molecules Article Porphyrin Cobalt(III) “Nitrene Radical” Reactivity; Hydrogen Atom Transfer from Ortho-YH Substituents to the Nitrene Moiety of Cobalt-Bound Aryl Nitrene Intermediates (Y = O, NH) Monalisa Goswami, Christophe Rebreyend and Bas de Bruin * Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; [email protected] (M.G.); [email protected] (C.R.) * Correspondence: [email protected]; Tel.: +31-205-256-495 Academic Editor: Klaus Banert Received: 16 January 2016; Accepted: 16 February 2016; Published: 20 February 2016 Abstract: In the field of cobalt(II) porphyrin-catalyzed metallo-radical reactions, organic azides have emerged as successful nitrene transfer reagents. In the pursuit of employing ortho-YH substituted (Y = O, NH) aryl azides in Co(II) porphyrin-catalyzed nitrene transfer reactions, unexpected hydrogen atom transfer (HAT) from the OH or NH2 group in the ortho-position to the nitrene moiety of the key radical-intermediate was observed. This leads to formation of reactive ortho-iminoquinonoid (Y = O) and phenylene diimine (Y = NH) species. These intermediates convert to subsequent products in non-catalyzed reactions, as is typical for these free organic compounds. As such, the observed reactions prevent the anticipated cobalt-mediated catalytic radical-type coupling of the nitrene radical intermediates to alkynes or alkenes. Nonetheless, the observed reactions provide valuable insights into the reactivity of transition metal nitrene-radical intermediates, and give access to ortho-iminoquinonoid and phenylene diimine intermediates from ortho-YH substituted aryl azides in a catalytic manner. The latter can be employed as intermediates in one-pot catalytic transformations. From the ortho-hydroxy aryl azide substrates both phenoxizinones and benzoxazines could be synthesized in high yields. From the ortho-amino aryl azide substrates azabenzene compounds were obtained as the main products. Computational studies support these observations, and reveal that HAT from the neighboring OH and NH2 moiety to the nitrene radical moiety has a low energy barrier. Keywords: aryl azides; cobalt(II) porphyrins; nitrene radicals; hydrogen atom transfer; azabenzenes; ortho-iminoquinonoid; phenylene diimine 1. Introduction In the context of homogeneously catalyzed organic transformations carbene and nitrene transfer reactions provide interesting possibilities [1–7]. In these transformations metal catalysts that can activate carbene or nitrene precursors are employed, typically leading to the formation of metal carbenoid or nitrenoid species. The thus formed carbenoids and nitrenoids can then add to a variety of unsaturated bonds in alkenes and alkynes. In addition, metal-catalyzed carbene transfer can be used in reaction in which carbene moieties formally insert into X´H bonds (X = O, N, S, Si) [2]. Given the ubiquity of nitrogen atoms in biologically active compounds, it is also interesting to find ways in which C–N bonds can be formed by addition or insertion of nitrenoids to a C=C or C”C bond or into a C–H bond. Metal-catalyzed nitrene transfer reactions are therefore promising and worth investigating. Cobalt(II) porpyhrins have proven to be quite successful in this field [2,8–25]. Besides being efficient in carbene transfer reactions, cobalt(II) porphyrins have also attracted attention in several Molecules 2016, 21, 242; doi:10.3390/molecules21020242 www.mdpi.com/journal/molecules Molecules 2016, 21, 242 2 of 16 nitrene transfer reactions [11,14–16,18,21,22,26–28]. In the early stages of this type of catalysis it was quite common to use iminoiodanes or haloamine-T compounds as nitrene sources for transfer to other moleculesMolecules [201629–,33 21,]. 242 These are, however, not the most convenient and benign nitrene sources,2 of as 16 they are poorly soluble and lead to the formation of undesirable side products like phenyl iodide and otherquite halogen-containing common to use iminoiodanes compounds. Organicor haloamine-T azides arecompounds potentially as nitrene more interesting sources for nitrene-transfer transfer to reagentsother [molecules3,5,6], as [29–33]. they are These more are, soluble however, and not the the only most byproduct convenient formed and benign during nitrene the sources, generation as of nitrenesthey are from poorly azides soluble is dinitrogen. and lead to the formation of undesirable side products like phenyl iodide and otherMechanistically halogen-containing these compounds. systems are Organic quite uniqueazides are as potentially they operate more via inte cobalt(III)resting nitrene-transfer nitrene radical species,reagents formed [3,5,6], by as electron they are transfermore soluble from and cobalt(II) the only to byproduct the nitrene formed moiety during upon the activationgeneration ofof the nitrenes from azides is dinitrogen. azide. This leads to discrete radical character of the reactive nitrenoid intermediate. The detailed Mechanistically these systems are quite unique as they operate via cobalt(III) nitrene radical mechanistic aspects of two such catalytic nitrene transfer reactions with cobalt porphyrins have species, formed by electron transfer from cobalt(II) to the nitrene moiety upon activation of the azide. ´ beenThis elucidated leads to discrete by our radical group character previously of the (Scheme reactive1 nitrenoid)[ 12,18 ,intermediate.34,35]. The The mechanism detailed mechanistic of C H bond aminationaspects of two ethylbenzene, such catalytic toluene, nitrene transfer and tetralin reaction (1,2,3,4-s with cobalt tetrahydronaphthalene) porphyrins have been was elucidated studied by with a varietyour group of organic previously azides (Scheme like N 1)3 C(O)OMe,[12,18,34,35]. N The3SO mechanism2Ph, etc. using of C− densityH bond amination functional of theoryethylbenzene, (DFT) and electrontoluene, paramagnetic and tetralin (1,2,3,4- resonance tetrahydronaphthalen (EPR) spectroscopye) was (Scheme studied1 a)with [ 18 a ].variety The mechanismof organic azides of cobalt(II) like porphyrin-mediatedN3C(O)OMe, N3SO aziridination2Ph, etc. using ofdensity styrene functional with PhSO theory2N 3(DFT)was alsoand electron studied paramagnetic (Scheme1b)[ resonance21]. For both amination(EPR) spectroscopy and aziridination (Scheme reactions,1a) [18]. The the mechanism DFT calculations of cobalt(II) revealedporphyrin-me a stepwisediated aziridination radical process of involvingstyrene coordinationwith PhSO2N3 of was the also azide studied to the (Scheme cobalt(II) 1b) center,[21]. For followed both amination by release and ofaziridination dinitrogen to producereactions, an unusual the DFT calculations “nitrene radical” revealed intermediate a stepwise radicalC (Scheme process 1involving). In addition, coordination experimental of the azide EPR spectroscopicto the cobalt(II) studies, center, combined followed with by release DFT EPR of di propertynitrogen calculationsto produce an being unusual in good “nitrene agreement radical” with intermediate C (Scheme 1). In addition, experimental EPR spectroscopic studies, combined with DFT the experimental data, revealed the formation of a (por)CoIII´N‚Y nitrene radical adduct C from EPR property calculations being in good agreement with the experimental data, revealed the formation the catalyst in the presence of an excess of the azide in benzene. Formation of a nitrene moiety at of a (por)CoIII−N•Y nitrene radical adduct C from the catalyst in the presence of an excess of the azide cobalt(II)porphyrin effectively leads to electron transfer from the metal to the nitrene, thus reflecting in benzene. Formation of a nitrene moiety at cobalt(II)porphyrin effectively leads to electron transfer the redoxfrom the non-innocence metal to the nitrene, of the nitrenethus reflecting substrate the ligand.redox non-innocence The spin density of the of nitrene this intermediate substrate ligand. resides almostThe entirely spin density on the of this nitrogen intermediate atom of resides the nitrene almost moiety.entirely Moreon the recently,nitrogen atom the intermediate of the nitrene Cmoiety.was fully characterizedMore recently, using the anintermediate array of spectroscopic C was fully characterized methods [ 12using]. an array of spectroscopic methods [12]. SchemeScheme 1. Mechanisms 1. Mechanisms of of cobalt(II) cobalt(II)porphyrin porphyrin catalyzed amination amination (a () aand) and aziridination aziridination (b). (b). Molecules 2016, 21, 242 3 of 16 Molecules 2016, 21, 242 3 of 16 In orderorder toto expandexpand thethe scopescope ofof cobalt(II)cobalt(II) porphyrinporphyrin catalyzedcatalyzed nitrenenitrene transfertransfer reactions we sought to to use use ortho-ortho-substitutedsubstituted aryl aryl azides azides as substrates, as substrates, which which on activation on activation by Co(II) by Co(II) porphyrins porphyrins could couldundergo undergo subsequent subsequent reactions reactions with unsaturated with unsaturated bonds. The bonds. idea The was idea in part was inspired in part inspiredby our work by our on workrelated on ortho- relatedhydroxyarylortho-hydroxyaryl carbene radicals carbene [20]. radicals Activation [20]. Activationof the carbene of the precursor carbene and precursor subsequent and subsequentreaction of reactionthe thus of generated the thus generated cobalt(III) cobalt(III) carbene carbene radical radical with phenyl with phenyl acetylene acetylene allowed allowed us usto tosynthesize synthesize 2H 2-chromenesH-chromenes in in good good yields