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

• organocatalysis using chiral phosphoric acids has also been studied (Scheme 1b) [26][27][28]. In 2010, Magnus Rueping and his co-workers developped an enantioselective Brønsted acid-catalyzed transfer hydrogenation of 3H-indoles [29]. In 2020, Song and Yu successfully applied a new chiral Brønsted acid

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• the nitro group with subsequent cyclization of the reduced intermediate (Scheme 2, conditions iv). We tried to carry out these reactions either with Zn in acetic acid/dichloromethane or by transfer hydrogenation with ammonium formate in the presence of Pd on charcoal. Both types of reductive

• get reduced to quinolones 5/8, which were isolated in good yields (Table 3 and Table 4). In the case of the Pd-catalyzed transfer hydrogenation of intermediates 3 the yields of products 5 in most cases were lower than those obtained with Zn/AcOH, regardless of the reaction duration. On the other hand

• , because of concomitant reduction at the C–Cl bond. Intermediates 6, similarly to compounds 3, gave mixtures of products 7/8 under palladium-catalyzed transfer hydrogenation conditions. In contrast to 3, however, limiting the reaction time here did not help to develop a preparatively useful procedure for a

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

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• newly prepared thiophosphorus acids were not efficient in the asymmetric transfer hydrogenation of 2-phenylquinoline. However, they may find application in other model reactions. These days, stereoselective syntheses incorporating “green" chemical considerations are of utmost importance in medicinal

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

• asymmetric organocatalysis. In order to eliminate the need for C2-symmetry in common CPAs, various scaffolds containing C1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of

• 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

• thiophosphorus acid 2. Synthesis of N-biphenyl-DOPO CPA 4. Transfer hydrogenation of 2-phenylquinoline and transition-state proposed by Guinchard and coworkers [28]. P-stereogenic CPAs in the transfer hydrogenation of quinolines. Supporting Information Supporting Information File 332: Experimental procedures

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• either the salt 16a·HCl or the free amine 16a in good to excellent yield (Scheme 3). We also explored the asymmetric catalytic hydrogenation of adduct 14. Our first attempt at the reduction using organocatalyzed transfer hydrogenation was unsuccessful (see Supporting Information File 1). The (R)-Ru(OAc)2

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• . Compound 3a was obtained as a major product (26% yield) and 2a was obtained in 6% yield (Scheme 4a). Hydrogenation of the alkene moiety of 4a would proceed selectively, and 2a would be generated via a transfer hydrogenation reaction from 3a as a hydrogen donor [32][33][34][35]. These results suggest that

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) [59]. The catenane catalyst allows for the asymmetric transfer hydrogenation of 2-substituted quinolines by Hantzsch esters in a highly stereoselective fashion [60]. It was found that the catenated catalyst gives superior stereoselectivities in comparison to the macrocyclic and the acyclic reference

• desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42. Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47. Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47, (S)-48, and (S)-49. Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57. Results for

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -carbon precursor for the synthesis. The forward synthesis transformed 2-acetylfuran (20) to its corresponding alcohol 21 through an asymmetric transfer hydrogenation catalyzed by a ruthenium complex (0.5 mol %) in 98% yield with 95% ee (Scheme 2). The azeotropic mixture of HCO2H/Et3N 5:2 was employed as

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• transfer hydrogenation (CTH) methods from safer reagents have thus been developed and successfully applied to lignocellulose polymers [104][105]. 2.2 Catalysts Catalysts of various types, including homogeneous and heterogeneous, have been reported for the above-mentioned depolymerisation processes of

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• enantioselective hydrocupration of difluorocyclopropenes in the presence of chiral diphosphine ligands using stoichiometric hydride sources that included polymethylhydrosiloxane (PMHS) and organoboranes (Scheme 35) [79]. Cossy and co-workers have achieved the catalytic asymmetric transfer hydrogenation with

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• trifluoromethylpropargylamine is of general research interest [28][29][30][31][32]. The asymmetric Ru/(R)-CPA-catalyzed chemoselectivie biomimetic reduction [33] and the organocatalytic transfer hydrogenation [34] of fluorinated alkynylketimines have been developed for the synthesis of fluorinated propargylamines in good

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• the (R,R)-ProPhenol ligand [16] to accomplish a catalytic asymmetric addition of methyl propynoate to acetaldehyde to give 18 in high enantiopurity (98% ee). Jacobsen’s group [17][18] utilized the Noyori Ru-catalyzed transfer hydrogenation [19] of the 3-butyne-2-one 19, which gave 20 with 97% ee. The

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• treatment with HClO4-SiO2 [34]; (c) selective acetylation of the primary hydroxy group, and (d) removal of the benzyl groups by catalytic transfer hydrogenation [35] using triethylsilane in the presence of Pearlman’s catalyst [36] to furnish the desired tetrasaccharide 1 in 50% overall yield with the two O

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• ligands that were obtained from readily available natural (1S)-β-pinene and (1S)-α-pinene [18]. We applied these ligands for the formation of the ruthenium complexes, which were successfully used as catalysts in asymmetric transfer hydrogenation of prochiral ketones. In continuation of our studies on the

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• products that then complicated the purification without increasing the yield. In our hands, this new method was found to be reproducible (gram scale) and was thus used to generate mononitrocalix[4]arene 9 for use in subsequent steps. Reduction of mononitrocalix[4]arene 9 under transfer hydrogenation

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• formal synthesis of triptolide and triptonide (Figure 2, route M) [48]. This synthesis highlights the use of Noyori’s ruthenium-catalyzed enantioselective transfer hydrogenation to introduce the chiral center; the indium(III)-catalyzed cationic polyene cyclization to construct the tricyclic A-, B- and C

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• stainless steel ones, since the latter caused the reactive mixture to adhere to the jars, which was not the case of the former. In another example, for the metal-free transfer hydrogenation of carbonyl compounds, PTFE was used instead of steel to eliminate the possibility of catalysis from the milling media

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• yields varying from poor to good (10–87% yields, Scheme 2). The transfer hydrogenation was selected as common hydrogenation using conditions with hydrogen gas and palladium on carbon lead to very low yields or no recovered product during the synthesis of 1a,b. Unfortunately, no arenes bearing halogen

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• use of heated CSTRs would be useful to explore. The formation of both imines 20 and 21 are of interest as an asymmetric reduction would give an optically pure amine. To demonstrate this, imine 20, formed in situ, underwent asymmetric-transfer hydrogenation in both batch and flow modes, using [IrCp*Cl2

• imines reported within our study. Of these examples, the latter was further explored by immediate asymmetric-transfer hydrogenation of an in situ formed imine under continuous-flow conditions, as a potentially productive route to chiral amines. Continuous-flow process to produce and react N-chloramines

• . Left: Laboratory scale CSTR developed by our group [8]. Right: 5-stage CSTR configuration using co-feeds of amine in toluene and aqueous NaOCl. Continuous-flow amide 18 formation using 1-stage CSTR. Blue squares: FeCl3 included; red circles: FeCl3 not included. Continuous-flow transfer hydrogenation of

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• reduction utilizing solid mixes of sodium borohydride, lithium chloride and celite [12], and the Ley group were able to demonstrate a green transfer hydrogenation of ketones under flow using catalytic lithium tert-butoxide in isopropanol [13]. We recently published a batch–flow hybrid synthesis of the

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• semihydrogenation of internal alkynes may be achieved by two main catalytic methods: with molecular hydrogen using Lindlar’s catalyst [25][26] or by transfer hydrogenation with hydrogen donors [27][28]. Additionally, alkynes undergo reduction with diimide to produce cis-alkenes [29]. Li et al. carried out the

• . Conclusion In conclusion, we described here an efficient synthetic microwave procedure for the synthesis of novel phenylalkynyl derivatives of 13α-estrone (1) and its 3-methyl ether 2. The steroidal alkynes were chemo- and stereoselectively hydrogenated by transfer hydrogenation in a microwave reactor

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• -doped mesoporous titania film (95% sel. at 30% conversion, 323 K) [150] (Table 1, entries 31–33). The reduction of 7 to 7a was also reported by transfer hydrogenation using formic acid / triethylamine as hydrogen source and packed Au@TiO2 (rutile) catalyst [151]. An outstanding 99.7% yield was achieved

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• concentrations of 1 mmol L−1 in single-scan experiments. As a proof-of-concept, they studied the transfer hydrogenation process of acetophenone with isopropanol catalysed by iridium complexes. The reaction was performed in batch and the sample was introduced into the magnet with a pump and Teflon tubing to form