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

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

• between the aryl substrates 30.1 and the amides 30.2 for the synthesis of the Weinreb amides 30.3 using DCA (OD5) as an organic dye. Under visible-light irradiation, the SET oxidation of 30.2 by the excited state of DCA, followed by a deprotonation, afforded the amidyl radical. This radical behaved as a

• fluorinated amides 33.3, employing the α-amido-oxy acids 33.2 and Mes-Acr-Me+ (OD2, Scheme 33) [149]. The same electrophore allowed a remote functionalization of amides to take place, as disclosed by the Leonori group [135]. 4CzIPN (OD6) was reported to be a suitable dye for the SET oxidation of such

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• absolute configuration of the Trp residue was determined using a chiral derivatizing reagent, phenylglycine methyl ester (PGME) [21]. Compound 1 was reacted with both enantiomers of PGME to give (R)- and (S)-PGME amides 5a and 5b, and the difference of the 1H NMR chemical shifts ΔδS−R was calculated around

• linear gradient of MeCN from 15% to 85% over 30 min. Retention times for the amino acid standards were 20.1 min for ʟ-Pro-ʟ-FDLA, 21.1 min for ᴅ-Pro-ʟ-FDLA, while the ʟ-FDLA-hydrolysate of 1 gave a peak at 20.1 min (Figure S8 in Supporting Information File 1). (R)- and (S)-PGME amides of 1 (5a and 5b) To

• pseudosporamicins A–C (2–4). COSY, key HMBC and ROESY correlations of pseudosporamide (1). 1H NMR ΔδS−R values for PGME amides 5a and 5b obtained from compound 1. The opposite axial chirality around the biaryl C-6–C-7'' bond influenced by the C-2 configuration in compound 1. 3D structures 1a-1 and 1b-1 are the most

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• (Te), Italy 10.3762/bjoc.16.95 Abstract Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki–Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the free amines gave amides 28a,b. Treatment of the latter with aqueous potassium hydroxide finally afforded (S)-2-amino-3-(2,3,4,5-tetrafluorophenyl)propionic acid (29a) and (S)-2-amino-3-(2,3,5,6-tetrafluorophenyl)propionic acid (29b) [42] (Scheme 6). Alternatively, phenylalanines 29a,b were also

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• compounds can be obtained in excellent yields and good enantioselectivities under mild conditions, by using brominated amides and arylboronic acids as substrates, as well as palladium and chiral-bridged biphenyl monophosphine ligands as catalysts. Results and Discussion 2-Bromo-3-methyl-N-phenylbenzamide

• -alkyl substituted amides were found to produce better yields than N-branched alkyl chain amides, though they performed similar ee values (3a, 3b). N-Cycloalkyl-substituted amides enabled the reaction to achieve a quantitative conversion with good ee value (97% yield, 76% ee for 3c; 98% yield, 75% ee for

• 3d). The yield and ee value of an oxazolidinone amide were slightly lower than those of tetrahydropyrrolamide (3e, 3f). Various aromatic substituted amides were investigated. The results show that electron-rich or electron-deficient substituents on the phenyl ring have no significant influence on the

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

• -bromo amides (Scheme 6). Many metalloporphyrins are applied as catalysts in industrial processes, such as in the oxidation of cyclohexane to cyclohexanone catalyzed by Co(II) tetraphenylporphyrin on a ton-scale [21]. Recently, Sarkar and co-workers reported the use of nickel(II) tetraphenylporphyrin

• amides (71–99% yields) and with 5–66% ee (Scheme 42). In 2018, Meng and co-workers developed a bifunctional photo-organocatalyst combining both the photosensitizer and the chirality inducer. Relevant enantiomeric excesses were observed (up to 86% ee) in the oxidation of both β-keto esters and β-keto

• amides (Scheme 43) [93]. Singlet oxygen in heteroatom oxidations Singlet oxygen reacts readily with electron pairs of heteroatoms, such as sulfur, selenium, phosphorus, and nitrogen, due to their electrophilicity. The interaction between singlet oxygen and the heteroatom occurs in both physical and

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• supported the energy transfer pathway. Thus, the proposed triplet sensitization mechanism of the photocatalytic ATRA reaction is depicted in Scheme 25. In 2016, Ji and co-workers developed a new photoredox cross-dehydrogenative coupling (CDC) method for the α-heteroarylation of amides (α to nitrogen, e.g

• ., formamide) and ethers through C–H activation using various five- and six-membered heteroarenes (e.g., benzothiazole) and employing benzaldehyde (8) as the photoinitiator [56]. This protocol was compatible with both C(sp3)–H activation (N-alkyl C–H bonds of amides or Cα–H bonds of ethers) and C(sp2)–H

• activation (carbonyl C–H bonds of formamides). Some of the amides or ethers found to be compatible with this method are shown in Scheme 26. A wide range of heteroarenes 114 was also found compatible with this method, including substituted benzothiazole substrates, substituted benzimidazoles, and thiazoles

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• , China College of Pharmacy, Jinzhou Medical University, Jinzhou, 121001, China College of Pharmacy, Jiamusi University, Jiamusi, 154007, China 10.3762/bjoc.16.73 Abstract In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures

• conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported. Keywords: 18β-glycyrrhetinic acid; piperazinyl amides; synthesis; Introduction Glycyrrhizin was the major bioactive component in Glycyrrhiza uralensis

• amides of 18β-glycyrrhetinic acid (c) are synthesized using various methods. A method involves the C30-position of the acyl chloride with symmetric piperazine [16][17]. In this case, the acyl chloride can be prepared without purification, and the total yield over two steps can reach 81% [16]. Such

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

• , for the first time, a silyl transfer to lactams in both high chemical yields and high ees [60]. In this case, a comparatively higher (5 mol %) copper loading was necessary. Not only lactams (Scheme 25) but also acyclic, unsaturated amides could be efficiently silylated under these conditions

• . Interestingly, this protocol was applied to the total synthesis of (R)-oxiracetam (142), a drug used for the treatment of Alzheimer’s disease [61]. In a similar way, a ligand-free, intramolecular silylarylation of unsaturated amides 143 could be performed, albeit following a radical pathway leading to cyclic

• , could be intercepted at the intermediate radical stage (149) with radical initiator TBHP present in excess, leading to silylated peroxy products 151–156. This approach was applied to different types of conjugated systems, including esters, ketones, amides, alkynes, etc. (Scheme 27). Kleeberg [64] et al

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• generate new pterin amides (Figure 1) [14][17]. The same process used in generating RTA inhibitors was later used as a key step in the development of new aldolase reductase inhibitors [8]. The benefit of DBU as an additive in these previous reports was largely empirical, and reaction times were still in

• smoothly reacted affording product 9 in good yield under reaction conditions identical to those for the unhindered primary amines (5 min, 60 °C). Consistent with previous NMR studies of secondary amides, each of these were observed as a resolved mixture of the s-cis and s-trans rotamers [19]. Product 16

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

• chlorides [20]. This ATRA reaction was carried out with various fluoroalkylsulfonyl chlorides, such as CFH2SO2Cl, CF2HSO2Cl, CF3SO2Cl, CF3CH2SO2Cl, and C4F9SO2Cl, electron-deficient alkenes, including α,β-unsaturated ketones, amides, esters, carboxylic acids, sulfones, and phosphonates (Scheme 4). In

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• -deficient functions (i.e., aldehydes, thioesters, acylimidazoles, N-acyloxazolidinones, N-acylpyrrolidinones, amides, N-acylpyrroles) were recently investigated. Remarkably, only a few chiral copper-based catalytic systems have successfully achieved the conjugate addition of different organometallic

• -acyloxazolidinones, N-acylpyrrolidinones, amides, and N-acylpyrroles have been scarcely investigated in Cu ECA despite their usefulness for postfunctionalizations. This tutorial review aims to describe the early examples and recent advances in copper-catalyzed asymmetric conjugate additions of dialkylzinc, Grignard

• , the acylimidazole moiety constituted a privileged surrogate of esters, amides, ketones, and aldehydes. Indeed, this peculiar function, which was readily accessible from the corresponding aldehydes or Weinreb amides, could be efficiently converted into a wide range of carbonyl derivatives, as depicted

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• different compounds, such as (−)-kainic acid [51][52]. Previous similar approaches reported only planar pyrrolocyclopentenones starting from propargyl alcohol–cobalt complexes and allyl amides [50], or carbohydrate-derived allylpropargylamine [49] (Scheme 1a). Results and Discussion Cyclohexanone (1) and

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• were synthetized and the liquid crystal properties studied. Thioureas were obtained using a condensation reaction of benzoyl chlorides, arylamines and ammonium thiocyanate. The amides, on the other hand, were the byproduct of a quantitative reaction which used potassium cyanate as the starting material

• . Thiourea and amide derivatives were predominantly SmA mesophase inductors. A nematic mesophase was observed only for thioureas and amides containing an isoxazole ring. Additionaly, the liquid crystal behavior was also dependent on the relative position of nitrogen and oxygen atoms on the 5-membered

• heterocycle. Keywords: amides; isoxazole; isoxazoline; liquid crystal; thiourea; Introduction Thioureas are a structurally diversified group of organic compounds, with technological applications in different areas. The structural diversity of the thiourea moiety is linked to possibly one or both nitrogen

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• ], iron nanoparticle-catalyzed reactions of 2-naphthol with benzaldehyde and some of its derivatives with thiourea [22], isothiocyanato oxindoles with ketones [23], ammonium isothiocyanates with chalcones [24], and α-isothiocyanato esters with α-keto amides [25]. Among the synthetic methods available for

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• generated using a strong base, such as LDA or similar amides in combination with trialkylsilyl chlorides as silylating agents at low temperature under strictly anhydrous conditions [3][16][17]. An alternative method employs tertiary amines as bases in combination with more reactive silylating agents, such

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• therefore an excellent nucleophile and is usually generated from nitriles using metal amides or other strong bases [14][15]. Under our reaction conditions at rt, we propose that the presence of a catalytic amount of IPA increases the dielectric constant of the solvent as a whole, thereby increasing the

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• tolerate such strong electron-donating group. Hecht and co-workers had shown in their original paper that two amides connected to 2FAB and 4FAB via nitrogen atoms also lost much of the excellent features of the parent 4FAB chromophore [12]. (Note, "1FAB" also has a very short thermal half-life of the cis

• maintains the near-ideal chemical properties of Hecht’s 4FAB chromophores [12][13] (see below). The final synthetic challenge was the installation of a maleimide onto chromophore 2. The original AB photoswitchable probes which were cross-linked to cysteine mutants had amides with a reverse orientation [19

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• . Pharmacokinetic studies in mouse showed CNS penetration of 1 is very low with a brain/plasma concentration ratio of just 0.01. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. Although significant Notum

• inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux. Conclusion: Mouse pharmacokinetic studies demonstrate that 1 is unsuitable for use in models of disease where brain

• brain tissue. Amide analogues of 1 to explore CNS penetration and future opportunities With a peripherally restricted control in hand, we elected to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. A small library of amides 17 were prepared from acid 1

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• 1994, Zielinski and Schäfer made a vital contribution in the field of asymmetric electrosynthesis in terms of the diastereoselective cathodic reduction of the carbonyl group of chiral phenylglyoxamides 150 and 152 [89][90]. After initial conversion to its corresponding amides using chiral auxiliaries

• 2007, Feroci disclosed an electrochemical strategy for the cis-stereoselective synthesis of chiral β-lactams 180 via a 4-exo-tet cyclization of bromo amides 178 with an acidic methylene group and bearing a chiral auxiliary [101]. The cyclization occurred via deprotonation of the acidic methylene group

• ω-hydroxyl amides [102]. Upon constant current electrolysis, substrates 181 were oxidized to 182, which underwent in situ cyclization by intramolecular nucleophilic hydroxy group addition to afford a diastereomeric mixture of 183. The study also revealed that when cyclic amines were used as

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• the π-acidic character of pyridine rings, such as 2-oxo-6-oxypyridine, is rather weak [9][10]. Thus, pyridine[4]arenes may be expected to show a dual binding behavior towards anions and cations [8]. In addition to anion complexes also 2:1 complex formation with neutral carboxylic acids and amides have

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• δ 2.0 ppm, integrating for three protons, was assigned to the NHCOCH3. In the 13C NMR spectrum, the appearance of five signals in the downfield region (at δ 171.6, 170.9, 167.5, 165.0, and 164.0 ppm) indicated the presence of three amides, lactone carbonyl and imine carbon (-C=N) suggesting the

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

• diastereoselectivities. Based on the PIP auxiliary developed by Shi, Ge’s group [48] developed a similar direct, highly site- and diastereoselective fluorination of aliphatic amides (Scheme 11b). Although the roles of Fe(OAc)2 and Ag2CO3 were unclear, their addition significantly improved the reaction yield. A catalytic

• ]. Additionally, a diverse range of N-heterocycles, amides and motifs commonly encountered in medicinal chemistry were used as handles to direct C–H fluorination for the synthesis of pharmaceutical drugs (Scheme 24) [25]. Copper catalysis Despite the success of Pd-catalyzed fluorinations, the more widespread use

• developed independently by the groups of Buchwald [111] and Wang [112] (Scheme 54). Under similar mild conditions using Togni's reagent II, the desired allyl–CF3 products were obtained and the methods well tolerated a variety of functional groups (e.g., esters, epoxides, amides, alcohols, or aldehydes

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

• diastereomeric amides 39. Collins oxidation of 39 gave an aldehyde intermediate, which subsequently subjected to an aldol condensation using a ten-fold weight excess of neutral alumina quantitatively provided 40 and 41 in a small-scale reaction. The yield varied in large-scale reactions mainly due to the

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia 10.3762/bjoc.15.186 Abstract A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated

• molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics. Keywords: N-fluorosulfonyl amides; primary amides; sulfuryl fluoride (SO2F2); Introduction Sulfur(VI) fluoride exchange (SuFEx) is a new class of click chemistry developed by

• aromatic amines with SO2F2 or the fluorosulfurylimidazolium salt have been achieved for assembly of N-sulfonyl fluorides [1][30], which have served as important active precursors for the development of noncovalent inhibitors (Scheme 1, (1)) [1][30][31]. Amides are the key connections in proteins, amides