Organic super-electron-donors: initiators in transition metal-free haloarene–arene coupling

Abstract

Recent papers report transition metal-free couplings of haloarenes to arenes to form biaryls, triggered by alkali metal tert-butoxides in the presence of various additives. These reactions proceed through radical intermediates, but understanding the origin of the radicals has been problematic. Electron transfer from a complex formed from potassium tert-butoxide with additives, such as phenanthroline, has been suggested to initiate the radical process. However, our computational results encouraged us to search for alternatives. We report that heterocycle-derived organic electron donors achieve the coupling reactions and these donors can form in situ in the above cases. We show that an electron transfer route can operate either with phenanthrolines as additives or using pyridine as solvent, and we propose new heterocyclic structures for the respective electron donors involved in these cases. In the absence of additives, the coupling reactions are still successful, although more sluggish, and in those cases benzynes are proposed to play crucial roles in the initiation process. Results An explosion of interest has arisen in dehalogenative couplings between haloarenes and arenes to form biphenyls under transition metal-free conditions 1-28 since the original report of coupling of iodobenzene with pyridine and pyrazine by Itami in 2008. 1 The excitement is easily understood, since these reactions avoid the use of costly complexes of palladium, which are the normal catalysts. A common feature of the recent reactions is the use of sodium or potassium tert-butoxide as base. The absence of any signicant contamination with transition metals like palladium, 1,2 together with the properties of the new coupling reactions, has led to a general consensus that the reactions proceed by aryl radical intermediates. 1,6 The corollary coupling between haloarenes and styrenes, also triggered by alkali metal butoxides, 3,7,12 likely follows the same route. The general case for a radical mechanism was well summarised in an essay by Studer and Curran 9 and an attractive proposal from that source is shown in Fig. 1A. Here, the aryl radical 2 adds to benzene to form the arylcyclohexadienyl radical 3. Deprotonation by butoxide affords the radical anion 4,

Transition‐Metal‐Free C3 Arylation of Indoles with Aryl Halides

“…[44] There is a growing body of literature in which KOtBu plus associated ligands are capable of promoting transition metal-free cross-coupling reactions between arenes and aryl halides. [45][46][47][48][49][50][51][52][53][54][55][56][57] Computational [58,59] and empirical studies implicate radical intermediates and electron transfer processes. While the findings from these reports may, in part, be applicable to our work, the formation of cine substitution products in the title reaction necessitates that aryne intermediates be considered alongside.…”

Radikalische Hydrodehalogenierung von Arylbromiden und ‐chloriden mit Natriumhydrid und 1,4‐Dioxan

“…[20] Das beste Resultat wurde nach Reaktion von 1amit 1,10-Phenanthrolin (20 Mol-%) und NaH (3 ¾quiv. ) Im Folgenden wurde die Substratbreite untersucht: Elektronenreiche,d imethoxysubstituierte Brombenzole lieferten die Arene 2b (70 %) und 2c (65 %) in guten Ausbeuten.…”

Dual Roles for Potassium Hydride in Haloarene Reduction: CSNAr and Single Electron Transfer Reduction via Organic Electron Donors Formed in Benzene

“…In a manner reminiscent of other BHAS reactions, 18 a strong organic electron donor could be formed if KH deprotonates benzene to form PhK 47 (Scheme 6). Here, PhK would attack benzene to form phenylcyclohexadienyl potassium 35.…”

“…Addition of the benzyne, as a biradical, 18 to benzene affords biradical 21. This biradical has one very reactive radical, the aryl radical, and one highly delocalized radical (the cyclohexadienyl radical).…”

“…18,19 Our recent study critically examined the evidence presented for KOtBu as a single electron donor to haloarenes in a number of different reports and found that, in each case, organic additives initiate the BHAS reaction by forming organic electron donors in situ, 20 for example, electron donor 9 from phenanthroline 6 (Scheme 2A). 18 While organic additives are not absolutely required for most substrates in this transformation, 9,10,15 they significantly enhance the yield of the coupled products, simultaneously allowing reactions to be conducted at lower temperatures and for a shorter duration. 18,21−23 In the absence of suitable organic additives, 15 BHAS reactions can be initiated by arynes (benzynes), formed by base-induced elimination of HX from substrate haloarenes ArX such as 1 (see later, Scheme 4).…”