Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• derivative in good yield, albeit with a considerable diminishment in the ee (Scheme 4). Based on the literature reports and the stereochemical outcome, a plausible transition state is proposed, as shown in Figure 2. The activation of nitrosobenzene was achieved by the intramolecular hydrogen-bonding of the

• absolute configuration of C7 is S. Proposed transition state for the nitroso aldol reaction. Catalytic asymmetric nitroso aldol reaction. Variation of the amide moiety of malonamates. General conditions: 1 (0.20 mmol), 2a (0.24 mmol), 3a (0.04 mmol), toluene (3.0 mL). Yields refer to isolated yields after

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• to synchronous bond-making and bond-breaking, with a small negative charge development on the sulfur at the transition state, for the solvolytic process. Subsequent to this 1927 study, Hammett reported [5][6] in 1937, the development of the Hammett equation, involving the consideration of a scale

• group present and to a very similar value of +0.37 in the presence of a p-nitro group. Again, these low ρ values are consistent with a transition state with very similar amounts of bond-breaking and bond-making, such that only a small amount of charge develops at the α-carbon. Over an eleven-year period

• . The plots all deviated modestly from linearity but overall an SN2 pathway with some degree of variation between the structures at the transition state was a logical assessment of the mechanistic situation. In a following publication [20], the solvolytic behaviors of methane- and ethanesulfonyl

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• , while the mechanism by Akhila et al. [10] can proceed via low transition state barriers. As discussed above, the mistake in the mechanistic work by Faraldos et al. [14] seems to reside in an impure starting material (2-2H)FPP containing additional deuterium at C15, but it is difficult to understand the

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

• the DFT/M06-2X/cc-pVTZ level with DABCO and quinuclidine. The energy profiles include the separated reagent molecules (Reac. ∞), the reactants complex (RC), the transition state (TS), the products complex (PC) and the separated products (Prod. ∞). Figure 3 show the calculated Gibbs free energies for

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• this case, the nitroalkene could not be activated by hydrogen bonding via the (thio)urea moiety, however, it is also probably less sterically hindered (Figure 3a). The DFT calculated transition states support this analysis. The transition state TS-major-re-SR-cat leading to the major stereoisomer of

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• proposed mechanism is shown in Scheme 15. Under blue visible light, the haloalkane is reduced by the copper acetylide to form the alkyl radical intermediate R2•. If aryl halide is the haloalkane, the copper acetylide is attacked by the aryl halide to form transition-state intermediate A. The copper

• acetylide is transformed into a high-valent CuIII complex, which subsequently undergoes reductive elimination or dissociation of the transition-state intermediate in the case of aryl halide to generate the target product (Scheme 15). From 2015 to 2020, Hwang and co-workers [67][68][69][70][71] investigated

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• between the catalyst and the substrate, which exclusively stabilize the transition state that forms the major enantiomer. Furthermore, Gouverneur and co-workers established an enantioselective nucleophilic fluorination protocol using a chiral bis-urea catalyst 41 and CsF as an inorganic fluoride source

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• deactivate the ring in the transition state. The lowest yield was observed for compound 5j to which a cyclopentyl group is attached. Since the cyclopentyl group in this compound is directly attached to the carbon from which the carbocation is formed, byproducts are formed and the yield is reduced since

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

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

• reported [45], for which a detailed transition state model was developed. In that study, it was determined that the reaction proceeds via several competing low-energy transition states involving both O–H and N–H enolate binding modes, E and Z enolate isomers, and a range of H-bonding and other noncovalent

• organizational interactions. This complexity makes the detailed prediction of the transition state organization for the current process very challenging. However, we propose that the general structure 19 shown in Figure 3 is a reasonable representation of one of the likely pathways (the major ambiguities being

• enolate geometry and N–H vs O–H binding). From this transition state, addition of the enolate to the acrylate followed by rapid proton transfer would lead to the glutamate derivative 10 (path a, red dashed line). A competing pathway involving bond formation between the acrylate α-carbon and the imine

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

• proposed transition state includes activations of the enone via an iminium ion and the coumarin by hydrogen bonding. A series of optically active polycyclic pyranocoumarin derivatives 37 was obtained in high yields with excellent enantioselectivities (up to 97% ee) (Scheme 12). Kowalczyk and Albrecht

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

• the phenol hydroxy group in the transition state. This assumption could also explain the high o-selectivity obtained in the fluorinations of naphthol, phenylurethane, and trimethylsilyl ether of phenol, and the exclusive 6-selectivity observed in the fluorination of conjugated enol triisopropylsilyl

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• rationalized. Note that although a two-step process is discussed herein, it is also conceivable that the reaction towards ii proceeds via a single transition state involving the Michael acceptor, the Michael donor, and the alcohol. Furthermore, the different nucleophilicity of the generated alkoxides might

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

• then furnished the cycloisomerized product (Scheme 18). Carbon-centered radical additions via metal hydride hydrogen H atom transfer Tertiary carbon free radicals are useful intermediates in the construction of new all-carbon quaternary centers. The late stage transition state associated with the

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• group and methyl group to the carbenoid carbon atom was examined for each geometric isomer to locate the transition state [37]. While appropriate transition state structures were not found for the 1,2-shift of the methyl group in (E)-3e and the 1,2-shift of substituents in magnesium alkylidene carbenoid

• (Z)-3e, transition state structure (E)-3e‡ was found for the 1,2-shift of phenyl group in magnesium alkylidene carbenoid (E)-3e. The geometry around the carbenoid carbon atom in magnesium alkylidene carbenoids (E)-3e (C–Cl: 1.86 Å, C=C–Cl: 115°, C=C–Mg: 135°) significantly deviated from that of the

• standard sp2-hybridized carbon atom, suggesting that magnesium alkylidene carbenoids (E)-3e have partial vinylidene characteristics [19]. In the transition state structure (E)-3e‡, the ipso carbon atom (C3) of the phenyl group was located at the middle between the C=C bond (C2–C3: 1.72 Å, C1–C3: 1.70 Å

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

• -aziridine in 50% yield under the same conditions. The transition state is proposed with a six-membered chair-like transition containing a four-membered metallocycle. In cis-aziridine the enolate of methyl α-bromoacetate has E-geometry and the trans-aziridine 8a has Z-geometry [32][33]. In the transition

• state, the metal cation of the enolate is being coordinated with both nitrogen and oxygen atoms of the sulfinimine [25][26] (Scheme 3). In 1999, Ellman and co-workers described the reduction of sulfinyl imines using sodium borohydride (NaBH4) [34] or o ʟ-selectride [35]. Davis–Ellman transition state

• based on the operating transition states [37][38]. A cyclic transition state is proposed in the reaction with sodium borohydride. In this transition state, the oxygen of the sulfinyl group interacts with the boron atom, facilitating the release of the hydride, directing the attack to the Si-face of the

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

• the predictions of enantioselectivities for Pd(TFA)2 complexes of 27 new PyOx-type ligands (for the reaction of 3-methyl-2-cyclohexenone with phenylboronic acid) and 59 new enones (in reactions with phenylboronic acid catalysed by L9/Pd(TFA)2). The calculation performed was related to a transition

• state and included steric and inductive effects. Although this approach may be suitable for predicting theoretically achievable enantioselectivity and is very promising, it is not engineered to predict reactivity. Besides, the reactivity (conversion or yield) depends on the reaction medium which is not

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• performed on the model reaction α-11 + MeOH → α-13c to elucidate the influence of SO2 on the dissociation of the glycosidic C–F bond [78] (Figure 2). Indeed, it was found that the coordination of the Lewis acidic SO2 to the fluoride (transition state TS-A≠ versus TS-A(SO2)≠) decreases the C–F bond

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

• to give oxocarbenium ion 15, wherefrom two competing transition states, 15a and 15b, can possibly form. In the 6-membered chair-like transition state 15a, there is a 1,3-diaxial interaction between “H” and the substituent R2, while for the other five-membered transition state 15b, there is no such

• cyclization, Scheidt and co-workers introduced a new method to access highly functionalized chiral THP efficiently (Scheme 17) [52]. Furthermore, the possible reaction pathway indicates the formation of oxocarbenium ion 82, followed by C–C bond formation via a chair-like transition state to afford 83 (Scheme

• methyl ricinoleate (127) with various aldehydes to produce 2,3,6-trialkyl-substituted 4-chlorotetrahydropyran 128 with excellent stereocontrol in all-cis-configuration (Scheme 30) [66]. The stereochemical outcome of this cyclization was rationalized by a chair-like transition state to produce

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

• transition state model to explain the origin of the stereoinduction was proposed (Scheme 2), according to the Houk’s Brønsted acid hydrogen bonding model. Guo’s computational work in 2017 on the sulfa-Michael addition of thiols to enones in the presence of cinchona alkaloid-type organocatalysts showed that

• ). The solvent effects on the SMA of the chalcone derivatives and naphthalene-1-thiol are summarized in Figure 2. This behavior might be related to the better stabilization of the transition state of the substrates containing electron-withdrawing substituents or halogen atoms with THF, or vice versa. In

• . Structures of the screened organocatalysts. Comparison of the ee values of SMA in the presence of THF and DCM as solvent. Synthesis of organocatalyst 5. Proposed transition state for the SMA of 1-thionaphthol to trans-chalcones. Catalyst and solvent screening. Further screening results of the model reaction

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• examined [46]. Trifluoromethyl ketones (TFMKs) are valuable fluorine-containing synthetic targets of bioactive compounds [55][56] that behave as mimics of the tetrahedral transition-state intermediate of enzymatic hydrolysis of esters and amides by stabilizing their hydrates (Figure 1a) [57]. In fact, the

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• much faster than that of 45f by at least a factor of 10, encouraging the authors to suggest “a transition state resembling 48f in the rate-limiting step”. Sulfurane 53, bearing OC(CF3)3 groups, was also treated with triflic acid, affording dialkylsulfonium species 54 in 91% yield along with perfluoro

• kCH3/kCF3 = 5.4 × 105 was observed, while 85 promoted the Finkelstein reaction (SN2) about 11 times faster than 84 (kCH3/kCF3 = 8.9 × 10−2, Scheme 23). This is the result of a destabilized cationic intermediate in the first case and a stabilized negatively charged transition state in the second. When

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• File 1. The predicted reaction pathways for the formation of the exo- and endo-isomeric norbornene 2h using M062X are displayed in Figure 3. For each isomer one transition state exo-TS and endo-TS was identified. The former transition state is higher in energy and leads to the less exergonic product

• transition state and is more exergonic than the path resulting in the exo-2h isomer. Energies are given in kJ mol−1 and were calculated with M062X/6-311+G(d,p) at 383.15 K in o-xylene (the corresponding B3LYP reaction pathway is not shown). Kinetic curves for the reactions of nitrostyrene 1h with CPD (50–130

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• advantages of the macrocycles in photocatalysis including: i) substrate selectivity, ii) controllability of the rate of photochemical reactions, iii) the close proximity to substrates in a confined space, iv) the generation of a stabilized high-energy transition state, and v) macrocyclic-cavity-size