Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• is the binaphthol (BINOL)-derived phosphoric acid class of catalysts, firstly reported by Akiyama [25] and Terada [26]. Soon after, BINOL-derived phosphoric acids were employed in the enantioselective synthesis of 2,3-dihydroquinazolinones. The initial report in this area was made by List and co

• -workers, using an (S)-TRIP derivative as the chiral catalyst (Figure 1) [14]. Soon after, Rueping et al. developed a similar methodology catalyzed by other chiral BINOL-phosphoric acids [15]. However, the reaction suffered from limited scope to aromatic aldehydes without an ortho-substitution; the

• from preformed imines instead of aldehydes catalyzed by BINOL-phosphoric acid [17]. The corresponding aminals were prepared with a wide range of substitutions using aromatic, α,β-unsaturated, or aliphatic imines. Apart from chiral phosphoric acids, chiral quaternary ammonium salts were successfully

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• DIBAL-H reduction, and later to aldehydes 199 by Dess–Martin periodinane (DMP) oxidation. The aldehydes 199 were treated with BINOL-PO2H in chloroform, in the presence of air and light, to produce the corresponding anthraquinones 200 in excellent yields (93–99%) [82]. In this review, a more detailed

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

• compounds to produce the corresponding biaryl products with high enantiopurity using vanadium chelated with chiral ligands, such as tridentate asymmetric imine ligands, have been reported. For instance, (S)-binol derivatives could be successfully prepared from 2-naphthols using a dimeric vanadium complex

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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• using [{(R)-BINOL}Ti(IV){OCH(CF3)2}2] as a chiral promotor in PhCF3, followed by cyclization using R2CHCl(OMe) in the presence of TMSNTf2, as shown in Scheme 38 [73]. The internal chirality transfer during cyclization probably took place due to the geometrical preference of 162 to minimize the allylic

• subsequent trapping of the carbocation with the bromide ion led to all-cis-2,4,6-trisubstituted tetrahydropyran 297 (Scheme 69). Lalli and van de Weghe reported a chiral BINOL-derived bisphosphoric acid- and CuCl-catalyzed enantioselective tandem Prins–Friedel–Crafts cyclization between homoallylic alcohol

• with alcohol 307 to obtain 309 (Scheme 71) [113]. The introduction of electron-withdrawing nitro groups on the BINOL backbone in the catalysts significantly enhanced the reactivity and enantioselectivity. Zhou et al. reported an asymmetric Prins cyclization of in situ-generated quinone methides from

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

• provided aldehydes 59a and 59b (Scheme 7). The key step in this synthesis was the allylic transfer, conducted by the dropwise addition of 64 in PhCF3 at −20 °C to a mixture of 59a and 59b and the chiral catalyst S-BINOL-TiIV [OCH(CF3)2]2 providing alcohols 60a and 60b, after 12 h at −20 ºC. In addition to

• % (R = CH3) over three steps; ii) 64, (S)-BINOL-TiIV[OCH(CF3)2]2 (5 mol %), PhCF3, −20 °C, 84% (97% ee, R = n-C5H11) and 94% (90% ee, R = CH3); iii) DIAD, Ph3P, NH3, THF, 81% (R = n-C5H11) and 74% (R = CH3); iv) Ph3P, Et2O, 20 °C, 77% (R = n-C5H11) and 68% (R = CH3); v) 1. CF3SO3H (1.1 equiv), toluene

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• described the efficient asymmetric Biginelli reaction with a chiral ytterbium catalyst to provide excellent enantioselectivities up to >99% ee [12]. Later, Gong reported the first organocatalytic Biginelli reaction using 1,1'-bi-2-naphthol (BINOL) derived chiral phosphoric acids as catalysts, furnishing the

• DHPMs with up to 97% ee [13][14]. Though the BINOL-derived chiral phosphoric acids were successfully applied in the Biginelli reactions, the costs are essentially high because of complex preparative procedures, especially for the introduction of a substituent at the 3,3'-position of BINOL [15]. Besides

• BINOL, 2,2-dimethyltetraphenyl-1,3-dioxolane-4,5-dimethanol (TADDOL) was also widely used as a C2 chiral diol. However, TADDOL-derived phosphoric acids were not comprehensively investigated as catalysts in Biginelli and Biginelli-like reactions yet. The first example of their successful application was

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• limited Brønsted acidity of chiral phosphoric acids. Bearing this in mind, we then turned our attention to chiral disulfonimides developed by List, which have been established as a unique type of stronger Brønsted acids [45]. Putting it into practice, a range of BINOL-derived disulfonimides was used as

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• characteristics in the solid state. The crystal structures of the coupling products were also evaluated by single crystal X-ray analysis and the well-ordered intermolecular stacking arrangements appeared to be responsible for the enhanced CPL. Keywords: BINOL; C–H activation; circularly polarized luminescence

• -dimensional displays [22], information storage systems [23], molecular photoswitches [24], etc. Among a series of chiral scaffolds for CPL emitting molecules, axially chiral 1,1’-bi-2-naphthol (BINOL) has been frequently adopted for the core structure owing to the availability of both enantiomers as well as

• the ease of site-selective functionalization. Up to date, many BINOL-based CPL active compounds have been established by installing aromatic subunits on the periphery of the binaphthyl skeleton or on the hydroxy groups [25][26][27][28][29][30][31][32], extending the π-system [33], and linearly

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

• organocatalysts, including chiral squaramides, thioureas, alkaloids and their derivatives, taddols, binol, chiral phosphoric acid, (S)-proline and its derivatives, amide of tryptophan (Figure 1). These catalysts feature varying steric properties from sterically encumbered, such as C1, C5, C8, or C10, to less

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• reactions and a newly developed deoxygenative aromatization procedure. The first enantioselective Diels–Alder reaction, which is an intermolecular cycloaddition and lactonization between (Z)-3-iodo-4-methylpenta-2,4-dien-1-ol (29) and methyl acrylate (30) in the presence of Mikami’s (binol)TiCl2 catalyst to

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• atmosphere [50]. Product yields ranged from 18 to 96%, but in moderate enantioselectivities of 20–64% ee (Scheme 16). Sun and co-workers reported the use of BINOL-based Brønsted acid catalysts such as TRIP 60 for the asymmetric thiolysis of meso-epoxides with benzothiazoles 62 as nucleophiles as shown in

• ranged from –78 °C to room temperature. The use of amines, alcohols as well as alkyl and arylthiols as nucleophiles failed to provide the corresponding products. A year later, Antilla and co-workers found lithium-binol phosphate 64 to be an efficient catalyst for the desymmetrization of meso-epoxides

• complex. Enantioselective ring-opening reaction of stilbene oxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol–titanium complex. Asymmetric desymmetrization of meso-epoxides using BINOL-based Brønsted acid catalysts. Lithium-BINOL-phosphate-catalyzed desymmetrization of meso-epoxides with

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

• selectivity was the chiral oxazoline unit and not the inherent chirality of calixarene skeleton. Asymmetric hydrogenation Starting with distally O-dialkylated calixarene precursors, a series of BINOL-derived calix[4]arene-diphosphite ligands 40a–g were synthesized by Liu and Sandoval through phosphorylation

• applied in the palladium-catalyzed Tsuji–Trost allylation reaction. BINOL-derived calix[4]arene-diphosphite ligands. Inherently chiral calix[4]arene 43 containing a diarylmethanol structure. Calix[4]arene-based chiral primary amine–thiourea catalysts. Novel prolinamide organocatalysts based on the calix[4

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

• diastereomers (>90% de) in both uniformly excellent yields (90–98%) and enantioselectivities (94–99% ee). In only one case of substrate (Ar = 1-Naph), a lower yield (78%) albeit combined with a comparable very good enantioselectivity (93% ee) was obtained. The same year, (S)-BINOL-derived tin dibromide 30 was

• trimethylsilyl ether. However, also metal complexes (Zn, Sn) derived from N,N’-dioxide and BINOL-derived ligands have been employed affording the products with enantioselectivities of up to 90–99% ee. Moreover, comparable enantioselectivities of up to 99% ee were reported in aza-Morita–Baylis–Hilman reactions

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• have so far been reported [7][28][29][30]. In 2007, Gosselin and Britton et al. reported that treatment of ethyl trifluoropyruvate (1a) with (R)-BINOL-mediated organozincate as a chiral methylating regent provided the corresponding methylated tertiary alcohol 2a in moderate enantioselectivity (Scheme 1

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

• an additional hydrogen bond donor group was not tested in too much depth. Therefore, we have synthesized two binaphthol-based diastereomeric squaramide catalysts (Sa,R,R)-C8 and (Sa,S,S)-C8 (Scheme 3). Starting from (S)-BINOL (8), amine 9 was obtained in five steps following literature procedures

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• aldehydes as electrophiles [38]. Enantioselectivities of up to 84% ee were achieved by using a BINOL derivative as chiral ligand. Ever since, other types of chiral ligands including chiral Schiff bases [39], bisoxazolidines [40], 1,2-amino alcohols [41], indolinylmethanols [42], and diarylprolinols have

• alcohols and BINOL (1,1’-bi-2-naphthol) derivatives, ligand 53 was selected as optimal ligand when used at a stoichiometric amount in THF at −40 °C. As shown in Scheme 21, the corresponding fluorinated chiral β-amino alcohol 54 was formed in both moderate yield (60%) and enantioselectivity (37% ee

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• allylation with BINOL-titanium catalysts failed due to low conversion [14]; however, in spite of good experience with the Maruoka–Keck allylation in another total synthesis, the conversion was not satisfying in this case [15]. After protection and guanidinylation with triflylguanidine 14, the homoallylic

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

• catalytic (R)-3,3’-dibromo-BINOL (16) and stoichiometric SnCl4 [19] (Scheme 4). The authors proposed that complex 18 acted as a chiral proton source to protonate a tin-enolate intermediate based upon related complexes that the Yamamoto group had previously used for the enantioselective protonation of silyl

• lower enantioselectivities for the addition of para-substituted anilines to α,β-unsaturated imines [41]. Gil and Collin have also reported on the same reaction as Sodeoka, but using a samarium-BINOL catalyst system, which proceeded with lower enantioselectivity [42]. Sodeoka found that minimizing the

• co-workers demonstrated that chiral lanthanum and samarium tris(BINOL) complexes (Figure 3), developed by the Shibasaki group for asymmetric Michael additions using malonates and organometallic reagents, are effective catalysts for the sequential conjugate addition of 4-tert-butyl(thiophenol) to α,β

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• ’-position of the BINOL backbone had a remarkable effect on the catalytic activity and enantioselectivity. Based on this method, the authors also achieved the synthesis of a key intermediate efficiently (99% yield and 93% ee), which had been used in the total synthesis of (+)-folicanthine [68]. The Zhang

• enantioselectivity were observed when the reactions were performed only in the presence of 10 mol % cinchona alkaloid amine catalyst and TFA (30 mol %). It was found that (S)-BINOL-derived CPA catalyst can significantly improve the stereochemical control of the cinchona alkaloid amine catalyst, while (R)-CPA

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• aromatic formamidines (1a–c) starting from triethyl orthoformate and aromatic amines. Low-temperature lithiation of 1 and addition to achiral (R = Ph) and axially chiral (R2 = BINOL) chlorophosphines R2PCl gave ligands 2 and 3 in excellent yields (Scheme 1) [11]. If the correct stoichiometry is maintained

• -fluorophenyl; R = phenyl or BINOL. Yields: [2a-Rh(cod)]BF4 = 85%, [2b-Rh(cod)]BF4 = 75%, [2c-Rh(cod)]BF4 = 88%, [3a-Rh(cod)]BF4 = 74%, [3b-Rh(cod)]BF4 = 90%, [3c-Rh(cod)]BF4 = 81%, [2a-Ir(cod)]BF4 = 77%, [2b-Ir(cod)]BF4 = 80%, [2c-Ir(cod)]BF4 = 88%, [3a-Ir(cod)]BF4 = 65%, [3b-Ir(cod)]BF4 = 81%, [3c-Ir(cod)]BF4

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• developed an aza-MBH process using β-ICPD in the reaction between N-sulfonyl-1-aza-1,3-butadienes and activated alkenes (Scheme 4) [25]. In this report, optimal selectivity required (R)-BINOL as a co-catalyst (see inset for proposed catalytic transition state – (R)-BINOL shown in red). Furthermore, the

• the flexible cinchona framework, which has a knock-on effect on the catalytic outcome. Interestingly, the chiral nature of the binol phosphoric acid catalyst (S)-49 in the anti-selective process was not thought to be hugely influential upon the stereochemical outcome. Indeed replacing it with diphenyl

• processes catalyzed by β-ICPD, as demonstrated by Shi and Li and co-workers. (b) Takizawa and co-workers demonstrated similar chemistry, but also utilized the catalyst α-ICPN (inset). (a) Chen’s asymmetric MBH reaction. Good selectivity was dependent upon the presence of (R)-BINOL (shown in red) as well as

Self and directed assembly: people and molecules

• Tony D. James

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

• important it is to read and keep up to date with the literature. Taking that one step further, it is also very important to keep abreast of papers that cite your own work. This is clearly illustrated using a paper by Todd A. Houston, who discovered that the racemic form of our chiral binol boronic acid 8

• formed very strongly complexes with tartaric acid [60]. This paper made us realise that our chiral binol boronic acid 8 should be able to discriminate the enantiomers of tartaric acid and also bind strongly with other sugar acids. Therefore, with Jianzhang Zhao an outstanding Postdoctoral Research Fellow

• enantiomers of tartaric acid and also bound bind strongly with other sugar acids [61] (Figure 9). While, we were very happy with these results, we realised that the system could be improved by changing the fluorophore from binol, to a much better fluorophore such as anthracene. Therefore, we combined the

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• advantage of a chiral (R)-BINOL-bridge to link the two aromatic acids and obtained the coupling product with excellent stereocontrol (up to 100% de) (Scheme 1) [16][17][18][19]. In 1998, Martin et al. [20] applied this strategy to the asymmetric intramolecular biaryl coupling of sugar derivatives carrying 2

• )butanoates with CuI/BINOL-derived ligands in 2013, affording the chiral coupling products and recovered starting material with high enantioselectivity (Scheme 21). Recently, the aforementioned kinetic resolution strategy was applied to another type of substrates [51], leading to the formation of cyano

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• 5,5’-bitriazoles from acetylenic amide. The amine-functionalized polysiloxane-mediated divergent synthesis of trizaoles and bitriazoles. The cyclic BINOL-based 5,5’-bitriazoles. The one-pot click–click reactions for the synthesis of bistriazoles. The synthesis of bis(indolyl)methane-derivatized 1,2,3