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

• 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

• esters and β-keto amides by singlet oxygen using PTC-2 as a chiral organocatalyst. Bifunctional photo-organocatalyst used for the asymmetric oxidation of β-keto esters and β-keto amides by singlet oxygen. Mechanism of singlet oxygen oxidation of sulfides to sulfoxides. Controlled oxidation of sulfides to

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

• be the most effective organocatalyst. In the absence of light or 4-anisaldehyde (52), no transformation was observed. No transformation was observed either in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl, 2,6-di-tert-butyl-4-methylphenol or air, indicating a radical mechanism. The reaction

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

• reaction. This represents the first example done in a water/THF solvent system at room temperature, giving moderate chemical yields and ees. It has been proposed that the ligand itself acts as an organocatalyst, eliminating the need for a copper catalyst. 1.3 Additions to aldehydes The Oestreich group [42

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

• vinyl sulfones as electrophiles (Scheme 3). Of note, both the anti- and the syn-product could be predominantly formed (with a anti:syn ratio from 83:17 to 15:85), and no diastereocontrol occurred in the absence of the organocatalyst. Interestingly, this simple protocol was successfully applied to the

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

• significant role in the Ireland–Claisen rearrangement of 1c. Surprisingly, all catalysts led to a decreased yield of the acid 3c (28–62%) in comparison to 74% yield obtained without any chiral organocatalyst. Further, none of the chiral organocatalysts considerably affected the diastereoselectivity and acid

• 3c was obtained in racemic form in the presence of either tested chiral organocatalyst. Similar results were obtained with ester 1a. The reaction was tested also in the more polar solvent acetonitrile using catalyst C1, but also in this case no enantioselectivity was observed. Sigmatropic

• catalyst’s action in the rearrangement, we have studied the effect of catalyst loading in the reaction of ester 1c with squaramide C1. The reaction with Et3N as a base and Me3SiOTf without any chiral organocatalyst afforded acid 3c with 74% yield. Repeating the reaction in the presence of squaramide C1 (5

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• found to occur between the fulvene and an enamine generated through the reaction of the formyl group with the organocatalyst, diphenylprolinol silyl ether. Variation of the spacer structure provided access to a range of triquinane derivatives (Scheme 11), an important precursor in biomimetic and natural

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• originating from an aldehyde and an organocatalyst) interact with each other in such a way that one side of the enamine is predominantly shielded from singlet oxygen. As a result, small alterations to the aldehyde structure require detailed optimization of the catalyst structure [14]. Preliminary data for α

• , 4) as an organocatalyst and meso-tetraphenylporphyrin (H2TPP, 5) as a photosensitizer followed by in situ reduction with NaBH4, proceeded similarly to the reported results for simple, achiral aldehydes giving the desired diols 6–8 in 31–41% yields with moderate conversion and alcohols 9–11 as

• % ee [α]D20 −147.0 (c 0.6, CHCl3). Enantiomer R,R (syn-6) 99% ee, [α]D20 −104.0 (c 0.4, CHCl3). General procedure for α-photooxygenation with phosphate buffer solution To a 10 mL vial a solution of meso-tetraphenylporphyrin (H2TPP, 0.4 mg, 0.63 µmol, 0.25 mol %) in CCl4 (1 mL) and organocatalyst (S)-17

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• ) is one of the benchmark reactions for photoredox catalysis because it combines photoredox catalysis with organocatalysis [53]. Initially, [Ru(bpy)3]Cl2 was applied by MacMillan et al. as photoredox catalyst together with the chiral imidazolidinone 15 as organocatalyst to achieve enantioselectivity

• :1 was used. 20 mol % of organocatalyst 15 were applied. 2,6-Lutidine was added as base to trap protons that are potentially formed during the reaction and to ensure enamine formation with the organocatalyst 15. Under these conditions, a moderate conversion of 13 (65%) and a low yield of product 14

• control reaction without light did not show conversion at all. Control reactions with light, but without NDI 1 showed, however, a low conversion of 24% and a low yield of 18%. This is due to the UV-A absorption of the enamine that is formed as intermediate between 1-octanal (12) and the organocatalyst 15

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• synthesis of diversely functionalized pyrroloacridinones in aqueous medium. A library of compounds was synthesized in a one-step pathway utilizing 10 mol % of the nanoreactor following a sustainable methodology in water with high yields. Keywords: heteroditopic macrocycle; organocatalyst; nanoreactor

• issue for the stabilization of the activated complex by a hydrophobic catalyst [31]. Again, the efficiency of an organocatalyst could be enhanced by downsizing the catalyst at nanorange distribution (i.e., nanoreactor) [13][14]. This is because a nanoreactor allows for precise interactions with the

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions. Keywords: C-; O-; N- and S-linked glycosides; enosides; Ferrier-rearrangement; organocatalyst

• perflurophenylboronic acid as a versatile organocatalyst for the Ferrier rearrangement reaction. We noted that the yields of the disaccharides 3n and 3o and sulfonamides 3t and 3u can be increased with increase in the temperature (60 °C) and extension of the reaction time. The results in Table 1 are superior to the

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• ) – derived from a renewable resource like sugar cane biomass – for the incorporation of chiral pyrrolidine-based motifs capable to catalyze relevant asymmetric reactions. The incorporation of an organocatalyst into a polymer support requires either conjugation to the polymer or functionalization with a

• catalysts for applications in continuous-flow catalysis [8]. In an endeavor to develop a cheaper and renewable polymer-supported organocatalyst, herein we describe the multicomponent synthesis of furfuryl-containing prolyl pseudo-peptide catalysts and their subsequent utilization in the preparation of PFA

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• important for chain-length control. Liquid-assisted grinding was applied for the synthesis of high molecular weight polymers, but it failed to protect the polymer chain from mechanical degradation. Keywords: aliphatic polycarbonate; green polymerization; mechanochemistry; organocatalyst; poly(trimethylene

• mechanism is currently obscure. To have a better understanding of LAG on chain protection, extensive studies are currently in progress. Conclusion A mechanochemical method, ball milling, was applied to the synthesis of poly(trimethylene carbonate). The representative organocatalyst, DBU, exhibited excellent

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• hydrogen bonding organocatalyst for the reaction between 1-dimethylamino-3-tert-butyldimethylsilyloxy-1,3-butadiene (Rawal’s diene) and aldehydes with excellent enantioselectivities (aromatic aldehyde: up to 86–98% ee) in 2003 [27]. Activation via a single-point hydrogen bond between one of the hydroxy

• groups of the TADDOL and the carbonyl oxygen of the aldehyde was proposed to be a crucial factor for the success of this organocatalyst in the reaction. Two years later, they reported another efficient diol-based hydrogen bonding organocatalyst, BAMOL, for catalyzing the same oxo-DA reactions with a

• library of aldehydes (aromatic: 97–99% ee; aliphatic: 84–98% ee) [28]. Thereafter, many different kinds of hydrogen bonding-based organocatalysts have been developed for oxo-DA reactions [29][30][31][32][33][34][35]. One kind of organocatalyst in particular, which is based on an oxazoline template with

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• lower toxicity, air sensitivity and lower costs [34]. A huge repertoire of organocatalyzed reactions have been published in recent years with high efficiencies and selectivities [29][33][35][36][37][38][39]. Proline as a natural amino acid is a perfect example of an organocatalyst. Both enantiomers are

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• with activated dipolarophiles. As synthetic tools being able to provide 1,2,3-triazoles using an organocatalyst or other non-metal catalysts, this method shows distinctive advantages in enabling the production of 1,2,3-triazoles free of any heavy metal contamination [36][37][38]. Generally, the

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• different nitroolefins catalyzed by organocatalyst 2. Reagents and conditions: catalyst 2 (5 mol %), nitroolefin (0.5 mmol), acetylacetone (1 mmol), toluene (0.32 mL) and water (0.16 mL), rt. Catalysts synthesized and screened in this study. Synthetic routes for organocatalysts 1–4. Possible proposed

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• bromines to alkenes, using ortho-substituted iodobenzene 62 as an organocatalyst (Scheme 19) [75]. A control experiment indicated that only trace amounts of products were observed in the absence of iodoarene catalyst (2%). A similar work involving a rearrangement of imides, which delivered α,α

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• calixarene; organocatalyst; supramolecular catalyst; Introduction The catalysis of organic reactions by macrocyclic host compounds is a longstanding proposed application of supramolecular chemistry and utilizes the use of noncovalent interactions in catalytic systems to achieve higher reaction rates, more

• asymmetric Michael addition reaction of thiophenol could be catalyzed by inherently chiral calixarenes bearing amino alcohol/phenol structure [47][48]. In order to see the effect of the diarylmethanol moiety, Shirakawa and Shimizu used 43 (Figure 6) as organocatalyst in the Michael addition reaction between

• both catalysts gave the Michael adduct in excellent yields, high ees were obtained only when 54b was used as organocatalyst (up to 94% ee, Scheme 16). During the last decade, squaramide catalysts have become a powerful alternative to the urea/thiourea and guanidine catalysts as multiple hydrogen bond

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

• an enantioselective organocatalytic Mannich reaction between isatin-derived benzhydrylketimines 12 and trimethylsiloxyfuran 13 [38]. Using 10 mol % of another type of organocatalyst, such as chiral phosphoric acid 14, the process led at −40 °C in THF to the corresponding butenolides 11 in moderate to

• enantioselectivities (90–94% ee), as shown in Scheme 5. The synthetic utility of this novel methodology was demonstrated through the total synthesis of the natural product (−)-psychotriasine (Scheme 5) and the biologically active compound AG-041R (Scheme 1). By using another type of organocatalyst, such as L

• a carbon–carbon bond-forming reaction occurring between the α-position of an activated alkene and a carbon electrophile such as an aldehyde. Employing a nucleophilic organocatalyst [26], such as a tertiary amine or a phosphine, this simple reaction provides densely functionalized products, such as α

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• . Conclusion An operationally simple route to 5-fluoromethyl-2-oxazolines from readily accessible N-allylcarboxamides is disclosed based on an I(I)/I(III) catalysis manifold. This metal-free fluorocyclisation employs p-iodotoluene (10 mol %) as an inexpensive organocatalyst and Selectfluor® as oxidant. The

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• the latter reaction DBU acts both as base and as organocatalyst [14]. In all cases, an excess of a strong base or high temperature are necessary for the reaction to proceed. An overview on the importance of the Corey–Fuchs reaction for the synthesis of natural products has been pointed out by Heravi

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• depicted in Figure 2, PQS (4a) has an OH moiety that allows for its linkage to the organocatalyst proline 4b. Also, PQS has a lipophilic component that acts as a reaction solvent for hydrophobic dienes. The latter feature allows aldol reactions to take place efficiently in water. The aldol reaction between

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• faster than the NMR time scale. The EDC adduct is then expected to react with the organocatalyst, yielding the alkylimidazolium nucleotide that acts as the kinetically most relevant monomer in the extension reaction. The ethylimidazolium species can be observed as a small peak in 31P NMR spectra. The

• approaches that reduce inhibition or slow conversion. Among them is the removal of hydrolyzed monomer, improved activation chemistries, or in situ (re)activation with the support of an organocatalyst. Despite progress in the field, the ultimate goal of demonstrating enzyme-free replication of RNA strands

• organocatalyst. Acknowledgements We would like to thank H.-P. Mattelaer and E. Kervio for critical comments on the manuscript. The work of the authors on enzyme-free copying is supported by DFG grant No. RI 1063/16-1 to C.R.

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• reached only for specific substitution patterns on the amide nitrogen atom and to a lesser extent on the Michael acceptor. In order to overcome these limitations, we decided to incorporate a chiral auxiliary in our substrates combined with a proper chiral phase-transfer organocatalyst to operate an

• diastereoselectivity could not be obtained and we looked for improvements through the use of an appropriate chiral organocatalyst [63][64][65]. Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone (S)-3a with higher de (54%), (Table 1, entry 5). We assumed such de

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• successful Michael additions to nitroalkenes in aqueous media [20][21], we have also tested the Michael addition of dimethyl malonate to nitroalkene 6 in brine. For this experiment, we have employed the more lipophilic organocatalyst C4, but the desired adduct 7 was formed only in small amount (14

• nitroalkene is bound to the catalyst via a squaramide moiety including an ancillary C–H···O hydrogen bond [45][46]. The dimethyl malonate anion binds via the protonated tertiary amide group. The calculations suggest that using organocatalyst C7 the preferred enantiomers of the product, within like and unlike

• synthesized from ethyl 3-methylbutanoate. The key step is an organocatalytic Michael addition of dimethyl malonate to racemic nitroalkene 6. Using chiral squaramide organocatalyst, the desired Michael adduct 7 was obtained in 75% yield as a mixture of diastereomers (dr 68:32) with very high enantiomeric