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

• 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

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• that revealed a molecular ion at m/z 237.0874 (calcd for C11H13N2O4−, 237.0880). A thorough analysis of 1H and 2D NMR data (see Table 1 and Supporting Information File 1) showed four aromatic methines, two aliphatic methines, one methyl, and four quaternary carbons signals at δC 162.9 (C-1), 113.2 (C-6

• acid unit, confirmed by long-range correlations observed in the HMBC spectrum from H-2, H-4 to C-6 (δC 113.2), and H-5 to the quaternary carbon C-7 (δC 170.0). On the other hand, the COSY spectrum confirmed the presence of a CH3–CH–CH spin system (H3-12, H-11, and H-9) reminiscent of a threonine unit

• carboxamide C-10 (δC 172.9) and the quaternary carbon C-16 (δC 140.2), between H2-15 and H-18/20 to the quaternary carbon C-16, and a strong correlation from H-15 and H-19 to C-17/20 (δC 129.9). The new oxazoline derivative 5 was named pseudomonbactin B. The absolute configuration of the threonine residue in

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• for the synthesis of 1,4-dihydroquinoline 129 possessing a quaternary carbon center from 128 [93]. The reaction was reported via a seven-membered bicyclic hemiaminal as mentioned in the mechanism. This catalytic rearrangement protocol was successfully applied for the construction of complex carbon

• Yamamoto et al [116]. The catalytic pathway was proved to involve the direct H-transfer to the vinylmercury complex from the aromatic ring. It involved Hg(OTf)2-catalyzed cyclization of aryl 1,1-disubstituted allenes with the formation of a quaternary carbon center followed by the formation of a cationic

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• ester moieties at C-3 have been shown to participate in enantioselective phase-transfer-catalysed alkylations promoted by ad-hoc designed quaternary ammonium salts derived from quinine bearing hydrogen-bond donating substituents. For the first time in such phase-transfer-catalysed enolate alkylations

• previously been applied to phase-transfer-catalysed SN2 enolate alkylation reactions and represents an effective process for the generation of carbonaceous quaternary stereocentres. The process generates malleable di-ester and mono-ester benzylated oxindole substrates which can easily give access to products

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• , 200.7, and 204.5. In addition, 13C NMR and HSQC analyses revealed the presence of six sp2 carbon atoms (five are proton-bearing), two quaternary sp3 carbon atoms, two oxygen-bearing nonprotonated carbon atoms, six sp3 methine groups (two are oxygenated), six sp3 methylene moieties, and four methyl

• then coupled with the other COSY-defined fragment, C22/C21/C29/C30, by the correlations from H22 to C18 and C23, yielding a cyclohexene ring. This ring was joined together with the dehydrodecalin moiety at the quaternary carbon atom C18 by HMBC correlations from H17 to C18, C19, and C23. As for the

• , 13C NMR, and HSQC spectra revealed the presence of four oxygenated sp2 carbon atoms, three nonprotonated sp2 carbon atoms, six sp2 methine groups, one sp2 methylene unit, one quaternary carbon atom, six sp3 methine groups (two are oxygenated), four sp3 methylene units, and five sp3 methyl groups

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• unusual di-tert-butylmethyl ester moiety and was limited solely to the alanine derivative [38]. Finally, a Baylis–Hillman-type approach has been employed to realize enantioselective reactions, albeit with a limited scope of substituents at the quaternary carbon [39]. Thus, the development of a general

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• the selectivity of olefin bonds during a CM reaction [38][39][40][41][42][43]. Investigations of various types of olefins in CM, such as substituted and functionalized styrenes, unsaturated tertiary alcohols, olefins with quaternary carbon centers, acrylates, allyl ethers or allyl acetates gave a

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• and produce long and uniform polysaccharides. Solvent systems like DMAc/LiCl or quaternary ammonium electrolytes are able to dissolve cellulose and could overcome the precipitation issues during synthesis [55][56]; however, these systems are not always compatible with reaction conditions [57]. The

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• stereogenic centers. Review A plethora of highly effective small‐molecule organocatalysts have enriched the field of organic synthesis [27], including chiral proline derivatives, N‐heterocyclic carbenes, chiral thioureas and Brønsted acids as well as phase‐transfer catalysts (PTC), such as the quaternary

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

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• . disclosed the quaternary ammonium N-F reagent, N-fluoroquinuclidinium fluoride (6-1) [43]. They subsequently followed with more detailed results in 1988 [44]. Quinuclidine was fluorinated by neat fluorine in trichlorofluoromethane at −72 °C, affording the product 6-1 in 86% yield (Scheme 15). Fluorination

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• established as an excellent strategy for the construction of elaborate molecules. In particular, the hydroalkylation of olefins represents a straightforward strategy for the synthesis of new C(sp3)–C(sp3) bonds, with concomitant formation of challenging quaternary carbon centers. In the last 20 years

• as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation

• reactions an ideal platform for the synthesis of molecules with increased molecular complexity. Keywords: hydroalkylation; hydrogen atom transfer; quaternary carbon center; radical addition; unactivated olefins; Introduction Natural product structures remain some of the main sources of inspiration for the

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• of modified hyaluronic acid fragments [16]. 13C NMR of 5 confirmed the presence of a new quaternary carbon (tetrazole Cq, δC = 155.8 ppm) alongside disappearance of the C6-nitrile (δC = 117.0 ppm). Furthermore, 1H NMR analysis indicated the common H5 doublet was further downfield (δH = 5.64 ppm

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

• ]. However, synthetic methods for efficient synthesis of unsymmetrical 3,3'-DIMs with a quaternary carbon center, including trifluoromethyl-substituted 3,3'-DIMs, are still rare. Sasaki et al. reported the reaction of trifluoromethyl(indolyl)phenylmethanols with indoles in the presence of trifluoroacetic

• substrate scope and functional group tolerance is highly desirable. As part of our continuous efforts to prepare biologically active DIM derivatives [38], we herein report an innovative approach to synthesize unsymmetrical 3,3'-diindolylmethanes (DIMs) with a fluoromethyl-containing quaternary carbon center

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• due to two methylenes at δC 38.8 (C-8) and 39.2 (C-9); three methines at δC 46.4 (C-11), 58.4 (C-6), and 77.6 (C-7) as well as two quaternary carbons at δC 45.6 (C-8) and 82.8 (C-10). Correlating 1D data with 2D NMR experiments (1H,1H COSY, 1H,13C HMBC, 1H,1H ROESY, see Figure 2) led to an underlying

• -14, and a methine (C-10, δC 39.3) instead of a hydroxylated quaternary carbon. The presence of the methine C-11 was confirmed by measuring 1D/2D NMR spectra of 3 in chloroform-d (see Table S1 in Supporting Information File 1). The corresponding proton H-11 (δH 3.38) forms again a spin system with H-5

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• ]. Guareschi imides have been extensively investigated because of their bioactivity profile, the use as building blocks to access other classes of heterocycles as well as quaternary centres, and their remarkable chemistry [54]. By far, the most intriguing reaction of these is the so-called “1897 reaction

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

• -cost [135]. These fibres are also suitable for flow systems as they can be easily shaped into the reactors. As an example, Tao’s group optimised several reactions in batch exploiting a quaternary ammonium functionalised PANF as catalyst (PANQAB-8F). They also reported the Henry reaction of 4

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• simple modification (temperature, catalyst loading) combined with the iterative addition of boronic acids (1 equiv immediately and 1 equiv after 3 hours) [49]. Following Stoltz's works [11][27][47][48][49][51][52], Stanley et al. published the first example for the formation of all-carbon quaternary

• the solvent (86% yield, 71% ee, Scheme 19) [54]. Significant successes of the Stanley group were achieved in the subsequent study of the as yet unexplored asymmetric addition of arylboronic acids to 3-aryl-2-cyclohexenones, where double benzyl quaternary stereogenic centres were formed [55]. The

• boronic acids, there were enantioselectivities of about 90% ee and average to excellent yields of 43–97% (Table 36) [62]. This catalytic system worked for 3-unsubstituted enones but was much more powerful in the case of addition reactions to 3-substituted enones that lead to all-carbon quaternary

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• , specifically because of the decreased electron density at the 9-oxyanion by linear conjugation with the quaternary nitrogen atom [39]. Nevertheless, the reactivity of intermediate 6 is still relatively low, as indicated by the low yields of the Cu2+-catalyzed coupling reaction, thus resembling the parent

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

• cyclization reaction of allyl bromide (228) with a carbonyl compound promoted by BBIMBr/SnBr2 complex under solvent-free conditions has been explored [97]. The mechanism of the reaction was shown to include a Barbier reaction of allyl bromide with an aldehyde in the presence of SnBr3 and a quaternary ammonium

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• atom transfer) occurs in nitrogen radical 14 to give radical 16, which further transforms to radical 17 after the addition of sulfur dioxide. Finally, HAT happens between 15 and 17, yielding quaternary ammonium salt 18 and product 12, respectively. In 2017, Chen and colleagues [47] accomplished the

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• ON (TG4T) with all phosphates replaced by a 4-(trimethylammonio)butylsulfonyl phosphoramidate group (N+, Scheme 1). The sequence was designed to obtain the formally charge-neutral zwitterionic N+TG4T [38]. Each negatively charged phosphoramidate is neutralised by the positively charged quaternary

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

• unit cyclized exclusively in the 5-exo-trig mode and provided the pyrrolidone 12f with a quaternary center at C4 in moderate yield and similar diastereoselectivity as for 12a–d (Table 3, entry 7); a product of potentially competing 6-endo cyclization was not detected. Amides 9g,k with trisubstituted

• ratio of lactam 12f with a quaternary center at C4 did not change at all, neither at room temperature nor at 50 °C (Table 4, entry 6). Lactam 12g with a benzyl group as well as pyrrolidones 12i–k bearing branched 1-arylethyl groups on the nitrogen required warming to 50 °C to induce epimerization at C3

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• IDPs upon tertiary and quaternary complex formation [79]. The Myc-Max heterodimer is a well-known oncogenic transcription factor complex able to bind to enhancer box (E-box) regions (5’-CACGTG-3’) of DNA with low-nanomolar affinity, what triggers its biological function as a transcriptional regulator

• tagging and PRE NMR spectroscopy to probe and trace the conformational changes experienced by disordered Myc upon Myc‐Max heterodimerization. Going beyond, they also employed 19F NMR to interrogate the changes induced in the Myc-Max heterodimer structure upon full quaternary complex formation in the

• agreement to those predicted for modelled MTSL-TFET pairs in adjacent subunits in the X-ray structure, showing only small discrepancies. Overall, the results of this work clearly demonstrated the value of solution 19F NMR for quaternary structure determination and as an alternative approach for generating