HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• 99%), with a low catalyst loading (2 mol %) in only 30 minutes, and allows the successful use of aliphatic aldehydes, substrates not so frequently explored with most usual catalysts for this reaction. Furthermore, the aforementioned advantages make this methodology very attractive and superior to the

• catalyst in ethanol under microwave (μw) heating. This convenient environmentally benign methodology is broad in scope, provides the heterobicyclic products in high yields (up to 99%), with a low catalyst loading (2 mol %) in only 30 minutes. Results and Discussion A search in the literature revealed a

• benign methodology is broad in scope (68 products were obtained, many of them not previously reported), provides the heterobicyclic products in moderate to excellent yields (23–99%), with a low catalyst loading (2 mol %). The reactions are fast, and the method can be applied to a wide range of aromatic

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• . demonstrated an unexpected Br2-catalyzed synthesis of BIMs from indole and carbonyl compounds in water (Scheme 9) [92]. First, the reaction took place in acetonitrile with a low catalyst loading (2 mol %), proving sufficient to achieve optimal product yields of up to 98% after just 1 minute, when the reaction

• associated with low catalyst loading, extremely high efficiency and broad substrate scope and the possibility of use of both organic solvents or water, with the drawback however, of the employment of conventional heating [92]. In 2019, Toy et al. proposed an alternative approach for the Friedel–Crafts

• be addressed. The most recent application of halogen bonding in the synthesis of BIMs was introduced in 2023 by Galathri et al., who employed an N-heterocyclic iod(az)olium salt as the monodentate catalyst [96]. This approach utilized water as the reaction solvent and employed a low catalyst loading

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

• , synthesized in situ from a chiral boron phosphate complex with water, for asymmetric indole reduction (Scheme 1b) [30]. The mild reaction conditions, low catalyst loading, and high enantioselectivity rendered this transformation an attractive approach to synthesize optically active indolines. However, these

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• tricyclic imidazonaphthyridinone derivative having antibacterial properties, with low catalyst loading (0.1 mol %) (Scheme 20b). Later, in 2014, the same authors, using an amide as directing group (DG), developed a protocol for the regioselective C3-alkenylation of pyridines through syn-addition of alkynes

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

•  31). The reaction conditions were screened with several biarylphosphine ligands and Pd sources. Excellent yields were achieved with a low catalyst loading of RuPhos (L6) fourth generation palladacycle precatalyst L6 Pd G4 (Scheme 31). The authors evaluated an extensive series of aryl halides. The

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• iridium-catalyzed ADC reaction. This method has some advantages, such as easy availability of raw materials, mild reaction conditions, wide range of substrates, and environmental friendliness which conforms to the principles of green chemistry. Furthermore, a gram-scale experiment with low catalyst

• loading offers the potential to access the aryl/heteroaryl quinolones in suitable amounts. In addition, the antibacterial and antifungal activities of the synthesized quinolines were evaluated in vitro, and the experimental results showed that the antibacterial activities of compounds 3ab, 3ad, and 3ah

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• cyanation of resultant aldimine intermediate to afford the α-amino nitriles (Scheme 20). This reaction worked well under eco-friendly conditions with low catalyst loading, and utilizing O2 as green oxidant to give excellent yields of the products. They also disclosed the efficiency of these Ru(II) complexes

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• and good to excellent enantioselectivities at room temperature. The notable features of this reaction are access to both the (R) and (S) enantiomers of the products, solvent-free synthesis, mild reaction conditions, low catalyst loading, and use of only a small excess of nitromethane (2.5 equivalents

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• and the methodologies were found to be good choices to achieve functionalized coumarins, such as the use of immobilized squaramide catalyst, which allowed the catalyst to be recycled twice with high ee. Moreover, the squaramide catalyst could also be used with low catalyst loading (1–2 mol

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• catalyst precipitated and was recovered by centrifugation and discarding the supernatant liquid. This process was complicated by a low catalyst loading and high phase-transition temperature leading to the loss of mass during this procedure. The authors, however, did not try the preparation of a polymer

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• synthetic organic chemistry [22]. Thus, the SMA with thiols and α,β-unsaturated ketones are generally carried out at low temperatures and with high catalyst loading [23][24][25][26]. The studies that employ mild conditions and low catalyst loading use thiophenol derivatives or simple alkylthiols as

• values. Thus, THF was selected as the best solvent despite the longer reaction duration. Then, the catalyst loading was varied between 0.1 and 10 mol % to investigate its effect on the enantioselectivity (Table 2, entries 1–6). At an extremely low catalyst loading of 0.1 mol %, the reaction was too

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• an alkynyl ketone to produce the required stereocenter. Of the syntheses to date, Jacobsen’s use of an asymmetric Cr(III)-catalyzed cycloaddition stands as the most efficient route, in terms of synthetic steps and low catalyst loading, to the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran and the

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• under ultrasound irradiation. Notable advantages of this methodology include the clean reaction profile, broad substrate scope, simplicity of the process and handling, low catalyst loading, and the easy and quick isolation of the products in good to excellent yield. Besides, the products obtained were

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• x increases with the removal of electrons). On the other hand, complex t-BuPhCuO.S.2, showing a reversible oxidation behavior very efficiently performs dehydrogenation of benzyl alcohol with low catalyst loading (0.1 mol %) and high turnover numbers (TONs up to 184). Besides the oxidation of benzyl

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• ][13]. The approach required five isolations only. Unlike Magano [1], the authors could not avoid the use of the potentially explosive azide chemistry. The azide intermediate was not isolated to address the safety concerns posed by azides. Positively, their approach was characterised by low catalyst

• loading, no protecting group chemistry and absence of halogenated solvents [1][13]. Generally, this approach is attractive for large scale manufacturing, however, the safety concerns posed by the use of azide chemistry needs to be addressed especially at large scale where the risk is very high. In an

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

• (Scheme 10). Notably, this reaction used an air and moisture-stable chiral palladium complex as the catalyst, which worked well at low catalyst loading (as low as 0.5 mol %). In 2015, Shi et al. [47] introduced a Pd(II)/Pd(IV)-catalyzed fluorination of β-methylene C(sp3)–H bonds of α-amino acid

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• ethenolysis products 71 and 72 (Scheme 7), and provided good yields and TONs at 50 °C and low catalyst loading (100 ppm, Table 2). Furthermore, many of the screened catalysts showed good stability toward propagation as a methylidene species. The observed selectivity seems to be controlled by the NHC sterics

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• reasonable yields over shorter reaction times and at low catalyst loading. The regioselectivity of the reactions was strongly dependent on the acidity or basicity of the reaction conditions. Under acidic conditions, nucleophilic attack of the thiol at the more-substituted α-carbon was favored while under

• catalyst loading required as well as recoverability and reusability without any significant loss of activity in terms of reaction time, selectivity and yield. For reactions that are sluggish and mostly require heating, microwave irradiation is reported to significantly improve reaction rates, selectivities

• -carbon of the epoxide. The nature of the substituent on the aromatic ring of the thiophenol did not have any effect on the reaction except for those moieties that are strongly coordinating such as the amino and carboxyl groups. ZnCl2 was chosen as the preferred Zn(II) salt due to its low cost, the low

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• 2015 by Enders et al. at a remarkably low catalyst loading (0.0225 mol %) to promote the enantioselective Mannich reaction of ethyl nitroacetate (2) with N-Boc-isatin imines 3 [35]. The process afforded, after a subsequent denitration, the corresponding chiral 3-amino-2-oxindoles 4 in moderate to high

• -bromo-substituted derivative (R2 = 5-Br) which afforded the corresponding product in only 41% ee. An advantage of this methodology was the use of a very low catalyst loading (1 mol %). Earlier in 2016, Silvani and Lesma described the synthesis of chiral 3-amino-2-oxindole butenolides 11 on the basis of

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• reaction for gram-scale synthesis with a remarkably low catalyst loading of 0.1 mol %. Oxygen plays an important role in the proposed mechanism: it regenerates the catalyst by aerobic oxidation and oxidizes the carbon-centred radical intermediate, obtained by radical addition of a thiocyanate radical to

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• within 30 min (Scheme 4). Excellent stereoselectivity was also achieved with a diastereomeric ratio of 98:2 and enantiomeric ratio up to 99:1. Simple flash column chromatographic purification methods, low catalyst loading, gram scale synthesis, etc. were advantageous for the reaction [52]. Morita–Baylis

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• reaction was carried out in a short reaction time and with low catalyst loading, leading to high turnover frequency (TOFs of the order of 100 h−1). The advantages like operational simplicity, high robustness, efficiency and turnover frequency, the utilization of aqueous media and simple product work-up

• bromides with electron-withdrawing groups as coupling partners, such as 4-bromoacetophenone (1a) and 4-bromobenzophenone (1b), the reactions were carried out in short times, employing low catalyst loading, obtaining the (E)-stilbenes 3 and 4 with excellent yields and selectivity (entries 1 and 2, Table 2

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

• mild aerobic conditions (Scheme 27). Low catalyst loading was required with a diverse substrate scope. The robustness of the reaction was demonstrated via gram-scale synthesis of the desired product. Recently, an aerobic photooxidative synthesis of quinazoline from 2-aminobenzylamine and aldehyde in

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• conditions. Our research group has already established molecularly defined dicopper catalysts with unprecedented activity under diluted conditions with low catalyst loading [37][40]. Thus, we aimed at an even more facile synthesis of dicopper complexes with bis-N-heterocyclic carbene ancillary ligands