Applications of Ferrocenium Salts in Organic Synthesis

SYNTHESIS0039-78811437-210X © Georg Thieme Verlag Stuttgart · New York 2015, 47, 1683–1695 1683 review

Syn thesis Š. Toma, R. Šebesta Review

O Štefan Toma* O Radovan Šebesta* R1 2 O R O Fe A 1 Department of Organic Chemistry, Faculty of Natural Sciences, O R O 2 2 R1 R Comenius University in Bratislava, Mlynska dolina CH-2, 84215, N R Bratislava, Slovakia H O R1 R2 [email protected] e Ar [email protected] N R CO2R N Ar Ar O CO2R Fe Cl R O O Ar H CO R 2 H

Received: 27.02.2015 years ago by quantum chemical calculations of iron bond- Accepted after revision: 09.04.2015 ing in the ferrocene molecule. According to the calculations, Published online: 23.04.2015 DOI: 10.1055/s-0034-1379920; Art ID: ss-2015-e0130-r there are two electrons located in the hybridized iron orbital, and one electron oxidation must, therefore, result in the Abstract Ferrocenium salts can be easily obtained from ferrocene by cation radical (Scheme 1).5 either synthetic preparation or in situ reaction. The ferrocenium ion can act as a one-electron oxidant and thus initiate or promote a range of radical processes. Ferrocene itself can donate electrons to suitable sub- – e– strates, resulting in useful transformations. Ferrocenium salts can also Fe Fe act as mild Lewis acids. This paper highlights various uses of ferrocenium ions in organic reactions. Scheme 1 1 Introduction 2 Ferrocenium Salts as Lewis Acids 3 Ferrocenium Salts as One-Electron Oxidants 4 Ferrocene as an Electron Donor A more subtle look at molecular orbitals confirms this 5 Catalysis with Other Ferrocenium Derivatives notion. The ferrocenium ion is in its ground state a low-spin 6 Conclusions d5 complex with one unpaired electron. Its frontier-orbital 3 2 Key words catalysis, organometallic reagents, cations, ferrocene, fer- configuration is (e2g) (a′1g) . This description is supported rocenium by band intensities of the photoelectron spectrum, which

indicate that the first ionization results from an e2 molecular orbital. Furthermore, EPR spectra and the magnetic mo- 1 Introduction ment of ferrocenium ion also support the orbitally degener- 2 6 ate ground state E2g.

Ferrocene and its derivatives are among the most im- Ferrocenium salts are typically a dark blue color and This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. portant organometallic compounds. The ferrocene frame- they are paramagnetic. Soon after the discovery of ferro- work features in many chiral and achiral catalysts,1 materi- cene, its easy oxidation to the ferrocenium cation by als, and even some potential medicines.2 The ability of fer- iron(III) chloride or benzoquinone was described.7 Thus, the rocene to undergo reversible one-electron oxidation to the first isolated ferrocenium salt was ferrocenium tetrachloro- ferrocenium cation is important for many applications of ferrate. The ferrocenium ion can be prepared with various ferrocene and its derivatives in electrochemistry. Nowa- counterions, such as tetrafluoroborate (BF4), hexafluoro- days, the ferrocene/ferrocenium cation couple can serves as phosphate (PF6), hexafluoroantimonate (SbF6), or tetra- 3 a reference material in cyclic voltammetry. The redox po- phenylborate (BPh4). Ferrocenium hexafluorophosphate + + – + – tential of Fc /Fc is 0.64 V vs. the standard hydrogen elec- (Cp2Fe PF6 ) and ferrocenium tetrafluoroborate (Cp2Fe BF4 ) trode.4 Furthermore, the oxidation potential of ferrocenium are the most commonly employed ferrocenium salts in or- ion can be modified by altering the substitution on the cy- ganic synthesis; they are also commercially available. Ferro- clopentadienyl rings. With respect to its structure, the cenium hexafluorophosphate can be efficiently prepared by question can be asked: is the ferrocenium ion a cation radi- oxidation of ferrocene with iron(III) chloride and treating cal or just a cation? The question was answered over 50 the resulting solution with ammonium hexafluorophos-

Syn thesis Š. Toma, R. Šebesta Review phate.8 The synthesis of ferrocenium tetrafluoroborate in- philic anions, such as trifluoromethanesulfonimide or volves the oxidation of ferrocene with p-benzoquinone in tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF).13 1- the presence of tetrafluoroboric acid–diethyl ether com- Amino- and 1,1′-diamino-functionalized ferrocenium salts plex.9 Several methods have been described for the prepa- have been described.14 Ferrocenyl dendrimers have been ration of substituted ferrocenium salts. Acetylferrocenium synthesized that can be used as multi-electron redox tetrafluoroborate is prepared by the oxidation of acetylfer- agents.15 rocene with dry silver(I) tetrafluoroborate in diethyl Ferrocenium salts take part in various transformations ether.10 Ferrocenium salts derived from 1-bromo-, and 1,1′- within the concept of redox catalysis. Interestingly, ferroce- dibromoferrocene, as well as 1-ethyl-, and 1,1′-diethylferro- nium ions can participate in both branches of redox cataly- 16 cene, with the trifluoromethanesulfonimide anion (NTf2) sis, hole catalysis and electron catalysis. Ferrocene can ini- were prepared by oxidation of the corresponding starting tiate various transformations by injection of an electron to materials by dry silver(I) trifluoromethanesulfonimide– the starting material. On the other hand, the ferrocenium acetonitrile complex.11 Very thorough investigation of the ion can start a catalytic sequence by removal of the electron oxidation of ferrocene derivatives by benzoquinone, 2,3-di- from an appropriate substrate. To the best of our knowl- chloro-5,6-dicyano-1,4-benzoquinone, and 2,2,6,6-te- edge, the applications of ferrocenium salts in organic syn- tramethylpiperidin-1-oxyl (TEMPO) was performed by Jahn thesis have not yet been reviewed, only their application as and co-workers.12 They found that 2,3-dichloro-5,6-dicya- redox agents in organometallic chemistry.4 Apart from their no-1,4-benzoquinone is preferred for the oxidation of ferro- redox properties and accompanying use in various oxido- cene derivatives with strong electron-attracting groups, reduction processes, ferrocenium salts can act also as weak like Bz, CO2i-Pr, POPh2, etc. The prepared ferrocenium cat- Lewis acids, although there are only a few examples of this ions were isolated as the hexafluorophosphate salts and application. This review gives an overview of applications they were stable in acetonitrile or dichloromethane, but of ferrocenium ions in organic synthesis. slowly reduced to the starting ferrocene derivatives in ethe- With respect to terminology, terms ‘ferricenium’ or ‘fer- real solvents, N,N-dimethylformamide, or dimethyl sulfox- ricinium cation’ were sometimes used in older literature; ide. Ferrocenium hexafluorophosphate salts are poorly sol- they refer to the same compound, that is the ferrocenium uble in apolar solvents, and for applications in such solvents cation. The term ferrocenium is preferable and in this re- it is advisable to prepare ferrocenium salts with more lipo- view it shall be used exclusively.

Biographical Sketches

Professor Štefan Toma graduat- sor Emeritus. Immediately after um complexes. He has made ed from Comenius University in graduation he began research in contributions in sonochemistry Bratislava (1960) and also ferrocene chemistry, later, after and microwave chemistry. In gained Ph.D. (1965) and D.Sc. a postdoctoral stay with Profes- years, he has been heavily en- (1982) degrees from the same sor P. L. Pauson (1970–1971), gaged in the study of stereose- university. From 1983, he was a he also became interested in lective reactions catalyzed by full professor of organic chemis- the synthesis and reactivity of transitional-metal complexes or try at Comenius University in dienetricarbonyliron complexes organocatalysts using an ionic This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Bratislava and he is now Profes- and benzenetricarbonylchromi- liquid as the solvent.

Radovan Šebesta, born in synthesis of β-amino acids and has been an Associate Professor 1975, studied chemistry at the peptides. He then worked with of organic chemistry; in 2014 Faculty of Natural Sciences, Prof. Ben L. Feringa at Gronin- he obtained a D.Sc. from Come- Comenius University in Bratisla- gen University on asymmetric nius University. His research in- va, where he received a Ph.D. in catalysis with phosphoramid- terests include the development organic chemistry in 2002. He ites. In 2005, he joined Prof. of new asymmetric catalytic carried out postdoctoral re- Stefan Toma’s group at the transformations with ferrocene search with Prof. Dieter Seebach Comenius University as an As- catalysts or organocatalysts. at ETH Zürich, working on the sistant Professor. Since 2008, he

Syn thesis Š. Toma, R. Šebesta Review

2 Ferrocenium Salts as Lewis Acids Another application of a ferrocenium salt as a Lewis acidic catalyst is in the aminolysis of epoxides (Scheme 4).21 Some researchers consider the ferrocenium ion to be Cyclopentene and cyclohexene oxides 5 underwent ring non-Lewis acidic cation as it is unlikely that it will form a opening with several anilines in a reaction catalyzed by 5 stable 19-electron complex upon coordination with a Lewis mol% of ferrocenium tetrafluoroborate; the corresponding base. However, there are several reports in which the ferro- amino alcohols 6 were obtained in good yields even at low- cenium ion is thought to act as a weak Lewis acid. One of er temperatures. the first examples is the ferrocenium ion catalyzed Diels– 17 NH2 Alder reaction. It was shown that ferrocenium hexafluoro- + R Cp2Fe BF4 H N phosphate was able to increase the rate of the reaction of (5 mol%) O + both cyclic and acyclic dienes with α,β-unsaturated alde- solvent-free n R 5 °C – r.t. n OH hydes and ketones. Modest rate enhancement of the Diels– 53 6, 61–97% Alder reaction was also noted when ferrocenium ions were n = 0,1 R = H, Me, OMe derived from [4]-ferrocenophane.18 Scheme 4 Ferrocenium hexafluorophosphate can accelerate the solvent-free cyanosilylation of carbonyl compounds; aromatic aldehydes and ketones 1 afforded the corresponding On the other hand, reactions with aliphatic amines silylated cyanohydrins 2 (Scheme 2).19 were carried out at 60 °C and longer reaction times were, generally, necessary. Competitive experiments were per- R O OTMS R formed using piperidine and aniline as the amines and an + CN Cp2Fe PF6 interesting temperature effect was observed. The reaction (2.5 mol%) + TMSCN at room temperature gave a mixture of piperidine- and ani- solvent-free X 10 min, r.t. line-derived products in 96:4 ratio, but the same reaction at X 1 60 °C gave a mixture with 87:13 ratio. This reaction worked R = H, Me 2, 73–94% well with other epoxides, even with epichlorohydrin (7), X = H, Cl, F, Me, OMe, OEt which afforded the expected amino alcohol 8 accompanied Scheme 2 by a smaller amount of product 9. Interestingly, no substitution of chlorine was observed (Scheme 5). Cyanosilylations also proceed well with naphthalene-2- OH carbaldehyde (85%), furan-2-carbaldehyde (65%), thio- H Cl N + Ph phene-2-carbaldehyde (68%), cinnamaldehyde (70%), and Cp2Fe BF4 O (5 mol%) 8, 68% 3-phenylpropanal (74%) and with other aliphatic aldehydes PhNH Cl + 2 + (75–92%). Under the same conditions, cyanosilylation was solvent-free OH 5 °C – r.t. 7 Cl successful with various ketones. It was proposed that the OH ferrocenium ion acts as a Lewis acid in these reactions; its Cl N function is to polarize the carbonyl functionality in the sub- Ph 9, 23% strates. In the Strecker reaction of aldehydes and ketones with Scheme 5 aromatic amines 3 and trimethylsilyl cyanide,20 a small amount of ferrocenium hexafluorophosphate accelerated The ring opening of epoxides 10 with alcohols can be 22 the reaction with aliphatic aldehydes as well as aliphatic catalyzed by ferrocenium salts. Other Lewis acids, such as This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. ketones; the corresponding amino nitriles 4 were obtained iron(III) chloride, indium(III) chloride, or zirconium(IV) in high yields (Scheme 3). chloride, were also able to promote the reaction, but ferrocenium tetrafluoroborate was the most efficient (Scheme CN R O TMSCN R NHAr 6). + Cp2Fe PF6 (5 mol%) + ArNH 2 solvent-free 20 min, r.t. X X 1 3 4, 81–94% R = H, Me, Et X = H, Me, Br, F, NO2 Scheme 3

Syn thesis Š. Toma, R. Šebesta Review

+ Cp2Fe BF4 OMe O (5 mol%) + MeOH OH Fe BF4 R R 10 11 12 n = 4 14% 33–99% O 5 9% 6 18% R = ClCH , 2-naphthyl-OCH , Ph-O-CH , 4-O N-C H -OCH , + 2 2 2 2 6 4 2 7 23% O O CH Cl 4-MeO-C6H4-OCH2, C10H21 2 2 8 16% MW, 120 °C 9 OH n 6% 30 min OH O O O 18 19 20 Fe Scheme 6 Scheme 8 3 Ferrocenium Salts as One-Electron Oxi- dants The ferrocenium cation radical is most frequently used as a mild, one-electron oxidant of electron-rich species, such as enolate anions. The Jahn research group has focused Ferrocenium salts have been used to generate thioalkyl extensively on this topic. They showed that alkenylmalonic cations from 2-(tributylstannyl)-1,3-dithianes and 1- esters 21 can be cyclized to bicyclic lactones 26 by intramo- (tributylstannyl)alkyl sulfides; the corresponding radicals lecular radical addition to the C=C bond (Scheme 9).29 The reacted with olefinic nucleophiles.23 Ferrocenium salts reaction comprises of formation of the enolate 22, which is were used for the oxidation of tetrakis(amino)benzenes to then oxidized by the ferrocenium ion to the corresponding the corresponding dications.24 Ferrocenium ions also oxi- radical 23, which then cyclizes to intermediate 24, and this dize ketene silyl acetals and other organosilanes.25 is further oxidized to cation 25. Ferrocenium salts have been used extensively for de- Ph OEt 26 O Ph complexation of dienetricarbonyliron complexes. As an EtO2C EtO C LiN(i-Pr) LiO Cp Fe+ PF example of this methodology, the synthesis of carbazole al- 2 Ph 2 Ph 2 6 27 – Cp Fe kaloid mukonine (17), is presented (Scheme 7). EtO 2 21 22 CO Me Ph Ph 2 EtO C EtO C + (OC)3Fe H 2 2 Cp2Fe PF6 CO2Me EtO C EtO C + MeCN 2 Ph 2 Ph (OC)3Fe – Cp Fe + 2 25–82 °C BF OMe H2N 4 24 23 Et 13 NH2 OMe CO2Et 14 15, 61% Ph Ph O O CO2Et EtO2C Ph CO2Me + – CO Me EtO2C Cp2Fe PF6 2 Ph EtO2C H + (OC)3Fe Na2CO3 TFA, toluene N ClCH2CH2Cl 25 26, 64% Ph H OMe N 27, 12% air, 25 °C 83 °C H OMe Ph 16, 50% mukonine (17), 50% Scheme 9 Scheme 7

Ferrocenium salts, such as ferrocenium hexafluoro-

An interesting application of a ferrocenium salt is in the phosphate, were involved in the oxidation of the enolate This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. synthesis of para-tert-butycalixarenes.28 The reaction of 4- anion to the corresponding radical as well as in the oxida- tert-butylphenol (18) and s-trioxane (19) in the presence of tion of cyclized radical to the corresponding carbenium ion. ferrocenium tetrafluoroborate afforded a mixture of the de- For this reason it was necessary to use 2.5 molar excess of sired calixarenes 20. Catalysis by the ferrocenium ion led to ferrocenium salt in this reaction, but the majority of the much better results (57% yield) than with Brønsted acid ferrocene (70–80%) was recovered after workup of the reac- (TsOH) catalyzed reactions. Even more importantly, the re- tion mixture. The use of various bases, such as butyllithium, action was more selective, proceeding without the forma- butylmagnesium bromide, lithium hexamethyldisilazanide, tion of undesired larger (10–20) calixarenes (Scheme 8). or lithium diisopropylamide, was examined for the genera- The mechanism of the reaction is unclear, but it is suggest- tion of the starting ester enolate, but the best results were ed that the ferrocenium ion participates in the one-electron observed with lithium diisopropylamide. Several other oxi- oxidation of phenol to the phenoxy radical. Disappointing- dants have also been tested. For instance tris(4-bromophe- ly, no such radical species were detected by EPR and no nyl)aminium hexachloroantimonate gave the correspond- products of phenol dimerization were observed. However, ing lactone in just 32%, whereas ammonium cerium(IV) ni- the reaction did not proceed with O-alkylated phenols. trate and manganese(III) acetate were not effective.

Syn thesis Š. Toma, R. Šebesta Review

Intramolecular cyclization of ω-silylallyl esters 28 was icals 36 were trapped with TEMPO at –78 °C. 2,2,6,6-Te- used for the synthesis of cyclopentanoid monoterpenes, tramethylpiperidin-1-yloxy adducts 37, which were formed such as dihydronepetalactone (32) (Scheme 10).30 In this in good yields, were usually accompanied by small amount transformation, the initially formed enolate 29 reacted with of dimerization product 38. The initially used reaction con- ethyl chloroformate to afford intermediate 30, which was ditions gave a complicated mixture of compounds, but then cyclized by the action of the ferrocenium ion to cyclo- modification of these conditions by the addition of six pentane derivative 31. equivalents of hexamethylphosphoramide to the lithium diisopropylamide prior to enolate formation considerably SiMe 3 OLi SiMe3 improved results (Scheme 12). The adducts 37 were then EtO C 2 LiTMP EtO ClCO2Et transformed into corresponding hydroxy derivatives 39 by H Me Me DME, –78 °C reduction with zinc in acetic acid. Me Me 28 29 1. HMPA Me H LDA (130 mol%) H TEMPO Li OEt SiMe3 O EtO2C THF, –78 °C (150 mol%) CO2Et CO2Et Cp Fe+ PF n-Bu O 2 6 EtO2C + n-Bu 2. Cp2Fe PF6 –78 °C Me H H EtO Me (150 mol%) 35 Me 31, 93% – 78°C 36 30 H O CO2Et Zn O n-Bu H Me AcOH–H O–THF 32, 75% 2 H H O CO Et H 3:1:1 2 3 steps dihydronepetalactone N n-Bu Me 50 °C OH Scheme 10 37, 67% 39, 88% + EtO2C CO2Et Jahn and co-workers investigated an alkylation of dieth- C5H11 C5H11 yl malonate with pent-4-enyl halides, tosylates, and 38, 25% mesylates as means of producing the corresponding diethyl Scheme 12 2-(pent-4-enyl)malonates for oxidative cyclization;31 the alkylation was most effective if 20 mol% of sodium iodide was added to the preformed diethyl malonate carbanion in a Similar reactions were performed with seven different tetrahydrofuran–N,N-dimethylformamide mixture. The use esters. The formation of a radical intermediate is supported of several bases and oxidants was examined in the oxidative by the formation of up to 73% of dimeric product as a mix- cyclization of diethyl 2-(pent-4-enyl)malonate 33. Lithium ture of meso and d/l isomers when TEMPO was not added to diisopropylamide again proved to be the best base for this the reaction mixture. This methodology was later utilized transformation. As for oxidant, apart from ferrocenium in the synthesis of functionalized pyrrolidines.33 Michael hexafluorophosphate, similar results were achieved using addition of lithium amides 41 to α,β-unsaturated esters 40 copper(II) chloride. Being solid, both oxidants required por- afforded derivatives 42, which served as the starting mate- tionwise addition to the preformed lithium enolate ion rials for ferrocenium-promoted radical cyclization to pyrro- (Scheme 11). lidines 43. Small amounts (5–11%) of acyclic side product 44 were also isolated (Scheme 13). + Cp2Fe PF6 Ph or CuCl Ph O 2 O R2 2 CO2Et Ot-Bu Ot-Bu R This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Ph LDA (150 mol%) Ph R2 CO Et H O 2 2 CO2Et 1. THF, –78 °C R + DME, –78 °C DME, 0 °C LiO Cp2Fe PF6 + 30 min 2. H2O 1 TEMPO 33 R 34 R1 LiN N + – 3 3 64% with Cp2Fe PF6 40R 41 R 69% with CuCl2 42, 70–99% R1 = Me, Ph; R2 = H, Me; R3 = allyl, Bn Scheme 11 R2 R2 t-BuO C 2 O N t-BuO N The Jahn group trapped the intermediate radicals with 1 O R R2 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO). The N O R3 R1 2 N R first paper in this series described the synthesis of α-hy- 43 32 R3 droxy esters. Enolates generated using lithium diisopro- 28–85%, cis–trans 1:2.4–7.2:1 44 pylamide from the corresponding esters 35 were oxidized Scheme 13 by ferrocenium hexafluorophosphate and the resulting rad-

Syn thesis Š. Toma, R. Šebesta Review

This methodology was used also for the cyclization of (S)-N-Boc-pyrroglutamate 49 worked well and more impor- intermediates 45 to functionalized cyclopentanes 46 tantly it proceeded with complete conservation of stereo- (Scheme 14) in a model synthesis for prostaglandins.34 In- genic information at C2 of the product 50 (Scheme 16). terestingly, the reactions worked well if an additional donor group was present on the skeleton. On the other hand, no cyclization was observed if there was an electron-with- 1. LiHMDS THF, LiCl N drawing group near the reacting centers (Scheme 14). –78 °C, 20 min CO2Et O O N 2. TEMPO CO Et HO Boc + 2 HO 3. Cp2Fe PCl6 O N CO2t-Bu CO2t-Bu 49 Boc 1. LDA–HMPA 50 C8 + 70%, d.r. 1.2:1 t-BuO2C THF, 2 h C8 –78 to –10 °C 99% ee + O 2. Cp2Fe SbF6 N O HO N Scheme 16 TEMPO 45 46a, 8α/8β 2–3:1 46b,8α/8β 2–2.5:1 The Jahn group also attempted α-hydroxylation of free (6Z, 8E) 31% 29% (6E, 8E) 34% 31% heptanoic acid, but they obtained the hydroxylated product in only 51% yield together with the dimers (14%) and hept- Scheme 14 2-enoic acid (9%). On the other hand, hydroxylation of various acyclic as well as cyclic ketones 51 proceeded very well. The Jahn group have described the hydroxylation of a The corresponding products 52 were obtained in good broad range of carbonyl compounds using this strategy.35 yields. Only in the case of alkyl phenyl ketones was the hy- The previously developed methodology was modified by al- droxylation accompanied by the formation of larger tering the order of addition of ferrocenium salt and TEMPO. amounts of the corresponding dimers 53 (Scheme 17). The TEMPO was added to the enolate solution in one por- O tion at –78 °C and this was followed by the addition of solid 1. LDA, THF LiCl, –78 °C R1 O 2 2 2 ferrocenium hexachlorophosphate in small portions at a 20 min R R OC COR R1 + R2 O rate corresponding with its consumption, which was moni- 2. TEMPO N 1 1 + R R tored by disappearance of the blue color of the reaction H 3. Cp2Fe PF6 mixture. In this way, various esters, amides, nitriles, and ke- 51 tones were hydroxylated in the α-position. The reaction 52 53 R1 = Me, R2 = Et 90% – conditions were optimized for the hydroxylation of ethyl 1 2 R , R = -(CH2)4- 77% – 1 2 heptanoate and it was found that lower amounts of the rad- R , R = -(CH2)3- 84% – ical dimers were formed when hexamethylphosphoramide R1 = Me, R2 = Ph 78% 21% R1 = Et, R2 = Ph 70% 30% or lithium chloride were added to the enolate solution. Hydroxylation of a range of structurally diverse deriva- Scheme 17 tives 47 with electron-withdrawing groups afforded the corresponding 2,2,6,6-tetramethylpiperidin-1-yloxy ad- Trisubstituted pyrrolidines were assembled by electron- ducts 48 (Scheme 15). transfer-induced oxidative cyclizations of N-allyl β-amino ester enolates.36 1. LDA (130 mol%) 2 The Jahn group has improved the conditions for this THF, LiCl R R1 EWG 1 37 R EWG – 78 °C, 20 min type of anion-radical reaction. It was realized that ferro- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. O cene and 2,2,6,6-tetramethyl-1-oxopiperidinium hexafluo- R2 2. TEMPO (110 mol%) N + 3. Cp2Fe PCl6 rophosphate is in equilibrium with the corresponding fer- 47 (150 mol%) rocenium salt and the equilibrium is shifted towards the 48, 28–94% ferrocenium ion. Therefore, they used only small amount of 1 R = Me, Et, i-Pr, n-Pent, C6H13, c-C3H5, Ph, CO2Me R2 = H, Me ferrocene (1–5 mol%) and added the TEMPO salt to the mix-

EWG = CO2Me, CO2Et, CO2t-Bu, CN, CONBn2, CONMe2 ture of a chiral lithium amide 54 and unsaturated ester 40. Scheme 15 Under these conditions, tandem aza-Michael/radical cyclization proceeded and afforded densely functionalized pyrrolidines 55 (Scheme 18). Even lactams can be successfully hydroxylated. The hydroxylation of N-methylpyrrolidin-2-one gave the α-hydroxylated product in 57% yield. The hydroxylation of chiral

Syn thesis Š. Toma, R. Šebesta Review

PF6 Me 1. Et3N, MeOCOCl Me H Fe + Fe + OH THF, 0 °C, 1 h N N N N O O 2. Me N O PF 6 Me H S O 56 57 O O LiN 1. LHMDS, Et3N 2 1 N R R S THF, –78 °C n-BuLi R2 O O O + – O THF, –78 °C 5 2. Cp2Fe PF6 , 12 °C 1 CO2R R3 R + 4 5 R OR R3 Me NH Cp2Fe (5 mol%) Me 4 TEMPO-PF R 6 N O Me H Ph H 54 40 N 1. BzCl, 70 °C N Me Ph N 1 2 3 H R , R , R = H, Me 55, 25–75% S CO2H 2. TBAH, H O R4, R5 = Me, t-Bu, Ph d.r. 1.3-6:1 2 2 O 2-methylbut-2-ene O O (S)-ketorolac (59) DME, –10 °C, 3 h 58 Scheme 18 90% ee Scheme 19

The Jahn group have developed an ingenuous route to metal enolates. These species were generated by organome- 1. LiO R2 O O tallic addition to α,β-unsaturated aldehydes, which afford- O O THF, –40 °C, 3–10 h p-Tol S S p-Tol p-Tol S S 2 ed allylic alcoholates that were isomerized by ruthenium + – 1 R p-Tol 2. Cp2Fe BF4 (3 equiv) R catalysis. Enolates formed in this way underwent addition TEMPO (2 equiv) O OTMP R1 –20 °C, 2 h to Michael acceptors followed by radical cyclization and ox- 60 61 1 1 2 ygenation with TEMPO.38 These methodologies were ap- R = Ph, 2-(PhO)-C6H4, i-Pr R = 2-(PhO)-C6H4, R = H, 56% R1 = Ph, R2 = H, 59% plied to the syntheses of natural products, such as isopros- R1 = i-Pr, R2 = H, 41% tanes.39 R1 = Ph, R2 = Ph, 48%, dr 1.1:1 Oxidative enolate dimerization promoted by the ferro- Scheme 20 cenium ion has been applied in the synthesis of the lomai- viticin family of natural products, which display potent cy- tive couple the titanium enolate of 3-(phenylacetyl)oxazoli- totoxic activity.40 Ferrocenium hexachlorophosphate has din-2-one (62),47 to achieve stereoselective coupling the re- also been used in an oxidative coupling of enolates of 3- action was performed in the presence of chiral ligands. The phenylpropanoic acid derivatives leading to synthesis of best results were achieved when TADDOL was used as the ent-hinokinon. However, the ferrocenium ion was a less ef- ligand, which gave the dimer 63 in 91% yield and 76% ee fective oxidant in this case than other oxidants, such as io- (Scheme 21). dine or copper(II) pentanoate.41 Ph The direct coupling of pyrroles with carbonyl com- Ph pounds under oxidative conditions has been reported. Cop- O OH per salts, such as copper(II) 2-ethylhexanoate were the O OH most efficient for this transformation.42 However, in the Ph Ph short synthesis of (S)-ketorolac (59), only ferrocenium TADDOL O O Ph O hexafluorophosphate was able to mediate intramolecular TiCl4, Et3N Ph 43 O N coupling (Scheme 19). This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. ON + N O O Cp2Fe BF4 Bis-sulfinyl radicals 60 can also participate in radical cy- Ph O clizations and TEMPO trapping to give 3,3-bis-sulfinyl tet- 62 O 63 44 rahydrofuran 61 (Scheme 20). 91%, dl/meso 25:75 Ferrocenium/TEMPO methodology was applied in the 76% ee total synthesis of fusarisetin A, a metabolite from Fusarium Scheme 21 fungi with considerable anticancer activity.45 This methodology has been utilized in the synthesis of An interesting discussion has evolved around presumed bulky nitroxides and alkoxyamines derived from TEMPO. role of the ferrocenium ion in organo-SOMO activated reac- These compounds were used as initiators/regulators in the tions. Ferrocenium salts have been used in the organocata- controlled radical polymerization of butyl acrylate and sty- lytic α-oxyamination of aldehydes (Scheme 22).48 The reac- rene.46 tion was accelerated by pyrrolidine and MacMillan’s oxazo- As previously discussed, small amounts of intermediate lidinone organocatalysts, in which case high radical dimerization products were formed in the hydroxyl- stereoselectivity was observed. The reaction was initially ation of different carbonyl derivatives. In attempts to oxida- assumed to proceed via MacMillan’s SOMO pathway, in

Syn thesis Š. Toma, R. Šebesta Review which ferrocenium ion was believed to oxidize the enamine rivatives. Interestingly, ferrocene was a better catalyst than intermediate. Later, MacMillan showed that this reaction iron(II) sulfate. An example is the reaction of 2-acetyl-1- does not proceed via the SOMO activation pathway, but methyl-1H-pyrrole (66) to give ethyl (5-acetyl-1-methyl- rather via enamine activation.49 The rate-determining step 1H-pyrrol-2-yl)difluoroacetate (67) (Scheme 23).55 of the process is the addition of TEMPO to the enamine and 3+ BrCF2CO2Et this adduct is then oxidized by Fe ions forming an imini- Me Me Cp2Fe (10 mol%) CF2CO2Et um cation that is finally hydrolyzed to the product. The ac- N N O H2O2, DMSO O tivity of the ferrocenium ion in this transformation was ex- Me r.t., 12 h Me 3+ plained by its decomposition to Fe in N,N-dimethylform- 66 67, 88% amide, which activated TEMPO for the addition. Scheme 23

1. O Me N Me Ferrocene is a useful initiator for the decomposition of Bn N Me 56,57 H arenediazonium salts to aryl radicals. THF, r.t. HBF4 Meerwein arylation of ethyl vinyl ether with arenedia- + – Ph H Cp2Fe BF4 O + zonium salts 69 using substoichiometric amounts of ferro- N Ph OH O 2. NaBH4, r.t. cene promotes decomposition of the arenediazonium salts O 64 65, 87%, 80% ee to aryl radicals, which then undergo addition to the double bond of ethyl vinyl ether. This transformation afforded a Scheme 22 range of monoarylated acetaldehydes 70 in good yields. Furthermore, whole process was advantageously per- Ferrocenium tetrafluoroborate was used as a co-catalyst formed in a flow system (Scheme 24).58 to control Kumada coupling activity via a redox-active N- N OEt heterocyclic carbene. The catalyst was a cobaltocenium salt NH2 1. Cl and the ferrocenium ion acted as re-oxidant for cobalto- N NaNO2, HCl 3 M in acetone 50 cene. R 2. Cp Fe acetone–H2O R 2 0.03 M in acetone 8.5 min 68 69 4 Ferrocene as an Electron Donor

O R = F, Cl, Br, I, CF , CN, R 3 CO2t-Bu, NO2, OMe, OCF3, Various reactions are promoted by ferrocene, which do- H OPh (in various positions) nates an electron to a substrate or reagent. This process 70, 59–76% generates the ferrocenium ion in situ, which often partici- Scheme 24 pates in another redox process. Ferrocene co-catalysis in a metal-catalyzed living radical polymerization of methyl methacrylate has been described.51 In this reaction, ferro- Addition of ferrocene substantially accelerate RAFT po- cene was oxidized to the ferrocenium ion by a rutheni- lymerization of methyl methacrylate with 2-cyanoprop-2- 59 um(III) catalyst, namely RuCl(Cp*)(PPh3)2. The addition of yl naphthalene-1-carbodithioate (CPDN). ferrocene enabled significantly lower ruthenium catalyst A mesoporous phenylene-silica that was derivatized loading. Furthermore, the reaction afforded the corre- with ferrocene catalyzed the oxidation of styrene to benzal- 60 sponding polymer with a low distribution of molecular dehyde. Apart from the main product, styrene oxide, 1- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. weights. In the photodecomposition of chloroform by ferro- phenylethanol and benzoic acid were found as side prod- cene/ferrocenium ion,52 ferrocene is photo-oxidized to the ucts. Hydrogen peroxide or tert-butyl hydroperoxide were, ferrocenium ion, which then decomposed chloroform to in this case, used as the oxidants. The reaction started with

HCl, Cl3COOH, and C2Cl6. The addition of ferrocene cata- oxidation of ferrocene to a ferrocenium ion. The oxidation lyzed the degradation of methylene blue under Fenton con- of different alkylbenzenes 71 and secondary alcohols 73 ditions;53 ferrocene in this reaction was oxidized to the fer- and 75 by 30% aqueous hydrogen peroxide was catalyzed rocenium ion by hydrogen peroxide. either by ferrocene Schiff base anchored on polymer C1 or Ferrocene also promotes the addition of 2,2-dichloro- by its iron(III) chloride complex C2.61 Schiff base complex carboxylates to alk-1-enes. The role of ferrocene is to gener- C2 was a much better catalyst. Presumably, the actual cata- ate the corresponding alkyl radical by homolytic cleavage of lyst of the reaction was the ferrocenium ion, which was the C–Cl bond.54 A similar effect for ferrocene (acceleration again formed by the oxidation of the ferrocenyl moiety in of radical formation) was observed in the (ethoxycarbon- the Schiff base by hydrogen peroxide (Scheme 25). yl)difluoromethylation of aromatic and heteroaromatic de-

Syn thesis Š. Toma, R. Šebesta Review

m-chloroperoxybenzoic acid followed by the addition of the HN N C Fc HN N C Fc H H ferrocene derivative. The key step in the proposed mecha- Fe nism is reduction of hydroxylammonium species 78 to N- Cl Cl Cl OH2 C1 centered cation radical 80, and then oxidation of α-aminyl C2 radical 81 to iminium intermediate 82, which upon hydro- 30% H2O2 O (2 equiv) lysis gave demethylated product 83. Deoxygenated N-me- R R thylamines 84 were also observed (Scheme 26). MeCN, 60 °C, 10 h C1 or C2 X 71 X 72 Fe(II) OH R = H, Me, Et 14–26% (C1) O OH H N N Fe(II) 47–74% (C2) N Me X = H, Cl, NO2 Me Me 79 77 78 OH O H 30% H2O2 (2 equiv) H Fe(II) Fe(III) MeCN, 60 °C, 10 h C1 or C2 X 74 N Me Fe(III) + H O X N CH2 N CH2 + 2 73 26–31% (C1) – H X = H, Cl, NO2 87–90% (C2) 82 81 80 Fe(II) hydrolysis 30% H O 1 1 2 2 R Fe(III) R (2 equiv) OH O MeCN, 60 °C, 10 h 2 2 R N H + OCH R 76 2 N Me 75 C1 or C2 1 2 21–29% (C1) 83 R , R = Me, C5H9, Ph 68–86% (C2) 84 Scheme 25 Scheme 26

The ferrocenium cation was involved in the direct alke- Ferrocenium salts were involved also in N-demethyla- nylation of a sp3 (C–H) bond by decarboxylation of cinnamic tion of N-methylalkaloids (Figure 1). This reaction was cata- acids 85 and 87 under ligand-free conditions.63 The corre- lyzed by ferrocene and some of its derivatives.62 The cata- sponding alkenyl products 86 and 88 were obtained in good lyst loading was usually between 20–25 mol% of the ferro- yields. The mechanism comprises of the formation of ben- cene derivative and the best results were achieved when zyl radicals, which add to the double bond of the cinnamic reactions were carried out in chloroform, or in the case of acid, followed by decarboxylation and oxidation of the in- less soluble N-methylalkaloid N-oxides in chloroform–pro- termediary radical (Scheme 27). pan-2-ol (3:1) mixture at 50 °C. The most effective catalyst t-Bu was ferrocenylacetic acid. The corresponding demethyla- O O (2 equiv) tion products were isolated in 72–86% yields. O t-Bu Cp2Fe (15 mol%) OH X RO X toluene MeO 120 °C, 24 h, Ar 86 OMe 85

X = H, Cl, F, OMe, Me 63–86% X = NO2, CN, COOMe 21–45% O instead of phenyl can be 2-furyl , 2-thienyl, 3-pyridyl, 1-naphthyl 78–85% O NMe Me NMe MeN MeO Me HO Y thebaine (R = Me) MeO MeO CO2H oripavine (R = H) dextromethorphan codeine Y This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Cp2Fe, DTBP MeO MeO MeO 120 °C, 24 h, Ar 88 CO2H CO H 2 87 Y = Cl, I, COMe, CH2Cl, etc. 60–80% Fe Fe Fe O

NMe ArMe + O ArCH2

MeO Me2Fc FcCO2H FcCH2CO2H Cp2Fe COMe COOH COO Cp Fe Cp Fe, (Cp*) Fe Ar Ar 2 thevinone 2 2 DTBP Figure 1 N-Methylalkaloids studied in ferrocene-catalyzed demethyla- Ar ArCH tion 2 Ar Cp2Fe Ar Ar – CO2 COO – Cp2Fe The demethylation reaction was also studied on the Scheme 27 amine N-oxides 77. The reaction was performed as a one- pot procedure, which comprised oxidation of alkaloids with

Syn thesis Š. Toma, R. Šebesta Review

Participation of the ferrocenium salt was proposed for O the ferrocene-catalyzed synthesis of arylboronic acids from arenediazonium salts (Scheme 28).64 Arenediazonium R1 R2 FeCp2 O tetrafluoroborates 89 were treated with ferrocene and an (1 mol%) O aminoborane. Intermediary aryl(amino)boranes 90 were 94, 30–68% TBHP (2.2 equiv) then transformed into pinacol boronates 81. However, bo- R1 R2 MeCN, 90 °C 24 h ronic acid, potassium trifluoroborate, or diaminonaphthyl- O n O borane could also be obtained. Both electron-donating and 92, n = 0 FeCp2 electron-withdrawing groups were tolerated in the starting 93, n = 1 (0.1 mol%)

1 2 material and the product yield ranged from 60 to 70%. The R1, R2 = F, Cl, Br, Me, t-Bu, OMe R R proposed reaction mechanism is shown in Scheme 29. 95, 56–84% Scheme 30 FeCp2 (0.1%) BH -N(i-Pr) R 2 2 (2 equiv) R N(i-Pr)2 protected α-amino acids. The reaction conditions were op- N BF 2 4 B timized with [(dimethylamino)methyl]ferrocene (96) and MeCN, r.t., 2 h H 89 butyl acrylate (97) (Scheme 31). 90 R = Me, MeO, NO2, F3C, F, Cl, Br, I (in various positions) O O(n-Bu) NMe2 O 1. MeOH R Pd(OAc) (5 mol%) B Fe 2 K CO (30 mol%) 2. pinacol O 2 3 96 TBAB (50 mol%) NMe2 91, 47–91% + O(n-Bu) L* (10 mol%) Fe Scheme 28 DMF, air, 60 °C O 5 h III FeCp2 + ArN2BF4 Ar + [Fe Cp2]BF4 + N2 97 (3 equiv) 98, 62–98%, 40–99% ee H i-Pr Scheme 31 Ar + BH2NH(i-Pr)2 Ar BN H i-Pr H i-Pr

Ar BN + ArN2BF4 Ar + ArBHN(i-Pr)2 + N2 + HBF4 The most efficient chiral ligands were Boc-protected H i-Pr tert-leucine, phenylalanine, leucine, or isoleucine (up to H i-Pr 98% yield and 99% ee). Seventeen different alkenes were ex- III Ar BN FeCp ArBHN(i-Pr) [Fe Cp2]BF4 + 2 + 2 + HBF4 amined in this reaction and in all cases, the corresponding H i-Pr products were isolated in high yield and enantiomeric puri- H i-Pr H i-Pr 2 ties. An important intermediate in the reaction is the [(di- Ar BN Ar B N H + ArBHN(i-Pr)2 H i-Pr H i-Pr methylamino)methyl]ferrocenium cation formed by air oxidation. It reoxidizes Pd(0) to Pd(II) and thus helps to close BH2NH(i-Pr)2 III [Fe Cp2]BF4 FeCp2 the catalytic cycle (Scheme 32). The formation of this inter- or ArBHN(i-Pr)2 mediate is supported by a control experiment using N,N-di- Scheme 29 methylbenzylamine as the substrate in air, which afforded only trace amounts of the desired product. A small amount of ferrocene can initiate the intramolec- The involvement of a ferrocenium ion was proposed in

ular cross dehydrogenative coupling of ortho-formylbiphe- the unexpected vinylic nucleophilic substitution of a fluo- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. nyls 92 or ortho-formyl diphenyl ethers 93.65 The reaction ride anion by a hydroxide anion.67 The reaction occurred occurs via base-mediated homolytic aromatic substitution with 1,1′-bis(trifluorovinyl)ferrocene upon its oxidation by and affords a range of xanthones 94 and fluorenones 95 in silica gel or potassium hexacyanoferrate(III). preparatively useful yields (Scheme 30). Ferrocene can catalyze radical C–H imidation of (hete- Ferrocenium salt were involved in an interesting asym- ro)arenes 99.68 A range of aromatic and heteroaromatic metric dehydrogenative Heck reaction on [(dimethylami- compounds were derivatized in this way. The methodology no)methyl]ferrocene (96).66 The reaction was catalyzed by tolerated both oxidizable, acid-labile functionalities, as well palladium(II) acetate and chiral ligands, in this case mono- as multiple heteroatoms and aryl iodides (Scheme 33).

Syn thesis Š. Toma, R. Šebesta Review

O2 (air) – O NMe2 O – t-BuO , – CO2 – acetone Fe O CO t-Bu N 3 N + e–

O O NMe2 100 Boc-L-Phe-OH 102 Het Fe Pd(II) NMe2 99 Fe Fe O-t-Bu

Pd(0) Ph H Fe N O O R Boc H Het N N O O – H+, – e– Het Pd NMe2 NMe2 H O O 101 103

Boc-L-Phe-OPd Fe Scheme 34 Fe R

Ferrocene can be used in the aryldifluoromethylation of Me N 2 activated alkenes 104 (Scheme 35).69 Ferrocene is first oxi- Boc H N Pd Fe dized by hydrogen peroxide to the ferrocenium ion. By the O R action of hydroxyl radicals on dimethyl sulfoxide, methyl Ph O radicals were likely formed that help to generate the de- Scheme 32 sired sulfonyldifluoromethyl radical. These species add to the conjugated double bond of the substrate and initiate the

O radical cyclization. In the last step, the ferrocenium ion oxi- R Het 99 Cp2Fe (5 mol%) dizes the intermediary radical to the product 105. R Het N + O CH2Cl2, 50 °C O 3 1 Cp Fe (10 mol%) 1 R O R 3 2 R CF2SO2Ph O O-t-Bu R H O (3 equiv) N O 101 2 2 O PhSO CF I (1.5 equiv) N O 100 N O 2 2 2 DMSO–THF, 60 °C, 8 h R2 OMe R OMe 104 105, 48–92% NR2 NR2 1 NR2 NR2 R = Me, MeO, F, Cl, Br, I, CF3O, CF3 R2 = Me, Bn 3 N MeO N OMe R = Me, Bn, CH2OMe, CH2OAc, CH2NPhth CO2Me 46% 63% 58% 47% O S O OH NR2 O Me DMSO Me OH MeO N OMe H2O2 OH S Me Me N N Me Me NR2 RCF I N N 2 R2N O N N TIPS MeI Cl Me Fe(II) Fe(III) OH 60% 56% 40% RCF2

H CF2R 104 Scheme 33 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. CF2R O 105 Ph N N O H2O Ferrocene functions as an electron shuttle in the de- Me Me composition of perester reagent 100; this decomposition Scheme 35 affords succinimidyl radical 102, which adds to the aromatic system. Finally, the electron is removed by a ferrocenium 5 Catalysis with Other Ferrocenium Deriva- ion from intermediary radical 103 to afford final products 101 (Scheme 34). tives

A SciFinder search for ‘ferrocenium salts as catalyst’ re- sulted in more than 50 references, mostly patents on photo- chemical initiation of oxirane and other monomers polymerization. Generally, these reactions use atypical ferrocenium salts, various iron complexes of the type (η6-arene)(η5-

Syn thesis Š. Toma, R. Šebesta Review

cyclopentadienyl)iron(+). Such salts are produced by BASF, (2) Štepnička, P. Ferrocene: Ligands, Materials and Biomolecules; Ciba-Geigy, and Syngenta and are used in industry. For in- Wiley: Chichester, 2008. terested readers, several such structures are depicted in Fig- (3) Gagne, R. R.; Koval, C. A.; Lisensky, G. C. Inorg. Chem. 1980, 19, ure 2.70 2854. (4) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877. (5) Rosenblum, M. Chemistry of the Iron Group Metallocenes: Ferro- cene, Ruthenocene, Osmocene; Interscience Publishers: New Fe PF6 Fe PF6 York, 1965. i-Pr (6) Green, J. C. Gas Phase Photoelectron Spectra of d- and f-Block NH 2 Organometallic Compounds, In Bonding Problems; Vol. 43, 37-1; Springer: Berlin, 1981, 12. irgacure 261 (BASF) CFN (7) Wilkinson, G.; Rosenblum, M.; Whiting, M. C.; Woodward, R. B. J. Am. Chem. Soc. 1952, 74, 2125. (8) Smart, J. C.; Pinsky, B. L. J. Am. Chem. Soc. 1980, 102, 1009. Fe PF Fe PF6 6 (9) Gray, H. B.; Hendrickson, D. N.; Sohn, Y. S. Inorg. Chem. 1971, 10, 1559.

N N (10) Steffen, P.; Unkelbach, C.; Christmann, M.; Hiller, W.; H Strohmann, C. Angew. Chem. Int. Ed. 2013, 52, 9836. (11) Daeneke, T.; Mozer, A. J.; Kwon, T.-H.; Duffy, N. W.; Holmes, A. CFC CFE B.; Bach, U.; Spiccia, L. Energy Environ. Sci. 2012, 5, 7090. Figure 2 (12) Khobragade, D. A.; Mahamulkar, S. G.; Pospíšil, L.; Císařová, I.; Rulíšek, L.; Jahn, U. Chem.–Eur. J. 2012, 18, 12267. (13) Chávez, I.; Alvarez-Carena, A.; Molins, E.; Roig, A.; 6 Conclusions Maniukiewicz, W.; Arancibia, A.; Arancibia, V.; Brand, H.; Manríquez, J. M. J. Organomet. Chem. 2000, 601, 126. Ferrocenium salts have various uses in organic synthe- (14) (a) Bradley, S.; Camm, K. D.; Liu, X.; McGowan, P. C.; Mumtaz, sis. The major application is connected with its suitable re- R.; Oughton, K. A.; Podesta, T. J.; Thornton-Pett, M. Inorg. Chem. 2002, 41, 715. (b) Furtado, S. J.; Gott, A. L.; McGowan, P. C. dox properties. Therefore, the ferrocenium ion is preferen- Dalton Trans. 2004, 436. tially used as a mild, one-electron, oxidant for different car- (15) Astruc, D. New J. Chem. 2011, 35, 764. banions or enolate ions. The corresponding radicals, which (16) Studer, A.; Curran, D. P. Nat. Chem. 2014, 6, 765. are formed in this way, enter into different radical reac- (17) Kelly, T. R.; Maity, S. K.; Meghani, P.; Chandrakumar, N. S. Tetra- tions. The Lewis acidity of the ferrocenium ion is rather hedron Lett. 1989, 30, 1357. weak; nevertheless, there are several examples where the (18) (a) Locke, A. J.; Richards, C. J. Organometallics 1999, 18, 3750. (b) Gibis, K.-L.; Helmchen, G.; Huttner, G.; Zsolnai, L. ferrocenium ion is employed as a Lewis acidic catalyst. The J. Organomet. Chem. 1993, 445, 181. ferrocenium ion can activate an epoxide for ring opening or (19) Khan, N.-u. H.; Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Singh, S.; a carbonyl group for additions or cycloadditions. The ferro- Jasra, R. V. J. Organomet. Chem. 2007, 692, 4361. cenium ion participates in several reactions that are initiat- (20) Khan, N.-u. H.; Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Singh, S.; ed by donation of an electron from ferrocene to the sub- Suresh, E.; Jasra, R. V. Tetrahedron Lett. 2008, 49, 640. strate and later the electron is accepted back by the ferroce- (21) Yadav, G. D.; Chauhan, M. S.; Singh, S. Synthesis 2014, 46, 629. nium ion. (22) Yadav, G. D.; Singh, S. Tetrahedron Lett. 2014, 55, 3979. (23) Narasaka, K.; Arai, N.; Okauchi, T. Bull. Chem. Soc. Jpn. 1993, 66, The easy availability, low price, stability, and nontoxici- 2995. ty of ferrocenium salts makes them interesting reagent for (24) Adams, C. J.; da Costa, R. C.; Edge, R.; Evans, D. H.; Hood, M. F. various organic reactions that rely on redox transforma- J. Org. Chem. 2010, 75, 1168.

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Syn thesis Š. Toma, R. Šebesta Review

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