Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• binding simultaneously to the chloride or through a cooperative 2H abstraction mechanism. These findings proved to be decisive in the development of new and more efficient anion-binding catalysts. By introducing a methyl group (R = Me) into the pyrrolidine moiety of the initial catalyst design, the amide

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 colleagues proposed an asymmetric [3 + 2] cycloaddition employing a coumarin dipolarophile 43 with azomethine ylides 60 organocatalyzed by quinidine (62) for the formation of fused pyrrolidine compounds through activation of the coumarin substrate by hydrogen bonding [53]. The methodology enabled

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• . Moreover, TMS-substituted alkyne was suitable for this Huisgen reaction to achieve the desired triazole product. Next, some triazene scaffolds, such as dimethylamino-, pyrrolidine-, piperidine-, morpholine-, and piperazine-derived triazenes were screened. Aryl azides containing Br, I, Me, and MeO as well

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• ; pyrrolidine-2,3-dione; Introduction The Michael reaction is a powerful reaction that has been so far applied for the formation of carbon–carbon and carbon–heteroatom bonds in organic synthesis [1][2]. After the renaissance of organocatalysis in the year 2000, this field has been applied tremendously for the

• suitable for the reaction though a moderate enantiomeric excess was detected. Finally, the best catalyst turned out to be the pyrrolidine-containing bifunctional thiourea catalyst VII and the desired product was isolated in 80% yield with 80% ee. Then, solvent optimization was carried out to obtain better

• ). Finally, nitroketone 2n with a cyclohexyl group was engaged in the reaction and a moderate enantioselectivity was detected for product 3n (Table 2, entry 14). In the next step, we investigated the scope of the reaction of substrate 2a with a variety of pyrrolidine-2,3-diones 1 having different benzylidene

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• protection of 16 followed by introduction of an azide group in the C-2′ position of the molecule to afford nucleoside 22. The treatment of azide 22 with pyrrolidine in acetonitrile followed by hydrogenation afforded aminonucleoside 23, which was used as a key intermediate for the synthesis of the double

• and treatment with pyrrolidine in acetonitrile to afford the C-3’-aminonucleoside 58. The reaction of this key intermediate with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in a solvent mixture of benzene and DMF, followed by acidification with sulfuric acid produced the

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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• . Asymmetric synthesis of pyrrolidines The pyrrolidine ring is more represented within natural products than the 3- and 4-membered nitrogen-containing heterocycles. This molecular array is also found in drugs and other biologically active molecules. For this reason, there are numerous examples of synthetic

• methodologies for these compounds in the literature. In most cases, the pyrrolidine ring is formed from an amine with a hydrocarbon chain that also carries a functional group at the appropriate distance that allows the cyclization process to take place. In the case of substituted pyrrolidines, the

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• reaction by using hydroxylamine as a nucleophile to substitute the thiomethyl group, followed by pyrrolidine addition on the cyano group to form the corresponding hydroxybiguanidine that was used as an IDO-1 inhibitor (Scheme 37) [77]. In conclusion, despite the obvious synthetic constraints such as the

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• LiAlH4 pyrrolidone trans-12b was reduced to pyrrolidine trans-15 in 95% yield, whereas no reaction was observed with DIBAL-H, NaBH4 or LiHBEt3 as the reducing agents; the starting material was typically recovered in 95% yield. However, the reduction of trans-12b by Red-Al in the presence of KOt-Bu was

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• molecule libraries against a bacterial TGase, an iminocyclitol was conjugated with a pyrophosphate mimic. After in situ screening, the first potent iminocyclitol-based inhibitor against bacterial TGases was efficiently developed [27]. The synthesis of N-pyrrolidine-derived β-phosphonodepsipeptides 64 is

• and oxidation with sodium periodate, benzyl 2-azido-3-(((benzyloxy)(2-oxoethyl)phosphoryl)oxy)-2-methylpropanoate (69) was obtained. The latter was further transformed to the final phosphonodepsipeptide library 64 after the reductive amination with pyrrolidine derivatives 70 and acylation with a

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• residue that appear altered in fluoroprolines. The first one to mention is the conformation of the pyrrolidine ring, which exhibits a dynamic transition between several distinct states in a relatively fast kinetic mode (roughly on a GHz scale) [48][49]. For simplicity, two conformations are considered

• has a remarkable relevance. In principle, the whole pyrrolidine ring is conjunct with the backbone, and thus there is no conformational transition that would occur separately in the backbone and in the side chain; both should occur at the same time. In this way, the pucker influences the backbone

• extracellular matrix in higher animals. When introduced at a certain position in the structure, R-Flp and S-Flp exhibit prominent effects on the thermal stability of the protein. The effect originates from the stabilization of the pyrrolidine ring puckers, which has an effect on the packing of the triple helix

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• reported values are within 5 ppm of the calculated theoretical values. Melting points were recorded on a Griffin mp apparatus and are uncorrected. (S)-tert-Butyl 2-(2-cyanopropanoyl)pyrrolidine-1-carboxylate (16) To a solution of LHMDS (100 mL, 1.0 M in THF, 100 mmol), cooled to −78 °C and under a N2

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• (Scheme 4). A proposed mechanism for the recyclization of hydroxypyrrolines 1 with hydrazides 2 is shown in Scheme 5. The protonation of the starting hydroxypyrroline 1 with TFA leads to the formation of cation A, which reacts with hydrazide 2 to give the pyrrolidine derivative B. The latter undergoes a

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• (76) furnishing product 77. In SelfSORT-I, 27% of the product 77 was afforded under standardized conditions, because both equiv of pyrrolidine 75 are free in solution. Upon the addition of one equiv of copper(I) ions, i.e., in SelfSORT-II, the yield of 77 increased by 12% to a total yield of 39%. This

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• pyrrolidine byproduct. Using the Stork–Zhao conditions [23], the Nicolaou group performed an α-methyliodomethylenation of 24 to give 33 with a good stereoselectivity (Z:E ≈ 95:5, Scheme 4) [24][25]. After the hydrolysis of the dimethylaminal and the reaction of the resultant amine with phthalic anhydride, a

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• were generated in 92% and 93% yield, respectively. Reactions with amines and thiols such as pyrrolidine and 2-mercaptobenzothiazole, gave rise to the products Z-25 and E-1c in 96% yield, respectively. These reactions were carried out in dichloromethane in the presence of Et3N. It should be noted that

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• C4-exo conformation of the pyrrolidine ring. Keywords: amino acids; cis–trans isomerism; fluorine; polarity; proline; Introduction Polarity is among the key features essential for understanding the behavior of organic molecules of biological origin. In particular, there is a set of polarity-related

• -bonded structures, such as γ- and δ-turns (also called C7- and C5-bonds, respectively) [61][62]. Thus, it was decided to examine the model compounds 1–4 and molecular effects therein. Conformation of the proline ring Due to its cyclic nature, the pyrrolidine ring in proline can adopt a few distinct

• conformational states [61][63]. The envelope conformation of the 5-membered pyrrolidine ring is commonly assumed to transit between two situations: 1) the one in which the C4-atom is displaced from the main plain in the same direction as the carboxylic group (C4-endo or down pucker), and 2) the one with the

Synthesis and highly efficient light-induced rearrangements of diphenylmethylene(2-benzo[b]thienyl)fulgides and fulgimides

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Valerii V. Tkachev,
• Andrey N. Utenyshev,
• Olga Yu. Karlutova,
• Alexander D. Dubonosov,
• Vladimir A. Bren,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2020, 16, 1820–1829, doi:10.3762/bjoc.16.149

• )pyrrolidine-2,5-dione (E- and Z-forms, 4) and 1-benzyl-3-((3-chlorobenzo[b]thiophen-2-yl)methylene)-4-(diphenylmethylene)pyrrolidine-2,5-dione (E-form 8). In contrast to the compounds with less voluminous dimethyl methylene groups, which under irradiation in solution formed deeply colored ring-closed forms

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• combination of DABCO and DMSO also afforded the desired product via a clean reaction within 20 min, although only 60% yield of the product was obtained (Table 1, entry 10). This promising result using DABCO encouraged us to explore other amines like DBU, ʟ-proline, pyridine, DMAP, and pyrrolidine as an

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• cyclized product was observed when using the trifluoromethyl ketone derivative 12d. Secondly, PKR with enynes 14 containing fluorinated propargyl alcohol groups yielded diastereoisomeric mixtures of pyrrolidine ring-fused cyclopentenones 15 in good yields (67–85%) but low diastereoselectivities. Finally

• % yield (18:82 ratio of trans/cis stereoisomers), respectively (Scheme 10). Ichikawa and co-workers described an attractive route to synthesize pyrrolidine ring-fused fluorinated cyclopentenone analogs via intramolecular PKR starting from 2-bromo-3,3,3-trifluoroprop-1-ene [50][51]. To this end, N

• ). The cyclization of internal alkyne substrate 24b yielded pyrrolidine ring-fused cyclopentenone 25b in similar yield but lower diastereoselectivity. Finally, N-propargyl-N-[2-(trifluoromethyl)allyl] ether 24d, containing an ether linkage instead of the aforementioned sulfonamide linkage, gave furan

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• chromatography. Pleasingly, the sequence proceeded in high yields (63–83%) for all substrates with no chromatography required. Despite relatively high yields, significant racemisation was seen in the synthesis of piperidine 20 and pyrrolidine cores 23. Pyrrolidine 23 was obtained with an ee of only 30

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• tolerated in this process (Scheme 1). The use of benzylamine, pyrrolidine, and ammonia all gave the corresponding β-trifluoromethyl-β-hydroxyamide product in ≈75:25 dr, with purification giving 8–10, respectively, as a single diastereoisomer in 42–55% yield and excellent enantioselectivity. Using methanol

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• reactions to make it a green synthetic method with pot, atom and step economy (PASE) [55][56]. Results and Discussion Following the reported procedures for amino ester- and amino acid-based [3 + 2] cycloaddition reactions, pyrrolidine adducts 5 and 6 were synthesized by a three-component reaction of 1 or 2

• achieved by the combination of a three-component reaction with one-pot reactions. This synthetic sequence is a new addition of our [3 + 2] cycloaddition-initiated reactions for making diverse cyclic scaffolds. Experimental General procedure for the synthesis of pyrrolidine adducts 5 A solution of amino

• the synthesis of pyrrolidine adducts 6 A solution of 2-aminoisobutyric acid (2, 1.2 mmol), 2-bromobenzaldehyde 3 (1 mmol) and maleimide 4 (1 mmol) in MeCN (3 mL) with AcOH (0.3 mmol) was heated at 110 °C for 6 h in a sealed vial. The concentrated reaction mixture was isolated by column chromatography