Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• quinuclidine moiety can act as a base activating a nucleophile, secondly the secondary hydroxy group can participate in hydrogen bonding or can behave as a Brønsted acid (Figure 5). Additionally, the quinoline moiety can interact through π–π stacking with the reactants. On the other hand, the (DHQD)2-based

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• bonds (Scheme 25a) [34]. Besides, the same group published a comprehensive analysis on N-ammonium ylide mediators, which were found to be superior to quinuclidine scaffolds for a chemoselective C(sp3)–H oxidation (Scheme 25b) [35]. The electrochemical C(sp3)–H fluorination of unactivated C–H bonds is

• another important transformation via anodic oxidation realized by the Baran group [36]. The choice of Selectfluor, which plays multiple roles, was crucial. In addition to functioning as a fluorine source, Selectfluor also acts as a mediator similar to quinuclidine and serves as an electrolyte. The method

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• corresponding free amines by hydrolysis with aqueous HCl. The reaction proceeded in good yields and with complete retention of stereointegrity. In a proposed mechanism, isatin carbonate 137 reacts with a quinuclidine unit of the catalyst 138 by an SN2’ attack to form cationic intermediate 142. The t-BuO− anion

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• observed when AQ-3 was applied. Besides, the modifications of the quinuclidine ring through replacing the vinyl substituent in the parent quinine core by a triple bond (AQ-5) led to no substantial improvement in the mixer mill, but the decrease of enantioselectivity in the reaction performed in the

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• selectivity, features a 1,2,3-triazole-4-yl unit as the substituent at the tertiary amine-containing quinuclidine motif, whereas C30 and C31 have an ethyl group attached to the ring in this position. Additionally, catalyst C31 has a longer-chain linker, but its squaramide NH groups are more acidic due to

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• assembly 4 (Scheme 5). It is known that Brønsted acids facilitate the iminium ion formation step [38][39] and the counteranion of the acid plays an important role in the stereocontrolling event [38][40]. On the other hand, the protonated quinuclidine nitrogen atom of the catalyst II (in the iminium ion

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• Swing Road, Greensboro, North Carolina, NC 27409, USA 10.3762/bjoc.20.41 Abstract Solutions of 1,3-diketones and 1,3-ketoester derivatives react with fluorine to give the corresponding 2,2-difluoro-1,3-dicarbonyl derivatives in the presence of quinuclidine. Quinuclidine reacts with fluorine in situ to

• quinuclidine to direct fluorination reactions of 1,3-diketone and 1,3-ketoester substrates using fluorine gas can give difluorinated products by a simple batch process, offering a potentially valuable route to the synthesis of difluoromethylene compounds that is suitable for inexpensive scale-up. Results 2

• ) gave only relatively low conversions to 2a and 3a. Other organic nitrogen bases were tested, and we found that quinuclidine (entries 8 and 9, Table 1) gave high conversion to difluorinated product 3a, with very little monofluorinated product 2a being observed. Suspensions of caesium carbonate or sodium

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

• unfavorable (DABCO, quinuclidine) and in the case of triarylamines containing no hydrogen atoms at carbon atoms connected to the cation radical center. Cation radicals of aromatic amines or N-heterocyclic cation radicals are usually involved in electron transfer processes due to their low affinity to hydrogen

• atoms (instability of the corresponding ammonium cations), whereas cation radicals of aliphatic bicyclic amines are effective in hydrogen atom abstraction (Scheme 17). For example, the electrochemical CH-oxidation of unactivated substrates mediated by quinuclidine was demonstrated [106] (Scheme 18A). In

• several cases, a good regioselectivity was achieved for complex molecules. Quinuclidine cation radicals were also involved in the generation of nucleophilic α-hydroxyalkyl radicals from alcohols for the addition to the electron-deficient C=C bond of methyl acrylate followed by lactonization [107] (Scheme

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• bifunctional hydrogen-bonding catalyst would activate both CPD via a tertiary amino group of a quinuclidine moiety acting as a base via anion-binding, and an oxindole through the squaramide or thiourea moieties of the catalyst as hydrogen bond donors (Figure 1) [29][30][31][32]. Therefore, squaramide and

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the

• very attractive as HAT catalysts as demonstrated by previous works using secondary amides [8][9], sulfonamides [10] and quinuclidine [11][12], the latter being broadly explored in the literature for several functionalizations along with its derivatives [11][12][13][14][15][16][17][18][19][20]. DABCO is

• a common inexpensive organic base with two nitrogen atoms in a bicyclic cage structure. The interaction between these two nitrogen atoms makes DABCO easier to oxidize and improves the lifetime of the radical cation species when compared to quinuclidine [7]. Investigation of DABCO as a hydrogen

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

• derivatives Squaramides are related to cinchona alkaloids but are much more effective organocatalysts than the latter due to the ability of dual hydrogen bonding besides a tertiary nitrogen atom of quinuclidine nucleus which may serve both as an H-bond acceptor and a base in asymmetric Michael addition

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiBr2·dtbbpy, quinuclidine, and K2CO3 in dioxane under blue light irradiation at ambient reaction temperature (Scheme 46) [129]. Besides aryl bromides, alkenyl and alkyl bromides were found to be viable substrates and showcased the catalytic conditions versatility. Based

• reported by Liu and co-workers [130]. Here, stoichiometric quantities of quinuclidine were used to get optimal results. Carboxylation Over the past few decades, significant attention has been devoted to exploit carbon dioxide (CO2) as the C1 resource [131][132]. In particular, the C–H functionalization

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

• -dicarbonyl compounds using Selectfluor (16-3a) [61]. In 1995, the same group reported that Selectfluor reacted with quinuclidine to form N-fluoroquinuclidinium tetrafluoroborate in quantitative yield [62] (Scheme 35). They described this as a “transfer fluorination” since there was an intermolecular transfer

• of the fluorine atom of Selectfluor to the nitrogen of quinuclidine. In 1996, full details were published on the reactivities of all 16-3 reagents and the syntheses of 16-3 and intermediates 16-2 including additionally C2H5 and C8H17 as R group and PF6− and FSO3− as anion X− [63][64]. The generous

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• Houk’s mode of activation was of lower energy than Wynberg’s activation mode, in which the activation and orientation of the nucleophile is done by the quinuclidine core [43]. According to our proposed model, the protonated quinuclidinium ion stabilizes the newly forming alkoxide on the electrophile

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

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

• and Lu investigated the enantioselective electrocarboxylation of 4-methylpropiophenone (27) on a stainless steel cathode in which the enantiodiscrimination was controlled by the nucleophilic quinuclidine nitrogen atom and the -OH group of the inductor alkaloid [35]. Mechanistically, cinchonine (CN

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• enantioselective reactions (mainly because of the nucleophilic center on the chiral quinuclidine skeleton) [20]. More importantly, they are a privileged class of chiral catalysts, which are well known for their use in Michael additions [21], Morita–Baylis–Hillman reactions [22], and aldol reactions [23], among

• triazole (8.21 ppm), thus confirming the successful attachment of the cinchona alkaloid to the CD skeleton through the CuAAC click reaction. The second part of the 1H NMR spectrum comprises the resolved signal for the double bond on the quinuclidine skeleton of the cinchona alkaloid (5.93 ppm). The third

• signal for H-6I is separately visible around 4.75 ppm (especially in the HSQC and 1H,1H COSY spectra). This part of the spectrum also includes the primary rim OH groups (4.49–4.34 ppm) and secondary rim OH groups (5.91–5.53 ppm). Finally, the quinuclidine skeleton part of the cinchona alkaloid is

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• of Schrock’s original catalyst V can be enhanced by adding an external ligand like quinuclidine to the reaction mixture [61]. Thereby, the self-metathesis yield of 1-heptyne could be increased to 80% at elevated temperatures. Based on this approach, the dinuclear tungsten complex [W2(MMPO)6] (VI

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

• proton shift mediated by the organocatalyst occurred with the least steric hindrance between the quinuclidine moiety of the catalyst and the aromatic ring of the isatin imine. The same year, Chimni et al. reported organocatalyzed aza-Morita–Baylis–Hillman reactions of N-Boc-isatin imines 3 with

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

• enantioselective oxaziridination using mCPBA as the oxidant (Scheme 17) [55]. The authors propose that the quinuclidine nitrogen is protonated by the peracid, giving rise to a tight ion pair, whilst the 6’-OH coordinates to the sulfonyl group oxygen, thus bringing the reactants together. Subsequent reaction then

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• quinuclidine moiety in catalyst 4 and the piperidine scaffold in catalyst 6) are the key parameters influencing this different arrangement for the nitroacetate pronucleophile [27]. Conclusion We have developed an asymmetric catalytic diastereodivergent route for the synthesis of 2,4-dinitro esters taking

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• . [13] used dioxane/water in a 1:1 ratio, while Aggarwal et al. [14] used quinuclidine in methanol to carry out the MBH reaction of acrylamide. Connon et al. [15] utilized phenol and/or a H2O/t-BuOH 7:3 system for rate acceleration and Guo et al. used aryl activation [16][17]. Other reports made use of

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• : aromatic quinoline and chiral aliphatic quinuclidine, and a hydroxy function on the stereogenic carbon atom. Such an architecture combined with the presence of nucleophilic and electrophilic centers buried in a hydrophobic environment predestinates the molecule to asymmetric applications, such as: chiral

• (R/S). The homologous aldehyde can be prepared by oxidation of the double bond in a hydroboration–oxidation sequence, however, the presence of the nitrogen atoms, particularly that of the tertiary amino group of quinuclidine, may be troubleshooting [28][29]. Borane complexes with heteroaromatic and

• with trimethylamine oxide [31]. As the oxide also released the borane–quinuclidine complex at elevated temperature the free alcohol was obtained in a satisfactory yield. This alcohol was subjected to Swern oxidation, recommended for multifunctional compounds [32], to produce the target aldehyde 8 in 65

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• (14) [11]. In order to reduce the amount of acrylate and to increase the yield of compound (±)-16, the Baylis–Hillman reaction between the aldehyde 14 and ethyl acrylate (15) was tried using different catalysts such as DBU, quinuclidine [12] and n-Bu3P. DABCO was found to be a better catalyst and the

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• scientists and consists of a chiral hydroisoquinoline linked to a (R)-quinuclidinol unit through a carbamate linkage (Figure 6). Upon protonation the tertiary amine of the quinuclidine is expected to resemble the ammonium substructure of muscarine (2.58) [76]. This molecule can be prepared by direct coupling

• racemic quinuclidinol. However, an improved approach makes use of a Noyori-type asymmetric reduction employing a BINAP ligated RuCl2 and a chiral diamine to yield the desired (R)-quinuclidine in high yield and enantioselectivity [78]. The enantioselective synthesis of the tetrahydroisoquinoline fragment