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

• azetidines Azetidine [76][77] has attracted less attention than aziridines, pyrrolidines and piperidines, among small and medium size aza-heterocycles, because there are no general methods for their preparation. However, four-membered nitrogen-containing heterocycles have recently found applicability in

• . 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

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

• ; electron transfer; γ-lactams; tandem reactions; Introduction Nitrogen-containing heterocycles are widely distributed in biologically active compounds [1][2][3][4]. Saturated nitrogen heterocycles such as pyrrolidines [5][6][7][8][9], piperidines, pyrrolizidines or indolizidines [10][11][12][13][14][15][16

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• variety of defensive alkaloids that makes them unpleasant for various predators [1]. Over 50 alkaloids have been characterized from ladybirds until now, including perhydroazaphenalenes, aliphatic and aromatic amines, piperidines, pyrrolidines, azamacrolides, dimeric alkaloids and homotropanes [2]. The

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.16.174 Abstract A new synthetic strategy toward nonracemic phosphoryl-substituted pyrrolidines and tetrahydropyranes with three and five contiguous stereocenters is presented. Readily available β-keto phosphonates react with

• reactions with aldehydes yielding tetrahydropyranylphosphonates as individual stereoisomers. These nonracemic heterocycles containing phosphoryl moieties are useful for designing new pharmacologically active compounds. Keywords: asymmetric catalysis; Michael addition; phosphonates; pyrrolidines

• heterocycles. The present work reports on the synthesis of nonracemic phosphoryl-substituted pyrrolidines and tetrahydropyranes via Ni(II)-catalyzed asymmetric Michael addition of β-keto phosphonates to conjugated nitroolefins. Results and Discussion For the synthesis of nonracemic polysubstituted pyrrolidin-3

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• high regioselectivity [4]. Based on this reaction, Maruoka reported in 2016 that N-tosylvinylaziridines and alkenes could undergo cyclization reactions to generate pyrrolidines, catalyzed by substituted aryl disulfides under ultraviolet-light irradiation (Scheme 1) [5]. In 1997, Jung and co-workers

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

• stabilized azomethine ylides I-a generated from the condensation of aldehydes and amino esters for making pyrrolidines II-a have been well-reported [23][24][25][26], while the [3 + 2] cycloaddition of the less stable azomethine ylides I-b generated from the reaction of aldehydes and amino acids for

• pyrrolidines II-b was less explored [27][28][29]. In recent years, our lab has reported a series of 1,3-dipolar cycloaddition-initiated methods for the synthesis of diverse heterocycles A–J bearing fused polycyclic rings such as tetrahydroepiminobenzo[b]azocines, tetrahydropyrrolobenzodiazepinones

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• chromatography. Scope of the fragment-based library generation: BCP-amines and azetidines. See Supporting Information File 1 for experimental details. Scope of the fragment-based library generation: pyrrolidines, piperidines and morpholines. See Supporting Information File 1 for experimental details. Supporting

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

• methodology, affording the products 143 and 145a–d in good yield. The N-substituted pyrrolidines 144a/d–g were also compatible, providing the desired products in good yields, except from the N-acetyl (144e) and N-pivaloylpyrrolidines (144f), for which the yields dropped considerably. The alkylation of the

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

• aryl iodides and bromides into the corresponding aryl radical to use the latter in further transformations (Scheme 21). First, a 5-exo-trig cyclization was carried out to access indolines, dihydrobenzofurans, indanes, cyclopentane, and pyrrolidines. The cyclized products were isolated in good to

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

• synthesized chiral compounds based on phosphorus esters and investigated their effects as chiral auxiliaries in the α-alkylation of secondary amines via anodic oxidation [100]. The constant current methoxylation of N-protected chiral pyrrolidines 173 in an undivided cell resulted in 174 in excellent yield

• . Further nucleophilic substitution of 174 with allyltrimethylsilane in the presence of a Lewis acid afforded α-alkylated products 175. The highest de was obtained in the case of 175d. The deprotection of 175 with LAH enabled access to α-alkylated pyrrolidines 176 with the release of 177 (Scheme 56). In

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• as tert-butyldiphenylsilyl ethers, individually transformed into 2-(3-hydroxypropyl)pyrrolidines by LiAlH4 reduction and deprotected. Diamines PF-00951966 (Scheme 18) belongs to a fluoroquinolone family of antibiotics which is substituted at C7 with a (3R)-3-[(1S)-2-cyano-1-(methylamino)ethyl

• methyl esters. Although docking simulation predicted binding of these compounds to isoleucyl-tRNA synthetase (IleRS) none of them showed inhibitory activity. Alkaloids Pyrrolidines: Pyrrolidine alkaloids and among them polyhydroxypyrrolidines like 1,4-dideoxy-1,4-imino-ʟ-ribitol (2S,3S,4R)-182 were found

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• tetroxide-mediated oxidation of cyclopentane, tetrahydrofuran, tetrahydrothiophene and N-substituted pyrrolidines has been studied computationally by DFT and topological (analysis of the electron localization function, ELF) methods. In agreement with experimental observations and previous DFT calculations

• carbocation. In the case of pyrrolidines, the carbocation is completely stabilized as an energy minimum in the form of an iminium ion and the reaction takes place in two steps. Keywords: alkanes; carbocations; DFT; oxidations; ruthenium tetroxide; Introduction Ruthenium-catalyzed oxidations [1][2] and, in

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• recently shown [8]. These allenes give rise to pyrrolidines [9], pyrroles [10], chromenes [11], benzoazepinones [12], macrolides [13], and some other carbo- and heterocycles [14][15][16]. It should be specially emphasized that many compounds containing SO2 groups are drugs, such as, dapson [17], oxicams

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• to form a wide range of functionalized dihydrofurans and pyrrolidines 56 in good yields (Scheme 33a) [93]. By tuning the diphosphine ligands, the reaction was extended to aromatic aldehyde 55a, where slightly electron-deficient ethylene diphosphine ligand delivered hydroarylation product 56a, but a

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• target GMIIb enzyme. In contrast, no inhibition effect of the pyrrolidines against LManII was observed. The modification of the imino-L-lyxitol core is therefore a suitable motif for the design of inhibitors with desired selectivity against the target GMIIb enzyme. Keywords: azasugars; hydrolases

• ; inhibitors; pyrrolidines; synthesis; Introduction Carbohydrates as chiral templates for a construction of bioactive compounds are of steady interest in medicinal chemistry [1][2][3]. The polyfunctional nature of carbohydrate units offers many possibilities for the design of a wide variety of new compounds

• properties of these compounds [13][14]. Another advantage of the iminosugars is a possibility to introduce a functional group onto the nitrogen atom. The importance of iminosugars is documented by a number of reports dealing with the synthesis of polyhydroxylated piperidines, pyrrolidines, pyrolizidines

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• ][19]. This way, they could access a variety of α-tertiary pyrrolidines carrying a β-trifluoromethyl group, in high yields and enantioselectivities (Scheme 13). The reaction conditions were compatible with various substituents on both aryl rings, as well as with unbranched substrates. Interestingly

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• and co-workers reported the use of CF3SO2Na in combination with iodide pentoxide in a similar way to their iodotrifluoromethylation of alkenes (see earlier in the text) [42] (Scheme 29a) [51]. Interestingly, this cascade reaction was also applied to enynes for the synthesis of pyrrolidines 52 (Scheme

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• examples of such reactions are for instance syntheses of multisubstituted indolines [23][24][25], pyrrolidines [26][27][28][29], dihydropyrroles [29], tetrahydrofurans [27][28], and 2,5-dihydrofurans [31][32], which proceed as intramolecular interaction of generated ammonium or oxonium ylides with carbonyl

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• isomeric pyrrolidines with preserved configuration in the fragment of the former dipolarophile [39]. Furthermore, the configuration of the ester groups at C2 and C5 corresponded with the structure of the intermediate azomethine ylide predicted for thermal ring opening of the starting aziridine. Also in

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• hydrolysis transition states as well as having many other interesting properties. They are found in nature as pyrrolidines, piperidines, indolizidines, pyrrolizidines or nortropane alkaloids with a variety of ring substituents, typically hydroxy groups, carboxylic acids and amides [1]. The ability of

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• aldehydes to nitroolefins and enantioselectivities up to 85% ee were achieved. Keywords: enantioselective synthesis; Michael addition; organocatalysis; pyrrolidines; synthetic methods; Introduction In the first decades of the 21st century, the enantioselective organocatalysis has witnessed a tremendous

• chiral pool, we have now focused on the synthesis of new chiral pyrrolidines capable of creating a sterically demanding environment due to the presence of a bulky 2,2-disubstituted-1,3-dioxolan-4-yl moiety at C2 from chiral imines derived from (R)-glyceraldehyde. The Michael addition of aldehydes to

• nitroolefins was selected as a model reaction to evaluate the effectiveness of the new pyrrolidine-based organocatalysts in aminocatalysis. Results and Discussion We reasoned that pyrrolidines of type C with a bulky 2,2-disubstituted-1,3-dioxolan-4-yl moiety at C2 could provide the appropriate environment to

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• (MAO) type B inhibitors [6] often used for the treatment of neuropsychiatric disorders such as Alzheimer’s and Parkinson diseases. These alkynylamines are also important building blocks for the synthesis of N-bearing compounds such as β-lactams [7][8], pyrroles [9], pyrrolidines [10], pyrrolophanes [11

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• cyano group activates the [3 + 2] cycloaddition of azomethine ylides and is then removed to yield 5-unsubstituted pyrrolidines [74]. These substructures appear in several biologically active natural products and drugs [75]. A range of decyanation conditions were screened such as NaBH4 in THF or MeOH

• of phenanthroindolizidines and phenanthroquinolizidines [71]. Two-step synthesis of 5-unsubstituted pyrrolidines (25 examples and 1 synthetic application, see below). The two yields refer successively to the cycloaddition (14) and decyanation (15) steps [74]. Boc = tert-butoxycarbonyl. EWG = electron

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• approach to the synthesis of indolines via intramolecular trapping of ammonium ylides with ketones [11] and double bonds [12] was developed. C. J. Moody and co-workers elaborated an efficient way for the synthesis of pyrrolidines by trapping of ammonium ylides with ketones [13], whereas J. Sun and

• system of the amino ester to afford N-arylpyrrolidines B (Scheme 1). It was suggested that this strategy for the synthesis of pyrrolidines could be extended to diazo compounds of other types and structures, and, as with diazoesters, multi-substituted pyrrolidines are the principal reaction products in

• of p-methoxy-substituted diazoketone 2a the yield of the principal reaction product 4 was close to 99% (Table 1, entry 1). At the same time, no formation of the assumed pyrrolidines of type B was observed. The structure of formamide 4 was reliably established using 1H, 13C and H,H-COSY NMR

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• more broadly in the substrate scope. Substrate scope Unfortunately, the conditions developed for the Tris-protected [4.1.0] bicycle 35 did not extend to other similarly protected 1,7-enynes [43]. We decided to shift our focus from 1,7- to 1,6-enynes to determine if bicyclic [3.1.0] pyrrolidines are

• reaction for the synthesis of Tris-protected [3.1.0] pyrrolidines, it occurred to us that protecting groups other than Tris may be equally effective for the [3.1.0] system. The Tris group was chosen during our optimization of the six-membered ring system (Table 5), which may have significantly different

• lithium aluminum hydride in excellent yield. The absolute configuration of the [3.1.0] pyrrolidines was assigned by analogy to 76, which was determined to be (R,R) by single crystal X-ray crystallography. Mechanistic studies After having successfully developed this synthetic methodology, a few questions