A Facile Construction of Bisheterocyclic Methane Scaffolds through Palladium‐Catalyzed Domino Cyclization

Abstract

Main observation and conclusion A convenient palladium‐catalyzed domino cyclization reaction for the construction of bis(benzofuranyl)methane scaffolds bearing an all‐carbon quaternary center has been described. In the cascade process, one C(sp2)—O bond, two C(sp2)—C(sp3) bonds as well as two benzofuran rings are formed in a single synthetic sequence. The approach shows wide scope of substrates and good functional‐group tolerance. Moreover, this methodology is successfully extended to the synthesis of benzofuranyl methyl chromane derivatives.

Palladium-catalyzed cyclizative cross coupling of ynone oximes with 2-haloaryl N-acrylamides for isoxazolyl indoline bis-heterocycles

“…Nevertheless, improving the strategy further, the post coupling could be planned with a second cyclization at the coupling partner in order to produce multi-cyclic scaffolds. Representatives of such cascades 26 include the synthesis of bicycles accomplished by trapping an intramolecular Heck-coupling Pd intermediate with 2-alkynyl aniline as recently reported by Lautens 9 and Lin 10 et al and the synthesis of methylene-bridged benzofuranyl indolines achieved by trapping an oxindolyl-Pd intermediate with phenol derivatives as reported by Chen et al 11 Another impressive study was reported by Xu et al 12 for the synthesis of substituted indole scaffolds via dual cyclizative annulation of halo phenyl cyclobutanones with 2-alkynyl aniline. Recently, the Liu group 13 reported the synthesis of indolizine and indolizinone-derived bis-heterocycles through difunctionalization of acrylamide olefin and relay coupling of propargylic systems.…”

“…1,2 Hence, numerous efforts have been made to produce these key scaffolds. 3 In light of the increasing focus on methylene-bridged bis-heterocyclic systems 9–11,25 for pharmaceutical applications, the linking of these two heterocycles would be expected to provide a gateway to a new class of molecules of therapeutic interest. To reduce the chemical waste, time and purification problems associated with constructing such systems in traditional linear pathways, 23 domino pathways from simpler and accessible starting materials are highly desirable to use.…”

Electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes

“…Due to the immense importance of this scaffold, a variety of synthetic approaches have already been developed. 10 One of the most successful modular strategies established over the years is based on a radical-triggered addition-cyclization of 1,6-enynes, which enables different bifunctionalizations of benzofuran scaffolds, including dioxygenation, 11 a oxo-nitration, 11 b oxo-sulfonylation, 11 c – f hydro-oxygenation, 11 g hydro-sulfonylation, 11 h iodo-perfluoroalkylation, 11 i trifluoromethyl-carbamylation, 11 j aryl-difluoroalkylation, 11 k difluoroalkyl-phosphinoylation, 11 l hydroamination 11 m and oxo-thiolation. 11 n The requirement of over-stoichiometric amounts of oxidants 11 d – f or heavy metal catalysts 11 g – m in most cases is a drawback.…”