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A Powerful Combination: Recent Achievements on Using TBAI and TBHP as Oxidation System Cite this: DOI: 10.1039/x0xx00000x Xiao-Feng Wu,a,b* Jin-Long Gong,a and Xinxin Qia Manuscript

Received 00th January 2012, The recent achievements on using TBAI (tetrabutylammonium iodide) and TBHP (tert-butyl Accepted 00th January 2012 hydroperoxide) as oxidation system have been summarized and discussed.

DOI: 10.1039/x0xx00000x

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Introduction Accepted Oxidative transformation is one of the fundamental reactions in TBAI-catalyzed C-C bonds formation modern organic synthesis, which have experienced impressive [1] progress during the last decades. Among the numerous The group of Shia reported an intramolecular radical cascade of achievements, epoxidation reactions are representative example the α-cyano-TMS (TMS- = Me3Si-)/aryl-capped alkynyl aryl [2] from academic point of view while p-xylene oxidation is vital alkyl ketones in 2012.[7] The reaction using TBAI as their [3] from the point of industrial importance. Epoxidation have catalyst and TBHP as the oxidant, a variety of [6,6,5] tricyclic been verified by the Nobel Prize of Chemistry in 2001; while frameworks were constructed which containing a high level of terephthalic acid is an aromatic carboxylic acid core to functionalization efficiently (Scheme 1). One main issue is the polyester fibers production which mainly produced by p-xylene reaction should be performed in benzene. Regarding the oxidation. However, large percentage of the known procedures reaction mechanism, this cascade process was proposed to be demands the presence of transition metals as catalysts. initiated with abstracting H-atom, α to both cyano and carbonyl th Chemistry Since the end of 20 century, sustainable development has been groups, by the free radical species t-BuO• or t-BuOO• generated taken as one of the main targets of our society development. by a catalytic cycle of oxidants TBHP and I2. Under this background, ‘Green Chemistry’ started to be considered more and more by chemists in developing new Scheme 1. Intramolecular radical cyclization. synthetic methodologies.[4] In the respect of oxidation reactions, catalytic systems without the need of metal catalysts are more O O 1 CN R appealing than the traditional transition metal relied oxidative R2 CN TBAI (20 mol%), TBHP (1.1 equiv.) transformations. Recently, iodide or hypervalent iodine- o Benzene, 80 C, 0.5-1h promoted organic reactions have received considerable R1 R R2 R attentions which have already experienced impressive R3 R3 advancements during the past few years.[5] Although these 15 examples - . - 72-98% reactions can avoid the usage of metal salts, the stability and tBuOOH + I tBuO + I2 + OH toxicity of these compounds lead those transformations have to + + - . - tBuOOH I2 OH tBuOO + I + H2O be paid special attentions. More recently, the using of O O

tetrabutylammonium iodide (TBAI) as catalyst with the Biomolecular CN CN combination of tert-butyl hydroperoxide (TBHP) as a powerful tBuO. or tBuOO. oxidation system has received unique attentions. In the light of R1 1

R & R2 R2 the advantages of TBAI, such as inexpensive, stable and etc., R3 R3 increasing efforts are being put on this topic. Even though the populating of TBAI catalyst in organic synthesis, a general [6] review on this topic is still absent. Taking all these points into O 1 1 CN R O R R2 CN 2 consideration and our own interests on TBAI-catalyzed . R oxidations, we started to prepare a review on this topic. The -H main achievements on this topic will be discussed and 3 catalogued by the bonds formed (C-C, C-N, C-O, C-S, N-N). R R3 The reaction mechanisms will be discussed and compared. Selected examples of substrates will be listed as well and a Nachtsheim and co-workers developed an iodocyclization Organic [8] personal outlook will be given at the end. reaction of o-alkynylphenyl carboxaldehydes. Highly

This journal is © The Royal Society of Chemistry 2013 J. Name., 2013, 00, 1-3 | 1 Organic & Biomolecular Chemistry Page 2 of 12 ARTICLE Journal Name substituted 1-naphthalenones were prepared in high yields (up Wang and co-workers developed an interesting TBAI-catalyzed to 91%). In their catalyst system, tetrabutylammonium iodide C3-formylation of indoles with N-methylaniline as the (TBAI) was applied as the electrophilic iodine source, Oxone source.[11] This method can be applied to N-H and N-substituted was used as a non-nucleophilic co-oxidant, and HFIP indoles without using toxic phosphorus oxychloride and (1,1,1,3,3,3-hexafluoro-2-propanol) as a fluorinated protic transition metal catalyst. Good yields of formylated indoles solvent. TBHP, which was intensively used as co-oxidant in were produced (Scheme 3). tert-Butyl peroxybenzoate (TBPB) previous (hypo)iodite-catalyzed reactions, seemed to be a was used as the oxidant. Notably, under the optimized reaction nonsuitable co-oxidant due to the nucleophilic properties of the conditions, TBHP was completely ineffective at 80 oC, and - o emerging t-BuO anion which could undergo undesired only a trace product was obtained at 100 C. The use of H2O2 nucleophilic addition to the reaction intermediate. led to no product formation either at 80 oC or 100 oC. The yield At the beginning of 2013, Itoh and co-workers reported a dropped from 82% to 15% in the absence of nBu4NI, which molecular iodine-catalyzed cross-dehydrogenative coupling indicated that the use of nBu4NI was critical for the success of (CDC) reaction between tertiary amine and a carbon this reaction. When a radical inhibitor, TEMPO (2,2,6,6- nucleophile using hydrogen peroxide as the terminal oxidant.[9] tetramethylpiperidine-N-oxyl), was added into the reaction

The corresponding aza-Henry products were formed in good system, the yield of the desired product decreased dramatically Manuscript yields using 0.1 equiv. of molecular iodine and 2 equiv. of to 30% under the optimized conditions. Taking all these into o H2O2 at 40 C (Scheme 2a). TBAI was tested as catalyst under consideration, the author proposed the reaction started with the the standard conditions as well, 24% of the desired product was reaction between an iodide (I-) ion and TBPB which provide a formed. However, when the authors tested their model system benzoyloxy radical (or tert-butyloxy radical) and iodine (I2). with 1 equiv. of molecular iodine in the absence of aq. Soon later, the same group found that replace N-methylaniline hydrogen peroxide, only 16% yield of the desired produced was with 4-substituted-N,N-dimethylanilines, a C3-formylation and formed and recovered 75% of their starting material. This result N-aminomethylation of indoles occurred using potassium suggested that the oxidation of amines requires both molecular iodide as the best catalyst (Scheme 3).[12] TBAI could gave iodine and hydrogen peroxide. NaI/H2O2/acid as a known moderate yield of the desired product in model study. In this system for generated HOI could gave the desired products in 65% two methodologies, pivalic acid was used as the additive as it yield as well. Additionally, BHT [2,6-bis(1,1-dimethylethyl)-4- has been shown to suppress decomposition of indoles under Accepted methylphenol] as a radical inhibitor was added in their reaction oxidative conditions.[13] system as well, the reaction was scarcely suppressed and gave 71% of the desired product. Based on these observations, they Scheme 3. TBAI-catalyzed formylation of indoles. proposed a HOI catalyzed reaction mechanism. In the same CHO year, the same group reported an improved reaction system NHMe [10] mo e u v. (Scheme 2b). They succeed to avoid the usage of H2O2 and TBAI (10 l%), TBPB (4 q i ) 17 examples Piv H 5 e uiv. DM o 7-82% further decreased the loading of iodine. Molecular oxygen was N O ( q ), SO, 80 C N R R applied as the terminal oxidant, and visible light from a R' R' general-purpose fluorescent lamp was necessary. In this new system, TBAI, CaI , KI, MgI and etc. can all be applied as the CHO 2 2 NMe2 catalyst and gave the corresponding product in good yield. In Chemistry KI 20 mol% , TBPB 6 equiv. ( ) ( ) 10 exam les the case when one equivalent of molecular iodine was used in o N p N PivOH (5 equiv.), DMSO, 60 C R 32-84% the absence of molecular oxygen and visible light irradiation, R H R' N only a trace amount of the corresponding product was obtained. R' The same as their precious system, BHT did not inhibit the tBuOOBz + I- u . + z . + reaction, which exclude the radical mechanism. tB O B O I2

Ar r Ar u . z . A I2 - Scheme 2. I2-catalyzed CDC reaction. N tB O /B O N N I

indole I 0.1 equiv. , H O 2 equiv. NuH 2 ( ) 2 2 ( ) N o N Ar 40-70 C r A Ar Ar tBuO./BzO. Nu N N NuH = MeNO2, EtNO2, CH2(CO2Me)2, acetone, iBuCOMe N N N N 18 examples r Ar 5-93% A a I 2 CHO Biomolecular TBAI (0.1 equiv.) MeNO2 N N v. o Ph 24% Ph H2O2 (2 equi ), 60 C - Ar N I r & CH NO N N A 2 2 N N Ar I 0.05 e uiv. , AcOH 5 e uiv. u 2 ( q ) ( q ) N N H N Ar rt, O2 (1 bar), visible light Ar Li et al. reported a TBAI-catalyzed intramolecular cross- Nu dehydrogenative coupling (CDC) reaction for the synthesis of [14] 10 examples 1H-indole derivatives. Intramolecular oxidative coupling of 32-84% N-arylenamines proceeded in the presence of a catalytic amount TBAI (0.05 equiv.) b of nBu4NI and tert-butyl hydroperoxide (TBHP) to afford the AcOH 5 equiv. MeNO ( ) N N 2 corresponding 1H-indole derivatives in good to excellent yields Organic ar v s e Ph 84% Ph O2 (1 b ), i ibl light (Scheme 4). The addition of TEMPO did not suppress the CH2NO2 reaction completely, which suggests that a radical pathway does

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not predominate in this system. The other iodide salts like LiI, NaI, NH4I gave worse results. As indicated in Scheme 5, they failed in the reaction between acetophenone with piperidine under their conditions. In another report, Prabhu and co-workers succeeded in this transformation Scheme 4. TBAI-catalyzed indoles synthesis. by using N-iodosuccinamide as the catalyst in MeCN at room temperature.[17] In this report, NaI was found to effective as R" R' catalyst as well. The combination of TBAI with TBHP was not TBAI (30 mol%), AcOH 20 exam les R' p tested here; only trance of product was formed in the case of R N TBHP 2.5 equiv. , DMF, 100oC 27-99% H ( ) N R" R H using TBAI and H2O2 as the oxidation system. TEMPO as a radical scavenger was tested in this system as well, good yield CO2Et CO2Et CO2Et CO2Et MeO I was formed which exclude the possibility of radical process. Ph Ph Ph Ph The authors proposed the corresponding α-iodo compound as N N N N H H H H the intermediate and followed by reaction with amine and 99% 84% 71% 80% further oxidation. In 2012, Wan and co-workers developed a TBAI-catalyzed Manuscript oxidative coupling of aldehydes and dialkylformamides.[18] TBHP was applied as the terminal oxidant, all the desired TBAI-catalyzed C-N bonds formation amides were isolated in good yields (Scheme 6). Interestingly, In 2012, a novel and easy practical direct synthesis of α- when dimethylamine was tested under the optimized conditions, ketoamides from aryl methyl ketones and dialkylformamides only less than 5% of the desired product was formed. was developed.[15] The procedure based on using TBAI as the catalyst, TBHP as the oxidant and water was required as the Scheme 6. TBAI-catalyzed synthesis of amides from aldehydes. reaction media. The desired products were isolated in good O yields (Scheme 5). DTBP and BPO (benzoyl peroxide) were O O TBAI 20 mol% exam es examined as the oxidant as well, but none of the two showed R ( ) R' 35 pl H N o r - Accepted Ar H TBHP (6 equiv.), 90 C A N 37 96% activation under the standard condition. In respect of the R' R substrates scope, in addition to the ketones, different CHO mo O dialkylformamides including N,N-diethylformamide, TBAI (20 l%) TEMPO o N piperidine-1-carbaldehyde, morpholine-4-carbaldehyde, 4- TBHP, DMF, 90 C O methylpiperazine-1-carbaldehyde were tested instead of DMF 64% and the corresponding products were obtained in moderate to - . high yields. Notably, no desired product was observed when tBuOOH + I tBuO O O O piperidine was used instead of piperidine-1-carbaldehyde in O R tBuO. u . - R R tB O N CO H N their catalyst system. Additionally, 1-arylethanols can be Ar H Ar N applied as substrates and give access to α-ketoamides in R' R' R' satisfactory yields while 2-oxo-2-phenylacetic acid failed to Chemistry coupling with DMF under the standard conditions. Regarding O the reaction mechanism, the authors proposed the reaction R' beginning with the tert-butoxyl radical generation under the Ar N assistance of the iodide anion. This radical traps H from the aryl R methyl ketone and DMF respectively to form the corresponding radicals and starts the reaction (Scheme 5). In this article, the In the same year, Zhu and co-workers described a TBAI- catalyzed synthesis of amides from alcohols and author demonstrated that iodine was not effective for this [19] transformation under the same conditions. Wang and co- dialkylformamides. Using TBHP as the oxidant, various workers later reported that by the addition of benzoic acid as amides were formed in good yields (Scheme 7). In their additive, this transformation can be achieved with iodine as the optimization process, reaction temperature was found to be catalyst in toluene at 80 oC.[16] Moderate to good yields of the critical as no product could be observed at 60 oC while 88% of desired products were isolated. the desired product was formed at 90 oC. When the reaction was carried out in 1,4-dioxane or THF, unsatisfactory yields were resulted. Further studies indicated that else catalysts Scheme 5. TBAI-catalyzed synthesis of α-ketoamides. including nBu4NCl, NaI, and CuI showed a lower catalytic activity. No reaction occurred with I as catalyst for this system. Biomolecular O 2 O O R TBAI 20 mol H O Interestingly, the report from Wang’s group shown that this R ( %), 2 N 24 examples H N o Ar R' - & Ar TBHP (5 equiv.), 100 C 54 90% transformation can be achieved with I2 by adding catalytic R' O amount of NaOH as additive.[20] tBuOOH + I- tBuO. Scheme 7. TBAI-catalyzed synthesis of amides from alcohols. O O O O R tBuO. . - R R tBuO N CO H N Ar Ar N R' R' R'

O R O R TBHP N Ar R' Organic N Ar R' O

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O O In 2012, TBAI as a reagent for in situ generation of hypoiodite TBAI (20 mol%) exam es R" OH R R' 20 pl [24] H N o - for aziridination of alkenes was reported. mCPBA (3- TBHP (6 equiv.), 90 C R" N 43 90% R' R chloroperbenzoic acid) was the oxidant needed, TBHP was not O O O effective at all in this case. Based on mechanistic study, they proposed the in situ generated hypoiodous acid, HOI, may be N Ph N N Ph the active species in this reaction. MeO Ph 90% 79% 66% In the report of Wan,[18] they demonstrated the reaction of Scheme 9. TBAI-catalyzed synthesis of amides from tertiary amines. aldehyde with dimethylamine was failed under their conditions. O This challenge can be resolved by using ammonium as amine O Ar mo [21] N TBAI (20 l%), DCE R' 24 examples source. Various primary amides were produced from the o R N 46-86% R H R' TBHP (4 equiv.), 90 C corresponding benzylic alcohols and aldehydes (Scheme 8). Ar The oxidative amidation of acetophenone was achieved as well O O Ph TBAI (20 mol%), DCE using ammonium iodide as both amine source and catalyst. The N 79 Ph Ph N % Manuscript H TBHP 4 equiv. , 90oC undesired nitriles were detected in all the cases. Especially ( ) Ph when using ammonia as amine source, 25% of benzonitrile was Ph Ph formed. In the mechanistic study, they found benzonitrile could N TBHP N not be transformed into benzamide under the standard O Ph Ph Ph conditions. The author proposed the attack of ammonia to N tBuO. N N aldehydes generating hemiaminals was the first step of this Ph procedure, which can then be converted into the corresponding Ph Ph N N N Ph primary amides via dehydrogenation. O N O Scheme 8. TBAI-catalyzed synthesis of primary amides.

Ph H Ph Accepted N N HCHO mo O TBAI (10 l%), DCE 19 exam les R O NH4HCO3 p TBHP 3 e uiv. , 70oC 26-90% H Ph ( q ) R NH2 RCHO N Product

O TBAI (10 mol%), DCE 12 examples R OH NH HCO 4 3 o 20-89% In 2011, TBAI was reported has the ability to catalyze the TBHP (4 equiv.), 70 C R NH2 direct oxidative C-N coupling of 2-aminopyridines with β-keto O O TBHP Me N 70o esters and 1,3-diones to give imidazo[1,2-α]pyridines (Scheme , C , C [25] NH4I NH2 40% Ph Ph 10). tert-Butyl hydroperoxide (TBHP) was applied as the O oxidant and reaction temperature was found has significant effect in this procedure (no product was detected at 60 oC while O OH OH tBuO. o NH3 good yield was formed at 80 C). Additionally, it is noteworthy Chemistry R H R NH2 R NH2 to demonstrate that using a catalytic amount of TBAI ensures a good result, while higher loading of TBAI has negative effect TBHP O on the reaction. The reaction also took place in the absence of BF3.Et2O, but the yield of product was lower. On the other hand, R NH 2 using 1.0 equiv. of BF3.Et2O was less favorable for the reaction. Besides TBAI, NaI and KI were also capable to catalyze this At the beginning of 2013, a TBAI-catalyzed oxidative synthesis reaction which indicates the not necessaricity of ammonium of amides from aldehydes and aromatic tertiary amines was counterion during the reaction. [22] developed. Various amides were isolated in good yields by using TBAI and TBHP as the catalytic system (Scheme 9). I2 Scheme 10. TBAI-catalyzed synthesis of imidazo[1,2-α]pyridines. was found to be non-effective for this transformation. Additionally, neither H2O2 nor DTBP showed any activation in N NH 2 O O TBAI 10 mol% , TBHP 2 e uiv. R' this transformation. Notably, this reaction could also proceed to ( ) ( q ) N o afford the desired amides under the optimal conditions by N R' R" BF3.Et2O (20 mol%), MeCN, 80 C R R O reacting N-alkylaniline with aldehydes. For example, N- R" Biomolecular 26 exam les methylaniline or N-ethylaniline reacted with benzaldehyde to N N N p 18-83 obtain the corresponding products in 53% and 75% yields, Ph Me Me % N N N & respectively. Interestingly, when 2-phenylacetaldehyde was 81% 65% 63% investigated with N,N-dimethylaniline under the optimal O O O EtO2C MeO2C Me conditions, N-methyl-N-phenylbenzamide was produced in 79% O O yield. Meanwhile, a similar system with lower loading of TBAI NH N 2 O O R' in refluxing ethyl acetate was reported [TBAI (2.5 mol %), R' R" N [23] N TBHP (2 equiv.), EtOAc (ethyl acetate), refluxing]. In this R' R" H2N N R R O report, aliphatic amines such as triethylamine and tributylamine R R" can be applied as the coupling partners as well. In both studies, the oxidation of tertiary amines to give secondary amines was Zhu and co-workers reported a TBAI-catalyzed oxidative Organic proposed to be the first step, and then followed by the reaction synthesis of oxazoles at the beginning of 2012.[26] The of secondary amines with aldehydes to give amides. corresponding products were formed in good yields in their

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system (Scheme 11). It should be noted that the cascade should be the active catalyst. Thus N-iodomorpholine reaction did not occur in place of nBu4NI with nBu4NCl or hydroiodide was synthesized and further investigated. The nBu4NBr. Additionally, TBHP in water gave better results than reaction of hydroiodide with benzoxazole gave the the TBHP in decane which suggested that a small amount of corresponding product in 33% yield. A two-fold excess of water was beneficial to the reaction. Surprisingly, when HOAc hydroiodide did not increase the yield. Nevertheless, when or BF3.Et2O was used as an additive, a less satisfactory yield catalytic amount of hydroiodide (10 mol%) was used, the was obtained. In the solvents testing, EtOAc afforded the best corresponding product was isolated in 92% yield. Based on all result, DCE, DMF or MeCN led to lower yield. Adding a these observations, the authors stated that the activation of the radical inhibitor BHT (2,6-di-tert-butyl-4-methylphenol) to the amine via in situ formation of a highly reactive N-I bond from reaction system of ethyl acetoacetate with benzylamine, no TBAI and the co-oxidant seems to be the reaction pathway significant influence was found. Moreover, no radical which could also explain the effect of carboxylic acids. intermediate was trapped by radical scavenger TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl). These results ruled out Scheme 12. TBAI-catalyzed synthesis of amination of benzoxazoles. the possibility of a radical mechanism. The authors suggested

O R' Manuscript the active iodine species ammonium hypoiodite ([n- O TBAI 5 mol% , MeCN + - + - R' R" ( ) N Bu4N] [IO] ) or iodite (n-[Bu4N] [IO2] ) plays an important role N N H H2O2 (5 equiv.), AcOH (5 equiv.), rt N R" in this reaction R or R o TBHP (1.5 equiv.), AcOH (3 equiv.), 80 C 19 examples 52-93% Scheme 11. TBAI-catalyzed synthesis of oxazoles. - + O TBAI + H2O2 + AcOH [I(OAc)2] [NBu4] + u c I NB 4OA Ar O O R O O TBAI (20 mol%), EtOAc 16 examples r N O A NH2 o 40-76% R' R TBHP (4 equiv.), 40 C R' O O N N O H

Me Ph Me Ph O Accepted O O O O I O Ph Ph Ph Ph O N N N N N N N I N CO2Et CO2Et COMe COPh O N 40 70% 67% 61% % NBu4OAc I O + - tBuOOH + - TBAI + tBuOOH [nBu4N] [IO] [nBu4N] [IO2] N O N NBn O n + - O O BnNH2 NHB O [nBu4N] [IO2] OEt Scheme 13. TBAI-catalyzed amination of toluenes. OEt OEt I HO ONBu4 H n N B NH2 TBAI (10 mol%) N N 24 exam les o p Chemistry O n TBHP 3 equiv. , 75 C NB O n R N ( ) N N 71-98 NB O R % HO OEt Et O OEt N Ph N Ph HN Ph N Tol N Tol N 90% 90% N N 91% N N N Me Me O O O O O Ph Ph O O N o o S o S CO Et N T l N T l N T l N Tol H 2 CO2Et Ph O 82% O 98% O 89% In 2011, an efficient procedure for amination of benzoxazoles + - tBuOOH + - based on the use of catalytic amount of TBAI and aqueous TBAI + tBuOOH [nBu4N] [IO] [nBu4N] [IO2] [27] solutions of H2O2 or TBHP as co-oxidant was developed. Highly desirable 2-aminobenzoxazoles were isolated in nBu N + IO - or nBu N + IO - excellent yields (Scheme 12). In their optimization process, [ 4 ] [ ] [ 4 ] [ 2] tetrabutylammoniumbromide and -chloride showed no catalytic R R Biomolecular activity at all. Addition of a base such as K2CO3 or NEt3 resulted in the complete loss of reactivity. In contrast, when NR2 HNR2 carboxylic acids, in particular acetic acid or benzoic acid, were & R R added to the reaction mixture, the yields of the desired product

increased significantly to 68% and 70% respectively. Regarding In 2013, Zhu and co-workers reported a novel n-Bu NI- the reaction mechanism, addition of radical scavenger TEMPO 4 catalyzed method for the oxidative coupling of benzylic C-H (2,2,6,6-tetramethylpiperidine-N-oxyl) had only a slight impact [28] substrates with unmodified amines. Various amination on the yield of the desired product. Furthermore no TEMPO- products were obtained in good to excellent yields by using bound intermediate could be observed. Thus a radical TBHP (70% in water) as an environmentally benign oxidant mechanism can be ruled out. Since catalytic amounts of I 2 (Scheme 13). This method affords a facile metal-free approach (without co-oxidant) did not yield the desired product, the in

for the synthesis of imidazole and purine nucleoside derivatives Organic situ generation of I and its subsequent function as a mild Lewis 2 and has also been easily scaled-up to the gram scale. In the acid can be excluded as well. Then the author proposed +I mechanism studies, when a radical inhibitor, BHT, was

This journal is © The Royal Society of Chemistry 2012 J. Name., 2012, 00, 1-3 | 5 Organic & Biomolecular Chemistry Page 6 of 12 ARTICLE Journal Name introduced into the reaction mixture, the formation of the of TBAI and TBHP, ketones, aldehydes, and 1,3-dicarbonyl desired product was completely suppressed. Furthermore, compounds were reacted with carboxylic acids and gave the replacing n-Bu4NI with I2 led to no product. Interestingly, the corresponding α-acyloxycarbonyl compounds in good to reaction proceeded smoothly by the combined use of n- excellent yields (Scheme 15). In the case of α-oxyacylation of Bu4NOH and I2, which could afford the desired product in 76% aldehydes, piperidine was needed as an additive and leads the yield. The authors proposed that the active hypoiodite [n- reaction under milder conditions. In the mechanism study, they + - + - Bu4N] [IO] or iodite [n-Bu4N] [IO2] plays an important role in confirmed the existence of hypoiodite or iodite. By the reaction the sp3 C-H amine reactions. Additionally, the benzyl radical of diphenylcyclopropyl ketone, they confirmed the reaction intermediate was trapped by a radical scavenger, TEMPO, and included a radical intermediate. the oxyamination product was isolated in 62% yield. More recently, Zhang and co-workers developed a TBAI- Scheme 15. TBAI-catalyzed α-oxyacylation of ketones and aldehydes. catalyzed oxidative imidation of ketones and imides.[29] α- Amino ketones were produced in good yields (Scheme 14). In O O TBAI (10 mol%), EtOAc R' 17 examples this reaction, the use of some other catalysts, such as NaI, NH4I, R" H R R' CO2 o 30-99% R TBHP 2 e uiv. , 75 C Manuscript nBu4NBr, nBu4NCl, I2, and NIS, the yields of the desired ( q ) OCOR" product decreased dramatically, or no product was observed. In all the tested oxidants, TBHP was the most effective peroxide TBAI (10 mol%), EtOAc OCOR" x m R CHO R"CO H 13 e a ples in the process, other peroxides such as K S O , di-tert- 2 . e u v. o - 2 2 8 TBHP (1 1 q i ), 50 C R CHO 62 89% butylperoxide (TBP), O2 and 30% H2O2 did not perform well. piperidine (5 mol%) Regarding the amines, amines like pyrrolidine and morpholine Ph O did not give the desired aminated products. In respect of the Ph Ph mo c Ph Ph O TBAI (10 l%), EtOA reaction mechanism, when TEMPO was added to the imidation PhCO2H o O 70% TBHP (2 equiv.), 75 C reaction of pentan-3-one under the optimal condition, after 3 h, Ph trace amount of the desired product was observed. The authors Ph Ph 10% proposed the radical addition of enol to provide the α- In 2012, the direct esterification of a benzyl C-H bond using Accepted functionalized ketone as a possible reaction pathway. [33] TBAI as catalyst and TBHP as co-oxidant was reported. Scheme 14. TBAI-catalyzed amination of ketones. Benzylic substrates were reacted smoothly with various carboxylic acids to give the desired esters with good to O O O excellent yields (Scheme 16). This method was also suitable for O R the O-protection of N-Boc amino acids (Boc = tert- TBAI (20 mol%), EtOAc R' NH o N butoxycarbonyl). Interestingly, the other iodides such as NaI R TBHP (2 equiv.), 130 C S S and CuI showed no catalytic activity for this transformation. O O O O R' Several mechanistic studies were performed. In the competitive 38 examples O O O O O O 46-94% esterifications involving toluene and its deuterated derivative 8 O O toluene-d , obvious kinetic isotope effects (kH/kD=9/1) was N N N observed, which indicating that the cleavage of benzyl C-H S Chemistry N O O O O bond was involved in the rate-determining step. The yield of S the reaction decreased when addition of the radical scavenger 91% 81% 92% O O 90% TEMPO or BHT to the reaction mixture. In the reaction with O O O O O O Ph TEMPO, the oxyamination product, which was formed through N N N the trapping of the benzyl radical by TEMPO, was separated in S 58% yield. This result indicates that the benzyl radical was O O 94% O 85% O 72% involved in the catalytic cycle of this esterification. Based on those observations, they proposed a reasonable reaction In 2011, Wan and co-workers described an efficient synthetic mechanism which is similar as shown in Scheme 13. The methodology for C-N bond formation based upon in situ reaction started with the oxidation of TBAI to form the [30] + - + - generation of TsN·NaI. N-Sulfonyl formamidines were {[Bu4N] [IO] } or {[Bu4N] [IO2] } species, which is going to produced from sulfonamides and formamides in good yields. induce the homolysis of a benzyl C-H bond to give a benzyl NaI was used as the catalyst and TBHP as the oxidant. As the radical which is the rate-determining step in the whole reaction. authors pointed out, TBAI was as effective as NaI for this The single electron of hydrogen is captured by hypoiodite transformation. which is subsequently reduced to Bu4NI and the benzyl radical Biomolecular is liable to be oxidized by the hypoiodite species to form the

benzyl cation. In this redox process, the excess oxygen atom of & TBAI-catalyzed C-O bonds formation hypoiodite captures the proton of benzoic acid to give the benzoate anion and a water molecule. The final coupling In 2010, Ishihara and co-workers reported a cycloetherification between the benzoate anion and benzyl cation gives the ester [31] of ketophenols. 2-Acyl-2,3-dihydrobenzofuran derivatives product. were isolated in excellent yields by using TBAI as the catalyst and H2O2 as the oxidant. When chiral quaternary ammonium Scheme 16. TBAI-catalyzed esterification of benzyl C-H bonds. iodide was applied as the catalyst, this oxidative transformation can be achieved in an enantioselective manner. In situ generated hypoiodite ([R N]+[IO]-) or iodite ([R N]+[IO ]- was

4 4 2 Organic proposed to be the active catalyst. Later on, they reported their achievements on the intermolecular version.[32] In the presence

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Ar R TBAI (20 mol%) 37 examples the combination of sodium benzoate and cyclohexene. 3- Ar R R'CO H 2 o 56-99% TBHP (2 equiv.), 80 C OCOR' Chloroperoxybenzoic acid, a known acyloxy radical donor, was also a suitable reaction partner for the transformation. Notably, O O O O a tert-butyl perester, from the coupling of the acyloxy and tert- Ph O Ph Ph O Ph O Ph Ph O butoxyl radicals, was detected by LC-MS in the reaction 97% 84% 95% 89% mixture of 4-bromobenzoic acid with cyclohexene. When hippuric acid was used as a reactant, both the tert-butyl perester In 2011, Wan and co-workers reported a TBAI-catalyzed and decarboxylation product were observed as by-products. The oxidative coupling of carboxylic acids with ethers.[34] Various formation of the desired allylic ester was completely suppressed α-oxyacylated ethers were isolated in good yields (Scheme 17). by introducing TEMPO to the reaction mixture. The compound In their model study on the coupling of benzoic acid with 1,4- from the reaction of TEMPO and the allylic radical was isolated dioxane, all the other oxidant like oxone, H2O2, O2 and etc. in 31% yield. Hence, proposed the tert-butoxyl and tert- were found to be ineffective when combined with TBAI. The butylperoxy radicals from TBHP abstract hydrogen atoms from using of metal catalysts like Pd(OAc)2, CuI, CuCl, and RuCl3 the substrates then giving the product.

instead of TBAI did not gave any of the desired product. In Manuscript mechanistic study, TEMPO was found suppressed the reaction. Scheme 19. TBAI-catalyzed difunctionalization of alkenes. No coupling occurred when TBAI was replaced with iodine and the desired product can be formed in low yield by switching the R R OH TBAI (10 mol%), nHexane O R" 20 examples catalyst to KI. Hence, the author proposed TBAI promoted r R" H r A CO2 o A - TBHP 3 equiv. , 120 C 72 92% decomposition of TBHP to the tert-butoxyl radical and a R' ( ) R' O hydroxyl anion started the transformation. R R OH R"' R" R"' TBAI (10 mol%), nHexane N 10 examples r r Scheme 17. TBAI-catalyzed oxidative C-O bond formation. A N o A R" 75-91% H TBHP 3 equiv. , 100 C R' ( ) R' R R OR' TBAI (20 mol%), EtOAc 28 examples Accepted R OR' R"CO2H O R . e u v. o 37-98% u . or u . TBHP (2 2 q i ), 80 C OCOR" tB O tB OO Ar R' O R" R"CO2H r R" O A O O Ph O O Ph O O Ph R' O O O O O O O [O] 95% 88% 93% R OH R O O Ph O O Ph O O Ph O Ph O R" H2O O r O R" Bu Et A Ar O O Pr O O R' O R' O 96% 86% 82% 86% More recently, Zhu and co-workers reported a nBu4NI- Scheme 18. TBAI-catalyzed coupling of carboxylic acids with allylic compounds. catalyzed regioselective difunctionalization of unactivated [36] alkenes. Various carboxylic acids and amines could react Chemistry R R1 smoothly with alkenes to give the corresponding dioxygenation 2 TBAI (20 mol%), benzene R R and oxyamidation products, respectively (Scheme 19). The R1 R4CO H 39 examples 2 . e u v. o - R3 TBHP (1 5 q i ), 80 C O O R3 23 98% substrate was rapidly consumed with only a trace amount of the R2 product was detected when K2S2O4 was used as an oxidant. R4 Other oxidants such as O2, H2O2, and DTBP gave O O O O unsatisfactory results. Additionally, control experiments O Ph O O O Ph demonstrated that no desired product could be identified when either nBu4NI or TBHP was absent. And the best result was afforded in n-hexane. 90% 79% 83% 80% O O O Scheme 20. TBAI-catalyzed decarboxylative acyloxylation of sp3 C-H bond.

O O O Ph

Cl Cl Cl 61% 85 23%

% Biomolecular O Ph O

O Ph O & Cl 98% Cl 68%

R1 R R1 O O R R2 O 2 4 4 R R O R 3 R3 R

Wan and co-workers developed a TBAI-catalyzed oxidative coupling of carboxylic acids with allylic compounds.[35] Allylic esters were synthesized by the selective coupling of acyloxy Organic and allylic radicals in good yields with TBHP as the oxidant (Scheme 18). In control experiments, no reaction occurred by

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Ar R' O O O mo R' TBAI 10 mol% , 80oC TBAI (20 l%) O O O 11 examples ( ) O OH N R Ar TBHP 2 e uiv. , 80oC 42-63% TBHP 6 equiv. ( q ) R R" ( ) O N R R R" 22 examples O O 71-98% OH TBAI 20 mol% Ar O O Ar ( ) 11 examples o TBHP (2 equiv.), 80 C O 85-98% O O O O O O O Ph O Ph O Ph O Ph Ph O Ph O O O O Ph O O 62% 63% 96% Ph O N H Ph O N O 95% 96% 85% 75% O

O O TBAI (20 mol%), EtOAc Wang and co-workers reported a TBAI-catalyzed benzylic C-H OH 7 Ph o 9 % TBHP (2 equiv.), 80 C Ph OH acyloxylation of 2-methylquinolines with readily available O [39] O O O aromatic aldehydes in 2012. The corresponding products TBAI 20 mol% Manuscript DMF ( ) were produced in good to excellent yields under mild and clean o Ph O N H 62% Ph OH TBHP (2 equiv.), 80 C reaction conditions using tert-butyl hydroperoxide as the green terminal oxidant (Scheme 22). This reaction could be inhibited In 2013, TBAI was applied as catalyst in the decarboxylative by the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy acyloxylation of an sp3 C-H bond in formamides and ethers.[37] (TEMPO) as well. Detailly, firstly, TBHP and TBPB (tert-butyl A variety of N-acyloxymethylamides and α-acyloxy ethers were peroxybenzoate) was decomposed by the iodide ion to generate a tert-butoxyl radical and benzoic acid. The iodide ion is easily synthesized in good yields (Scheme 20). For the reaction - - pathway, the authors proposed the corresponding carboxylic oxidized to the corresponding (hypo)iodites ([IO] or [IO2] ). acid as the intermediate, as benzoic acid was isolated in 97% Subsequently, the tert-butoxyl radical or (hypo)iodites abstract yield from phenylglyoxylic acid when the reaction was a hydrogen atom from the benzylic C-H bond of alkylarene to performed in ethyl acetate under the same conditions. On the afford benzylic radical, which was re-oxidized quickly by Accepted other hand, the reaction of benzoic acid with DMF also gave (hypo)iodites to provide benzyl cation. Finally, the reaction of the N-acyloxymethylamide in 62% isolated yield. Furthermore, benzyl cation with the benzoate anion affords the ester. Notably, the reaction was suppressed by addition of a radical scavenger, it has been reported that the reaction of 2-picoline N-oxide with acetic anhydride yields the 2-pyridylcarbinol acetate, together such as TEMPO. Hence, a radical pathway was anticipated. 2 Patel and co-workers developed for the first time a TBAI- with some sp C-H acyloxylation products. In the case of 2- [38] methylquinolines, neither 2-methylquinoline N-oxide nor the catalyzed oxidation of alkylbenzenes to benzylic esters. This 2 method gives a self-coupled product for mono or poly sp C-H acyloxylation product was detected. methylatedbenzenes (Scheme 21). The cross-coupled product can be prepared from ethylbenzene and methylbenzene where Scheme 22. TBAI-catalyzed reaction of alkylbenzenes with aldehydes. the acid part is derived from methylbenzene and the benzyl cation is derived from ethylbenzene. Various functional groups R' O R' TBAI 20 mol% , 80oC 32 exam les Chemistry are tolerated under the present reaction conditions. In their ( ) O Ar p ArCHO 15-96% TBHP 4 equiv. optimization process, no desired product could be obtained R ( ) R when oxidants H2O2, DDQ (2,3-dichloro-5,6- dicyanobenzoquinone), PhI(OAc)2 were used instead of TBHP. O O O N Ph O Other halogen species such as Bu4NBr, KI and I2 were found to O Ph Ph O Ph O Ph be completely ineffective. In the absence of either the catalyst 56% Ph O Ph (TBAI) or the oxidant (TBHP) failed to bring about the desired 76% 72% 33% transformation. Regarding the reaction mechanism, they + - proposed the active hypoiodite [Bu4N ][IO] species would Fu’s group found direct esterification of alcohols with toluene initiate a homolytic cleavage at the benzylic C-H bond of the derivatives could be achieved by using nBu4NI as the catalyst toluene to give a benzyl radical. Formation of a benzyl radical and tert-butyl hydroperoxide as the oxidant (Scheme 23).[40] In could be the rate determining step in the entire reaction. The this process, the addition of NaH2PO4 can improve the yield in benzylic radical was further oxidized by the hypoiodite species some distance and applying BHT as a radical inhibitor can + - [Bu4N ][IO] to a benzyl cation. Alternatively, some of the completely inhibited the reaction. 60% of 2,2,6,6- alkylbenzene could be converted to its alcohol via a radical tetramethylpiperidin-1-yl 1-naphthoate was isolated by adding Biomolecular oxidation path and subsequently to corresponding acid via an two equivalents of TEMPO to the reaction mixture. These aldehyde intermediate. After the formation of the acid, the observations suggested that the esterification reaction occurred & - oxygen atom of the hypoiodite species [IO] removes the acidic through a sequential oxidation involving: (1) radical initiated proton from the benzoic acid, giving a benzoate ion. Finally, oxidation of alcohol to aldehyde; (2) oxidation of aldehyde to the coupling between the in situ generated benzoate ion and the carboxylic acid via a carbonyl radical intermediate; (3) benzyl cation would give the desired ester. oxidative coupling of carboxylic acid and toluene to form benzyl ester. Additionally, for this system, when Bu4NI was Scheme 21. TBAI-catalyzed oxidative transformation of alkylbenzenes. replaced by KI, the yield of benzyl 1-naphthoate dropped to 11%. However, addition of a phase transfer reagent (benzo-18- crown-6) can improve the yield of the desired product to 74%.

Although no ester product was observed using I2 as the catalyst, Organic 84% yield of the ester was formed by adding additionally a catalytic amount of Bu4NBr. On the other hand, employ

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Bu4NBr only led to a dramatic decrease of the yield of the radicals generated from sulfonylhydrazides by the Bu4NI- desired ester. TBHP catalysis system underwent addition to a variety of α- methyl styrene derivatives to give the corresponding allylic Scheme 23. TBAI-catalyzed reaction of alkylbenzenes with alcohols. sulfones in moderate to good yields. A variety of substituted groups, such as methyl, methoxyl, fluoro, chloro, bromo, O trifluoromethyl and naphthyl, were well tolerated and the TBAI 20 mol% , 80oC 24 examples desired sulfones were produced selectively (Scheme 25a). In ( ) O Ar ArCH2OH 48-87% TBHP (6 equiv.), MeCN the control experiments, TEMPO, a radical-trapping reagent, R R was introduced into the reaction mixture and the formation of NaH2PO4 (1.2 equiv.) the desired sulfone was found been completely suppressed. CO Bn CO Bn CO Bn O 2 2 2 Then, α-methyl styrene alone was treated with TEMPO under O Ph the standard conditions, but no adduct of TEMPO and the 71% 78% 74% 72% allylic radical was isolated. At last, the coupling of styrene with O O O TsNHNH2 was found could take place as well and gave the

O Ph O Ph O Ph corresponding sulfone in 31% yield. Later on, this catalytic Manuscript system was applied in the synthesis of allyl aryl sulfone 50% 65% 75% derivatives from Baylis-Hillman acetates and [44] sulfonylhydrazides (Scheme 25b). In the tested solvents, water gave the best results and moderate yields were isolated in In 2011, Wan and co-workers developed a Bu4NI-catalyzed C- H oxidation of aldehydes with TBHP to produce tert-butyl most of the cases. More recently, a catalytic system consisting peresters.[41] This process represents the first synthesis of tert- of KI, 18-crown-6, and TBHP for the synthesis of sulfonated butyl peresters directly from aldehydes and TBHP, all the oxindoles was reported. They using activated alkenes and desired products were formed in good yields (Scheme 24). sulfonylhydrazides as substrates and water as solvent, the When TEMPO was added to the reaction, the product, adduct desired oxindoles were formed in moderate to good yields. The combination of TBAI and TBHP were tested as catalyst under

of acyl radical and TEMPO, was obtained in nearly quantitative Accepted the same conditions as well, and 45% of the desired product yield. The combination of Bu4NOH and iodine (in situ [45] + - was formed (Scheme 25c). For the reaction mechanisms in generation of [Bu4N] [IO] ) did not give any desired product. Based on the control experiments, a radical process was the latter two cases, they are similar with the previous one. proposed. Initially, the tert-butoxyl and tert-butylperoxy They all started with formation of sulfonyl radical. radicals were generated in the catalytic system. The resulting More recently, Deng and co-workers found that sulfonyl radical tert-butoxyl radical traps H from aldehyde to form the acyl can be generated from sodium sulfinates in acidic media in the presence of TBHP and TBAI as well. The generated sulfonyl radical. The coupling of the acyl radical and the tert- [46] butylperoxy radical affords the desired perester radical was applied in the 2-sulfonylation of indoles.

Scheme 25. TBAI-catalyzed sulfonylation of alkenes. Scheme 24. TBAI-catalyzed synthesis of peresters.

O TBAI (20 mol%), MeCN 19 examples Chemistry O mo o TsNHNH Ts TBAI (20 l%), 40 C 24 examples Ar 2 o Ar 37-90% O TBHP (2 equiv.), 80 C R O 5-90% R H TBHP (3 equiv.), H2O Ph Ts Ts Ts O O O Ph Ts a Ph Ts O O O Ph Ph O O Cy O 74% 71% 37% 78% 90% 84% 88% 43% TBAI (20 mol%), MeCN Ph TsNHNH Ts 31% 2 o Ph TBHP (2 equiv.), 80 C Barbas’ group developed a TBAI-catalyzed cross coupling OAc reaction of aldehydes with N-hydroxyimides, CO2Me [42] TBAI (20 mol%), H2O Ar CO2Me TsNHNH hexafluoroisopropyl alcohol, and sulfonimides in 2012. This Ar 2 o b TBHP 2 equiv. , 80 C method succeed to provide active esters and imides in moderate ( ) Ts to excellent yields. The resulting active intermediates can be 20 examples; 40-78% directly converted into amides or esters in one-pot manner. A

possible reaction mechanism was proposed. Initially, nBu NI O Biomolecular 4 TBAI 20 mol% , H O Ts TsNHNH ( ) 2 c was oxidized by TBHP to generate the active intermediate 2 o O N TBHP (2 equiv.), 80 C N

iodide and the tert-butoxyl and tert-butylperoxyl radicals. & 45% These radicals subsequently abstract a hydrogen atom from the acetal or aminal species, which formed from the reaction of the tBuOOH tBuO. + tBuOO. O nucleophiles with the aldehyde, and the resulting radical . . TsNHNH tBuO or tBuOO species were then further oxidized to the product esters or 2 Tol S imides. O

Ar

TBAI-catalyzed C-S bonds formation Ts Ts Ar r A Organic In 2013, Li and co-workers described the allylic sulfonylation of α-methyl styrenes by using TBAI as the catalyst.[43] Sulfonyl

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At the end of 2013, Cui and co-workers developed a KI- b Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert- catalyzed oxidative coupling of benzothiazoles with aryl Einstein-Strasse 29a, 18059 Rostock (Germany). aldehydes.[47] They using TBHP as an oxidant in neat water, various 2-aryl benzothiazoles were prepared in 36-79% yields (Scheme 26). TBAI showed the same reactivity as KI under the 1 J. E. Bäckvall, Modern Oxidation Methods, 2nd ed., Wiley-VCH, same conditions and the authors proved this transformation Weinheim, 2010. proceeded via a radical process. Notably, not the acyl radical as 2 a) G. De Faveri, G. Ilyashenko, M. Watkinson, Chem. Soc. Rev. 2011, normally estimated but thio radical. 40, 1722-1760; b) P. Saisaha, J. W. de Boer, W. R. Browne, Chem. Soc. Rev. 2013, 42, 2059-2074. Scheme 26. TBAI-catalyzed synthesis of 2-aryl benzothiazoles. 3 R. A. F. Tomas, J. C. M. Bordado, J. F. P. Gomes, Chem. Rev. 2013, 113, 7421-7469. S S KI (20 mol%), H2O 28 examples r Ar 4 a) N. Winterton, Chemistry for Sustainable Technologies, RSC A CHO o 36-79% TBHP (3 equiv.), 100 C N R N R Publishing, 2010; b) R. A. Sheldon, I. Arends, U. Hanefeld, Green

S Chemistry and Catalysis, Wiley-VCH, 2007; c) G. Rothenberg, Manuscript S S H O, TBHP ArCHO H 2 OH O N Catalysis: Concepts and Green Applications, Wiley-VCH, 2008. N N H Ar 5 a) H. Togo, S. Iida, Synlett 2006, 2159-2175; b) M. Ochiai, K. HO Miyamoto, Eur. J. Org. Chem. 2008, 4229-4239; c) M. Uyanik, K. - H2O Ishihara, ChemCatChem 2012, 4, 177-185; d) Z. Zheng, D. Zhang- S S Negrerie, Y. Du, K. Zhao, Sci. Chin. Chem. 2014, 57, 189-214. S CHO T.M. Ar 6 The contributions from Ishihara’s group on TBAI-catalyzed N N N H oxidation reactions have been mentioned by their own in 2012 in Ar Ar Ref. 5c.

7 Y. -C. Wong, C. -T. Tseng, T. -T. Kao, Y. -C. Yeh, K. -S. Shia, Org. Accepted In addition, Wan and co-workers developed a procedure for the synthesis of N-nitrosamines using nitromethane as the source of Lett. 2012, 14, 6024-6027. the nitroso group under catalytic conditions via C-N 8 U. Kloeckner, P. Finkbeiner, B. J. Nachtsheim, J. Org. Chem. 2013, cleavage.[48] TBAI was found to be as effective as KI, could 78, 2751-2756. gave the desired product in excellent yields. For the reaction 9 T. Nobuta, N. Tada, A. Fujiya, A. Kariya, T. Miura, A. Itoh, Org. mechanism, firstly, iodide is oxidized to hypoiodite by TBHP, Lett. 2013, 15, 574-577. followed by the formation of iodo(nitro)methane. The 10 T. Nobuta, A. Fujiya, T. Yamaguchi, N. Tada, T. Miura, A. Itoh, RSC iodo(nitro)methane formed rearranged and decomposed into Adv. 2013, 3, 10189-10192. formaldehyde and NO+ go through 2-oxo-1,2-oxaziridin-2-ium as the intermediate. Finally, nucleophilic attack of the amine on 11 L. -T. Li, J. Huang, H. -Y. Li, L. -J. Wen, P. Wang, B. Wang, Chem. NO+ gave the desired product. Tertiary amines can be Commun. 2012, 48, 5187-5189. transformed as well via oxidative C-N cleavage with higher 12 L. -T. Li, H. -Y. Li, L. -J. Xing, L. -J. Wen, P. Wang, B. Wang, Org. Chemistry loading of oxidant. Biomol. Chem. 2012, 10, 9519-9522. 13 a) W. Wu, W. Su, J. Am. Chem. Soc. 2011, 133, 11924-11927; b) E. M. Ferreira, B. M. Stoltz, J. Am. Chem. Soc. 2003, 125, 9578-9579. Summery 14 Z. Jia, T. Nagano, X. Li, A. S. C. Chan, Eur. J. Org. Chem. 2013, The contributions on TBAI-catalyzed oxidative transformations 858-861. with TBHP as oxidant have been collected and discussed. The 15 W. -P. Mai, H. -H. Wang, Z. -C. Li, J. -W. Yuan, Y. -M. Xiao, L. -R. combination of TBAI and TBHP as a powerful green catalyst Yang, P. Mao, L. -B. Qu, Chem. Commun. 2012, 48, 10117-10119. system, make the reactions which usually need metal catalysts 16 Q. Zhao, T. Miao, X. Zhang, W. Zhou, L. Wang, Org. Biomol. Chem. come to “metal-free”. The reaction conditions are generally 2013, 11, 1867-1873. mild and the functional group tolerance is excellent. Additionally, as the advantages of TBAI and TBHP, we are 17 M. Lamani, K. R. Prabhu, Chem. Eur. J. 2012, 18, 14638-14642. expecting a boom in this topic. 18 Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu, X. Wan, Angew. Chem. Int. Ed. 2012, 51, 3231-3235. 19 H. Li, J. Xie, Q. Xue, Y. Cheng, C. Zhu, Tetrahedron Lett. 2012, 53, Biomolecular Acknowledgements 6479-6482. & The authors thank the financial support from Zhejiang Sci-Tech 20 K. Xu, Y. Hu, S. Zhang, Z. Zha, Z. Wang, Chem. Eur. J. 2012, 18, University (1206838-Y). The general supports from Matthias 9793-9797. Beller in LIKAT are appreciated. 21 G. Wang, Q. -Y. Yu, S. -Y. Chen, X. -Q. Yu, Org. Biomol. Chem.

2014, 12, 414-417. Notes and references 22 W. -P. Mai, G. Song, J. -W. Yuan, L. -R. Yang, G. -C. Sun, Y. -M. a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Xiao, P. Mao, L. -B. Qu, RSC Adv. 2013, 3, 3869-3872. Campus, Hangzhou, Zhejiang Province, 310018, People’s Republic of 23 S. Wang, J. Wang, R. Guo, G. Wang, S. -Y. Chen, X. -Q. Yu, China. Tetrahedron Lett. 2013, 54, 6233-6236. E-mail: [email protected] Organic 24 A. Yoshimura, K. R. Middleton, C. Zhu, V. N. Nemykin, V. V. Zhdankin, Angew. Chem. Int. Ed. 2012, 51, 8059-8062.

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& Organic

This journal is © The Royal Society of Chemistry 2012 J. Name., 2012, 00, 1-3 | 11 Organic & Biomolecular Chemistry Page 12 of 12 ARTICLE Journal Name 1 + 1 > 2 TBAI + TBHP = Powerful Oxidation System

The recent achievements on using TBAI and TBHP as oxidation system have been summarized and discussed. Manuscript Accepted Chemistry Biomolecular & Organic

12 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 2012