SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• Hantzsch ester suppressed the formation of the desired product (Table 1, entries 8 and 9). Carrying out the reaction in the presence of sodium formate, which can play a dual role of H• donor and reductant [48][49], only led to a decreased of Ph-EBX (2) conversion, along with a diminished yield (Table 1

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

• ], have been employed as suitable photocatalysts (Scheme 4B). Under visible light irradiation the photocatalyst (PC) is excited into its corresponding excited state (*PC), where it can be reduced by a suitable electron donor such as DIPEA or Hantzsch ester to generate the reduced form of the photocatalyst

• example, the NHPI ester derived from pivalic acid 58 and Hantzsch ester HE form EDA complex 59 which participates in radical mediated hydroalkylation reactions [60][61] (Scheme 13A). In the presence of electron deficient olefin 60, classic Giese-type addition takes place under photocatalyst-free

• reductant, which can be an organic reductant, such as tetrakis(N,N-dimethylamino)ethylene (TDAE) or Hantzsch ester (HE), or a metal such as zinc (Zn0) or manganese (Mn0). Upon fragmentation, radical species 12 is captured by the oxidative addition complex 125, giving rise to NiIII complex 126. The cross

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• synthesis of optically active difluoro-substituted indoline derivatives starting from the corresponding 3H-indoles by chiral phosphoric acid-catalyzed transfer hydrogenation was developed. Using Hantzsch ester as the hydrogen source under mild reaction conditions, the target products can be obtained with

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• (1a) as the model substrate, Hantzsch ester (HE-Et) as the hydrogen source, and BINOL-derived chiral phosphoric acids (CPA) as the catalyst (Table 1). With chiral phosphoric acid CPA-1, the transfer hydrogenation reaction proceeded well in PhCF3 at room temperature and the target product 2a was

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to

• elegant strategies on direct conversion of in situ-activated carboxylic acids for ketone synthesis [27][35][38], we chose dimethyl dicarbonate (DMDC, A1) as the activating reagent. To our delight, the reaction of 1a and 2 in the presence of NiBr2(dtbbpy) (10 mol %), Hantzsch ester (HE) and A1 in DMAc

• -trifluoroethoxyphthalimide: In the glove box with nitrogen atmosphere, to an 8 mL vial equipped with a magnetic stir bar, NiBr2(dtbbpy) (19.6 mg, 0.04 mmol, 10 mol %), alkyl carboxylic acid 1 (0.4 mmol, 1.0 equiv), N-trifluoroethoxyphthalimide (2, 147.1 mg, 0.6 mmol, 1.5 equiv), Hantzsch ester (152.0 mg, 0.6 mmol, 1.5 equiv

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ) may superficially look like a sulfur-substituted acrolein derivative, with a reactive vinylogous thioester moiety, but in fact their reactivity is more akin to that of an arylaldehyde, as shown by the example of the synthesis of Hantzsch ester 20 from a condensation of ammonia with 18 and

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• radical reaction [87]. Indeed, when ʟ-tyrosine methyl ester (154), 1,4-cyclohexanedione monoethylene acetal (155), and dehydroalanine derivative 156 were allowed to react in the presence of TFA, molecular sieves, 1 mol % of fac-Ir(ppy)3, and Hantzsch ester under blue LED irradiation at 40 W, this resulted

• an α-carbonyl species. A HAT from Hantzsch ester, which takes place diastereoselectively from the more accessible face, afforded the lactone 158. Spirolactam 157 can effortlessly be produced after the cyclization of the aforementioned lactone. Redox manipulations from this point on brought about the

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• thioacid hybrid-CPAs (Scheme 5) [31]. The transfer hydrogenation of 2-phenylquinoline with a Hantzsch ester 19 is a test reaction commonly used in asymmetric synthesis. The best performing of Guinchard's thiophostones 18 was the pivalate ester (R1 = t-BuC(O)) with an 86% yield of 20 and a 52% ee (19 R2

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• the In(III)-catalyzed reductive cyclization of isatylidene malononitriles using the Hantzsch ester as reducing agent for the synthesis of dispirocyclopentanebisoxindole. Our work utilizes tosylhydrazine as chemoselective reducing agent for 3-phenacylideneoxindoles and thereafter base-catalyzed

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• donor absorbs light energy and changes to the excited state (TPEWP5G*) energy level. Through energy transfer from TPEWP5G* to ground state EsY the latter undergoes excitation to the excited state EsY* and is reduced by the Hantzsch ester to generate the radical anion EsY•−. Subsequently, electron

• transfer from EsY•− to the substrate α-bromoacetophenone (1a) gives the corresponding acetophenone radical, whilst EsY•− is oxidized to EsY. The acetophenone radical combines with a H-atom abstracted from the radical cation of the Hantzsch ester to form acetophenone (2a) as the final product and diethyl

• dehalogenation reactions in the presence of m-TPEWP5G-EsY nanoassembly under white light irradiation. Reaction conditions: Bromoacetophenone (0.1 mmol), Hantzsch ester (28 mg, 0.11 mmol), N,N-diisopropylethylamine (DIPEA, 35 μL, 0.2 mmol), m-TPEWP5G-EsY in water (0.5 mol %, 2.5 mL), 20 W white light, rt, N2, 2 h

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• synthetic elaborations. Noteworthy, AB was also able to efficiently reduce both isomers of tetrasubstituted nitroacrylate 5d, which showed poor reactivity in the Hantzsch ester-mediated reduction in toluene, where only a low yield of the product could be obtained. However, in glycerol, the reaction of 5d

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

• through an EDA complex under visible-light irradiation. The EDA complex formed by electron donor Hantzsch ester (HE) 79 and electron acceptor N-acyloxybenzamide 78 was produced by light-promoted SET, providing alkoxy radicals that could give carbon radicals by removing one molecule of acetaldehyde (Scheme

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• -covalent catalysis with photoredox catalysis was reported by Rono and Knowles in 2013 (Scheme 15) [57]. They showed that using a chiral phosphoric acid (CPA), a photoredox catalyst and Hantzsch ester (HEH) as a HAT reagent, a concerted proton-coupled electron transfer (PCET) process is promoted to form

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , Cheng and co-workers reported a hydrodifluoroacetamidation of alkenes in which disulfide served as the photocatalyst with the Hantzsch ester as the reducing agent (Scheme 15) [23]. These reactions do not require costly transition-metal complexes, and they do not involve the oxidative regeneration of a

• by homolysis of diphenyl disulfide under visible light triggers the HAT-initialized pathway 1. The hydrogen abstraction from the Hantzsch ester 44 by the thiyl radical 43 gives the ester radical 45. Then, the subsequent SET from the Hantzsch ester radical 45 to the acetamide 46 forms the amide

• regenerates for the next catalytic cycle. The other plausible reaction pathway 2 starts with a SET from the excited Hantzsch ester 44 to the acetamide 46 to form the intermediate difluoroamide radical 48 and the cationic radical 51. The subsequent addition of alkenes to the formed radical 48 and HAT from the

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• product 3a was unambiguously confirmed using X-ray crystallography [57]. To further extend the diversity of the reactivity of the imines in this process, we also attempted the use of a reducing agent in the reaction of 1a. Pleasingly, the reaction of 1a with 2 equivalents of the Hantzsch ester in CH3CN

• heterocoupling with aliphatic amines. Furthermore, the reduced amine product was also obtained by employing the Hantzsch ester. The developed method can be employed for the synthesis of bulky vicinal diamines with potential applications as ligands for stereoselective synthesis. Experimental An oven-dried

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

• cleavage of various benzyl halides 7.1 (I, Br, Cl). The radical is then intercepted by an H atom donor (Hantzsch ester), which delivers the corresponding toluene derivative 7.2. Other organic dyes can promote the reductive fragmentation of alkyl halides. For instance, König and Zeitler demonstrated that a

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• [28]. The authors reported that meso-5,10,15,20-tetraphenyl-21-monothiaporphyrin (STPP), combined with Hantzsch ester (HEH) and N,N-diisopropylethylamine (DIPEA), promoted the dehalogenation of α-functionalized carbonyl-containing compounds under red light (λ > 645 nm) in a reductive quenching. DIPEA

• -methoxyphenyl)porphyrin (CoTMPP) in the dark, furnishing the alkoxycarbonyl intermediate in 92% yield. The combination of this intermediate with a thiophenol derivative and Hantzsch ester (HEH) afforded ethylbenzene in 94% yield (86% overall yield) under both blue and green LED irradiation. The thiophenol and

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction. In the presence of 2 mol % of the catalyst, the Hantzsch ester (HEH), as a hydrogen atom donor, under blue light irradiation, a large panel of ketones and aldehydes was readily converted into the corresponding 1,2-diols in moderate to excellent yields. The functional group tolerance of the

• the Hantzsch ester allows the regeneration of the catalyst in the ground state. 2.5 Reaction based on an energy transfer (EnT) Reactions based on energy transfer represent an interesting class of photocatalyzed transformations. Indeed, this reaction sequence relies on the deactivation of an excited

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• hydrofluoroalkylation process using fac-Ir(ppy)3 as a photocatalyst in combination with a suitable donor of hydrogen atom. With triethylamine, no expected product was observed. At the same time, with Hantzsch ester (3 equiv), which can serve as a single-electron reductant and as a source of hydrogen [16], 54% of

• product 3a was formed. However, difficulties in removing the pyridine byproduct formed from Hantzsch ester and the use of a precious metal photocatalyst make this protocol less practical compared to that with sodium cyanoborohydride. Under the optimized conditions a series of gem-difluorinated iodides 1

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• lactol was formed, deoxygenation by BF3·OEt2 and reduction in presence of the Hantzsch ester afforded the desired β-anomer, while the use of Et3SiH gave the α-anomer [75]. Carbocyclic C-nucleosides In an attempt to synthesize carbocyclic C-nucleosides, Maier et al. found that reaction of aryl lithiums

• '-substituted D-ribonolactone via Mukaiyama aldol reaction. A series of 2'-O-alkyl, alkyl, cycloalkyl and deoxy D-ribonolactone were synthesized using this method. B. Use of Hantzsch ester to obtain the β-anomer of C-nucleosides. Synthesis of carbocyclic C-nucleosides using cyclopentanone [53]. A. Nucleophlic

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• 2008 the Bolm group explored the use of halogen bond donors in organocatalysis. They discovered that perfluorinated alkyl halides could activate 2-substituted quinolines toward reduction by Hantzsch ester (Scheme 15) [81]. These studies explored various C6 to C10 perfluorinated bromides and iodides. It

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• . Building on his asymmetric conjugate additions to α-substituted enones, Luo demonstrated that Hantzsch ester 133 chemoselectively reduces activated alkenes 132 in the presence of α-substituted vinyl ketones 118, generating carbon nucleophiles 135 in situ. These nucleophiles then reacted with the α

Visible light photoredox-catalyzed deoxygenation of alcohols

• Daniel Rackl,
• Viktor Kais,
• Peter Kreitmeier and
• Oliver Reiser

Beilstein J. Org. Chem. 2014, 10, 2157–2165, doi:10.3762/bjoc.10.223

• ; dtb-bpy = 4,4′-di-tert-butyl-2,2′-bipyridine] as photocatalysts, Hantzsch ester (diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) as hydrogen donor, and iPr2NEt as sacrificial electron donor in DMF (Scheme 3). Light generated from a high power LED was channeled into the reaction solution in

• ) was omitted significantly lower yields were obtained. Leaving out Hantzsch ester (Table 2, entry 8) apparently does not impede the deoxygenation while carrying out the reaction without Hünig’s base lowers the yield (Table 2, entry 9), nevertheless, 4 was still formed to a significant extent. These

• results suggest that Hantzsch ester is not necessary as the hydrogen source but likewise that reductive quenching of the photocatalyst is not exclusively accomplished by Hünig’s base. We assumed that the mechanism of the deoxygenation reaction involves an electron uptake of the ester moiety from the

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• used for the asymmetric synthesis of α-amino esters through reduction. The reduction condition scan was firstly focused on the examination of reductants. A number of reductants, including Hantzsch ester, silanes, organoaluminum and boranes were tested in the system. Unfortunately, silanes failed to

• trigger the reduction (Table 3, entries 2 and 3). Hantzsch ester and DIBAL were also not suitable for this reduction, and almost no desired product was obtained (Table 3, entries 1 and 5). Lithium triethylborohydride (Table 3, entry 4) and sodium borohydride (Table 3, entry 6) were decent choices, giving

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• donor functionality as the carboxylic acid group; it is worth mentioning that also phosphoric acid catalyzed reductions of C=N bonds with Hantzsch ester involve the coordination and activation of the substrate through the formation of a H-bond between the hydrogen atom of the phosphoric acid and the