A Gold‐ and Brønsted Acid Catalytic Interplay Towards the Synthesis of Highly Substituted Tetrahydrocarbazoles

Abstract

The reaction of indoles and stabilized cyclopropyl alkynes under gold‐ and/or gold & Brønsted acid‐catalysis provided access to highly substituted tetrahydrocarbazoles. A mechanistic study revealed the complex mechanism underlying these processes and the opportunistic cooperation of Lewis and Brønsted acid‐catalysts towards the formation of complex molecular scaffolds.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C−H Bond Functionalization

“…This electrophile interacts with indole nucleophiles forming a transient cyclopropyl Au-carbenoid 232 a followed by rear- with good regiochemical control. [224] In this sequence, trace amounts of in situ generated acid were reported to play a vital role in the selective cyclization of the key spirocyclic intermediate. According to Widenhoefer et al, cationic Au(I)-carbenes were competent to catalyze the hydroindolylation of methylenecyclopropanes 234 to produce indolyl-cyclopropane adducts 235 (Scheme 39, bottom).…”

Gold‐Catalyzed Functionalization Reactions of Indole

“…In both cases, final nucleophilic attack of indoles 1 on the cyclopropane rings in intermediates XLVII/XLVIII efficiently afforded five-or six-membered-ring products 99 and 100. [116] In 2014, Liang and co-workers studied the synthesis of functionalized spirotetrahydro--carbolines 102 through intramolecular gold-catalyzed carbocyclization/hydroamination of alkynylaziridine indoles 101 (Scheme 40). [112] A similar approach, involving the formation of a cyclopropyl carbenoid species, was also applied by Waldmann and Kumar, who reported the synthesis of tetracyclic indole derivatives starting from indolyl-1,6-enynes and aldehydes, [113] whereas other enyne-tethered indole sulfides were prepared and tested by Jha in the tandem gold-catalyzed synthesis of thiopyrano- [2,3-b]indoles.…”

“…[115] In addition, Nevado and co-workers reported the preparation of highly substituted tetrahydrocarbazoles through reactions between 1-ethynylcyclopropyl derivatives and indoles under gold catalysis conditions by way of a complex gold-mediated cascade sequence. [116] In 2014, Liang and co-workers studied the synthesis of functionalized spirotetrahydro--carbolines 102 through intramolecular gold-catalyzed carbocyclization/hydroamination of alkynylaziridine indoles 101 (Scheme 40). [117] In this case, initial indole C-3 nucleophilic addition to dually coordinated intermediates XLIX led to formation of the six-membered ring with concomitant opening of the aziridine to give intermediates L. Then, gold-activation of the allene moiety of L triggered hydroamination/cyclization and formation of final products 102. tion of indolylynamides 103 (Scheme 41).…”

An Assessment of Electrophilic N‐Transfer of Oxaziridine with Different 2‐, 3‐, and 4‐Carbon Donor–Acceptor Substrates to Furnish Diverse N‐Containing Heterocycles in a Single Step

“… 4b was prepared following the previously reported procedure, and spectroscopic data were identical to those. 4c was commercially purchased from Sigma Aldrich, and 4d was synthesized according to the previously reported procedure, and spectroscopic data were identical to those …”

“…[22] 4b was prepared following the previously reported procedure, and spectroscopic data were identical to those. [23] 4c was commercially purchased from Sigma Aldrich, and 4d was synthesized according to the previously reported procedure, and spectroscopic data were identical to those. [24] Synthesis of Cyclobutanes : Cyclobutanes 6a, 6c, 6d, and 6e were prepared following the previously reported procedure, and spectroscopic data were identical to those.…”