Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• rings that are transformed in only one or two enzyme-promoted reactions. These reactions involve generation of a carbocation by protonation or loss of a diphosphate group followed by cyclization, alkyl shift, hydride shift and/or proton transfer reactions to generate new, more complex, carbocations

• [82][83][84][85][86][87][88][89][90] have also been examined computationally [91][92][93]. First, the portion of the C20H33+ PES corresponding to the reactions depicted in Figure 9 was examined with several DFT methods [91]. This study revealed, quite unexpectedly, that intramolecular proton transfer

• these two carbocations proceeds via a TSS that resembles the secondary carbocation expected to be formed upon proton translocation (Figure 9, purple), i.e., the secondary carbocation again corresponds to a TSS rather than a minimum. Direct dynamics trajectories were run from the 1,5-proton transfer

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• the identical catalytic conditions [14]. Remarkably, these reactions were usually promoted by bifunctional catalysts, such as β-ICD, whose C6’-OH group served as a H-bond donor to facilitate the proton-transfer step and to stabilize the transition state in MBH reactions [11][12][13][14]. Nevertheless

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• the enone unit to afford the enolate 12. Isomerization of the exocyclic olefin moiety of 12 into the endocyclic position may be assisted by internal proton transfer. Tautomerization of the resultant enol 13 to its keto form affords the final product 8aa. It may be noted that the key carbon–carbon bond

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• , this reaction can be carried out in H2O, as well as PhMe. Nearly simultaneously, Knochel’s group reported an enantioselective CuBr/Quinap-catalyzed alkynylation to deliver propargylic amines with alkyl substitution at the stereocenter (Scheme 2) [18][19][20]. In this reaction, proton transfer from the

• ee’s could not be achieved using only a CuOAc/Ph-Pybox catalyst. Postulating that the acetate of CuOAc may facilitate proton transfer from the alkyne to the azomethine imine, a necessary step to form both the cationic iminium and the copper acetylide, Maruoka investigated the use of a chiral acid co

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• boidinii FDH due to its stability, the observed turnover for this enzyme is generally low. However, application of a bioelectrochemical system allowed production of formate from CO2 with proton transfer from an electrical source through NAD+ to this FDH [124]. Choe et al. [125][126] showed that a series of

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• diffraction. 2-(2-Benzoxa(thia)zolyl)-6-alkoxycarbonylphenols display intense green fluorescence with anomalous Stokes shifts caused by the excited state intramolecular proton transfer (ESIPT) effects. Keywords: β-tropolones; fluorescence; intramolecular hydrogen bond; tautomerism; X-ray analysis

• -closing step preceded by the formation of the norcaradiene intermediates 8 must include the stage of the proton transfer from the methylene group of the intermediate adduct 7 to the nitrogen atom of the heterocycle. The double proton transfer resulting in the (7A∙AcOH) → (7B∙AcOH) isomerization is the

• proton transfer accompanied by cyclization leads to the norcaradiene derivatives 8∙AcOH, which then rearrange to the dihydrotropolone derivatives 9∙AcOH. In the presence of acetic acid with the twofold excess of o-chloranil, the main channel of the subsequent transformation is determined by the oxidation

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• existence of life. It is also present in many small molecules acting as an intramolecular configurational lock. This is realized in hydrazones [1], heterocyclic urea derivatives [2], molecules exhibiting photoexcited proton transfer [3] and other compounds [4][5][6] reported also by us [7][8][9][10]. The

• 10. The lack of NH signals in the spectrum may be caused by: a) fast equilibrium or b) the proton transfer between 1 and naphthyridine dianion 10. While the proton transfer is more probable at higher temperatures and lowering the temperature causes the increase of the population of form with

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• 26, which was subsequently converted to the cyclophane 28 by a Mannich-type condensation reaction (40%) (Scheme 1). Michael addition: In 1999, Reißig and co-workers [85] have synthesized a functionalized cyclophane by a cascade reaction, which proceeds with desilylation, ring opening, proton transfer

Fluoride-driven ‘turn on’ ESPT in the binding with a novel benzimidazole-based sensor

• Kai Liu,
• Xiaojun Zhao,
• Qingxiang Liu,
• Jianzhong Huo,
• Bolin Zhu and
• Shihua Diao

Beilstein J. Org. Chem. 2015, 11, 563–567, doi:10.3762/bjoc.11.61

• proton transfer (ESPT), as an extensively exploited mechanism in many biological and chemical processes, has been employed poorly in anion recognition and sensing [2][11][12][13][14][15][16]. In the ESPT molecules, a five or six-membered intramolecular hydrogen-bonded ring formed, and a proton/hydrogen

• S5 and Figure S6 in Supporting Information File 1). This indicated that the proton transfer from BIP to F− [1]. Meanwhile, the NH signal of BIP at 12.41 ppm was shifted downfield, broadened and weakened, which was ascribed to the formation of an intermolecular hydrogen bond between F− and the above

Microsolvation and sp²-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

• Rudolf Knorr,
• Monika Knittl and
• Eva C. Rossmann

Beilstein J. Org. Chem. 2014, 10, 2521–2530, doi:10.3762/bjoc.10.263

• decayed at or above +3 °C through proton transfer from the solvent that was cleaved into ethylene and the enolate LiO–CH=CH2 [the latter identified through δH = 6.93 ppm (dd) and confirmed by δC = 81.9 and 158.9 ppm]. In t-BuOMe as the solvent, a purified sample of [6Li]4&TMEDA (entry 5, Table 1

• , [15]). The high concentration of (CH3Li)4 did not change during the slow decay of 4&TMEDA at rt through proton transfer from the solvent TMEDA [20][21] that formed olefin 8a, Me2N–CH=CH2, and LiNMe2. In Et2O/hydrocarbons (54:46) without TMEDA, the Sn/Li interchange reaction of 5 and n-Bu6Li was very

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• , facilitating proton transfer and catalyst regeneration in the reaction process. In the case of o-bromophenylimine, even 2.5 mol % of H3 could deliver the corresponding product without any loss of enantioselectivity (95% ee), albeit in slightly lower yield. Jacobsen and Fang proposed a possible transition state

• ylide intermediate. Subsequent proton transfer and β-elimination of the phosphine catalyst results in a γ-functionalized α,β-unsaturated enoate. The reaction, known as γ-umpolung addition, was reported by Trost [100] and Lu [101] in 1994 and 1995, respectively. Trost employed butynoates, which are

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• energy is the less reactive and fails to participate in the photo-Favorskii rearrangement. Wan’s work clearly demonstrates, however, that the excited state acidity of 1-naphthols is much greater than 2-naphthols and that excited-state intramolecular proton transfer (ESIPT) for 1-naphthols occurs at both

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• (amino)-protonated aminonitrile which occurs with an ΔE≠ value of 34.7 kcal/mol. In the Strecker reaction, the proton transfer along the hydrogen bonds plays a crucial role. Keywords: amide intermediate; DFT calculations; hydrogen bonds; Strecker reaction; transition state; Introduction In 1850, Adolph

• the proton transfer step from HCN to OH−. However, 9 is less stable than 4 by 1.8 kcal/mol, indicating that the OH− prefers to capture a proton from HCN rather than from the NH3+ group. As shown in Figure 2, the rate-determining step of this reaction stage is the proton migration from the NH3+ group

• to the water cluster (from 4 to 5), where the energy barrier is 17.1= [+9.6 − (−7.5)] kcal/mol. Other proton transfer steps facilely occur. These results are in consistent with the room-temperature experimental condition in Scheme 1. For the rate-determining step, we also checked an extended model

An experimental and theoretical NMR study of NH-benzimidazoles in solution and in the solid state: proton transfer and tautomerism

• Carla I. Nieto,
• Pilar Cabildo,
• M. Ángeles García,
• Rosa M. Claramunt,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2014, 10, 1620–1629, doi:10.3762/bjoc.10.168

• C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d18. Keywords: CPMAS; DNMR; GIAO; proton transfer; tautomerism; Introduction Of almost any class of

• possible to determine the barrier to proton transfer of benzimidazole itself in HMPA-d18, thus providing a missing value in heterocyclic tautomerism of azoles and benzazoles [33]. Experimental Four of the compounds reported in this paper are commercial (Sigma-Aldrich): 1, 2, 3 and 5. We reported the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• the tertiary amine enables proton transfer from phosphorus to carbon (Table 5). The organocatalyzed hydrophosphination of α,β-unsaturated aldehydes has been described by Carlone et al. [133] and Ibrahem et al. [134]. The method is based on activation of the aldehyde 59 via iminium-ion formation by

• hydrophosphination of vinyl nitriles catalyzed by a dicationic nickel complex (Table 3). The method is based on the activation of the electrophile. It was suggested that complexation of the nitrile 50 to the chiral nickel Lewis acid activates the double bond towards 1,4-addition of the phosphine 25b. A final proton

• transfer yields the phosphine product 51 [124][125]. A chiral Pincer-palladium complex 55 has been used for the addition of diarylphosphines 25c to enones 53 (Table 4) [126]. Several enones 53, having electron-donating or -withdrawing groups on the aromatic ring, reacted with a variety of electron-rich and

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• azodicarboxylates 2 generates the Huisgen zwitterion intermediate 8 [37][38]. Subsequent proton transfer and phosphonium migration between 8 and the MBH alcohol 1 produce an oxophosphonium intermediate 9 and a hydrazine anionic species 10 [36]. Finally, an expedient SN2' attack of species 10 on 9, probably

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• by very similar levels of diastereoselectivity of the double-bond formation. In contrast the formation of the merocyanines 10 starts with a proton transfer from the CH-acidic α-position of the iminium moiety of 13 to the amide enolate part. The resulting enol 15 is part of an allenyl enol, which is

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• processes form zwitterionic biradical intermediates 3, in which a proton transfer and an α-heterolytic fragmentation proceeds, produce biradicals 7 that are precursors of the heterocyclic products 6 (Scheme 2). Photochemical reactions of naphthalimides with electron donors have also been intensively studied

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• proton transfer to release the product 17 and regenerates the Au(I) catalyst. The authors also developed an enantioselective version of the approach. After an in-depth preliminary screening, the catalyst and the optimal reaction conditions were found to be the original arylsulfonylurea-containing trans-1

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• the solvent at ≥100 °C through an initial chlorine particle transfer to give a Cl,K-carbenoid. This short-lived intermediate disclosed its occurrence through a reversible proton transfer which competed with an oxygen transfer from DMSO that created dimethyl sulfide. The presumably resultant transitory

• competition with the abundant DMSO to give 15, dimsyl-K (11) may displace a chloride anion from the Cl,K-carbenoid 12 to generate the vinylpotassium derivative 27. Proton transfer steps should isomerize 27 into the energetically more stable allyl anion derivative 31. Either 29 or 32 may intercept 31 with

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• hydrazine (Me2C=N–NH2) was obtained. The channel involves two likely proton-transfer routes. However, it was found that the base-free reaction was unlikely at the N2 extrusion step from the isopropyl diimine intermediate (Me2C(H)–N=N–H). Two base-catalyzed reactions were investigated by models of the ketone

• CT complex may be supported by two hydrogen-bond networks. The CT complex is probable even by protic solvents as shown in Scheme 5. The CT complex assisted by hydrogen bonds was also obtained in the benzoic acid–ethylamine system by our recent study [37]. In (iii) of Figure 1, a proton transfer TS1

• was obtained along the first hydrogen bond. After this, an intermediate of (Me)2C(OH)–NH–NH2 is formed (iv). From the intermediate, the second proton transfer takes place along the second hydrogen bond (TS2, in (v)). After the transfer, acetone hydrazone, Me2C=N–NH2 [with (H2O)9], is afforded in (vi

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• that also water is a potential proton transfer agent in the protodeauration event of the catalytic cycle. 2.2 Selected examples Initial reports dealing with the gold-catalyzed addition of oxygen-based nucleophiles to isolated olefins required the use of relatively acidic nucleophiles. In their seminal

• the real mechanism of the protodeauration step. Interestingly the reaction profile with the lowest activation energy was distinguished in the TfO− promoted tautomerization of 11 to form 12 followed by direct proton transfer to afford the product 13 and regeneration of the catalyst. Intermediates of

• favoured. Interestingly, a strong hydrogen bond was established during the catalytic cycle between the hydroxy groups. The H-bond turned out to be a key interaction for the high reactivity of 94 toward cyclization, leading to an intramolecular proton transfer resulting into a better leaving group

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• activated nitrilium cation, which can be attacked by the alcohol component. Proton transfer (P.T.) yields the imidate hydrochloride [3]. Various transformations are possible with the imidate hydrochlorides: Hydrolysis at low pH leads to carboxylic esters, where basic hydrolysis yields imidates. Reaction

Electron self-exchange activation parameters of diethyl sulfide and tetrahydrothiophene

• Martin Goez and
• Martin Vogtherr

Beilstein J. Org. Chem. 2013, 9, 1448–1454, doi:10.3762/bjoc.9.164

• intricacies. The main complication arises from fast deprotonation of D•+ at the α carbon to give a neutral radical which can occur at the radical-pair stage in a direct reaction (base, A•−) or even at any stage of the reaction by a relayed proton transfer (relay base, D) [21][22][23] and turns the gross

An aniline dication-like transition state in the Bamberger rearrangement

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 1073–1082, doi:10.3762/bjoc.9.119

• activation energy similar to the experimental one was obtained. A new mechanism of the rearrangement including the aniline dication-like transition state was proposed. Keywords: Bamberger rearrangement; DFT calculations; N-phenylhydroxylamine; proton transfer; reactive intermediates; transition states

• Figure 6. They are similar to those of TS2(III) and TS2(III, [1,3]-shift) in Figure 4, respectively. Again, the aniline dication-like structures were obtained. The proton-transfer pattern depicted in Scheme 7 was confirmed. As for the activation energies of TS2(IV), Δ(ET + ZPE) = +27.58 kcal/mol by B3LYP