Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• gives access to B. The second shown option, path B, assumes a 1,6-ring closure of (R)-NPP to the bisabolyl cation G. Proceeding with a 1,2-hydride shift to H, the key step is a 1,6-proton shift to give the tertiary cation I. This idea is derived from a very similar proton transfer starting from the

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• kinetics of the BFDC reaction [29]. In a final note on model D, although the calculations show that proton transfer from N1' to Glu47 is not spontaneous in this model, the energy difference between the conjugated pairs AP/APH+, TC/TCH+, YI/YIH+ remains very low, suggesting the forms are readily

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• only in stationary low concentrations. In the past, we used electron mediators as additives (triethylamine) [19][26] or peptides with substrate-binding sites [31][32] to overcome this problem. For the current work, we propose a radical ion pair in a solvent cage that undergoes an extremely fast proton

• transfer followed by the intracage back-electron transfer, since triethylamine is no longer needed (vide infra). The evaluation of both the optical and electrochemical properties of the prepared phenothiazine derivatives 1–11 leads to the conclusion that only the dialkylamino derivatives 2, 10 and 11 come

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• “normal” C=O addition reaction was obviously faster than the deprotonation of 19 and also apparently irreversible under the reaction conditions, whereas the unobserved C=O addition of 19 to 2Li might be possible yet quickly reversible with a terminating proton transfer from 19 to 2Li as shown in Scheme 5

• ). Preparation and cleavage of the adduct 18 of fluoren-9-one (15). Proton transfer from dicyclopropyl ketone (19) to 2Li. Metal-free release of the carbanion unit in 25 and its seizure by t-BuCH=O (→ 7); Bu = n-butyl. Supporting Information Supporting Information File 336: Ion-pair intermediate through

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

• A. S. Antonov,
• A. F. Pozharskii,
• P. M. Tolstoy,
• A. Filarowski and
• O. V. Khoroshilova

Beilstein J. Org. Chem. 2018, 14, 2940–2948, doi:10.3762/bjoc.14.273

• temperature independent). One could expect that strong electron-donating OMe groups being placed in positions 2, 4 or 6 of a phenylimino substituent should increase the basicity of imine nitrogen. Thus, in CD3CN, both 4b and 5b, containing only one OMe group, show no proton transfer towards the imino function

• (Figure S13 in Supporting Information File 1). The addition of a second OMe group in the case of 6 leads to the formation of 25% 6b’. Upon the insertion of a third OMe group in 7, the amount of 7b’ expectedly increases to 33%. Switching of the solvent to acetone-d6 facilitates the proton transfer away

• lowest in energy for the imines 4, 6, 7 (Figure 5). In the solid state, no proton transfer to the imino group was observed: compounds 4a·HClO4 and 6b·EtOH crystallise in forms protonated at the proton sponge moiety (Figure 6). We expected that the proton transfer to the C=N group will force the nearest

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• formation of the quinoline is shown in Scheme 5 [27]. After initial formation of the enolate of ethyl acetoacetate with sodium hydroxide, water is generated in the reaction mixture, which then serves as a proton transfer agent. The resulting sodium enolate regioselectively attacks the more electrophilic

• intramolecular 6-exo-trig cyclization and subsequent proton transfer to the aminal oxygen D. Elimination of the 2-hydroxy group from D then affords the 4-quinolone E that tautomerizes via [1,5]-hydride shift to form quinoline 10. Given the success of employing ethyl acetoacetate in the quinoline

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• furnished through direct C–O bond formation at the para-position through ionic cleavage of the N–O bond by cationic Ru(III) as a much stronger Lewis acid, while it is also possible that the second migration of the alkoxycarbonyloxy group from ortho to para occurs prior to proton transfer (Scheme 5b) [25

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

• of these processes (Scheme 11 and Scheme 12) can be explained by the favored transition states proposed in Scheme 12 based on the fact that the proton transfer constitutes the rate-determining step in the aza-Morita–Baylis–Hillman reaction [58][59][60]. Indeed, in these favored transition states, the

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• (299) in good yield as a major product. The formation of this product has been described either by the initial formation of 298 followed by rearrangement or by a mechanism with 241B as an intermediate. Also, Aihara’s group reported excited-state intramolecular proton transfer (ESIPT) and aromaticity

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• computational methods [11][12][13][14]. Still, experimental studies with small molecular model compounds play an essential role in mechanistic studies of the enzymatic cleavage of nucleic acids. With small molecules, the importance of various elementary processes, such as proton transfer and metal ion binding

• occurrence of the proton transfer as part of the rate limiting step may be evaluated by altering the acidity of the proton donor (or acceptor). Plotting of log k against the pKa of the proton donor (or acceptor) gives the Brönsted α (β for the acceptor) that refers to the extent of proton transfer in the

• state start to play a role. That is why both normal and inverse effects are possible. The kinetic solvent isotope effect (KSIE) is another mechanistic tool frequently used to distinguish between alternative mechanisms. KSIE is an indication of a kinetically significant proton transfer that takes place

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• electric fields generated by ions and molecules in solution. This property along the ESIPT process (excited state intramolecular proton transfer) [35] makes them ideal for ratiometric environment-sensitive probes and sensors [36][37][38][39][40][41][42][43]. Among them the 4’-dimethylamino derivative (DMHF

• different concentrations are shown in Figure 3. Upon addition of ATP, a new band appears at 440 nm in the excitation spectra. This feature can be attributed to the specific intermolecular proton transfer from the hydroxy group of the flavone to the phosphate moiety of the ATP [34]. The fluorescence

• -based probes exploit the ESIPT nature of these fluorophores to generate multiple emission bands [39][41][42][43]. In this case, however, a new fluorescence band appears in the excitation spectra due to an intermolecular proton transfer from the flavone to the phosphate chain of the nucleotide. Therefore

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• be increased. To overcome this limitation, anilines were used as redox mediators, which are first oxidized by the photocatalyst and subsequently activate the aliphatic thiol via direct hydrogen abstraction or sequential electron- and proton-transfer steps. With this concept they were now able to

• the alkene moiety of the 1,7-enyne, two consecutive cyclizations lead to the final sulfonylated benzo[α]fluoren-5-one. Electron and proton transfer and subsequent formation of dihydrogen close the catalytic cycle and regenerate the photocatalyst. Sulfinamides Formation of sulfoxides A new method for

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• subsequent 1,2-proton transfer followed by the elimination of triphenylphosphine and ring closure via formation of the new C–N bond gave the final γ-lactam derivatives 80 (Scheme 50) [66]. In 2013 Mohebat et al. used 6-amino-N,N'-dimethyluracil as an NH-acid and precursor of the carbon nucleophile in the

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• catalyst, proton transfer and, finally, 1,3-shift of alkoxycarbonyl group in the intermediate imine D to produce thiophenes 3 and 5. However, this pathway seems to be less probable, since intramolecular cyclization B → C should have lower activation energy relative to intermolecular interaction of C=S

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• post-glycosylational modifications are also required. As a result, glycosylation that is already a four-step process (activation, dissociation, nucleophilic attack, proton transfer, Scheme 1a) has to be supplemented with additional manipulations that could lead to the decrease in over-all efficiency

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• SeO2 [8][69][70][71]. The only remaining route for the thermal transformation of 1 into 3 is path O. In this path, the hemiacetalization is the first step. We used a water molecule to facilitate the proton transfer in this stage. In the experiment, a hydroxylic group of other proximate germacranolide

• including a water molecule to facilitate the proton transfer. Schematic representations of the calculated C5 epimeric structures of 2 and 3. Relative electronic energies in kcal/mol. The energies are relative to 1a. Reaction paths of the Cope rearrangements of closed (dark blue and orange) and open (red and

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• regioselective 5-exo-dig cyclization–proton transfer–isomerization sequential process. They found that the easily available N-(propargylcarbamothioyl)amides 53 in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as the base in refluxing ethanol, rapidly cyclized and produced the corresponding dihydrothiazol

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• iminyl anion intermediate 27. The latter easily isomerizes to its isomer 28 where a sodium cation–π-interaction occurs. The last step involves a C–C bond cleavage and proton transfer with elimination of NaCN (Scheme 12). This proton transfer occurs with retention of configuration as experimentally

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• 492 nm, respectively, and are represented in Figure 3 and Figure 4. The hydrogen-bond interaction between the OH group in R1 and the guest anion is assisted through an intermolecular proton transfer (IPT) suggesting a proton abstraction from a OH group and introduction of a negative charge on the

• F− and AcO− ions to receptor R2, the absorption band at 459 nm red shifted to 560 nm indicative of the strong influence of –R and the −I effect of the NO2 substituent on the intermolecular proton-transfer process. A substantial enhancement of the ICT in R2 in comparison with R1 indicates a more

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• observed for the excited-state proton transfer (ESPT) of so-called photoacids. The latter are weak acids in the ground state, whereas their acidity in the excited state increases significantly [25][26][27]. As the activity of photoacids is triggered by light, they have a great potential to be employed as

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• products 32 catalyzed by tributylphosphine (33, 0.05 equivalents) (Scheme 9) [26]. In these transformations the initial reaction between 31 and 33 generated zwitterion 34, that underwent internal proton transfer to generate ylide 35. This in turn reacted with aldehyde 6 to form 32 and phenylsilane was used

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• for this transformation was postulated. It includes a nucleophilic attack of the thiourea sulfur atom on the C=C bond of the maleimide followed by a proton transfer and nucleophilic attack of the thiourea nitrogen atom on one of the two carbonyl groups; the latter step is considered rate determining

• the nature of the dynamic process observed in solutions of 2-aminothiazolidines. This phenomenon was first detected by UV spectroscopy [19] and believed to be caused by a proton transfer between nitrogen atoms (amino–imino tautomerism), however, contradictory information on the equilibrium ratio of

• tautomerization process of thiazolidine 3g in solution led to a very strong broadening of its signals in the 1H NMR spectrum at 23 °C (Figure 2). Decreasing the temperature to −20 °C slowed down the proton transfer and the two sets of signals could be clearly seen and were fully assigned to the two forms of 3g as

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• -N3 is associated with the catalysis during ribosomal peptide bond formation, a proposal about its role in proton transfer has been disputed heavily since the first ribosome crystal structures up to very recent investigations [8][9][10]. The involvement of N3, and not N1, is surprising with respect to

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• generated by plant enzymes [24][37][38]. Both enzymes from Salvia officinalis and from Streptomyces clavuligerus share the syn addition in the final cyclisation step which can be rationalised by a direct intramolecular proton transfer, circumventing the need of a low-energy neutral intermediate such as α

• -terpineol. However, in case of the sesquiterpene ethers corvol ethers A (19) and B (18) a reprotonation step was shown to proceed from the opposite face than the preceeding attack of water, thus excluding a direct proton transfer from oxygen to the neighbouring carbon (reactions from 12 to 14 in Scheme 2

• to 13C-labelled carbons. B) Intramolecular proton transfer from the protonated hydroxy function in (S)-7 to C-2. Cyclisation of GPP to 1 via the (R)-terpinyl cation ((R)-6, left) or the (S)-terpinyl cation ((S)-6, right). Mechanism for the cyclisation of FPP to corvol ethers A (19) and B (18). WMR

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . The resulting intermediate undergoes proton transfer and elimination of the phosphonium moiety, resulting in product 30 and regeneration of the catalyst. This exceptional demonstration of stereocontrol requires that the catalysts precisely organize both the electrophilic and nucleophilic reactants to