of Allenes

“…With common accessible oxidation states of 0, + 1, + 2, and + 3, it seems likely that the richc hemistry of nickel would include applications in hydroamination, because twounit oxidation state toggles are commoni nd irect metal-catalyzed hydroamination. [8] Unfortunately,o ne drawback of Ackermann's system is the high temperature (120 8C) needed to obtain significant reactivity.T he only well-definedr eport of nickel-catalyzed intermolecular hydroamination of unactivated CÀCm ultiple bonds is as ingle paper by Hartwig in which the intermolecular hydroamination of 1,3-dienes to form allylamine products is reported. These nickel-catalyzed transformations, as studied by To gni, [5] Zargarian [6] and Garcia, [7] support al ikely mechanism for nickel-catalyzed hydroamination of activated CÀCm ultiple bonds (mainly acrylonitrile and related compounds) based on the electrophilicity of the Ni center.I nr esearch moving beyondt heseh ighly activated systems, Ackermann has described the intramolecular hydroamination of alkynes to form indoles.…”

Divergent Palladium‐ and Platinum‐Catalyzed Intramolecular Hydroamination/Hydroarylation of O‐Propargyl‐2‐aminophenols

“…Using AgNO 3 as catalyst, no conversion of 1a was observed even if the reaction was placed under MW irradiation (Table , entries 4, 5), while the employment of copper iodide as catalyst gave a dimeric product, according to the Ullmann type reaction (Table , entry 6) . The reported literature hydroamination conditions under nickel catalysis were unfruitful (Table , entry 7), whilst the use of cationic iridium, gave an inseparable mixture of products containing the 3‐methylene‐2 H ‐benzo[ b ][1,4]oxazine, also testing the reaction on the free amino group [2‐(propargyloxy)aniline] (Table , entry 8) . The utilization of Pd(PPh 3 ) 4 catalyst under thermal heating, gave no coupling product (Table , entry 9), but the addition of 10 mol‐% of triphenylphosphine allowed the cyclization, affording 3‐methylene benzoxazine 2a in a good yield through a hydroamination process (Table , entry 10) .…”