Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• mechanism of the CPA-catalyzed transfer hydrogenation reaction was proposed (Figure 2). The activation of 3,3-difluoro-substituted 3H-indole 1 by protonation through the Brønsted acid generates the iminium A. Subsequent hydrogen transfer from the Hantzsch ester gives the chiral amine 2 and pyridinium salt B

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• electrophilic iminium carbon, leading to the amine product as racemic mixture. Consequently, examples for asymmetric Petasis borono-Mannich reactions are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts [10][11]. As part of our research program utilizing the in

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• presented in Scheme 31 [136]. An enantioselective oxidation can be achieved by combining a ketone catalyst with a chiral amine [137]. The resulting chiral oxaziridine intermediate promotes the hydroxylation of CH-acidic 1,3-dicarbonyl compounds in high yields and enantioselectivities (up to 99% ee) (Scheme

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• . Chiral thiophosphorus acids have been obtained by resolution with a chiral amine as early as 1958 [23][24][25][26][27], or from other precursors [28][29][30]. Having selected chiral thiophosphorus acids for our model study, further design requirements were included (Figure 2) to address some issues

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• (2R)-TKM-38 (3, see Figure 1) and the antipode 3*. For the synthesis of enantiomerically pure artificial glutamate analogs, we have previously developed an enantiospecific synthesis using a chiral amine as a starting material and have applied this to the synthesis of both enantiomers of IKM-159 (1 and

• carboxylic acid intermediates (rac)-7 and (rac)-19 with ʟ-(−)-menthol (8) [4] enables the chiral resolution of the heterotricyclic artificial glutamate analogs more practically than our previous method using a chiral amine as the starting material [3]. In the present study, the correctness of the

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

• (−)-adaline (1) and (+)-euphococcinine (2). The cyclooctatetraene derived selenides 82 and (+)-92 are, at some point, similar to the one obtained by Renbaun in the (−)-adaline (1) synthesis. Renbaun generated the quaternary center by adding a chiral amine to the cyclooctatetraene system. On the other hand

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

• , Luo’s group disclosed another potential application of integrating electrochemical oxidation with chiral amine catalysis [77]. Using chiral primary amine 130 as a catalyst, the authors reported an electricity-driven cross-dehydrogenative coupling of ketones 129 with tertiary amines 128. The

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

• sustainable approach to an industrial scale. Keywords: asymmetric catalysis; biotransformations; chiral amine; immobilized enzymes; ω-transaminases; Introduction Enantiomerically pure amines are important precursors to biologically active compounds with different industrial applications, including

• more sustainable method for chiral amine production [2][3][4][5]. TAs, also known as aminotransferases, are enzymes capable of transferring an amino group from an amine donor to an acceptor containing a carbonyl functionality in the presence of pyridoxal-5'-phosphate (PLP) as a cofactor and the enzymes

• carbonyl compounds. In a kinetic resolution, a maximum yield of 50% of the product can be obtained. Moreover, high quantities of the co-product might complicate the product separation and the recovery of the chiral amine. Thus, the asymmetric synthesis is generally preferable because a theoretically 100

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

• afford amides. Primary and secondary imines were produced under continuous conditions from the reaction of N-chloramines with base, with one example subsequently reduced under asymmetric conditions to produce a chiral amine in 94% ee. Keywords: continuous flow; CSTR; N-chloramine; synthetic methods

• of imine 20 and catalyst mixture were pumped into a heated CSTR over a 30-minutes tres, affording chiral amine 22 in 94% ee with complete conversion. It is unclear why a higher optical activity was seen using continuous flow. However, it is known that [IrCp*Cl2]2 can slowly racemise this amine which

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• aldol condensation of 2-methylpropanal with an aromatic aldehyde using a chiral amine as the catalyst. The attack of the hydroxy group of the resulting enantiomerically pure oxygen nucleophile 43 on vinyltriphenylphosphonium bromide (8) in the presence of a base, providing an ylide as an intermediate

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• ] annulation process [79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94], we started our investigation by carrying out the reaction between the commonly used D–A system dimethyl 2-vinylcyclopropane-1,1-dicarboxylate (1a) and trans-cinnamaldehyde (2a) catalyzed in the presence of a LA and chiral

• amine I in CH2Cl2 at rt for 48 h (Table 1). A series of Lewis acids were initially screened. FeCl3 and Cu(OTf)2 gave the 1,2-cycloaddition product tetrahydrofuran 4a (Table 1, entries 1 and 2). It is also disappointing that others Lewis acids, such as CuCl2, MgI2, ZnBr2, ZnCl2 and FeCl2 failed to

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• optimal reactivity and selectivity, each nucleophile required a slightly different chiral amine catalyst. Interestingly, vinylaniline 126f could also be added to enone 118 in moderate to good yield and with good enantioselectivity. N-Trifluoroacetyl-1,2-aminothiol (126d) reacted to give thioether products

• ) [65]. Interestingly, the optimal organocatalyst for the transformation was chiral only at sulfur, when chiral amine motifs were explored, e.g., 1,2-cyclohexanediamine, poor enantioselectivity was observed (≤75:25 er). A variety of R1 substituents on Meldrum’s acid 156 were compatible with the reaction

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• the chiral amine core of these alkaloids. For the synthesis of the nitrogen appending the quaternary center we tested a method developed by the Ellman group [46][47], which relies on an asymmetric addition of organometallic reagents to enantiopure tert-butanesulfinyl ketimines of type 29 and 30

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• substituents could be installed on the α-position (yield of the major product was given). Notably, when (+)-sparteine surrogate 28 was used as a ligand, product 38 was produced in 90% yield with 95:5 diastereoselectivity, but once the chiral amine ligand was simply switched from 28 to (−)-sparteine (21

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• tertiary chiral amine-thioureas, or a combination of catalysts. Products were obtained in one-pot or step-economic domino processes, achieving high increase of molecular complexity in step-economy transformations. There is no doubt that this scientific field will grow in the near future, providing more

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• catalyst of diastereoselective aza-Diels–Alder reactions [68] (Figure 14). While, the structure of the “chiral boron reagent” still remains unknown during our investigation of analogues we discovered a very interesting three-component self-assembly. Chiral binol, a chiral amine and 2-formylbenzeneboronic

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

• N-tert-butanesulfinylimine intermediates [11][12]. Due to its high diastereoselectivity and convenient cleavage of the N-tert-butanesulfinyl group, it has become an excellent chiral auxiliary in the synthesis of chiral amine compounds [13]. This work was devoted to develop an efficient synthetic

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• structurally similar aptazepine [8], we applied this protocol to the preparation of (S)-mianserin. The key step in the proposed synthetic pathway is the enantioselective reduction of an endocyclic imine that led to the chiral amine. Interestingly, starting from this intermediate we obtained mianserin and also

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• synthesis of β-peptides and 1,3-heterocycles in three steps. The steric effects of the isopropyl group at position 4 and of the α-methyl substituent of (R)-N-benzyl-N-α-methylbenzylamine on the reactivity were also studied and, upon application of a chiral amine, excellent stereoselectivity of the conjugate

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

• to prepare diverse chiral amine building blocks and react them with a common halo-purine intermediate to obtain the desired final products. The pyrrolo[2,3-d]pyrimidine core of PreQ0 was furnished following a method described by Klepper et al. [13] (Figure 3). The two step process started with the

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• determination of the enantiomeric excess of a chiral amine based on the use of phosphorinanes derivatives. Two synthetic pathways i) the AT reaction and ii) the direct use of chlorophosphate were evaluated for the derivatization of chiral amine (or alcohol) as reported in Scheme 6. For the AT reaction (i) [23

• . However, as reported in Scheme 32-ii, some chiral phosphoramidates and thiophosphoramidates can be readily synthesized with the AT reaction in high yield (85–88%) from dimethyl phosphite or O,O-dimethyl thiophosphite [106]. When the chiral amine was functionalized with a thiol group (Scheme 32-iii), the

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)amino]acetyl}amino)benzophenone; a case of configurationally stable stereogenic nitrogen

• Hiroki Moriwaki,
• Daniel Resch,
• Hengguang Li,
• Iwao Ojima,
• Ryosuke Takeda,
• José Luis Aceña and
• Vadim A. Soloshonok

Beilstein J. Org. Chem. 2014, 10, 442–448, doi:10.3762/bjoc.10.41

• glycine-Ni(II) complexes is that they, along with the chiral amine residue, have a configurationally stable stereogenic nitrogen, leading to formation of two diastereomers. Consequently, stereochemical assignments of the diastereomeric products, based on crystallographic data, and sense of stereochemical

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

• addition to imines [31][32] continue to be refined and relied on. Furthermore, enzymatic methods can offer competitive advantages that cannot be overlooked [33][34][35]. With this perspective, it is perhaps unsurprising that methods utilizing imines with chiral amine auxiliaries, i.e. N-chiral imines, can

• sometimes offer competitive solutions regarding the synthesis of challenging chiral amine structures [9][22]. Furthermore, it is common that alkaloid or amine containing pharmaceutical drug syntheses proceed through imine intermediates that lead to diastereomeric amine products [36][37][38][39][40]. With

• /trans ratios frequently provides unexpectedly good to excellent de for the corresponding chiral amine product. An early rationale was proposed by Harada, and invokes in situ cis-to-trans imine isomerization [51]. We were curious if conformational factors may be contributing to or even dominating the

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• 27. Although Shanti and co-workers used a chiral catalyst, no data was provided on the stereoselectivity of this reaction. In a study related to that of Shanti and co-workers, Yang and co-workers used chiral amine-thiourea catalyst 31 in a three-component enantioselective reaction of salicylaldehyde

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

• calcium hydride. The maleimides 1, the aldehydes 2, the amines 3 and the chiral amine organocatalyst (A–I) were purchased from the Aldrich Chemical Co. and used without further purification. Melting points were performed by using an Optimelt (MPA100) automated melting-point system (Sanford Research

• , 0.289 mmol, 1.0 equiv) in chloroform (3 mL) at 0 °C, followed by the appropriate chiral amine (A–I) (0.0289 mmol, 0.1 equiv) and the reaction mixture was stirred at the appropriate temperature for the appropriate length of time listed in Table 1. Water was added upon completion of the reaction and the