Direct Selective Oxidative Functionalization of C–H Bonds with H2O2: Mn-Aminopyridine Complexes Challenge the Dominance of Non-Heme Fe Catalysts

molecules

Review Direct Selective Oxidative Functionalization of C–H Bonds with H2O2: Mn-Aminopyridine Complexes Challenge the Dominance of Non-Heme Fe Catalysts

Roman V. Ottenbacher 1,2, Evgenii P. Talsi 1,2 and Konstantin P. Bryliakov 1,2,*

1 Chemistry Department, Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia; ottenbacher@catalysis.ru (R.V.O.); [email protected] (E.P.T.) 2 Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibirsk 630090, Russia * Correspondence: [email protected]; Tel.: +7-383-326-9451; Fax: +7-383-330-8056

Academic Editor: Georgiy B. Shul’pin Received: 28 September 2016; Accepted: 20 October 2016; Published: 31 October 2016

Abstract: Non-heme iron(II) complexes are widespread synthetic enzyme models, capable of conducting selective C–H oxidation with H2O2 in the presence of carboxylic acid additives. In the last years, structurally similar manganese(II) complexes have been shown to catalyze C–H oxidation with similarly high selectivity, and with much higher efﬁciency. In this mini-review, recent catalytic and mechanistic data on the selective C–H oxygenations with H2O2 in the presence of manganese complexes are overviewed. A distinctive feature of catalyst systems of the type Mn complex/H2O2/carboxylic is the existence of two alternative reaction pathways (as found for the oxidation of cumenes), one leading to the formation of alcohol, and the other to ester. The mechanisms of formation of the alcohol and the ester are brieﬂy discussed.

Keywords: C–H functionalization; enzyme models; hydrogen peroxide; manganese; mechanism; oxidation

1. Introduction Given increasing demand for efficient and scalable methods of fine organic syntheses (mostly the syntheses of natural products, pharmaceuticals, biologically active molecules), the design of rigorous synthetic approaches, ensuring precise control of the carbon skeleton and oxidation state, continues to be one of the foremost challenges of synthetic chemistry. In the last years, selective catalytic oxidations of unactivated C–H bonds have attracted great attention: this approach, if implemented on preparative scale, could provide easy and efficient methodologies for the directed introduction of oxygen atom into complex organic molecules at late stages of multistep syntheses, on the basis of novel synthetic strategies [1–11]. Selective C–H oxidation reactions may lead to formation of new C–C and C–X (e.g., C–O, C–N, C–S, C–halogen, etc. [10]) bonds; in this paper, we will solely focus on the oxygenation processes, converting alkane groups into C–OH or C=O functionalities. Metal-mediated C–H activation (including C–H bond cleavage and formation of C-metal σ-bonds) has been known for decades; one could mention in this context the works of Shilov [1,8,12], Periana [1,8,13], and others [1,8], dating back to the 1960s–1980s. Typically, C–H activation reactions require that the substrate should first coordinate to the catalytic complex of transition metal (Pt, Rh, Ir, etc.), which is relatively easy if the substrate has π electrons. In contrast to unsaturated substrates, alkanes have only σ electrons and thus are poor nucleophiles, coordinating only weakly to metals [8], which complicates the C–H activation step. On the other hand, to obtain a functionalized molecule, the activation step should be combined with subsequent functionalization step, which may represent some obstacles [8]. That is why in the last years, direct C–H oxofunctionalization, which does

Molecules 2016, 21, 1454; doi:10.3390/molecules21111454 www.mdpi.com/journal/molecules Molecules 2016, 21, 1454 2 of 16

Molecules 2016, 21, 1454 2 of 16 C–H oxofunctionalization, which does not imply the intermediate formation of a metal-carbon bond, has attracted close attention as a promising strategy for the selective oxidative modification notof challenging imply the substrates intermediate like formation alkanes. An of additional a metal-carbon advantage bond, of has the attracted direct C–H close oxidations attention is asthat a promisingmost of them strategy rely foron catalysts the selective based oxidative on comple modificationxes of cheap of challengingand abundant substrates first-row like transition alkanes. Anmetals additional (Fe, Cu, advantage Mn, V, etc.). of the direct C–H oxidations is that most of them rely on catalysts based on complexesNowadays, of cheap the and design abundant of homogeneous first-row transition catalysts metals for (Fe,the Cu, direct Mn, C–H V, etc.). oxygenation largely followsNowadays, the biomimetic the design approach, of homogeneous which catalystsimplies modeling for the direct the C–H catalytic oxygenation functions largely of followsnatural themetalloenzymes biomimetic approach, (like cytochrome which implies P450 or modeling methane the monooxygenase) catalytic functions with of synthetic natural metalloenzymes low-molecular (likeweight cytochrome complexes. P450 It is or not methane surprising monooxygenase) that the major with part synthetic of reported low-molecular examples weight of catalytic complexes. C–H Itoxidations is not surprising deal with thatcatalysts the majorbased on part complexes of reported of Fe—the examples latter of is catalytic the most C–H widespread oxidations metal deal in withnatural catalysts metalloenzymes based on [14–27]. complexes Most ofoften, Fe—the H2O2 latteris used is as the the most “green” widespread oxidant. metal in natural metalloenzymesToday, non-heme [14–27 ].(essentially Most often, nonporphyrinic) H2O2 is used as theFe “green”complexes oxidant. dominate the area, due to the versatilityToday, of non-heme the ligand (essentially structures, nonporphyrinic)and the rich possibilities Fe complexes of their dominate structural the modifications. area, due to First the versatilityexamples of of non-heme-Fe-cataly the ligand structures,zed andoxidations the rich appeared possibilities in early of their 1990s structural [24,28]; modifications.however, the Firstbreakthrough examples was of non-heme-Fe-catalyzedachieved after 2007, when oxidations White appearedwith co-workers in early 1990scontributed [24,28 ];a however,series of themilestone breakthrough works, presenting was achieved the afterbipyrrolidine-derived 2007, when White non-heme with co-workers iron catalyst contributed 1 (Figure a 1) series and its of milestonestructural works,analogs, presenting ensuring reasonably the bipyrrolidine-derived high level of predictability non-heme iron in the catalyst selective1 (Figure oxidation1) and of itsC(sp structural3)-H groups analogs, [29–34]. ensuring In competitive reasonably contributi high levelon, ofCostas predictability and co-workers in the selective showed oxidation that the ofintroduction C(sp3)-H groupsof additional [29–34 ].steric In competitive crowd at the contribution, pyridine moieties, Costas as and well co-workers as manipulating showed with that the introductionsymmetry of ofthe additional chiral ligand steric crowdcan divert at the the pyridine oxidation moieties, selectivity as well from as manipulating3° C(sp3)-H bonds with the to symmetrystronger 2° of C(sp the chiral3)-H bonds, ligand which can divert is critical the oxidation for the selectivityselective oxygenation from 3◦ C(sp 3of)-H complex bonds tomolecules stronger 2such◦ C(sp as3 )-Hnatural bonds, products which is[35–38]. critical The for themechanism selective oxygenationof non-heme of iron complex catalyzed molecules oxidations such ashas natural been productsextensively [35 studied–38]. The experimentally mechanism of [39]; non-heme it has ironnow catalyzed been accepted oxidations that hasthe C–H been extensivelyoxidation proceeds studied experimentallyvia the classical [39 rebound]; it has nowmechanism been accepted [40] (Figure that the 1) C–H, with oxidation participation proceeds of the via theelusive classical oxoperferryl rebound mechanismspecies [41–49]. [40] (Figure1), with participation of the elusive oxoperferryl species [41–49].

Figure 1. The structure of White’s catalyst 1 ((left) and thethe rebound-mechanismrebound-mechanism ((rightright).).

InIn contrastcontrast to to non-heme non-heme Fe Fe complexes, complexes, the catalyticthe catalytic activity activity (as well (as as well the mechanismas the mechanism of catalytic of action)catalytic of action) structurally of structurally related Mn related complexes Mn havecomplexes so far beenhave muchso far less been studied. much Nevertheless,less studied. theNevertheless, Mn based catalystthe Mn systemsbased catalyst for C–H systems oxidation, for reportedC–H oxidation, so far, demonstrate reported so goodfar, demonstrate practical promise; good thepractical Mn-catalyzed promise; C–Hthe Mn-catalyzed oxidation mechanism C–H oxidation seems tomechanism be mostly similarseems to to be that mostly for the similar Fe-mediated to that directfor the C–H Fe-mediated oxidation. direct In this C–H contribution, oxidation. weIn th willis contribution, brieﬂy summarize we will the briefly related summarize synthetic andthe mechanisticrelated synthetic data publishedand mechanistic to date, data and discusspublished a new to mechanisticdate, and discuss feature, a previouslynew mechanistic unobserved feature, for Fe-catalyzedpreviously unobserved C–H oxidations, for Fe-catalyzed which seems toC–H be characteristicoxidations, which of Mn-mediated seems to C–Hbe characteristic oxidations. of Mn-mediated C–H oxidations. 2. C–H Oxidations with H2O2 in the Presence of Mn Porphyrins 2. C–H Oxidations with H2O2 in the Presence of Mn Porphyrins In 1986, Mansuy with co-workers reported the catalytic oxidation of alkanes with H2O2 in the presenceIn 1986, of Mn Mansuy porphyrin with complexco-workers2 (Figure reported2)[ the50]. catalytic Upon slow oxidation addition of alkanes of H2O2 with(5 equiv.) H2O2 toin thethe acetonitrile:dichloromethanepresence of Mn porphyrin complex solution 2 of (Figure cyclohexane, 2) [50]. catalyst Upon slow2 (2.5 addition mol %), andof H imidazole2O2 (5 equiv.) as additive to the (60acetonitrile:dichloromethane mol %), led to the formation solu oftion cyclohexanol of cyclohexane, and cyclohexanone catalyst 2 (2.5 (Table mol1 ,%), entry and 1) [imidazole50]. The 3:1as cyclohexanol:cyclohexanoneadditive (60 mol %), led to the ratio, formation the high of (11.5) cyclohexanol 3◦:2◦ adamantane and cyclohexanone oxidation selectivity,(Table 1, entry the absence 1) [50]. ofThe effect 3:1 cyclohexanol:cyclohexanone of dioxygen on the oxidation ratio, outcome, the high and (11.5) selective 3°:2° (non-statistical) adamantane oxidation oxygenation selectivity, of heptane the wereabsence indicative of effect of of a metal-mediateddioxygen on the rather oxidation than radical-drivenoutcome, and oxidationselective mechanism(non-statistical) [51]. oxygenation The authors Molecules 2016, 21, 1454 3 of 16 of heptane were indicative of a metal-mediated rather than radical-driven oxidation mechanism [51].hypothesized The authors that hypothesized the oxidation couldthat the be performedoxidation could by the be Mn performedV=O intermediate, by the Mn theV=O role intermediate, of imidazole theconsisting role of imidazole in promoting consisting the heterolytic in promoting cleavage the heterolytic of the O–O cleavage bond, of to the form O–O the bond, manganese-oxo to form the manganese-oxospecies [52]. species [52].

Figure 2. Structures of Mn porphyrins, studied in C–H oxidations.

BanfiBanfi with co-workers considered a series of Mn-porphyrin complexes 2–4 as alkane oxidation catalysts and and found found that that the the introduction introduction of of a anitro nitro group group (3 ( 3andand 4 4vs.vs. 2) 2resulted) resulted in inan anincrease increase of activityof activity and andstability stability of the of catalysts, the catalysts, eventually eventually resulting resulting in higher in yields higher of yieldsoxygenated of oxygenated products products[53]. It was [53 shown]. It wasthat other shown heterocyclic that other bases heterocyclic may be basesefficiently may used be efficiently as additives, used in ascombination additives, within combination benzoic acid with (Table benzoic 1, entries acid (Table 2, 3).1 ,The entries proposed 2, 3). Themechanism proposed assumed mechanism the key assumed role of the a “MnV=O” intermediateV [53,54]. Complex 2 and its Br8-analog also demonstrated the capability of key role of a “Mn =O” intermediate [53,54]. Complex 2 and its Br8-analog also demonstrated catalyzingthe capability the ofoxidation catalyzing of aromatic the oxidation compounds of aromatic (such compoundsas anisole, naphthalene, (such as anisole, phenantrene) naphthalene, with H2O2, in the presence of imidazole as additive (Table 1, entries 4, 5) [55]. The yields were low, and phenantrene) with H2O2, in the presence of imidazole as additive (Table1, entries 4, 5) [ 55]. The yields werethe high low, selectivities and the high were selectivities only achieved were at onlyhigh achievedsubstrate/oxidant/Mn at high substrate/oxidant/Mn ratios (typically 700:10:1). ratios (typicallyThe hydroxylation 700:10:1). The of hydroxylationanisole occurred of anisole preferentially occurred preferentially at the p-position; at the p-position; furthermore, furthermore, some Osome-demethylationO-demethylation was detected was detected (Table (Table 1, entry1, entry 5) 5)[55]. [ 55 ].Mansuy Mansuy with with co-workers co-workers found found that ammonium acetate is a more efficient co-catalyst than imidazole [56], the use of CH3COONH4 led ammonium acetate is a more efficient co-catalyst than imidazole [56], the use of CH3COONH4 led (under similar conditions) to higher alkanealkane conversionsconversions (but lowerlower alcohol/ketonealcohol/ketone ratios, ratios, Table Table 11,, entries 6, 7).

Table 1. Examples of C–H oxidations catalyzed by porphyrinic Mn complexes. No. Cat. Substrate Additive Products (yield a) Ref. a No.1 Cat.2 cyclohexane Substrate imidazole Additive cyclohexanol Products (12), cyclohexanone (yield ) (4) [50] Ref. 12 32 cyclohexanecyclohexane p-tBu-pyridine/benzoic imidazole acid cyclohexanol cyclohexanol (233 (12),b), cyclohexanone cyclohexanone (47 (4) b) [53] [50 ] 23 43 cyclooctanecyclohexane p-ptBu-pyridine/benzoic-tBu-pyridine/benzoic acid acid cyclooctanol cyclohexanol (565 (233 b),b cyclooctanone), cyclohexanone (235 (47 b)b )[[53]53 ] 34 24 naphthalenecyclooctane p-tBu-pyridine/benzoic imidazole acid cyclooctanol 1-naphthol (565 (3.5),b), 2-naphthol cyclooctanone (0.4) (235 b)[ [55]53 ] 45 2 naphthaleneanisole imidazole imidazole p-OH-anisole 1-naphthol (4.7), o-OH-anisole (3.5), 2-naphthol (0.35), (0.4)phenol (0.2) [55] [55 ] 56 2 cyclohexaneanisole imidazole imidazole p-OH-anisole cyclohexanol (4.7), (12.4),o-OH-anisole cyclohexanone (0.35), phenol(1.6) (0.2) [56] [55 ] 6 2 cyclohexane imidazole cyclohexanol (12.4), cyclohexanone (1.6) [56] 7 2 cyclohexane CH3COONH4 cyclohexanol (20), cyclohexanone (5.2) [56] 7 2 cyclohexane CH COONH cyclohexanol (20), cyclohexanone (5.2) [56] 8 5 p-Et-toluene imidazole3 4 p-acetyltoluene (2.8), 1-(p-tolyl)ethanol (37.2, 57% ee) [57] 8 5 p-Et-toluene imidazole p-acetyltoluene (2.8), 1-(p-tolyl)ethanol (37.2, 57% ee) [57] a b aYieldYield of of oxygenatedoxygenated products products is givenis given in mol/mol in mol/mol Mn; b InMn; the originalIn the publication,original publication, alkane conversion alkane conversionwas reported. was reported. More recently, Simonneaux with co-workers developed the first Mn-porphyrin catalyzed More recently, Simonneaux with co-workers developed the ﬁrst Mn-porphyrin catalyzed enantioselective benzylic hydroxylations with H2O2 in the presence of catalyst 5 (Figure 2) [57]. The enantioselective benzylic hydroxylations with H O in the presence of catalyst 5 (Figure2)[ 57]. reactions could be readily performed in aqueous meth2 2 anolic solutions, due to the good solubility of The reactions could be readily performed in aqueous methanolic solutions, due to the good solubility complex 5. Enantioselectivities ranging from 32% to 57% ee were reported (Table 1, entry 8), and the of complex 5. Enantioselectivities ranging from 32% to 57% ee were reported (Table1, entry 8), catalyst performed up to 40 turnovers. The occurrence of asymmetric induction is evidence of and the catalyst performed up to 40 turnovers. The occurrence of asymmetric induction is evidence of non-radical hydroxylation mechanism. The highest enantioselectivities were documented for those non-radical hydroxylation mechanism. The highest enantioselectivities were documented for those substrates that ensured the highest alcohol selectivities at the same time (e.g., for the oxidation of substrates that ensured the highest alcohol selectivities at the same time (e.g., for the oxidation of 4-ethyltoluene: 97% conversion, alcohol/ketone = 93:7, enantioselectivity 57%), which rules out the 4-ethyltoluene: 97% conversion, alcohol/ketone = 93:7, enantioselectivity 57%), which rules out possibility for generation of ee at the kinetic resolution step. SO3Na was the best substituent; its the possibility for generation of ee at the kinetic resolution step. SO3Na was the best substituent; replacement with H, NMe2, or NO2 afforded less chemo- and enantioselective catalysts [58]. its replacement with H, NMe2, or NO2 afforded less chemo- and enantioselective catalysts [58]. Conducting the reaction in a biphasic system (CH2Cl2/H2O2) deteriorated the oxidation outcome [58]. Conducting the reaction in a biphasic system (CH Cl /H O ) deteriorated the oxidation outcome [58]. To date, the catalysts for C–H oxidation on2 the2 basis2 2 of Mn porphyrin complexes have been very rare (focusing on complex 2 or its modifications); the catalytic reactions have some Molecules 2016, 21, 1454 4 of 16

MoleculesTo date,2016, 21 the, 1454 catalysts for C–H oxidation on the basis of Mn porphyrin complexes have been4 veryof 16 rare (focusing on complex 2 or its modiﬁcations); the catalytic reactions have some characteristics ofcharacteristics metal-mediated of metal-mediated (non-radical) process(non-radical) (presumably process driven(presumably by high-valent driven by Mn=O high-valent species Mn=O [21]). However,species [21]). the However, mechanism the of Mn-porphyrin-catalyzedmechanism of Mn-porphyrin-catalyzed C–H hydroxylations C–H withhydroxylations H2O2 has not with yet H been2O2 reliablyhas not yet established. been reliably established.

3. C–H C–H Oxidations Oxidations with with H H2O2O2 2inin the the Presence Presence of of Mn Mn Complexes Complexes with with Me Me3tacn3tacn Derived Derived Ligands Ligands

The selective C–H oxidations with HH22O2 inin the presence of non-porphyrinicnon-porphyrinic Mn complexescomplexes have so far been been extensively extensively developed. developed. The The mile milestonestone in inthe the area area had had been been the the communication communication of ofShul’pin Shul’pin and and Lindsay Lindsay Smith Smith [59,60] [59,60 ]that that dinuclear dinuclear Mn(IV) Mn(IV) complex complex 66 (Wieghardt’s(Wieghardt’s complex IV IV [LMnIV(O)(O)33MnMnIVL](PFL](PF6)62,) 2where, where L L= = 1,4,7-trimethyl-1,4,7-triazacyclononane, 1,4,7-trimethyl-1,4,7-triazacyclononane, Me Me3tacn3tacn [61], [61], Figure Figure 33)) catalyzed the oxidation ofof alkanesalkanes (hexane,(hexane, cyclohexane,cyclohexane, cycloheptane)cycloheptane) withwith HH22O2.. In In acetonitrile, catalyst 66was was very very efﬁcient, efficient, performing performing up toup 1350 to turnovers1350 turnovers (Table 2(Table). Carboxylic 2). Carboxylic acid was acid reported was toreported be an essentialto be an catalyticessential additive,catalytic additive, and acetic and acid acetic was acid the bestwas inthe the best series in the [60 ].series The [60]. addition The ofaddition radical of scavenger radical scavenger BrCCl3 dramatically BrCCl3 dramatically suppressed suppressed the yield the of oxidized yield of products.oxidized products. On the other On hand,the other formation hand, formation of sizable of amounts sizable ofamounts alkyl hydroperoxides of alkyl hydroperoxides was detected, was anddetected, partial and erosion partial of stereochemistryerosion of stereochemistry upon the oxidation upon the of oxidationcis- and trans of cis-1,2-dimethylcyclohexanes- and trans-1,2-dimethylcyclohexanes was documented, was suggestingdocumented, considerable suggesting impactconsiderab of freele impact radical of driven free radical oxidation driven pathways oxidation [62]. pathways [62].

Figure 3. Structures of Mn complexes with Me3tacn derived ligands.

Catalyst 6 appeared to be extremely efficient efficient in the oxidation of light alkanes (methane, ethane: Table2 2,, entry entry 2), 2), as as well well as as higher higher normal normal and and branched branched alkanes alkanes at roomat room temperature temperature (performing (performing up toup 3100to 3100 turnovers) turnovers) [63 ,[63,64].64]. 3 A polymer-boundpolymer-bound complexcomplex was was prepared prepared starting starting from from Me Me3tacn-derivedtacn-derived ligand ligand7 (Figure 7 (Figure3) and 3) Mn(OAc)and Mn(OAc)2, which2, which also also conducted conducted alkane alkane oxygenation oxygenation with with H 2HO22O/AcOH,2/AcOH, demonstratingdemonstrating a lower activity asas compared compared to itsto homogeneous its homogeneous prototype prototype [65]. The reactivity[65]. The profile reactivity of the polymer-boundprofile of the catalystpolymer-bound was somewhat catalyst differentwas somewhat from thatdifferent of the from dinuclear that of catalyst the dinuclear6, in particular catalyst 6 higher, in particularkH/kD (higher2.8 vs. k 1.3H/k;D cyclohexane/cyclohexane-d (2.8 vs. 1.3; cyclohexane/cyclohexane-d12) and different12) and selectivity different for selectivity the hydroxylation for the hydroxylation of isooctane wereof isooctane documented were documented [65]. [65]. Shul’pin with with co-workers co-workers studied studied systematically systematically the the role role of additives. of additives. Without Without additives, additives, Mn 2 2 Mncomplex complex 6 did6 didnot notreact react with with H O H 2inO 2acetonitrile.in acetonitrile. However, However, even evensmall small amounts amounts of acetic of acetic acid acidpromoted promoted both both the thecatalytic catalytic decomposition decomposition of ofhydrog hydrogenen peroxide peroxide and and the the alka alkanene oxidation. oxidation. If If tiny amount of base was added to the acetic acid, the catalase activity of the 6 substantially increased, while the oxygenase activity decreased [[66,67].66,67]. 2 2 An interestinginteresting result result was was documented documented for thefor oxidationthe oxidation of alkanes of alkanes with H 2withO2 in H biphasicO in biphasic systems 2 3 (Hsystems2O/alkane, (H O/alkane, without without organic solvents)organic solvents) and in CH and3CN, in inCH theCN, presence in the ofpresence6 as catalyst, of 6 as and catalyst, oxalic acidand asoxalic additive acid [as68 ].additive The latter, [68]. used The as latter, co-catalytic used additive,as co-catalytic led to higheradditive, hydroxylation led to higher stereospecificities hydroxylation thanstereospecificities acetic acid (cis -1,2-dimethylcyclohexanethan acetic acid (cis-1,2-dimethylcyclohexane oxidation, 80% retention ofoxidation, configuration, 80%RC retention, with oxalic of acidconfiguration, vs. 48% RCRC,with with aceticoxalic acid).acid vs. Alkylhydroperoxides 48% RC with acetic wereacid). theAlkylhydroperoxides primary reaction products;were the theyprimary decomposed reaction products; in the course they ofdecomposed the reaction in tothe the course corresponding of the reaction ketones to the and corresponding alcohols [68]. Crucially,ketones and screening alcohols a[68]. series Crucially, of different screening (including a series aromatic) of different carboxylic (including acid aromatic) additives carboxylic revealed pyrazine-2,3-dicarboxylicacid additives revealed pyrazine-2,3-dicarboxylic and trifluoroacetic acids as and extremely trifluoroacetic efficient acids co-catalysts as extremely [69,70]. efficient co-catalysts [69,70]. Kim and co-workers studied the reactivity of the catalyst system 6/H2O2 (with the Mn catalyst prepared in situ) towards cyclohexane in aqueous acetone in the presence of several carboxylic acids and their sodium salts [71]. In all cases, cyclohexanone was the major reaction product. Molecules 2016, 21, 1454 5 of 16

Molecules 2016, 21, 1454 5 of 16

Kim and co-workers studied the reactivity of the catalyst system 6/H2O2 (with the Mn catalyst Interestingly,prepared in situ) in towardsthe presence cyclohexane of sodium in aqueous oxalate, acetone the oxidation in the presence of hexane of several demonstrated carboxylic a acidshigh selectivityand their sodium for saltshexanones [71]. In all(Table cases, cyclohexanone2, entry 3), was theand major the reactionoxidation product. of Interestingly,cis- and transin the-1,2-dimethylcyclohexanes presence of sodium oxalate, was highly the oxidation stereoretentive of hexane (>99% demonstrated RC), which, ain high combination selectivity with for thehexanones relatively (Table high2, entrykH/kD 3),for and cylcohexane the oxidation oxidation of cis- and(2.7),trans may-1,2-dimethylcyclohexanes be considered as evidence was against highly radicalstereoretentive type oxidation (>99% mechanismRC), which, [71]. in combination with the relatively high kH/kD for cylcohexane oxidationSrinivas (2.7), and may co-workers be considered examined as evidence the benzylic against oxidations radical type in oxidation the presence mechanism of a Mn [71 complex]. preparedSrinivas in situ and from co-workers Me3tacn examinedand MnSO the4 [72]. benzylic Ethylbenzene oxidations oxidations in the presencewith H2O of2 proceeded a Mn complex with goodprepared acetophenone in situ from selectivities, Me3tacn and while MnSO the 4addition[72]. Ethylbenzene of carboxylate oxidations buffers increased with H2O 2theproceeded yield of 1-phenylethanolwith good acetophenone (Table 2, selectivities,entry 4). High while ketone the se additionlectivities of carboxylatewere reported buffers for benzylic increased oxidations, the yield catalyzedof 1-phenylethanol by 6, in the (Table presence2, entry of trichloroacetic 4). High ketone acid selectivities [73]. were reported for benzylic oxidations, catalyzedA set byof 6Me, in3tacn the presencederivatives, of trichloroacetic including optically acid [ 73pure]. structures of the type 8 (Figure 3), were preparedA set and of tested Me3tacn as ligands derivatives, in Mn-catalyzed including optically oxidation pure of isopropyl structures alcohol of the and type several8 (Figure alkanes3), withwere H prepared2O2, either and with tested oxalate as ligandsor with ascorbic in Mn-catalyzed acid as co-catalysts oxidation [74]. of isopropyl alcohol and several 2 2 3 alkanesOverall, with HC–H2O2 ,oxidations either with with oxalate H orO with in the ascorbic presence acid of as co-catalystsMn complexes, [74]. ligated by Me tacn derivatives,Overall, has C–H been oxidations rather extensively with H2 Ostudied.2 in the To presence date, there of Mnare no complexes, decisive data ligated on the by common Me3tacn oxidationderivatives, mechanism, has been rather which, extensively owing to studied.the involvement To date, thereof atmospheric are no decisive dioxygen, data on appears the common to be veryoxidation complex. mechanism, The provisional which, owing mechanistic to the involvement picture can ofbe atmosphericfound in [62,66]. dioxygen, In [65,66], appears one to can be veryalso findcomplex. a useful The synopsis provisional of mechanisticearly Mn-Me picture3tacn type can becatalyst found systems, in [62,66 ].capable In [65 ,66of ],conducting one can also various ﬁnd a 2 2 oxidativeuseful synopsis transformations, of early Mn-Me using3 tacnH O type as oxidant. catalyst systems, capable of conducting various oxidative transformations, using H2O2 as oxidant. 4. C–H Oxidations with H2O2 in the Presence of Mn Complexes with N,O Donor Ligands 4. C–H Oxidations with H O in the Presence of Mn Complexes with N,O Donor Ligands Fernandes and co-workers2 2 reported the water-soluble manganese(II) complex with ligand 9 (FigureFernandes 4), of the and type co-workers [(9)Mn(η1-NO reported3)(η2-NO the3)], water-soluble which catalyzed manganese(II) the oxidation complex of cyclohexane with ligand with9 H(Figure2O2 (at4), 50 of the°C) type in CH [( 93)Mn(CN ηor1-NO in 3tBuOH)(η2-NO [75].3)], whichModerate catalyzed efficiencies the oxidation were reported of cyclohexane (up to with 62 ◦ turnovers),H2O2 (at 50 C)with in CH 3cyclohexylCN or in tBuOH hydroper [75]. Moderateoxide efﬁcienciesas the weremajor reported product (up to 62[75]. turnovers), The cyclohexanol/cyclohexanonewith cyclohexyl hydroperoxide ratios as thewere major in the product range 1.3-1.4, [75]. The indicating cyclohexanol/cyclohexanone a sizeable contribution ratios of a radicalwere in oxidation the range pathway. 1.3-1.4, indicating a sizeable contribution of a radical oxidation pathway.

Figure 4. StructuresStructures of Mn complexes with N,O-donor ligands.

Ogawa and co-workers contributed contributed Mn Mn complex complex 1010 (Figure(Figure 44)) withwith aa macrocyclicmacrocyclic ligand,ligand, which catalyzed the oxidation of C–H groups in different hydrocarbons (cyclohexane, cyclooctane, ethylbenzene, benzene), benzene), performing performing up up to to 9 9 catalytic catalytic cycles cycles without without any any co-catalytic co-catalytic additives additives [76]. [76]. For the oxidations of cyclohexane and cyclooctane,cyclooctane, alcohol/ketone ratios ratios of of 19 19 and and 8.2 were documented, without reported formation of cycloalkyl hydroperoxides [[76].76]. In 1997, Mn-Salen Mn-Salen type type complexes complexes 1111 and 12 were mentioned to catalyze the oxidation of ethylbenzene (preferentiall (preferentiallyy to acetophenone) with H2OO22; ;it it is is questionable, questionable, however, however, whether this oxidation can be considered “catalytic” since the reported turnover numbers (TNs) were less than unity [[77].77]. MuchMuch later,later, complex complex13 13was was shown shown to catalyzeto catalyze benzylic benzylic oxidations oxidations with with unexpectedly unexpectedly high high efficiency (up to several thousand TN) in acetonitrile at room temperature, without any co-catalysts, affording ketones with high selectivity (Table 2, entry 5) [78]. The reaction required a high excess of H2O2 (10–20 mol per mol of substrate). Apparently, pronounced decomposition of Molecules 2016, 21, 1454 6 of 16 efﬁciency (up to several thousand TN) in acetonitrile at room temperature, without any co-catalysts, affordingMolecules 2016 ketones, 21, 1454 with high selectivity (Table2, entry 5) [ 78]. The reaction required a high excess6 of of16 H2O2 (10–20 mol per mol of substrate). Apparently, pronounced decomposition of (added in one portion)(added in hydrogen one portion) peroxide hydrogen occurred. peroxide A series occurred. of structurally A series related of structurally salen and related salan (tetrahydrosalen) salen and salan complexes(tetrahydrosalen) were studied complexes as catalysts were instudied the oxidation as catalysts of diphenylmethane in the oxidation [79 of]. Thediphenylmethane ligand structure [79]. has beenThe ligand shown tostructure have crucial has been effect shown on the oxidationto have selectivitycrucial effect (the on benzophenone:diphenylmethanol the oxidation selectivity (the ratiobenzophenone:diphenylmethanol varying from 100:0 to 15:85). ratio varying from 100:0 to 15:85).

Table 2.2. Examples of C–HC–H oxidationsoxidations catalyzedcatalyzed by MnMn complexescomplexes withwith MeMe33tacn derived and with N,O-donor ligands.

a No.No. Cat. Cat. Substrate Substrate Additive Additive Products Products (yield (yield )a) Ref.Ref. 1 6 hexane AcOH hexanones (775), hexanols (575) [59] 1 6 hexane AcOH hexanones (775), hexanols (575) [59] 2 6 ethane (20 bar) AcOH EtOOH (260), EtOH (120), MeCHO (20) [64] 2 6 ethane (20 bar) AcOH EtOOH (260), EtOH (120), MeCHO (20) [64] 3 3 6 6 hexanehexane Na Na oxalate oxalate 2-hexanol 2-hexanol (4.5), (4.5), 3-hexanol 3-hexanol (4.5), (4.5), 2-hexanone 2-hexanone (29), (29), 3-hexanone 3-hexanone (29) (29) [ [71]71] 4 4 6 6 ethylbenzeneethylbenzene oxalate oxalate buffer buffer 1-phenylethanol 1-phenylethanol (48.5), (48.5), acetophenone acetophenone (102) (102) [ [72]72] 6 6 13 13 ethylbenzeneethylbenzene none none 1-phenylethanol 1-phenylethanol (7), (7), acetophenone acetophenone (683) (683) [ [78]78] a Yielda Yield of of oxygenated oxygenated products products is given is given in mol/mol in mol/mol Mn. Mn.

5. C–H C–H Oxidations Oxidations with with H H2O2O2 2inin the the Presence Presence of of Mn Mn Complexes Complexes with with Aminopyridine Aminopyridine Ligands Ligands

The current renascence of thethe MnMn catalyzedcatalyzed selectiveselective C–HC–H oxidationsoxidations withwith HH22OO22 is associatedassociated with the appearanceappearance ofof MnMn aminopyridineaminopyridine complexes.complexes. Initially, Costas and co-workers reported that complexescomplexes [(Me[(Me22Py-tacn)Mn(CF3SOSO33))2]2 ]((1414)) and and [((S,S)-bpmcn)Mn(CF33SOSO33)2)]2 ]((1515) )(Figure (Figure 55)) demonstrated moderate moderate oxidation oxidation reactivity reactivity towards towards cis-cis-1,2-dimethylcyclohexane1,2-dimethylcyclohexane (with (with 1% 1%and and8% 8%yields, yields, respectively) respectively) [80]. [80We]. also We alsohave haveto ment to mentionion the report the report by Golchoubian by Golchoubian and Ghasemi, and Ghasemi, who whoexamined examined the oxidation the oxidation of diphenylmethane of diphenylmethane with with a series a series of ofMn Mn complexes complexes with with N N44-donor-donor ligands, ligands, including two aminopyridine, ligands (complexes 16, 17)[) [79].79]. With both complexes, alcohol was preferentially formed [[79]79] (Table(Table3 3,, entry entry 1). 1).

Figure 5. Structures of Mn complexes with aminopyridine ligands.

Bryliakov and co-workers documented excellent catalytic efﬁciencies in the oxidations of ◦ ◦ a variety of 2 and 3 alkane C–H groups with H2O2, catalyzed by complexes 15, 18 and 19 Molecules 2016, 21, 1454 7 of 16

MoleculesBryliakov2016, 21, 1454 and co-workers documented excellent catalytic efficiencies in the oxidations7 of 16of a variety of 2° and 3° alkane C–H groups with H2O2, catalyzed by complexes 15, 18 and 19 in the presence of acetic acid [81]. The Mn complexes performed up to 970 catalytic cycles. in the presence of acetic acid [81]. The Mn complexes performed up to 970 catalytic cycles. Cyclohexanol/cyclohexanone ratios of 4.9-5.1 and high 3°/2° selectivities of adamantane oxidation Cyclohexanol/cyclohexanone ratios of 4.9-5.1 and high 3◦/2◦ selectivities of adamantane oxidation (40–49) pointed to a metal-mediated rather than a radical-driven oxidation mechanism. The high (40–49) pointed to a metal-mediated rather than a radical-driven oxidation mechanism. The high sensitivity of the oxygen-transferring species to electronic effects, and high selectivity and sensitivity of the oxygen-transferring species to electronic effects, and high selectivity and stereospecificity (>99% RC) in the oxidation of cis-1,2-dimethylcyclohexane also support the stereospecificity (>99% RC) in the oxidation of cis-1,2-dimethylcyclohexane also support the metal-mediated oxidation mechanism [81]. Under “practical” conditions, methylenic CH2 groups metal-mediated oxidation mechanism [81]. Under “practical” conditions, methylenic CH groups preferentially converted to ketone functionalities (Table 4, entry 1) [81]. 2 preferentially converted to ketone functionalities (Table4, entry 1) [81]. More recently, Sun with co-workers reported the catalyst system based on complex 20 (Figure 5) More recently, Sun with co-workers reported the catalyst system based on complex 20 [82]. In the presence of acetic acid as additive, the latter efficiently (up to 154 TN) catalyzed the (Figure5)[ 82]. In the presence of acetic acid as additive, the latter efficiently (up to 154 TN) catalyzed oxygenation of secondary benzylic and aliphatic C–H bonds, with preferential formation of ketones the oxygenation of secondary benzylic and aliphatic C–H bonds, with preferential formation of ketones (Table 3, entry 2). The same catalyst has shown good catalytic efficiency in the oxidation of (Table3, entry 2). The same catalyst has shown good catalytic efficiency in the oxidation of secondary secondary alcohols, performing up to 4700 catalytic turnovers [83]. Another laboratory has reported alcohols, performing up to 4700 catalytic turnovers [83]. Another laboratory has reported the oxidation the oxidation of alcohols with H2O2 in the presence of Mn complex, formed in situ from ligand 21 of alcohols with H2O2 in the presence of Mn complex, formed in situ from ligand 21 (Figure5) (Figure 5) and Mn(OTf)2 [84], with substantially lower catalytic efficiencies. The authors screened a and Mn(OTf) [84], with substantially lower catalytic efficiencies. The authors screened a series of series of different2 carboxylic acid additives, of which adamantane carboxylic acid was chosen as different carboxylic acid additives, of which adamantane carboxylic acid was chosen as ensuring the ensuring the highest yield of ketone. Interestingly, the oxidation of substrates bearing both olefinic highest yield of ketone. Interestingly, the oxidation of substrates bearing both olefinic and primary or and primary or secondary alcoholic moieties, proceeded selectively towards the formation of secondary alcoholic moieties, proceeded selectively towards the formation of α,β-unsaturated carbonyl α,β-unsaturated carbonyl compounds [84]. compounds [84]. Bryliakov and co-workers synthesized complexes 22 and 23, bearing electron-donating Bryliakov and co-workers synthesized complexes 22 and 23, bearing electron-donating substituents, that exhibited superior efficiencies (as compared with catalysts 15, 18, 19) in benzylic substituents, that exhibited superior efficiencies (as compared with catalysts 15, 18, 19) in benzylic oxidations (Table 3, entries 6 and 7) [85]. Cumenes were oxidized preferentially into the oxidations (Table3, entries 6 and 7) [ 85]. Cumenes were oxidized preferentially into the corresponding corresponding alcohols, while ethylbenzene afforded mostly acetophenone. alcohols, while ethylbenzene afforded mostly acetophenone. Recently, a comparative study by Malik and co-workers revealed the most evident advantages Recently, a comparative study by Malik and co-workers revealed the most evident advantages of of the catalyst systems based on the [((S,S)-pdp)Mn(OTf)2] type complexes (19, 20, 22–24, Figure 4) the catalyst systems based on the [((S,S)-pdp)Mn(OTf) ] type complexes (19, 20, 22–24, Figure4)[ 86]. [86]. Within the range of practically promising catalyst2 systems studied, the Mn-aminopyridine Within the range of practically promising catalyst systems studied, the Mn-aminopyridine catalysts catalysts (1) are used in very small amount (0.1 mol %; structurally similar Fe complexes are (1) are used in very small amount (0.1 mol %; structurally similar Fe complexes are typically used in up typically used in up to 15 mol % loadings [29–34]); (2) require a small (1.3 equiv.) excess of the to 15 mol % loadings [29–34]); (2) require a small (1.3 equiv.) excess of the green oxidant—commercially green oxidant—commercially available 30% aqueous H2O2; and (3) exhibit reasonably high yields in available 30% aqueous H O ; and (3) exhibit reasonably high yields in the oxidation of differently the oxidation of differently2 2 p-substituted cumenes, ensuring high cumyl alcohol selectivity [86]. p-substituted cumenes, ensuring high cumyl alcohol selectivity [86]. So far, Mn catalyzed selective oxidative syntheses of complex organic molecules, such as So far, Mn catalyzed selective oxidative syntheses of complex organic molecules, such as natural natural products, or biologically active compounds, have been rarely reported. A few procedures products, or biologically active compounds, have been rarely reported. A few procedures are collected are collected in Scheme 1. We expect the emergence of other practically relevant examples in the in Scheme1. We expect the emergence of other practically relevant examples in the near future. near future.

H H OH 19 (0.1 mol %) OAc OAc OAc Ref. [81] CH CN / AcOH 3 + H2O2 (1.3 equiv) 0°C H OH H

(-)-acetoxy-p-menthane 68 % 1.2 %

PivO PivO 20 (0.5 mol %)

Ref. [82] CH3CN / AcOH H2O2 (1.3 equiv) r.t. OH

cis-4-methylcyclohexyl- 35 % 1-pivalate

SchemeScheme 1. Cont. 1. Cont. Molecules 2016, 21, 1454 8 of 16 Molecules 2016, 21, 1454 8 of 16

H 22 (0.1 mol %) H Ref. [85] CH3CN / AcOH O H H O H2O2 (3 equiv) O 15 °C (-)-ambroxide (+)-sclareolide 52 % (isolated)

22 O NaOH O (2*0.1 mol %) O ONa HO CH3CN / AcOH [This work] γ O H2O2 (4.8 equiv) -butyrolactone tetrahydrofurane 0°C 47 % sodium oxybate + (used to treat excessive daytime spleepiness) O OH

30 %

Scheme 1. Examples of selective C–H oxidations of practical synthetic relevance in the presence of Schemeaminopyridine 1. Examples Mn complexes. of selective C–H oxidations of practical synthetic relevance in the presence of aminopyridine Mn complexes.

6. Elucidation of the Mechanism of C–H Oxidations with H2O2 in the Presence of Mn Complexes 6. Elucidation of the Mechanism of C–H Oxidations with H2O2 in the Presence of Mn Complexes So far, experimental data on the mechanism(s) of C–H oxygenation with H2O2 in the presence of MnSo far, complexes experimental have data been on rather the me restrictedchanism(s) in of the C–H literature. oxygenation On thewith basis H2O2of in indirectthe presence data, ofit Mn has complexes been generally have assumedbeen rather (see restricted Section 2in) thatthe literature. high-valent On Mn-oxo the basis complexes of indirect (presumably data, it has been[(L)Mn generallyV=O] or [(Lassumed•+)MnIV =O])(see areSection the most 2) likelythat activehigh-valent species inMn-oxo the catalyst complexes systems (presumably based on Mn [(L)MnV=O] or [(L•+)MnIV=O]) are the most likely active species in the catalyst systems based on MnV porphyrins/H2O2/additive (for mechanistic considerations and precedents of porphyrinic Mn O porphyrins/Hcomplexes see2O [212/additive,39,52,57 ](for and mechanistic references therein. considerations and precedents of porphyrinic MnVO complexes see [21,39,52,57] and references therein. On the contrary, catalyst systems based on Mn-Me3tacn type complexes exhibit various characteristicsOn the contrary, of radical-type catalyst mechanism systems (Sectionbased 3on), whichMn-Me may3tacn be evidencetype complexes of significant exhibit contribution various characteristicsof free-diffusing-radicals of radical-type into the mechanism oxidation outcome.(Section 3), which may be evidence of significant contributionTo date, of it free-di is onlyffusing-radicals the mechanism into of catalytic the oxidation C–H hydroxylation outcome. on Mn-aminopyridine catalysts To date, it is only the mechanism of catalytic C–H hydroxylation on Mn-aminopyridine that has been studied in more detail [85]; in particular, the analysis of kinetic isotope effect (kH/kD), catalystsisotopic labelingthat has data,been andstudied linear in free more energy detail relationships [85]; in particular, has been the reported. analysis Theof kinetic crucial isotope findings effect were (kH/kD), isotopic labeling data, and linear free energy relationships has been reported.2 The crucial the observation of (1) a primary kH/kD of 3.5–3.9 for the oxidation of cumene/α- H-cumene, indicating findingsthat the hydrogenwere the atom observation lies on the of reaction (1) a coordinate primary andkH/k participatesD of 3.5–3.9 in C–Hfor bondthe oxidation breaking step;of 2 cumene/(2) linearα- HammettH-cumene, correlation indicating for that the oxidationthe hydrogen of a series atom of liesp-substituted on the reaction cumenes, coordinate with the ρand+ of participates−1.0, witnessing in C–H electrophilic bond breaking active step; species, (2) andlinear electron-deficient Hammett correlation transition for state;the oxidation (3) linear of correlation a series + ofbetween p-substituted the C–H cumenes, bond dissociation with theenergies ρ of − (BDEs)1.0, witnessing of the substrates electrophilic and the active logarithms species, of ratesand electron-deficientof their oxidations, transition reflecting state; a common (3) linear oxidation correlation mechanism; between the and C–H (4) partialbond dissociation incorporation energies of 18O (BDEs)from added of the18 O-labeledsubstrates water and intothe thelogarithms hydroxylated of rates product, of their supporting oxidations, the “water-assisted”reflecting a common [87,88] 18 18 oxidationpathway formechanism; the formation and (4) of active,partial presumably incorporation oxomanganese(V), of O from added species O-labeled [85]. In water the presence into the of hydroxylatedcarboxylic acid product, additive, supporting the mechanism the “water-assis of formationted” ofthe [87,88] active pathway species isfor diverted the formation to the “carboxylic of active, presumablyacid assisted” oxomanganese(V), one (Scheme2)[ 44 species,89–92]. [85]. The hydroxylationIn the presence step of has carboxylic been concluded acid toadditive, proceed the via mechanismthe rebound of mechanism formation (Schemeof the active3, top). species This mechanistic is diverted landscape to the “carboxylic apparently acid dominates assisted” for one the (Schemeoxidation 2) of [44,89–92]. unactivated The C–H hydroxylation groups in aliphatic step ha compounds.s been concluded to proceed via the rebound mechanismVery recently, (Scheme the 3, mechanismtop). This mechanistic of formation landscape of the minor apparently oxidation dominates product—cumyl for the oxidation acetate hasof unactivatedbeen studied C–H in detail groups [93 in]. aliphatic Counter tocompounds. the earlier expectations [85], the possibility of esterification of the initiallyVery recently, formed the alcohol mechanism has been of ruledformation out since of the separate minor experimentsoxidation product—cumyl have shown that acetate under has the been studied in detail [93]. Counter to the earlier expectations [85], the possibility of esterification of the initially formed alcohol has been ruled out since separate experiments have shown that under Molecules 2016, 21, 1454 9 of 16 Molecules 2016,, 21,, 14541454 9 of 16 theoxidation oxidation conditions, conditions, cumyl cumyl alcohol alcohol does notdoes react not withreact acetic with acid.acetic Moreover, acid. Moreover, the isotopic the labelingisotopic labelingdata witness data thatwitness both that oxygen both atoms oxygen of atoms the acetate of th steme acetate exclusively stem exclusively from the aceticfrom the acid acetic molecule, acid whichmolecule, does which not conform does not to conform the common to the Fischer common esterification Fischer esterifica mechanismtion mechanism [93]. [93].

H2O H2O

LMnV O LMnV O O O O O R R R1-H III R1-H III LMnIII O H O LMnIII OOH HOOCR LMn O H2O2 LMn OOH HOOCR OH II 2 2 O OH [(L)MnIIX2] MeCN O [(L)Mn X2] MeCN H H R O R O R1-OH R1-OH

LMnIII O LMnIII O O O R R

H2O2 H2O2 Scheme 2. Proposed catalytic cycle for the selective C–H oxidations with H2O2 in the presence of Scheme 2. Proposed catalytic cycle for the selective C–H oxidations with HH22O2 inin the presence of aminopyridine manganese complexes andand carboxyliccarboxylic acidacid RCOOH.RCOOH.

Scheme 3. The proposed mechanism of Mn catalyzed C–H hydroxylation. Scheme 3. The proposed mechanism of Mn catalyzed C–H hydroxylation.

It has been concluded that the only feasible possibility remaining is the direct formation of the It has been concluded that the only feasible possibility remaining is the direct formation of the ester after the H abstraction step, via transfer of the acetoxy radical to the intermediate ester afterafter the the H abstractionH abstraction step, viastep, transfer via transfer of the acetoxy of the radical acetoxy to the radical intermediate to the carbon-centered intermediate carbon-centered organic radical. Based on the catalytic, isotopic labeling, and density functional carbon-centeredorganic radical. Basedorganic on ra thedical. catalytic, Based isotopic on the labeling,catalytic, and isotopic density labeling, functional and theorydensity (DFT) functional study, theory (DFT) study, the authors have proposed the “bifurcated rebound mechanism” (Scheme 3, theorythe authors (DFT) have study, proposed the authors the “bifurcated have proposed rebound the mechanism” “bifurcated (Schemerebound3 ,mechanism” bottom) which (Scheme explains 3, bottom) which explains the observed acetate formation [93]. One of the two alternative rebound bottom)the observed which acetate explains formation the observed [93]. One acetate of the form twoation alternative [93]. One rebound of the pathways,two alternative conducted rebound by pathways, conducted by the intermediate [(PDP)MnIV–OH(OC(O)R)] (Scheme 3) leads to the pathways,the intermediate conducted [(PDP)Mn by theIV–OH(OC(O)R)] intermediate (Scheme[(PDP)Mn3)IV leads–OH(OC(O)R)] to the alcohol (Scheme product, 3) andleads the to other, the alcohol product, and the other, associated with the intermediate [(PDP)MnIII–OH(OC(O•)R)]) alcoholassociated product, with the and intermediate the other, [(PDP)MnassociatedIII –OH(OC(Owith the intermediate•)R)]) affords [(PDP)Mn the ester.III–OH(OC(O The competitive•)R)]) affords the ester. The competitive •OC(O)R/•OH transfer has so far been unprecedented for affords•OC(O)R/ the• OHester. transfer The hascompetitive so far been •OC(O)R/ unprecedented•OH transfer for bioinspired has so far oxidations been unprecedented in the presence for of bioinspired oxidations in the presence of non-heme Fe and related Mn complexes, for which effect bioinspirednon-heme Fe oxidations and related in Mnthe complexes,presence of fornon-heme which effect Fe and the related term “bifurcated Mn complexes, rebound for which mechanism” effect the term “bifurcated rebound mechanism” has been proposed [93]. thehas term been “bifurcated proposed [93 rebound]. mechanism” has been proposed [93]. In the series of the Mn complexes studied, catalyst 24 (with the strongest electron-donor In the series of thethe MnMn complexescomplexes studied,studied, catalyst 24 (with the strongest electron-donor substituents) afforded the highest alcohol/acetate ratio (Table 3, entry 8 vs. entries 6, 7). The substituents) affordedafforded the the highest highest alcohol/acetate alcohol/acetate ratio ratio (Table (Table3, entry 3, 8entry vs. entries 8 vs. 6, entries 7). The oxidations6, 7). The oxidations of cumene with H2O2 in the presence of a series of different aliphatic carboxylic acids oxidationsof cumene withof cumene H O in with the presenceH2O2 in the of a presence series of differentof a series aliphatic of different carboxylic aliphatic acids carboxylic were conducted acids were conducted (Table2 2 4) [93]. The yield of the ester was lower (and the alcohol/ester ratio was (Tablewere conducted4)[ 93]. The (Table yield of4) the[93]. ester The was yield lower of the (and ester the alcohol/esterwas lower (and ratio the was alcohol/ester higher) for carboxylicratio was higher) for carboxylic acids with tertiary α-carbon, as compared to those with primary or secondary higher)acids with for tertiarycarboxylicα-carbon, acids with as compared tertiary α-carbon, to those as with compared primary to or those secondary with primaryα-carbon or (cf.secondary entries α-carbon (cf. entries 4–8 vs. 1–3). The highest alcohol/ester ratio of 44.7 has been documented for the α4–8-carbon vs. 1–3 (cf.). entries The highest 4–8 vs. alcohol/ester 1–3). The highest ratio alcoho of 44.7l/ester has beenratio documentedof 44.7 has been for documented the oxidation for with the oxidation with 2-ethylbutyric acid (EBA, Table 4, entry 8). The lowest yield of ester for the acids III • with tertiary α-C may be due to additional stabilization of the [(PDP)MnIII–OH(OC(O•)R)] intermediate, owing to the existence of tautomeric, α-C-centered radical species, attenuating its Molecules 2016, 21, 1454 10 of 16

2-ethylbutyric acid (EBA, Table4, entry 8). The lowest yield of ester for the acids with tertiary α-C may be due to additional stabilization of the [(PDP)MnIII–OH(OC(O•)R)] intermediate, owing to the Molecules 2016, 21, 1454 10 of 16 existence of tautomeric, α-C-centered radical species, attenuating its reactivity. The use of branched reactivity.(with tertiary The αuse-carbon of branched atom) carboxylic(with tertiary acids α-carbon can be atom) recommended carboxylic for acids practical can be hydroxylations, recommended forin orderpractical to improve hydroxylations, the alcohol in order formation to improve selectivity. the alcohol formation selectivity.

Table 3. Examples of C–H oxidations catalyzed by Mn aminopyridine complexes. Table 3. Examples of C–H oxidations catalyzed by Mn aminopyridine complexes.

No.No. Cat. Cat. Substrate Substrate Additive AdditiveProducts Products (yield a a)) Ref.Ref. 1 1 17 17 diphenylmethanediphenylmethane nonenone benzophenone benzophenone (250), (250), diphenylmethanol (530) (530) [79 [79]] 2 2 19 19 cyclohexanecyclohexane AcOH AcOH cyclohexanol cyclohexanol (28), (28), cyclohexanone (842) (842) [81 [81]] 3 3 20 20 cyclohexanecyclohexane AcOH AcOH cyclohexanone cyclohexanone (122)(122) [82 [82]] 4 4 20 20 1-Ph-ethanol1-Ph-ethanol AcOH AcOH acetophenone acetophenone (4700)(4700) [83 [83]] 5 21/Mn(OTf)2 cyclohexanol Ada-COOH cyclohexanone (38) [84] 5 6 21/Mn(OTf)19 2 cyclohexanolcumene Ada-COOH AcOH cumyl alcohol cyclohexanone (209), cumyl (38) acetate (139) [93 [84]] 6 7 19 23 cumenecumene AcOH AcOH cumyl alcohol cumyl (560),alcohol cumyl (209), acetate cumyl (75), acetate acetophenone (139) (30) [85 [93]] 7 8 23 24 cumenecumene AcOH AcOH cumyl cumyl alcohol alcohol (560), (492), cumyl acetateacetate (61), (75), acetophenone acetophenone (110) (30) [93 [85]] 8 24 cumenea Yield of oxygenated AcOH products cumyl alcohol is given (492), in mol/mol cumyl acetate Mn. (61), acetophenone (110) [93] a Yield of oxygenated products is given in mol/mol Mn.

Table 4. Oxidation of cumene with H2O2 in the presence of complex 25 and various carboxylic Table 4. Oxidation of cumene with H2O2 in the presence of complex 25 and various carboxylic acids [93]. acids [93].

NoNo Additive Conversion Conversion (%) (%) Yi Yieldeld of of Alcohol/Acetate/Other Alcohol/Acetate/Other a a(%)(%) Alcohol/Ester Alcohol/Ester Ratio Ratio 11 AA 82.9 82.9 62.9/12.1/7.9 62.9/12.1/7.9 5.2/1 5.2/1 22 BA 74.7 74.7 60.2/7.3/7.2 60.2/7.3/7.2 8.2/1 8.2/1 33 CA 56.5 56.5 46.6/4.3/5.6 46.6/4.3/5.6 10.8/1 10.8/1 44 CHA 34.3 34.3 30.3/2.0/2.0 30.3/2.0/2.0 15.4/1 15.4/1 55 IBA 61.8 61.8 51.7/3.2/6.9 51.7/3.2/6.9 16.2/1 16.2/1 66 EHA 29.8 29.8 26.1/1.6/2.1 26.1/1.6/2.1 16.3/1 16.3/1 77 PVA 38.6 38.6 34.5/0.9/3.2 34.5/0.9/3.2 36.7/1 36.7/1 88 EBA 39.2 39.2 35.4/0.8/3.0 35.4/0.8/3.0 44.7/1 44.7/1 a a sideside product: product: acetophenone. acetophenone.

7.7. Experimental Experimental Conditions Conditions OxidationOxidation of of tetrahydrofuran tetrahydrofuran (THF) (THF) to to γγ-butyrolactone-butyrolactone was was performed performed as as follows: follows: a a solution solution of of freshly distilled THF (40.5 µL, 500 µmol) and of manganese complex 22 (0.5 µmol) in CH CN (0.40 mL) freshly distilled THF (40.5 μL, 500 μmol) and of manganese complex 22 (0.5 μmol) in 3CH3CN (0.40 and AcOH (28.6 µL, 500 µmol) was thermostatted at 0 ◦C. 30% aqueous H O (1200 µmol, dissolved in mL) and AcOH (28.6 μL, 500 μmol) was thermostatted at 0 °C. 30% 2aqueous2 H2O2 (1200 μmol, CH CN, total volume 200 µL) was delivered to this mixture with a syringe pump over 60 min at 0 ◦C. dissolved3 in CH3CN, total volume 200 μL) was delivered to this mixture with a syringe pump over 60Then, min theat 0 second °C. Then, portion the second of manganese portion complexof manganese22 (0.5 complexµmol) was 22 (0.5 added, μmol) followed was added, by the followed syringe by the syringe pump addition (over 60 min) of the second portion of H2O2 (1200 μmol, 200 μL of solution in CH3CN). The mixture was stirred for additional 2 h at 0 °C. An internal standard (1,4-dioxane) was added and the mixture was subjected to gas chromatography–mass spectrometry (GC-MS) analysis. Molecules 2016, 21, 1454 11 of 16

pump addition (over 60 min) of the second portion of H2O2 (1200 µmol, 200 µL of solution in CH3CN). The mixture was stirred for additional 2 h at 0 ◦C. An internal standard (1,4-dioxane) was added and the mixture was subjected to gas chromatography–mass spectrometry (GC-MS) analysis.

8. Conclusions and Outlook Synthetic complexes of Mn with polydentate ligands demonstrate the ability to act as biomimetic catalysts of direct C–H oxidation with H2O2, converting organic molecules into the oxygenated products (alcohols, ketones, and others). To date, the available library of catalytically active Mn complexes is rather wide, providing catalysts suited for C–H oxidations, ranging from the oxidation of benzylic C–H groups, through unactivated aliphatic C–H, to C–H groups of arenes. The oxidations typically proceed in a selective (and sometimes enantioselective [57,58]) fashion. As a general trend, Mn based catalysts demonstrate higher (even much higher) oxidation efﬁciencies as compared to their Fe based structural analogs, with retention of similarly high selectivity. Moreover, in some cases Mn catalysts require a smaller excess of H2O2, down to only 1.3 equiv. relative to substrate. The mechanisms of Mn-catalyzed C–H oxidations (generally taken, i.e., the mechanism of active species formation and the mechanisms of C–H activation and functionalization) have so far been rather underinvestigated. The data available to date give evidence for close similarities between the mechanistic landscapes of C–H oxidations in the presence of Fe- and Mn-aminopyridine complexes; providing indirect proof for the oxomanganese(V) active species. An important distinctive feature of Mn-aminopyridine based catalysts is the possibility of existence of two alternative reaction pathways, one leading to the formation of alcohol, and the other to the ester. The mechanism of the ester formation has been proposed, assuming competitive •OC(O)R/•OH transfer to the alkyl radical formed at the H abstraction step. This mechanism, unprecedented for bioinspired oxidations in the presence of non-heme Fe and related Mn complexes, is proposed to be called “bifurcated rebound mechanism”. Mn based catalysts for selective C–H oxidations with H2O2 provide novel opportunities for direct (without coordination of the substrate to the catalyst or formation of metal-carbon bond) functionalization of C–H bonds. Although at the current, laboratory stage of their development, the oxidations with H2O2 have not yet been reported to generate technically useful amounts of required oxygenated materials [94], the authors believe that Mn based “green” C–H oxidation systems will go beyond the laboratory scale in the near future.

Acknowledgments: This work was partially supported by the Russian Academy of Sciences and Federal Agency of Scientific Organizations (project V.44.2.4). The authors also acknowledge the support from the Russian Foundation for Basic Research (grant 16-29-10666). Author Contributions: The authors equally contributed to this work. Conflicts of Interest: The authors declare no conflict of interest.

References

1. Shilov, A.E.; Shul’pin, G.B. Activation of C–H bonds by metal complexes. Chem. Rev. 1997, 97, 2879–2932. [CrossRef][PubMed] 2. Shilov, A.E.; Shteinman, A.A. Oxygen atom transfer into C–H bond in biological and model chemical systems. Mechanistic aspects. Acc. Chem. Res. 1999, 32, 763–771. [CrossRef] 3. Christmann, M. Selective Oxidation of Aliphatic C–H Bonds in the Synthesis of Complex Molecules. Angew. Chem. Int. Ed. 2008, 47, 2740–2742. [CrossRef][PubMed] 4. Newhouse, T.; Baran, P.S. If C–H Bonds Could Talk: Selective C–H Bond Oxidation. Angew. Chem. Int. Ed. 2011, 50, 3362–3374. [CrossRef][PubMed] 5. Che, C.M.; Kar-Yan Lo, V.; Zhou, C.Y.; Huang, J.S. Selective functionalisation of saturated C–H bonds with metalloporphyrin catalysts. Chem. Soc. Rev. 2011, 40, 1950–1975. [CrossRef][PubMed] 6. McMurray, L.; O’Hara, F.; Gaunt, M.J. Recent developments in natural product synthesis using metal-catalysed C–H bond functionalisation. Chem. Soc. Rev. 2011, 40, 1885–1898. [CrossRef][PubMed] Molecules 2016, 21, 1454 12 of 16

7. Yamaguchi, J.; Yamaguchi, A.D.; Itami, K. C–H Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals. Angew. Chem. Int. Ed. 2012, 51, 8960–9009. [CrossRef][PubMed] 8. Gunnoe, T.B. Alkane C–H Activation by Single-Site Metal Catalysis; Pérez, P.J., Ed.; Springer: Dordrecht, Germany, 2012; pp. 1–15. 9. Roduner, E.; Kaim, W.; Sarkar, B.; Urlacher, V.B.; Pleiss, J.; Gläser, R.; Einicke, W.D.; Sprenger, G.A.; Beifuß, U.; Klemm, E.; Liebner, C.; Hieronymus, H.; Hsu, S.F.; Plietker, B.; Laschat, S. Selective Catalytic Oxidation of C–H Bond with Molecular Oxygen. ChemCatChem 2013, 5, 82–112. [CrossRef] 10. Qiu, Y.; Gao, S. Trends in applying C–H oxidation to the total synthesis of natural products. Nat. Prod. Rep. 2016, 33, 562–581. [CrossRef][PubMed] 11. Shul’pin, G.B. New Trends in Oxidative Functionalization of Carbon-Hydrogen Bonds: A Review. Catalysts 2016, 6, 50. [CrossRef] 12. Gol’dshleger, N.F.; Tyabin, M.B.; Shilov, A.E.; Shteinman, A.A. Activation of Saturated Hydrocarbons. H/D Exchange in Solutions of Transition Metal Complexes. Zh. Fiz. Khim. 1969, 43, 2174–2175. (In Russian) 13. Periana, R.A.; Bergman, R.G. Oxidative Addition of Rhodium to Alkane C–H Bonds: Enhancement in Selectivity and Alkyl Group Functionalization. Organometallics 1984, 3, 508–510. [CrossRef] 14. Solomon, E.I.; Brunold, T.C.; Davis, M.I.; Kemsley, J.N.; Lee, S.K.; Lehnert, N.; Neese, F.; Skulan, A.J.; Yang, Y.S.; Zhou, J. Geometric and Electronic Structure/Function Correlations in Non-Heme Iron Enzymes. Chem. Rev. 2000, 100, 235–350. [CrossRef][PubMed] 15. Costas, M.; Chen, K.; Que, L., Jr. Biomimetic nonheme iron catalysts for alkane hydroxylation. Coord. Chem. Rev. 2000, 200, 517–544. [CrossRef] 16. Costas, M.; Mehn, M.P.; Jensen, M.P.; Que, L., Jr. Dioxygen Activation at Mononuclear Nonheme Iron Active Sites: Enzymes, Models, and Intermediates. Chem. Rev. 2004, 104, 939–986. [CrossRef][PubMed] 17. Tanase, S.; Bowman, E. Advances in Inorganic Chemistry; van Eldik, R., Reedijk, J., Eds.; Academic Press: Amsterdam, The Netherlands, 2006; pp. 29–75. 18. Battaini, G.; Granata, A.; Monzani, E.; Gullotti, M.; Casella, L. Advances in Inorganic Chemistry; van Eldik, R., Reedijk, J., Eds.; Academic Press: Amsterdam, The Netherlands, 2006; pp. 185–233. 19. Shteinman, A.A. Iron oxygenases: Structure, mechanism and modeling. Russ. Chem. Rev. 2008, 77, 945–966. [CrossRef] 20. Shul’pin, G.B. Hydrocarbon Oxygenations with Peroxides Catalyzed by Metal Compounds. Mini-Rev. Org. Chem. 2009, 6, 95–104. [CrossRef] 21. Costas, M. Selective C–H oxidation catalyzed by metalloporphyrins. Coord. Chem. Rev. 2011, 255, 2912–2932. [CrossRef] 22. Company, A.; Gómez, L.; Costas, M. Iron Containing Enzymes: Versatile Catalysts of Hydroxylation Reactions in Nature; de Visser, S.P., Kumar, D., Eds.; RCS Publishing: Cambridge, UK, 2011; pp. 148–208. 23. Talsi, E.P.; Bryliakov, K.P. Chemo- and stereoselective C–H oxidations and epoxidations/cis-dihydroxylations

with H2O2, catalyzed by non-heme iron and manganese complexes. Coord. Chem. Rev. 2012, 256, 1418–1434. [CrossRef] 24. Bryliakov, K.P. Environmentally Sustainable Catalytic Asymmetric Oxidations; CRC Press: Boca Raton, FL, USA, 2014; pp. 109–119. 25. Canta, M.; Rodriguez, M.; Costas, M. Recent Advances in the Selective Oxidation of Alkyl C–H Bonds Catalyzed by Iron Coordination Complexes. Top. Curr. Chem. 2016, 372, 27–54. [PubMed] 26. Afanasiev, P.; Sorokin, A.B. µ-Nitrido Diiron Macrocyclic Platform: Particular Structure for Particular Catalysis. Acc. Chem. Res. 2016, 49, 583–593. [CrossRef][PubMed] 27. Olivo, G.; Lanzalunga, O.; di Stefano, S. Non-Heme Imine-Based Iron Complexes as Catalysts for Oxidative Processes. Adv. Synth. Catal. 2016, 358, 843–863. [CrossRef] 28. Sheu, C.; Reichert, S.A.; Cofré, P.; Ross, B., Jr.; Sobkowiak, A.; Sawyer, D.T.; Kanofski, J.R. Iron-Induced

Activation of Hydrogen Peroxide for the Direct Ketonization of Methylenic Carbon [c-C6H12→c-C6H10(O)] and the Dioxygenation of Acetylenes and Aryloleﬁns. J. Am. Chem. Soc. 1990, 112, 1936–1942. [CrossRef] 29. Chen, M.S.; White, M.C. A Predictably Selective Aliphatic C–H Oxidation Reaction for Complex Molecule Synthesis. Science 2007, 318, 783–787. [CrossRef][PubMed] 30. Chen, M.S.; White, M.C. Combined Effects on Selectivity in Fe-Catalyzed Methylene Oxidation. Science 2010, 327, 566–571. [CrossRef][PubMed] Molecules 2016, 21, 1454 13 of 16

31. Bigi, M.A.; Reed, S.A.; White, M.C. Diverting non-haem iron catalysed aliphatic C–H hydroxylations towards desaturations. Nat. Chem. 2011, 3, 216–222. [CrossRef][PubMed] 32. Bigi, M.A.; Reed, S.A.; White, M.C. Directed Metal (Oxo) Aliphatic C–H Hydroxylations: Overriding Substrate Bias. J. Am. Chem. Soc. 2012, 134, 9721–9726. [CrossRef][PubMed] 33. Gormisky, P.; White, M.C. Catalyst-Controlled Aliphatic C–H Oxidations with a Predictive Model for Site-Selectivity. J. Am. Chem. Soc. 2013, 135, 14052–14055. [CrossRef][PubMed] 34. Howell, J.M.; Feng, K.; Clark, J.R.; Trzepkowski, L.J.; White, M.C. Remote Oxidation of Aliphatic C-H Bonds in Nitrogen-Containing Molecules. J. Am. Chem. Soc. 2015, 137, 14590–14593. [CrossRef][PubMed] 35. Prat, I.; Gomez, L.; Canta, M.; Ribas, X.; Costas, M. An Iron Catalyst for Oxidation of Alkyl CH Bonds Showing Enhanced Selectivity for Methylenic Sites. Chem. Eur. J. 2013, 19, 1908–1913. [CrossRef][PubMed] 36. Gomez, L.; Canta, M.; Font, D.; Prat, I.; Ribas, X.; Costas, M. Regioselective Oxidation of Nonactivated Alkyl C–H Groups Using Highly Structured Non-Heme Iron Catalysts. J. Org. Chem. 2013, 78, 1421–1433. [CrossRef][PubMed]

37. Canta, M.; Font, D.; Gomez, L.; Ribas, X.; Costas, M. The Iron(II) Complex [Fe(CF3SO3)2(mcp)] as a Convenient, Readily Available Catalyst for the Selective Oxidation of Methylenic Sites in Alkanes. Adv. Synth. Catal. 2014, 356, 818–830. [CrossRef] 38. Font, D.; Canta, M.; Milan, M.; Cusso, O.; Ribas, X.; Gebbink, R.J.M.K.; Costas, M. Readily Accessible Bulky Iron Catalysts Exhibiting Site Selectivity in the Oxidation of Steroidal Substrates. Angew. Chem. Int. Ed. 2016, 55, 5776–5779. [CrossRef][PubMed]

39. Bryliakov, K.P.; Talsi, E.P. Active sites and mechanisms of bioinspired oxidation with H2O2, catalyzed by non-heme Fe and related Mn complexes. Coord. Chem. Rev. 2014, 276, 73–96. [CrossRef] 40. Groves, J.T. High-valent iron in chemical and biological oxidations. J. Inorg. Biochem. 2006, 100, 434–447. [CrossRef][PubMed] 41. Lyakin, O.Y.; Bryliakov, K.P.; Britovsek, G.J.P.; Talsi, E.P. EPR Spectroscopic Trapping of the Active Species of Nonheme Iron-Catalyzed Oxidation. J. Am. Chem. Soc. 2009, 131, 10798–10799. [CrossRef][PubMed] 42. Lyakin, O.Y.; Bryliakov, K.P.; Talsi, E.P. EPR, 1H and 2H NMR, and Reactivity Studies of the Iron–Oxygen Intermediates in Bioinspired Catalyst Systems. Inorg. Chem. 2011, 50, 5526–5538. [CrossRef][PubMed] 43. Prat, I.; Mathieson, J.S.; Güell, M.; Ribas, X.; Luis, J.M.; Cronin, L.; Costas, M. Observation of Fe(V)=O using variable-temperature mass spectrometry and its enzyme-like C–H and C=C oxidation reactions. Nat. Chem. 2011, 3, 788–793. [CrossRef][PubMed]

44. Lyakin, O.Y.; Ottenbacher, R.V.; Bryliakov, K.P.; Talsi, E.P. Asymmetric Epoxidations with H2O2 on Fe and Mn Aminopyridine Catalysts: Probing the Nature of Active Species by Combined Electron Paramagnetic Resonance and Enantioselectivity Study. ACS Catal. 2012, 2, 1196–1202. [CrossRef] 45. Lyakin, O.Y.; Prat, I.; Bryliakov, K.P.; Costas, M.; Talsi, E.P. EPR detection of Fe(V)=O active species in nonheme iron-catalyzed oxidations. Catal. Commun. 2012, 29, 105–108. [CrossRef] 46. Oloo, W.N.; Meier, K.K.; Wang, Y.; Shaik, S.; Münck, E.; Que, L. Identiﬁcation of a low-spin acylperoxoiron(III) intermediate in bio-inspired non-heme iron-catalysed oxidations. Nat. Commun. 2014, 5, 3046. [CrossRef] [PubMed] 47. Lyakin, O.Y.; Zima, A.M.; Samsonenko, D.G.; Bryliakov, K.P.; Talsi, E.P. EPR Spectroscopic Detection of the Elusive FeV=O Intermediates in Selective Catalytic Oxofunctionalizations of Hydrocarbons Mediated by Biomimetic Ferric Complexes. ACS Catal. 2015, 5, 2702–2707. [CrossRef] 48. Serrano-Plana, J.; Oloo, W.N.; Acosta-Rueda, L.; Meier, K.K.; Verdejo, B.; García-España, E.; Basallote, M.G.; Münck, E.; Que, L., Jr.; Company, A.; Costas, M. Trapping a Highly Reactive Nonheme Iron Intermediate That Oxygenates Strong C–H Bonds with Stereoretention. J. Am. Chem. Soc. 2015, 137, 15833–15842. [CrossRef] [PubMed] 49. Zima, A.M.; Lyakin, O.Y.; Ottenbacher, R.V.; Bryliakov, K.P.; Talsi, E.P. Dramatic Effect of Carboxylic Acid on the Electronic Structure of the Active Species in Fe(PDP)-Catalyzed Asymmetric Epoxidation. ACS Catal. 2016, 6, 5399–5404. [CrossRef] 50. Battioni, P.; Renaud, J.P.; Bartoli, J.F.; Mansuy, D. Hydroxylation of alkanes by hydrogen peroxide: And efﬁcient system using manganese porphyrins and imidazole as catalysts. J. Chem. Soc. Chem. Commun. 1986, 341–343. [CrossRef]

51. Talsi, E.P.; Ottenbacher, R.V.; Bryliakov, K.P. Bioinspired oxidations of aliphatic C–H groups with H2O2 in the presence of manganese complexes. J. Organomet. Chem. 2015, 793, 102–107. [CrossRef] Molecules 2016, 21, 1454 14 of 16

52. Battioni, P.; Renaud, J.P.; Bartoli, J.F.; Reina-Artiles, M.; Fort, M.; Mansuy, D. Monooxygenase-like Oxidation

of Hydrocarbons by H2O2 Catalyzed by Manganese Porphyrins and Imidazole: Selection of the Best Catalytic System and Nature of the Active Oxygen Species. J. Am. Chem. Soc. 1988, 110, 8462–8470. [CrossRef] 53. Banfi, S.; Maiocchi, A.; Moggi, A.; Montanari, F.; Quici, S. Hydrogen peroxide oxygenation of alkanes catalysed by manganese(III)-tetraarylporphyrins: The remarkable co-catalytic effect of lipophilic carboxylic acids and heterocyclic bases. J. Chem. Soc. Chem. Commun. 1990, 24, 1794–1796. [CrossRef] 54. Banfi, S.; Legramandi, F.; Montanari, F.; Pozzi, G.; Quici, S. Biomimetic models of cytochrome P-450. A doubly tailed manganese(III)–tetraaryl porphyrin; an extremely efficient catalyst for hydrocarbon oxygenations

promoted by 30% H2O2. J. Chem. Soc. Chem. Commun. 1991, 18, 1285–1287. [CrossRef] 55. Carrier, M.N.; Scheer, C.; Gouvine, P.; Bartoli, J.F.; Battioni, P.; Mansuy, D. Biomimetic hydroxylation of aromatic compounds: Hydrogen peroxide and manganese-polyhalogenated porphyrins as a particularly good system. Tetrahedron Lett. 1990, 31, 6645–6648. [CrossRef] 56. Thellend, A.; Battioni, P.; Mansuy, D. Ammonium acetate as a very simple and efficient cocatalyst for manganese porphyrin-catalysed oxygenation of hydrocarbons by hydrogen peroxide. J. Chem. Soc. Chem. Commun. 1994, 1035–1036. [CrossRef] 57. Srour, H.; Le Maux, P.; Simonneaux, G. Enantioselective Manganese-Porphyrin-Catalyzed Epoxidation and C–H Hydroxylation with Hydrogen Peroxide in Water/Methanol Solutions. Inorg. Chem. 2012, 51, 5850–5856. [CrossRef][PubMed] 58. Amiri, N.; Le Maux, P.; Srour, H.; Nasri, H.; Simonneaux, G. Nitration of Halterman porphyrin: A new route for fine tuning chiral iron and manganese porphyrins with application in epoxidation and hydroxylation reactions using hydrogen peroxide as oxidant. Tetrahedron 2014, 70, 8836–8842. [CrossRef] 59. Lindsay Smith, J.R.; Shul’pin, G.B. Efficient stereoselective oxygenation of alkanes by peroxyacetic acid or hydrogen peroxide and acetic acid catalysed by a manganese(IV) 1,4,7-trimethyl-1,4,7-triazacyclononane complex. Tetrahedron Lett. 1998, 39, 4909–4912. [CrossRef]

60. Shul’pin, G.B.; Lindsay Smith, J.R. Oxidation with the “H2O2-managanese(IV) complex-carboxylic acid” reagent. 1. Oxidation of saturated hydrocarbons with peroxy acids and hydrogen peroxide. Russ. Chem. Bull. 1998, 47, 2379–2386. [CrossRef] 61. Wieghardt, K.; Bossek, U.; Nuber, B.; Weiss, J.; Bonvoisin, J.; Corbella, M.; Vitols, S.E.; Girerd, J.J. Synthesis, Crystal Structures, Reactivity, and Magnetochemistry of a Series of Binuclear Complexes of Manganese(II), IV IV -(III), and -(IV) of Biological Relevance. The Crystal Structure of [L’M (µ-O)3M L’](PF6)2·H2O Containing an Unprecedented Short Mn···Mn Distance of 2.296 Å. J. Am. Chem. Soc. 1998, 110, 7398–7411. 62. Shul’pin, G.B.; Nesterov, D.S.; Shul’pina, L.S.; Pombeiro, A.J.L. A hydroperoxo-rebound mechanism of alkane oxidation with hydrogen peroxide catalyzed by binuclear manganese(IV) complex in the presence of an acid with involvement of atmospheric dioxygen. Inorg. Chim. Acta 2016.[CrossRef] 63. Shul’pin, G.B.; Süss-Fink, G.; Lindsay Smith, J.R. Oxidations by the system “hydrogen peroxide—manganese(IV) complex—acetic acid”—Part II. Hydroperoxidation and hydroxylation of alkanes in acetonitrile. Tetrahedron 1999, 55, 5345–5358. [CrossRef] 64. Shul’pin, G.B.; Süss-Fink, G.; Shul’pina, L.S. Oxidations by the system “hydrogen peroxide–manganese(IV) complex–carboxylic acid”: Part 3. Oxygenation of ethane, higher alkanes, alcohols, olefins and sulfides. J. Mol. Catal. A Chem. 2001, 170, 17–34. [CrossRef] 65. Nizova, G.V.; Bolm, C.; Ceccarelli, S.; Pavan, C.; Shul’pin, G.B. Hydrocarbon Oxidations with Hydrogen Peroxide Catalyzed by a Soluble Polymer-Bound Manganese(IV) Complex with 1,4,7-Triazacyclononane. Adv. Synth. Catal. 2002, 344, 899–905. [CrossRef] 66. Shul’pin, G.B.; Nizova, G.V.; Kozlov, Y.N.; Pechenkina, I.G. Oxidations by the “hydrogen peroxide–manganese(IV) complex–carboxylic acid” system. Part 4. Efficient acid-base switching between

catalase and oxygenase activities of a dinuclear manganese(IV) complex in the reaction with H2O2 and an alkane. New J. Chem. 2002, 26, 1238–1245. [CrossRef] 67. Shul’pin, G.B. Metal-catalysed hydrocarbon oxidations. C. R. Chim. 2003, 6, 163–178. [CrossRef] 68. Shul’pin, G.B.; Nizova, G.V.; Kozlov, Y.N.; Arutyunov, V.S.; dos Santos, A.C.M.; Ferreira, A.C.T.;

Mandelli, D. Oxidations by the system “hydrogen peroxide–[Mn2L2O3][PF6]2(L = 1,4,7-trimethyl-1,4,7- triazacyclononane)–oxalic acid”. Part 6. Oxidation of methane and other alkanes and oleﬁns in water. J. Organomet. Chem. 2005, 690, 4498–4504. [CrossRef] Molecules 2016, 21, 1454 15 of 16

69. Nizova, G.V.; Shul’pin, G.B. A unique rate-accelerating effect of certain amino acids in the H2O2 oxidation of alkanes catalyzed by a dinuclear manganese complex containing 1,4,7-trimethyl-1,4,7-triazacyclononane. Tetrahedron 2007, 63, 7997–8001. [CrossRef] 70. Shul’pin, G.B.; Matthes, M.G.; Romakh, V.B.; Barbosa, M.I.F.; Aoyagi, J.L.T.; Mandelli, D. Oxidations by the

system ‘hydrogen peroxide–[Mn2L2O3][PF6]2(L=1,4,7-trimethyl-1,4,7-triazacyclononane)–carboxylic acid’. Part 10: Co-catalytic effect of different carboxylic acids in the oxidation of cyclohexane, cyclohexanol, and acetone. Tetrahedron 2008, 64, 2143–2152. [CrossRef] 71. Ryu, J.Y.; Kim, S.O.; Nam, W.; Heo, S.; Kim, J. Alkane Oxidation Catalyzed by Manganese-tmtacn Complexes

with H2O2. Bull. Korean Chem. Soc. 2003, 24, 1835–1837. [CrossRef] 72. Bennur, T.H.; Sabne, S.; Desphande, S.S.; Srinivas, D.; Sivasanker, S. Benzylic oxidation with H2O2 catalyzed by Mn complexes of N,N0,N00-trimethyl-1,4,7-triazacyclononane: Spectroscopic investigations of the active Mn species. J. Mol. Catal. A Chem. 2002, 185, 71–80. [CrossRef] 73. Saisaha, P.; Buettner, L.; van der Meer, M.; Hage, R.; Feringa, B.L.; Browne, W.R.; de Boer, J.W. Selective Catalytic Oxidation of Alcohols, Aldehydes, Alkanes and Alkenes Employing Manganese Catalysts and Hydrogen Peroxide. Adv. Synth. Catal. 2013, 355, 2591–2603. [CrossRef] 74. Romakh, V.B.; Therrien, B.; Süss-Fink, G.; Shul’pin, G.B. Dinuclear Manganese Complexes Containing Chiral 1,4,7-Triazacyclononane-Derived Ligands and Their Catalytic Potential for the Oxidation of Oleﬁns, Alkanes, and Alcohols. Inorg. Chem. 2007, 46, 1315–1331. [CrossRef][PubMed] 75. Lessa, J.A.; Horn, A.; Bull, É.S.; Rocha, M.R.; Benassi, M.; Catharino, R.R.; Eberlin, M.N.; Casellato, A.; Noble, C.J.; Hanson, G.R.; Schenk, G.; Giselle, C.; Silva, O.A.; Antunes, O.A.C.; Fernandes, C. Catalase

vs. Peroxidase Activity of a Manganese(II) Compound: Identification of a Mn(III)–(µ-O)2–Mn(IV) Reaction Intermediate by Electrospray Ionization Mass Spectrometry and Electron Paramagnetic Resonance Spectroscopy. Inorg. Chem. 2009, 48, 4569–4579. [CrossRef][PubMed] 76. Nakayama, N.; Tsuchiya, S.; Ogawa, S. Hydrocarbon oxidation with hydrogen peroxide and pentafluoroiodosylbenzene catalyzed by unusually distorted macrocycle manganese complexes. J. Mol Catal. A Chem. 2007, 277, 61–71. [CrossRef] 77. Lee, N.H.; Lee, C.S.; Jung, D.S. Selective Oxidation of Benzylic Hydrocarbons to Carbonyl Compounds Catalyzed by Mn(III) Salen Complexes. Tetrahedron Lett. 1998, 39, 1385–1388. [CrossRef] 78. Mardani, H.P.; Golchoubian, H. Selective and efficient C–H oxidation of alkanes with hydrogen peroxide catalyzed by a manganese(III) Schiff base complex. J. Mol. Catal. A. Chem. 2006, 259, 197–200. [CrossRef] 79. Golchoubian, H.; Ghasemi, N. Diphenylmethane Oxidation Catalyzed by Mononuclear Mn(III) Complexes. J. Chin. Chem. Soc. 2011, 58, 470–473. [CrossRef] 80. Gómez, I.; Garcia-Bosch, A.; Company, J.; Benet-Buchholz, A.; Polo, X.; Sala, X.; Ribas, M.; Costas, M.

Stereospeciﬁc C–H Oxidation with H2O2 Catalyzed by a Chemically Robust Site-Isolated Iron Catalyst. Angew. Chem. Int. Ed. 2009, 48, 5720–5723. [CrossRef][PubMed] 81. Ottenbacher, R.V.; Samsonenko, D.G.; Talsi, E.P.; Bryliakov, K.P. Highly Efﬁcient, Regioselective,

and Stereospecific Oxidation of Aliphatic C–H Groups with H2O2, Catalyzed by Aminopyridine Manganese Complexes. Org. Lett. 2012, 14, 4310–4313. [CrossRef][PubMed] 82. Shen, D.; Miao, C.; Wang, S.; Xia, C.; Sun, W. Efficient Benzylic and Aliphatic C–H Oxidation with Selectivity for Methylenic Sites Catalyzed by a Bioinspired Manganese Complex. Org. Lett. 2014, 16, 1108–1111. [CrossRef][PubMed] 83. Shen, D.; Miao, C.; Xu, D.; Xia, C.; Sun, W. Highly Efficient Oxidation of Secondary Alcohols to Ketones

Catalyzed by Manganese Complexes of N4 Ligands with H2O2. Org. Lett. 2015, 17, 54–57. [CrossRef] [PubMed] 84. Dai, W.; Lv, Y.; Wang, L.; Shang, S.; Chen, B.; Li, G.; Gao, S. Highly efﬁcient oxidation of alcohols ca4alyzed by a porphyrin-inspired manganese complex. Chem. Commun. 2015, 51, 11268–11271. [CrossRef][PubMed] 85. Ottenbacher, R.V.; Talsi, E.P.; Bryliakov, K.P. Mechanism of Selective C–H Hydroxylation Mediated by Manganese Aminopyridine Enzyme Models. ACS Catal. 2015, 5, 39–44. [CrossRef] 86. Adams, A.M.; Du Bois, J.; Malik, H.A. Comparative Study of the Limitations and Challenges in AtomTransfer C–H Oxidations. Org. Lett. 2015, 17, 6066–6069. [CrossRef][PubMed] 87. Costas, M.; Que, L., Jr. Ligand Topology Tuning of Iron-Catalyzed Hydrocarbon Oxidations. Angew. Chem. Int. Ed. 2002, 41, 2179–2181. [CrossRef] Molecules 2016, 21, 1454 16 of 16

88. Chen, K.; Costas, M.; Que, L., Jr. Spin state tuning of non-heme iron-catalyzed hydrocarbon oxidations: Participation of FeIII–OOH and FeV=O intermediates. J. Chem. Soc. Dalton Trans. 2002, 672–679. [CrossRef] 89. Que, L., Jr. The Road to Non-Heme Oxoferryls and Beyond. Acc. Chem. Res. 2007, 40, 493–500. [CrossRef] [PubMed] 90. Mas-Ballesté, R.; Que, L., Jr. Iron-Catalyzed Oleﬁn Epoxidation in the Presence of Acetic Acid: Insights into the Nature of the Metal-Based Oxidant. J. Am. Chem. Soc. 2007, 129, 15964–15972. [CrossRef][PubMed] 91. Mas-Ballesté, R.; Fujita, M.; Que, L., Jr. High-valent iron-mediated cis-hydroxyacetoxylation of oleﬁns. Dalton Trans. 2008, 1828–1830. [CrossRef][PubMed] 92. Ottenbacher, R.V.; Samsonenko, D.G.; Talsi, E.P.; Bryliakov, K.P. Highly Enantioselective Bioinspired

Epoxidation of Electron-Deﬁcient Oleﬁns with H2O2 on Aminopyridine Mn Catalysts. ACS Catal. 2014, 4, 1599–1606. [CrossRef] 93. Ottenbacher, R.V.; Shubin, A.A.; Shashkov, M.V.; Talsi, E.P.; Bryliakov, K.P. Evidence for “Bifurcated Rebound Mechanism” in Biomimetic C–H Hydroxylation Mediated by Manganese-Aminopyridine Complexes. 2016, Submitted. 94. Hartwig, J.F.; Larsen, M.A. Undirected, Homogeneous C–H Bond Functionalization: Challenges and Opportunities. ACS Cent. Sci. 2016, 2, 281–292. [CrossRef][PubMed]

© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).