Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• afford various N-substituted pyrroles 27 in 89–94% yields (Scheme 12). A major advantage of this protocol is that in the case of chiral amines, pyrrole formation proceeds without detectable epimerization. In 2013 Azizi et al. [66] have demonstrated a simple and environmentally friendly protocol for the

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• asymmetric aza-MR. Thus, the review includes the examples wherein cinchona alkaloids, squaramides, chiral amines, phase-transfer catalysts and chiral bifunctional thioureas have been used, which activate the substrates through hydrogen bond formation. Most of these reactions are accompanied by high yields

• enantioselectivity (47–98% ee). The observed results were rationalized with density functional theory calculations (Table 8) [42]. 1.3 Reactions catalyzed by chiral amines He and co-workers developed heterogeneous synergistic catalysis using chiral amines SBA-15 (cat. 44), which promote aza-Michael–Henry cascade

• additions of these heteroarenes with crotonaldehyde yielded the adducts in moderate to good enantioselectivity under dual catalysis of chiral amines (Scheme 5) [69]. Conclusion The asymmetric aza-Michael reaction being a useful synthetic strategy for constructing C–N bonds to make a variety of nitrogen

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• , valuable precursors of chiral amines. Experimental Experimental procedure for the reduction in glycerol The desired nitroolefin (0.4 mmol) was suspended in glycerol (4 mL) in a 7 mL vial equipped with a 3.5 cm-long magnetic stir bar. Ammonia borane (12 mg, 0.4 mmol) was added to the suspension at room

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• are the reduction of prochiral ketones to chiral secondary alcohols, transamination of prochiral ketones to chiral amines, hydrolysis of symmetrical diesters to a chiral monoester, and esterification of prochiral diacids or diols. In desymmetrisation reactions, the enzyme initially produces the two

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• -(amino)cyanocyclopropane derivatives not contaminated by intermediates or ring-opening byproducts [21], whereas the asymmetric Strecker synthesis induced by chiral amines was successfully conducted by sonication in the presence of silica gel [22]. Pursuing our interest in developing environmentally

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• to proceed via the excited-state enamine [36]. While there is an abundance of known photoredox reactions that generate iminium ions catalytically either as a side product [37], or for further transformations [38], the use of iminium ions generated by chiral amines in combination with photoredox

• there is much progress yet to be made. Brønsted acid catalysis Using chiral amines and NHCs as catalysts to generate asymmetry relies upon the formation of covalently bonded intermediates such as enamines, iminium ions or Breslow intermediates within the catalytic cycle. The first example of merging non

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

• conversion and the racemic 1,4-product. Additionally, amide substrates featuring a bis(para-methoxybenzyl) moiety could be converted into relevant β-alkyl-substituted chiral amines, ubiquitous in numerous pharmaceutical ingredients, such as 52, a direct precursor of a drug candidate. Moreover, tandem ECA

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

• methodologies enabling their functionalization, particularly in a stereoselective manner. Among them, asymmetric α-oxygenation of aldehydes still represents a challenging task. Most efficient methods require simultaneous use of chiral amines or Brønsted acids, and harsh oxidants like nitrosobenzene [1][2][3

• starting material and the catalyst. Results and Discussion Our previous studies on α-photooxygenation of achiral aldehydes with 1O2 in the presence of chiral amines supported by DFT calculations indicate that the reaction is highly enantioselective only when both enamine structural fragments (substituents

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• chemistry. In the present study we demonstrate that resorcin[4]arene sulfonic acid (RSA) interacts with chiral amines (amino acid derivatives and aminocavitands) to form inclusion complexes and capsules based on electrostatic interactions. The complexes were characterized by circular dichroism and DOSY NMR

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• chiral amines, very low diastereoselectivity was obtained, probably due to the harsh reaction conditions employed. In addition to carbonyl and carboxyl derivatives, pyridine was also used successfully as an electron-withdrawing group (EWG) in the Michael acceptor 105. A simple control experiment allowed

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• are easily regenerated in situ without the need for another enzyme. In principle, enantiomerically pure chiral amines can be prepared following two approaches: through kinetic resolution starting from racemic amines or by asymmetric synthesis starting from suitable substrates, e.g., the corresponding

• configuration. Recent studies have favored the application of TAs at the industrial level, so it is not surprising that they are frequently found among the enzymes designed for the large-scale synthesis of chiral amines [2][4]. Moreover, immobilization of TAs has been developed in order to increase stability

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• imine intermediates to produce chiral amines. Results and Discussion N-Chloramine formation N-(Di)alkyl-N-chloramines have been prepared in continuous organic–aqueous biphasic flow using either static mixers or a single-stage CSTR [26]. The choice of reactor and definition of tres for this reaction is

• imines reported within our study. Of these examples, the latter was further explored by immediate asymmetric-transfer hydrogenation of an in situ formed imine under continuous-flow conditions, as a potentially productive route to chiral amines. Continuous-flow process to produce and react N-chloramines

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• aromatic rings followed by reduction is the most classical entry for the preparation of anilines [1][2]. Lately, also aliphatic nitro derivatives have become more and more popular: a wide variety of highly functionalized and chiral aliphatic nitro compounds, precursors of the corresponding chiral amines

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• chiral counterions in less polar solvents. Up to 61% ee could be obtained using cinchona alkaloids as catalysts [26]. The subsequent work of Tan and co-workers with guanidine catalyst 8 achieved enantioselectivities as high as 99% ee [19]. In recent years functionalized chiral amines have been

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , no report of valuable diastereocontrol by them has appeared so far. Successful examples of diastereoselective Ugi reactions have been reported only with chiral amines [15][16][17][18][19] or with chiral cyclic imines (Ugi–Joullié reaction) [20][21][22][23], although in the latter case, racemization

• point of view of atom- and step-economy, the use of chiral amines that are retained in the final products will be more valuable [27]. In this case they are not "chiral auxiliaries" and are not removed after the multicomponent reaction, and they contribute to the diversity of the final products. However

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• acetate aldol reaction [10]. However, these methods are undermined by poor yield, low enantioselectivity, and complex synthetic procedure. Chiral tert-butanesulfinamide, developed by García Ruano and Ellman, has been proven to be a broadly useful reagent for the preparation of chiral amines via the chiral

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• additional substituent in position 8 is described. Due to 1,3-diaxial interactions a pronounced diastereoselectivity for the menthylamines is found. Keywords: cathodic reduction; chiral amines; electrosynthesis; menthylamines; oximes; Introduction Optically active amines serve as powerful and versatile

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• diverse nature usually proceeds smoothly and allows for a clean pivalamide deprotection [29]. For this reason we decided to couple the chiral amines of interest and remove protecting groups in a one-pot procedure. First we investigated a more synthetically accessible (1RS,2SR,3RS)-3-aminocyclopentane-1,2

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• ensuing experimental and computational (DFT) results favor the former, pre-existing, explanation. Keywords: chiral amines; cis/trans isomerization; imine isomerization; imine reduction; reductive amination; Introduction A class of chiral compounds drawing ever more attention is α-chiral amines (chiral

• amines). Amines are known to be potent pharmacophores, and medicinal chemists have further leveraged their beneficial properties by using chiral versions to enhance protein binding affinities. Furthermore, chiral amines continue to find expanded roles: in organocatalysis [1][2][3][4], as ligands for

• transition metal catalysis [5][6][7][8] and as resolving agents [9]. Despite their high demand, the ability to produce structurally diverse chiral amines has not kept pace. Spurred by this shortcoming, innovative and improved chemical methods have been developed over the last fifteen years. Among them

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• [10][11][12] or epoxides [13][14][15] provides facile access to various chiral amines and alcohols and their derivatives with two adjacent stereogenic centers, which are widely used as building blocks in pharmaceutical and organic synthesis. The enantioselective catalytic desymmetrization of meso

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• organocatalysts were found to accelerate a variety of reactions. Due to the value of the Diels–Alder reaction for the synthetic community, different organocatalysts have been developed to catalyze this atom-economical cycloaddition in a highly enantioselective fashion. Thereby, chiral amines, heterocyclic

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• under different protocols in which the stereoselectivity of the reaction can be introduced through the use of a chiral catalyst [9][10] (Lewis acid, Brønsted acids, L-proline, Cinchona alkaloids derivatives, thioureas, etc.), or by the addition of chiral amines to α,β-unsaturated esters [11][12] or the

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• ]. Planar chiral 1,2-disubstituted ferrocene derivatives are usually synthesized by using diastereoselective ortho-lithiation of monosubstituted ferrocenes with an appropriate chiral ortho-directing substituent such as chiral amines, sulfoxides, and oxazolines [3]. However, this method suffers from low atom

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• protocol, we explored the use of various chiral amines in the conjugate addition reaction of propionaldehyde (2{1}) to N-phenylmaleimide (1{1}) (Table 1). Although the achiral pyrrolidine was found to be an efficient catalyst in the reaction [12], this led to a ~1:1 mixture of racemic succinimide

• diastereomers 3{1,1}, even at lowered temperatures (Table 1, entries 1 and 2). While a number of chiral amines failed to produce any significant amounts of the desired succinimide product (Table 1, entries 3–9), we were pleased to find that the use of protected diphenylprolinol catalyst I at room temperature

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• points of view: The conjugate addition of hetero-centered nucleophiles to α,β-unsaturated compounds; in a more complex approach through tandem/domino/cascade-Michael reactions; and by using chiral amines as organocatalysts for the enantioselective synthesis of functionalized chiral chromenes