Promoting Reductive Tandem Reactions of Nitrostyrenes with Mo(CO)₆ and a Palladium Catalyst To Produce 3H-Indoles

Abstract

The combination of Mo(CO)6 and 10 mol % of palladium acetate catalyzes the transformation of 2-nitroarenes to 3H-indoles through a tandem cyclization-[1,2] shift reaction of in situ generated nitrosoarenes. Mo(CO)6 appears to have dual roles in this transformation: generate CO and promote C-N bond formation to increase the yield of the N-heterocycle product.

An unexpected tandem cycloaddition reaction of α,β-unsaturated acid chloride with amines: Synthesis of dihydropyrancarboxamide derivatives and biological activity

“…There are several kinds of known organic reactions available to use in tandem cycloaddition reactions those are particularly attractive in organic synthesis [1][2][3][4][5]. Tandem reactions are referred to multistep one-pot reactions [6], these have many advantages over a series of individual reaction where it allow construction of complex structure in as few steps as possible, no need for a purification step, save on cost and amounts of reagents and reduce the amount of waste that is generated.…”

Palladium‐Catalyzed Formation of N‐Heteroarenes from Nitroarenes using Molybdenum Hexacarbonyl as the Source of Carbon Monoxide

“…[4,5] Because of the challenges of substrate synthesis ands afety concerns with introducing the azide functional group, [6] we turned our attention toward developing metal-catalyzed processest hat employed an alternative electrophilic nitrogen-atom source.W e discovered that the combination of [Mo(CO) 6 ], phenanthroline and[Pd(OAc) 2 ]could trigger similar reactivity from a,b,b-trisubstituted nitrostyrenes to enable access to 3H-indoles (Scheme 1). [7] At the conclusion of this study,w ew erei nterestedi nd etermining if [Mo(CO) 6 ]c ould function as the reductant for the synthesiso fh eteroarenes,s uch as indoles. While these heterocycles have been synthesizedf rom nitroarenes or nitroalkenes using [Pd(OAc) 2 ]a nd CO, [8,9] we believed that using [Mo(CO) 6 ]a st he reductant would provide au seful alternative to these methodsb ecause it is an easily weighable solid, whose use would obviate the need to manipulate ag as.…”

“…[10] To our surprise, when we exposed a-phenylnitrostyrene to [Mo(CO) 6 ], [Pd(OAc) 2 ]a nd phenanthroline only traces of the 3-phenylindole waso bserved. In light of our mechanistic studies, [7] which indicated that molybdenum played am ore complexr ole than just the source of CO,w e anticipated that these important N-heterocycles could be constructed from nitrostyrenes using the [Mo(CO) 6 ]s ource if the molybendum complex was segregated from the nitroarene.R ecently,S krydstrup and co-workers have reported the development of two-and three-chamber reaction vessels for Pd-catalyzed carbonylation reactions where CO is generated in one chamber, and the Pd-catalyzed process takes place in as eparate chamber. [11] Inspired by their work, we report herein aP d-catalyzed synthesis of indoles and benzimidazoles using [Mo(CO) 6 ]a st he carbon monoxide source using as imple two-chamber reactor.…”

“…Theo pposite behaviour was observedw ith trisubstituted nitrostryrene 18: segregating Mo(CO) 6 from the amination reactionb y using at wo-chamber reactor hadadeleteriouse ffect on 3H-indole formation to produce 19 in only 32% -reducedf rom 73% in ao ne-chamber reactor. [7] Since the volatility of [Mo(CO) 6 ]i sw elle stablished, [22] the potential of molybdenum carbonyl complexes to traverse from chamber1to chamber 2i no rder to catalyze indole formation was investigated. In ao nechamber reactor, nitrostilbene 6a was exposed to 5mol% of [Mo(CO) 6 ]a nd 1.5 atm CO.O nly trace amountso f2 -phenylindole were produced.…”

Aqueous Titanium Trichloride Promoted Reductive Cyclization of o‐Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

“…[12] Recently,D river and co-workers reported an efficient synthesis of 3H-indoles by reductive cyclization of nitrostyrenes in the presence of Mo(CO) 6 and ac atalytic amount of Pd(OAc) 2 . [13] While o-nitrostyrenes have been recognized to be ideal precursors for indoles,t he potential of this transformation has not been fully exploited because of the moderate synthetic efficiency and harsh conditions often associated with the established protocols.I nconnection with our ongoing research program, we serendipitously discovered that aqueous titanous chloride was able to promote the reductive cyclization of o-nitrostyrenes to indoles in good to excellent yields. [14] Literature search after our own observation revealed as ingle isolated example from the group of Banwell.…”