Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• of transannular cycloadditions of cycloalkenone hydrazones catalyzed by BINOL-derived phosphoric acid are reported in the Full Research Paper by Vicario, Merino, and co-workers [10]. Their methodologies can now be used to predict the reactivity of different substrates in other cycloaddition reactions

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

• (1a) as the model substrate, Hantzsch ester (HE-Et) as the hydrogen source, and BINOL-derived chiral phosphoric acids (CPA) as the catalyst (Table 1). With chiral phosphoric acid CPA-1, the transfer hydrogenation reaction proceeded well in PhCF3 at room temperature and the target product 2a was

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• 2004. In this methodology, a 1,1’-bi-2-naphthol (BINOL)-derived chiral phosphoric acid P1 was used as the catalytic reagent to couple 2-methoxyfuran (1) and N-Boc-protected aldimines 2 to incorporate an aza-tertiary stereocenter into the 2’ position of the heteroaromatic products 3 (Scheme 1) [24

• various asymmetric chemical transformations. These compounds play a dual role in the catalytic cycle due to their intrinsic Brønsted acidity and the ability to H-bond formation. Organophosphoric acids can perform as both H-bond acceptors and donors. 1,1’-Bi-2-naphthol (BINOL) and 1,1’-spirobiindane-7,7

• aza-Friedel–Crafts process between indoles 4 and cyclic N-sulfonyl ketimines 5. The authors employed the BINOL-based chiral phosphoric acid P2 bearing two imidazoline moieties at the ortho-positions as the catalyst which activates both reactants through H-bonding where the NH group of the nucleophile

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• hexaphenylbenzene 68 in an 85% yield. Then the Scholl cyclodehydrogenation of compound 68 was carried out in DDQ/TfOH to afford NG 69 in a 64% yield. By the selective dimerization of azopine-containing, HBC-monomer 69, the novel BINOL-like, atropisomeric chiral oxa-nanographene 70 was obtained in high yield

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

• (ELF and NCI analysis) of a series of transannular cycloadditions of hydrazones catalyzed by BINOL phosphoric acids, indicated that the process is an apolar concerted process in which all the events (bonds breaking/formation) take place in a concomitant way. In spite of the polarity of the reacting

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• first example of Al‒O/B‒H exchange in catalysis was reported by Woodward, in the enantioselective catalytic hydroboration of ketones with HBcat as the terminal reductant (Scheme 23) [103]. A mixture of 1,1′-bi-2-naphthol (BINOL), 1,1'-binaphthalene-2,2'-dithiol (DTBH2), or 2-hydroxy-2'-mercapto-1,1

• achieved. When AgOTf was replaced with silver (R)-BINOL phosphate, the asymmetric allylation proceeded in a moderate yield (60%) and enantioselectivity (40% ee). The structure of the ‘GaIOTf’ species was explored in more detail by Slattery, and a monovalent [GaI(18-crown-6)OTf] complex was isolated and

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

• Prize in Chemistry awarded to McMillan and List. A subclass of organocatalysts introduced independently by Akiyama and Terada in 2004 [1][2], are the C2-symmetrical chiral phosphorus acids (CPAs) initially derived from the BINOL scaffold, and later extended to other scaffolds such as VAPOL [3] and

• hydroxyphosphoryl (P(=O)OH) moiety which renders the phosphorus atom achiral. Substituents can be introduced on the ring system by ortho-functionalization with R groups on each ring. This functionalization helps introduce steric bulk and a range of electron densities extending the C2-symmetry of the BINOL, creating

• -syntheses that are required [1][2][3][4]. Additionally, whereas either enantiomer of BINOL is relatively inexpensive (109 $/mol), it is not the case with SPINOL (17,000 $/mol), and VAPOL is not commercially available. Although one could synthesize these precursors as well, this multistep synthesis is time

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• rotaxanes. MIMs show interesting structural and topological features and offer conceptually new possibilities as catalysts. In their minireview, Krajnc and Niemeyer [21] highlighted the use of the axially chiral 1,1'-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in MIMs. The authors comment on

• the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and stereoselective chemosensing. In their minireview, Prodip Howlader and Michael Schmittel [22] highlighted the recent results

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• that the chiral moiety should be incorporated in the ligand unit in order to provide an enantiopure assembly with an asymmetric cavity. 1,1'-Binaphthol (BINOL) is one such chiral building block, which has been successfully utilized to carry out numerous asymmetric catalytic reactions [74]. Keeping this

• in mind, Stang and co-workers constructed heteroleptic triangles via the assembly of a BINOL-based ditopic ligand and 180° trans-Pt(II) acceptors. The 3,3'-dipyridyl-substituted chiral BINOL donor (S)-37 has a bite angle of 60° and when treated with linear 180° acceptors 38 and 39, it produced the

• differently sized triangles (S)-40 and (S)-41 depending on the length of the organic spacer in the acceptor unit (Figure 9) [75]. Since the interior cavity of the homochiral macrocycles was equipped with BINOL units, they were utilized as catalysts for the asymmetric conjugate addition of chalcone 42 with

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• '-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in mechanically interlocked molecules (MIMs). We describe the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and their use in

• stereoselective chemosensing. Given the growing importance of mechanically interlocked molecules and the key advantages of the privileged chiral BINOL backbone, we believe that this research area will continue to grow and deliver many useful applications in the future. Keywords: axial chirality; BINOL; catenanes

• planar chirality into at least one of the subcomponents. One of the most important chiral molecular frameworks in general is the 1,1'-binaphthyl-2,2'-diol unit (BINOL, see Figure 1). BINOL is an axially chiral molecule with a high configurational stability and a well-established synthetic chemistry

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• metal-catalyzed reactions [31][32][33][34][35][36]. The most successful among them are the ʟ-proline-catalyzed reactions of enolizable aldehydes with nitrosoarenes [37][38][39][40][41][42][43]. Besides ʟ-proline and its derivatives, various secondary amines derived from BINOL and cinchona alkaloids were

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ][21] (Figure 2), and chiral building blocks in modern organic synthesis [5]. During the past decades, both C2 and non-C2 symmetric axially chiral biaryl compounds such as BINAP, BINAM, NOBIN and their derivatives BINOL have played a crucial role as ligands in the development of transition-metal

• excellent enantioselectivity [31]. The widespread use of phosphoric acids and phosphates as chiral acids, chiral anions, and ligands is one of the most important achievements of modern enantioselective catalysis. The atropochiral BINOL, H8-BINOL and SPINOL [32] derived phosphoric acids (Figure 4) [33][34

• excellent enantioselectivity when either CAT 1 (93–97% ee) or CPA 7 (93–96% ee) was used as catalyst (Scheme 21). The authors described that, BINOL-derived CPAs and pThr-type CPA scaffolds were found to be effective for atroposelective cyclodehydrations. Both the DFT and catalyst correlation studies showed

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

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

• alkaloids, (+)-deethylibophyllidine (88) and (+)-limaspermidine (89) from the reaction of para-dienone imide 84 with benzylamine (85) in the presence of bifunctional thiourea organocatalyst (Scheme 4) [56]. 1.6 Reactions catalyzed by chiral binol-derived phosphoric acids Binol-derived chiral phosphoric

• -quinolones 92 in very good yields (67–95%) with high ee (82–97%) (Table 20) [59]. Following a similar approach, Yang et al. reported asymmetric aza-Michael additions of anilines 94 to β-nitrostyrenes 93 using a chiral binol-derived phosphoric acid diester catalyst (cat. 95). They succeeded in preparing β

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