C−H and C−N Activation at Redox‐Active Pyridine Complexes of Iron

Abstract

Pyridine activation by inexpensive iron catalysts has great utility, but the steps through which iron species can break the strong (105-111 kcal/mol) C-H bonds of pyridine substrates are unknown. In this work, we report the rapid room-temperature cleavage of C-H bonds in pyridine, 4-tertbutylpyridine, and 2-phenylpyridine by an iron(I) species, to give well-characterized iron(II) products. In addition, 4-dimethylaminopyridine (DMAP) undergoes room-temperature C-N bond cleavage, which forms a dimethylamidoiron(II) complex and a pyridyl-bridged tetrairon(II) square. These facile bond-cleaving reactions are proposed to occur through intermediates having a twoelectron reduced pyridine that bridges two iron centers. Thus, the redox non-innocence of the pyridine can play a key role in enabling high regioselectivity for difficult reactions. Graphical abstractAn iron(I) complex can activate C-H and C-N bonds in pyridines, using a mechanism that takes advantage of pyridine's redox activity. KeywordsPyridine; Iron; Redox-Active; Bond Cleavage Pyridines are widespread in pharmaceuticals, natural products, and polymers, and therefore their expedient synthesis is crucial. [1] However, pyridines are relatively unreactive in the absence of prior activation. [2] Direct cleavage of C-H bonds in unfunctionalized pyridines is uncommon, but has made substantial progress recently. [3] A recent exciting development has been the C-H arylation of pyridines using catalytic mixtures generated in situ from simple iron salts and an excess of Grignard reagent. [4] This recipe presumably generates reduced Correspondence to: Patrick L. Holland. a These authors contributed to this work equally, and should be considered co-first authors.Supporting information for this article can be found under: http://dx.doi.org/10.1002/anie.XXXX HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript iron species that are the catalysts, but little is known about reduced iron-pyridine compounds and what stoichiometric steps to expect under these conditions. In this communication, we report well-characterized iron products that result from pyridine C-H bond cleavage. We also show an unprecedented C-N bond cleavage of 4-dimethylaminopyridine (DMAP) and construct a reasonable mechanistic scaffold that is based on the ability of pyridines to accept charge from low-valent iron.Pyridines are well-known redox-active ligands. [5] We have shown that the addition of one or more equiv of pyridine to the iron(I) complex LFe(C 6 H 6 ) (L = β-diketiminate ligand, shown in Scheme 1) yields products in which the pyridine ligands are reduced by 1-2 electrons. [6] However, we have now discovered that addition of smaller amounts of pyridine leads to formation of a surprising new compound (1). Solutions of 1 are in equilibrium with the previously characterized pyridine-bound complexes and with LFe(C 6 H 6 ), as shown by 1 H NMR spectra of C 6 D 6 solutions of 1 with various amounts of pyridine ( Figure S5). Compound 1 can be isolated by...

Direct Aerobic Generation of a Ferric Hydroperoxo Intermediate via a Preorganized Secondary Coordination Sphere

“…[12][13][14][15][16] While the reactivity and ultimate products of oxidases are varied, the initial steps in O2 activation can be quite general, proceeding through initial binding of O2 to generate an Fe superoxide intermediate before further activation to an Fe(III)-hydroperoxo intermediate by the addition of a formal H-atom from the active site. [12][13][14][15][16][17][18][19] Molecular chemists have drawn inspiration from these elegant biological examples, and the use of ancillary ligands with designed hydrogen bonding networks, [20][21][22][23] hydrogen shuttling functionalities, [24][25][26][27][28][29][30] or redox reservoirs have emerged as promising strategies in transition metal reactivity and catalysis. [31][32][33][34][35][36][37][38][39][40] While these strategies are effective individually, natural systems are not limited to one interaction type in the secondary coordination sphere but instead leverage all of these effects.…”