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

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• quaternary amines with hydroxy groups is not common but has been observed [90][91][92]. The electrostatic interaction of naphthol-based molecule ions are known to be at least of ΔH = −50 kJ/mol [32]. This suggests that here not only one charge interacts, instead, for ΔH3 it has to be between three charges

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

• ), isolated from the Colorado blue spruce Picea pungens, are members of this alkaloid family. Their unique bicyclic system with a quaternary stereocenter, and the potent biological activity exerted by these homotropane alkaloids, make them attractive synthetic targets. This work aims briefly to review the

• have provided new opportunities to develop synthetic strategies [21][22][23]. Structurally, it has an unsymmetrical bicyclic arrangement, incorporating a secondary amine and bearing a quaternary center. Since the pioneering Tursch’s work [24], a variety of approaches to obtain these alkaloids have been

• occurred by removing the TBDMS and formyl (CHO) groups via treatment with TBAF in dry THF and lithium–ethylenediamine complex, respectively. Finally, the resulting alcohol (+)-56 was oxidized in the presence of PCC to provide (−)-adaline (1). In this work, the quaternary center was successfully generated

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• , stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all

• -carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020

• , biologically important natural products [1][2][3][4][5][6][7] (Figure 1). Meanwhile, the construction of quaternary carbon stereocenter(s) is, at present, a distinct challenge in modern synthetic chemistry [8][9][10][11]. Therefore, the synthesis of highly-substituted five-membered carbocycles bearing

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• anions is becoming more and more significant [12][13][14]. There are many strategies aiming at anion recognition in the literature. Most of the receptors, however, rely on electrostatic interactions. These systems are represented by positively charged molecules, such as quaternary N-, S-, and P

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

• hydrolysis provides the radical conjugate addition (RCA) products 55 with a quaternary stereocentre in excellent yields and enantioselectivities (21 examples, up to 99:1 er). The quantum yield was measured to be <1 (Φ = 0.4) for the iridium-catalysed reaction, suggesting that a radical chain process is not

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• was successfully utilized for the synthesis of several bioactive molecules [79][80][81]. Herein we present its adaptation for the enantioselective fluorination of 2-oxo-aldehyde-derived Ugi adducts 8 leading to the installment of a fluorine-bound quaternary stereocenter at the peptidyl position. It

• should be stressed that the exploration of methods for the enantioselective fluorination continues to be an important topic considering the ever-growing role of fluorine derivatives in drug design and development [82][83]. An alternative strategy to prepare related quaternary carbon-containing adducts

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• substituents, electron-neutral and electron-rich rings with several substitution patterns performed well. However, pyridine-based 48j resulted in a low yield. Noteworthy, the PKR of chiral enynes 48 led to a bridgehead quaternary stereocenter containing a C–F bond in a single step. Besides the intrinsic

• difficulty in generating quaternary stereocenters, the goal achieved is even more significant given the attention that the asymmetric introduction of fluorine at sp3 carbon centers has received in recent years [62][63]. A gram-scale synthesis was also successfully performed in five steps starting from the

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• five methyl groups, nine methylene and eight methine moieties (one olefin: C-16 (δ 117.5), and two oxygen bearing groups: C-11 (δ 68.4) and C-19 (δ 98.9)), and seven quaternary carbons, as obvious from a DEPT135 spectrum. The 1H NMR spectrum showed unusual upfield resonances, diagnostic for a

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• transformations employed quaternary phosphonium salts as favourable catalysts [36]. Their synthetic utility was not only confined to catalysis, but they were also used as intermediates for the synthesis of 1H-indazoles [37], as promoters for stereoselective rearrangements [38], and as temporary protectors of O,P

• -acetals [39], which branded them as promising motifs. The above reports and the Lewis acid character of quaternary phosphonium salts (QPS) [40][41][42][43][44][45][46][47][48] qualifies them as reliable catalysts for the proposed methodology. The most elaborate process in the proposed methodology is the

• protection and elimination of the allylic hydroxy group. We believe that this crucial strategy could be primarily resolved by a quaternary phosphonium salt. After the initial screening of various quaternary phosphonium salts, the azidophosphonium salt [Ph3P+CBr3]N3−, reported by Blanco and co-workers, was

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• singlet exchangeable proton (δH 11.30). The four methine unit (C5–C6–C7–C8) was connected to the two quaternary carbons (δC 137.4 and 115.8: C8a and C4a) to form a disubstituted benzene ring by HMBC correlations H5/C8a, H6/C4a, H7/C8a, H8/C4a, and H8/C8a. On the other hand, the remaining parts were

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• , 1C), 28.0 (t, 1C), 26.5 (t, 1C), 21.7 (t, 1C), 11.7 (t, 1C), signals for 2 quaternary C-atoms were not observed; MS m/z (% relative intensity): 282 (100), 283 (18.4), 284 (1.6). Preparative irradiation of phthalimide 3 with AN and with β-CD Phthalimide 3 (150 mg, 0.461 mmol) was dissolved in CH3CN

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• (products 135a,d–h) and alkyl substituents (products 135b,c) at the oxime fragment (R1). An oxime with a disubstituted double bond (R2 = Me) also reacts with the formation of isoxazoline 135g having a quaternary carbon atom. Under the action of t-BuOOH (TBHP), β,γ-unsaturated oximes 136 undergo a cascade

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• )=C bond disappeared and two new signals appeared at around 68–69 ppm (quaternary C) and 51–60 ppm (CH). These facts are consistent with the expected hybridization change from Csp2 to Csp3 after formation of the cyclobutane ring. Determination of the crystal structure of complex 4a, which is shown in

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• ). Meldrum’s acid and its derivatives are versatile reagents in organic synthesis that can be transformed into a wide range of compounds. In 2006, the group of Fillion described the highly enantioselective synthesis of all-carbon benzylic quaternary stereocentres via a conjugate addition of dialkylzinc

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• ), lynestrenol (2) and desogestrel (3) gave alkylated products 5–7 in good yields and were readily engaged in the RCEYM reaction. The RCEYM reaction was then undertaken post alkylation. In fact, these quaternary propargyl ethers are particularly hindered. For such hindered substrates, we previously employed the

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• ) or KOH (Table 1, entry 3). However, no product was formed (Table 1, entries 2 and 3), and it was observerd that reactant 2a separated from the aqueous phase. This makes us add quaternary salts into the reaction, which could make the interface between organic and aqueous phase. Very interestingly, the

• , entry 6). It indicates that quaternary salts mediate the reaction in the presence of a base through the formation of the interface between the organic and aqueous phase. As a next step, different bases were investigated by using TBPB. In the presence of KOH and the Cs2CO3, the formation of the product

• triphosphate (Table 1, entry 12; 76%) did not improve the yield. These results suggest that K2CO3 is the best catalyst for the reaction among the bases investigated. To find the best catalytic system, other quaternary salts were invested in the reaction. When tetrabutylammonium chloride (TBAC) or

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• Suginome’s reagent along with LiCl, which completely overrode the need for a Grignard reagent and led to good chemical yields of the desired product (e.g., 272). In one case examined, a bulky silyl Grignard reagent gave the linear silyl derivative selectively. In addition, a quaternary carbon bearing the

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst

• . Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C–H coupling to produce indolinone derivative 5. Keywords: copper catalyst; 1,3-enyne; functionalized quaternary carbon; indolinone; tandem alkyl radical addition

• related coupling reactions [2][3][4]. Although there are many reports on alkyne transformations, one recent development in this area has been the reaction of alkynes with tertiary alkyl electrophiles to produce functionalized quaternary carbon atoms via addition [5][6][7][8][9][10] or coupling [11][12][13

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• synthesis” protocol. The quaternary salt byproduct that is formed when using an amine as the base can be easily separated by filtration. Bis(phosphine)amines with a P–N–P framework are more flexible to manipulate than diphosphines with a P–C–P framework [98]. The P–N–P cone angle and geometry on the

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

• studied, leading to the expected 1,4-products in excellent yields and remarkable enantioselectivities. More recently, tremendous breakthroughs were achieved in this field, notably by the formation of all-carbon quaternary chiral centers [6] and the challenging 1,6-, 1,8-, or 1,10-selective addition to