(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• Carlos R. Azpilcueta-Nicolas Jean-Philip Lumb Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada 10.3762/bjoc.20.35 Abstract Due to their ease of preparation, stability, and diverse reactivity, N-hydroxyphthalimide (NHPI) esters have found

• activated under these electrochemical conditions (Scheme 36). Conclusion Given their rich history and their continued use in diverse methodologies, N-hydroxyphthalimide esters have been and will remain to be important tools in synthetic organic chemistry. In this perspective, we have surveyed recent

• photochemical instability, as evidenced by their low N–O bond dissociation energy (BDE ≈ 42 kcal/mol) [28], the reliance on toxic tin hydrides as reductants and the undesired radical recombination with reactive 2-pyridylthiyl radicals that leads to (alkylthio)pyridine byproducts [26]. More recently, N

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• and colleagues introduced an interesting metal- and oxidant-free photocatalytic C–H alkylation method for coumarins 18 [17]. The method utilized triphenylphosphine and sodium iodide, along with readily available alkyl N-hydroxyphthalimide esters (NHPIs) 3 as the alkylation reagents (Scheme 10

• novel metallaphotoredox catalysis by combining the NaI/PPh3 photoredox catalyst with a Cu(I) catalyst to accomplish diverse C–O/N cross-couplings of alkyl N-hydroxyphthalimide esters 3 with various phenols/secondary amines 30 (Scheme 13) [24]. It was anticipated the utilization of computational methods

•  15) [27]. This method involved a series of steps, including the formation of an EDA complex, decarboxylation, radical addition, C–H functionalization, and annulation. Various primary, secondary, and tertiary alkyl N-hydroxyphthalimide esters 33 showed potential as viable substrates for the synthesis

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• involved in the activation of DDQ by coordinating the carbonyl oxygen atom which leads to an increase in the oxidation activity of DDQ. Subsequently, Li et al. improved the above method, using a mixture of indium and copper salts as a catalyst, NHPI (N-hydroxyphthalimide) as a co-catalyst to achieve the

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• carboxylate anion and/or reduction of the corresponding N-hydroxyphthalimide- (NHPI)-derived redox-active ester, although it destroys their stereochemical information [46][47][48][49][50][51]. In addition, the side-chains of aromatic amino acids (mainly electron-rich tryptophan and tyrosine) can be

• synthetic route of ergot alkaloids and may offer new opportunities for drug discovery and biochemistry applications. As natural and unnatural tryptophan-derived redox-active N-hydroxyphthalimide esters have already been used in photoredox catalysis, we decided to use them as the initial substrates [77][78

• ]. Regioselective palladium-catalyzed prenylation of 2 with prenylboronic acid pinacol ester and subsequent hydrolysis with LiOH provided the linear prenylated acid 4 in good yield. Coupling acid 4 with N-hydroxyphthalimide using DCC and a catalytic amount of DMAP afforded the key intermediate 5 in 59% yield. With

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• reported a Ru(bpy)3Cl2-catalyzed synthesis of N-Boc proline oxindole derivatives under visible-light assistance [47]. Therein, N-hydroxyphthalimide (NPhth) esters were utilized as alkyl radical precursors, which can be readily prepared from highly available carboxylic acids. In 2015, Cheng and co-workers

• similar efficiency, affording oxindole 3aj as a 1:1.1 mixture of diastereomers. Interestingly, this method also enabled the synthesis of the highly sterically demanding oxindole 3ak in good yield when using a tert-butyl N-hydroxyphthalimide ester as the tert-butyl radical precursor. Importantly, a redox

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• -functionalization reactions [74][75][76][77] due to their high reactivity in hydrogen atom abstraction and relatively slow self-decay. One of the most synthetically available and effective catalysts of this family is N-hydroxyphthalimide (NHPI). In the presence of co-catalysts, such as Co(OAc)2, it is partially

• [74][76][80][86][87][88]. To facilitate the anodic oxidation of N-hydroxyphthalimide, basic pyridine derivatives are used as the N-hydroxyphthalimide proton acceptors [87]. In many cases electrolysis can be performed in the galvanostatic mode in a simple undivided cell, which is convenient for

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• Dongming Zhang Bin Lv Pan Gao Xiaodong Jia Yu Yuan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. of China 10.3762/bjoc.18.65 Abstract An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as

• applied in amination reactions [17][18][19][20][21][22][23][24]. Especially, N-hydroxyphthalimide can react with arenes directly in the presence of palladium [25] or gold [26] (Scheme 1, reactions 1 and 2). Recently, we found that iron catalyzes the amination of arenes with N-hydroxyphthalimide under air

• (reaction 3) [27]. Herein, we report a method for the construction of aromatic amines via the copper-catalyzed intermolecular radical amination of arenes with N-hydroxyphthalimide (NHPI) under air. Results and Discussion Initially, N-hydroxyphthalimide (NHPI, 2a) was reacted with benzene, catalyzed by CuBr

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• nitrate (CAN) [41], 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO)/CuCl [51], K2S2O8 [36], dimethyl sulfoxide (DMSO)/O2 [52], PhI(OAc)2/benzoyl peroxide (BPO) [47], Dess-Martin periodinane, N-bromosuccinimide (NBS), N-hydroxyphthalimide (NHPI)/Co(OAc)2/O2 [53], H2O2/tetrabutylammonium iodide (TBAI) [43], CBr4

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

•  9). In addition to perfluoroalkyl iodides, this protocol was further extended to alkyl halides, trifluoromethylthiolate, amines, cycloketone oxime esters, and carboxylic acid N-hydroxyphthalimide esters (NHPI). In 2018, Peters and Fu [57] explored the copper-catalyzed three-component coupling of

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• .17.89 Abstract A visible light-mediated heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile has been established using K-modified carbon nitride (CN-K) as a recyclable semiconductor photocatalyst. This protocol, employing readily accessible alkyl N-hydroxyphthalimide (NHPI

• the generation of cyanomethyl radicals from readily available acetonitrile has not been reported yet. Herein, we disclose a CN-K-catalyzed cyanomethylarylation of both unactivated and activated alkenes with acetonitrile utilizing readily available alkyl N-hydroxyphthalimide (NHPI) esters as the

• recyclability, broad substrate scope, and high functional group tolerance (Scheme 1). Results and Discussion Our initial investigation focused on the CN-K photocatalyzed cascade alkyl radical addition/cyclization reaction of the N-arylallylamine 1a with tert-butyl N-hydroxyphthalimide (NHPI) ester (2a), a

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• an EDA complex. First, the N-hydroxyphthalimide (NHPI) ester 142 is excited to electron acceptor 142* through visible-light intersystem crossing (ISC); diborate 143 combining with pyridine results in electron donor 145. Upon the formation of the EDA complex between 145 and 142*, electron transfer

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• reported a visible light-promoted photochemical reductive decarboxylation/alkylation of carboxylic acid analogs (Scheme 4) [45]. In this protocol, the carboxylic acids are converted into the corresponding RAE 4.1 by a condensation with N-hydroxyphthalimide. The organic dye eosin Y (OD13, E(PC/PC−) ≈ −1.1 V

• reduced by the photocatalyst, and thus closing the catalytic cycle. Finally, Yadav and co-workers developed a method for a chalcone synthesis using an H abstraction approach to access an acyl radical (Scheme 20) [92]. The authors proposed that the excited triplet state of the photocatalyst N

• -hydroxyphthalimide (NHPI, OD22, similar to the benzophenone photocatalysts OD9 and OD10) can abstract an H atom from the aldehyde substrate 20.1. The resulting acyl radical adds to the (E)-β-nitrostyrene 20.2, and the following denitrosylation affords the chalcones 20.3. Alkenyl and aryl radical ions (radical

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• explored on redox-active alkyl esters derived from N-hydroxyphthalimide (NHPI, 37), in which case the reactions proceeded through a similar radical pathway due to, in part, the alkyl radical surrogate nature of the NHPI esters. The radical generated via decarboxylation of these esters is easily trapped by

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• radical precursor N-hydroxyphthalimide (NHPI), an anionic phase-transfer catalyst (KB(C6F5)4), and a Cu(I)-bisimine complex, to give the corresponding monofluorinated product (Scheme 25). One year later, Weng and co-workers [68] synthesized and characterized a new copper(I) fluoride complex ligated by a

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• hypervalent iodine species as a terminal oxidant. Combinations of ammonium iodate and catalytic N-hydroxyphthalimide (NHPI) were shown to be effective in the selective oxidation of n-butylbenzene directly to 1-phenylbutyl acetate in high yield (86%). This method shows moderate substrate tolerance in the

• dyes and transition metal complexes, hypohalous acids, and persulfate anions [12][34][35][36][37][38][39][40]. An important class of catalyzed benzylic C–H to C–O transformations are those catalyzed by N-oxyl radicals. Specifically, N-oxyl radical catalysts based upon the N-hydroxyphthalimide (NHPI

• NO and HNO3 [46][47][48]. In the work that follows, we report the selective monooxygenation of secondary benzylic C–H bonds of simple aryl alkanes using a combination of iodate and catalytic N-hydroxyphthalimide (NHPI), which complements the selectivity and capabilities of existing published work

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• The starting adamantyloxyamine (4) was prepared from 1-bromoadamantane, which in the presence of an equimolar amount of AgBF4 in boiling dimethoxyethane (DME) reacts with N-hydroxyphthalimide to give the O-alkylation product 5 [20] (Scheme 2). The latter was converted to 4, obtained in 86% yield

• Stuart SMP30 apparatus with automatic temperature monitoring. Starting materials: Adamantyloxyamine (4) was prepared following a modified published procedure [20]. For the first step, the O-adamantylation of N-hydroxyphthalimide, the recommended diethyl ether as a solvent was replaced by 1,2

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• radicals that is generated from an inexpensive N-hydroxyphthalimide (NHPI). This radical was used in various aerobic oxidations of bulk chemicals [18][19][43][44]. In the present work imide-N-oxyl radicals were used for the addition to the C=C bonds of styrenes with subsequent functionalization of the

• resulting benzylic radicals. Recently, the precursors of N-oxyl radicals, such as N-hydroxyphthalimide (NHPI), N-hydroxysuccinimide (NHSI), N-hydroxybenzotriazole (HOBt) and hydroxamic acids, have been used in the reactions of radical oxygenation of styrenes [45]. Growth of interest is observed concerning

• formation of C–I and C–O bonds, which implies the radical pathway of the reaction. The iodo-oxyimidation of styrenes was studied in the model reaction of styrene (1a) with N-hydroxyphthalimide (2a). During the optimization, the oxidant and the iodine source, as well as the nature of the solvent and the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• (6.3), N-hydroxyphthalimide was early considered in Mitsunobu reactions, for example by Grochowski and Jurczak to form an anomeric phthalimide–oxy bond as shown in several sugar series [109][110][111]. This gives access to new O-glycosylhydroxylamines, namely for the construction of glycosidic N–O

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• reaction was facilitated at room temperature by N-hydroxyphthalimide (NHPI) and cobalt acetate (Co(OAc)2) as catalysts in acetonitrile (Scheme 20). The reaction followed a free radical mechanism as exemplified by the oxidative dehydrogenation of DHPs. The initial step involved the formation of the

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• did not work with ortho-substituted arenes. In 2013, Jiao and co-workers reported a hydroxylation protocol for (2-pyridyl)arenes using PdCl2 and N-hydroxyphthalimide (NHPI) as catalyst and molecular oxygen as oxidant [60]. (2-Pyridyl)arenes were converted to the hydroxylated products in toluene at 100

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• conditions. Oxidations of this kind using Oxone® [10][11], NaOCl [12] or especially peroxides [13][14][15][16][17][18][19] as the terminal oxidant are quite numerous. However, transformations using molecular oxygen are rare. Ishii showed that organocatalysts such as N-hydroxyphthalimide (NHPI) in combination

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• Yan Li Xue Zhou Guangfan Zheng Qian Zhang Department of Chemistry, Northeast Normal University, Changchun 130024, China 10.3762/bjoc.11.293 Abstract A copper-catalyzed aminooxygenation reaction of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives has been developed

• . The aminooxygenation product could be converted into the corresponding alcohol or free amine through the cleavage of the N–O or C–N bond of the N-hydroxyphthalimide moiety. Keywords: aminooxygenation of styrenes; copper catalysts; N-fluorobenzenesulfonimide; N-hydroxyphthalimide derivatives

• amination of allenes [46]. Encouraged by these results, we try to develop copper-catalyzed aminooxygenation of alkenes by using NFSI. Herein, we report a simple and efficient copper-catalyzed three-component aminooxygenation reaction of styrenes with NFSI and N-hydroxyphthalimide (NHPI) derivatives (Scheme

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• a catalytic system consisting of (BPMED)CuI (copper(I) bisimine complex), N-hydroxyphthalimide (NHPI), KB(C6F5)4 and KI. The protocol allowed the selective fluorination of various substrates, including cycloalkanes and benzylic compounds using commercially available Selectfluor as fluorine source