Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• of the various protective groups are also clearly reflected in their ability to alter the base strength of the transition state mimicking amine deoxynojirimycin (Figure 2) [22]. The acetylated amine 16 is vastly less basic than the benzylated analogue 17, which is still less basic than the

• more reactive axial conformation in the transition state. This explains the comparatively large rate enhancements observed by TBS and TIPS groups compared to unprotected OH and also that TIPS, which is more bulky than TBS, but essentially has the same inductive effect, causes a greater rate enhancement

• also cause an enhancing effect by favoring conformational inversion to the stereoelectronically more stable conformer in the transition state. The reactivity of TBS-protected thioglycosides was further investigated by Scanlan and co-workers who made the fucosyl donor 34 (Scheme 6) [28]. Interestingly

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• chemistry have demonstrated that hydrogen bonds formed by C–H bonds are not necessarily “weak”, and in certain cases are almost as strong as more traditional A–H···A bonds [20]. The C–H hydrogen bonding between the substrate and the catalyst could be of great significance for transition state organization

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• 4-membered transition state, followed by oxidative addition of ArI to Cu(I) [63]. Oxidative addition of arylhalide to Cu(I) produces Cu(III) intermediates, for which there is substantial evidence [64][65][66][67]. However, under catalytic conditions, there is no requirement that the copper catalyst

• pass through an intermediate with a formal oxidation state of +3, which may undoubtedly have a large activation energy. Rather, a concerted pathway through a 4-membered transition state will have less localization of charge. A concerted process for coupling of nucleophiles with arylhalides on copper

• centers have been proposed by Bacon [68] and were elaborated by Litvak [69] who proposed SET within the 4-membered transition state. It is noteworthy that modern DFT calculations [63] also produce cyclic transition states. Conclusion In conclusion, we observe direct arylation reactions (C–X/C–H; X

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• molecules and products can be associated with a local minimum on the potential energy surface (PES) as proven by calculation of the vibrational frequencies among which not an imaginary value was found. Transition state geometries were proven by the presence of the only imaginary frequency appropriate to the

• reaction’s pathway. Geometry optimization performed on the starting enamine 1a allowed localizing four minimums on the PES with geometries shown in Figure 5. The transition state between the lowest energy E- and Z-isomers of 1a, 1a_1 and 1a_3, respectively, was calculated by scanning the dihedral angle

• around the double bond, and found to be 38.09 kcal∙mol−1 above 1a_1 in free energy. Calculations of the suggested mechanisms (Scheme 3) performed for E-isomer 1a_1 and nitrile oxide 6a allowed localizing a concerted transition state for both, observed and not observed regioisomers 3 and 8, respectively

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects. Complementary reductions of the intermediate inososes were possible by changing the reaction conditions, and two isomeric inositol derivatives were

• an attempt to find an explanation of the stereochemical outcome of the reaction, we directed our attention toward the open-transition-state models. These have been proposed to explain the prevalent formation of syn products, irrespective of the enolate geometry [41], in aldol reactions performed in

• the absence of a coordinating metal center (for instance, in the case of tin and zirconium enolates, and of “naked” enolates generated from enolsilanes [42]). In the open-transition-state model, the enolate and the carbonyl group are orientated in an antiperiplanar fashion, maximazing the distance

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• diastereomer is obtained in good to high yields, although multiple (five) stereocenters are present in products 4. The possible approaches of the azomethine ylide are shown in Figure 8. The X-ray diffraction structures of 4c, 4e, and 4r reflect that the cycloaddition proceeds via an exo-transition state

• , because the corresponding endo-transition state would require more energy of activation, as it would result in an electrostatic repulsion between the cis carbonyls thus increasing the free energy of activation [46][47]. As expected, the azomethine ylide adds at the double bond of 1a–c from that side in

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• (Table 2), this reaction, most probably, proceeds through an SN2 pathway, where “pure” heteroaromatic cation B is not formed. At least the reaction may go through late transition state, in which the C–O bond in the CH2O+H2 group is rather elongated, resulting in a larger positive charge on this carbon

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• −C13−C3’−C9’ ≈ 180°) and 42 kJ/mol for TS2 (ωC12−C13−C3’−C9’ ≈ 0°) from the preliminary torsional scans, indicating free rotation at room temperature (Figure 5). Transition state (TS) calculations started from the energy scans’ maxima resulted in TS structures with somewhat higher energies than those

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• Pioneering computational studies on the mechanism of the intermolecular nitroso hetero-Diels–Alder reaction by Houk [79][80] demonstrated that the reaction proceeds in a concerted fashion through an asynchronous transition state. In the two calculated transition states (endo and exo), the ratio of the

• distance between C–O to that between C–N was more than one, whereas in the product, this was reversed (Figure 2). Using RB3LYP/6-31G*//RB3LYP/6-31G* theory, for the model reaction between HNO and butadiene, the favored endo-transition state activation energy was found to be 8.6 kcal/mol lower than for the

• exo state. When a number of substituted nitroso compounds were subsequently investigated, the endo-transition state persisted in having a lower activation energy for all compounds tested, relative to the exo. This preference is due to the “exo lone pair effect” resulting from the repulsion between the

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• configuration, it also forms S,S-25 preferentially. Accordingly, transition-state structures in the reactions of guanidines 8 and 10 must differ from each other. Structure of guanidines 1–10. Crystal structure of guanidine 10 as a benzoate salt. Only one of the ion pairs is shown for the sake of clarity. A

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• theoretically studied mechanism of the oxidation reaction promoted by H2O2 and the Lewis acid BF3 [217][219]. In the first step, the hydrogen peroxide–boron trifluoride complex 8 reacts with ketone 9 to form adduct 10. The latter intermediate rearranges through transition state 11 into the tetrahedral

• peroxyacetal intermediate 12. Then BF3 migrates to another oxygen atom through transition state 13 to give the second Criegee intermediate 14. The decomposition of intermediate 14 finally produces 15, hydrogen fluoride (16) and ester 17. Despite the fact that the Baeyer–Villiger reaction is known since 1899

• shown that the ionic cleavage of 2-methoxy-2-propyl perester 129 to p-nitrobenzoic acid (132), methyl acetate (133) and dimethyl ether (134) occurred through transition state 130 with generation of dimethoxycarbonium ion 131 (Scheme 40). Investigations using aromatic peroxy esters 129 demonstrated that

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• reaction was proceeding via a linear transition state (Figure 2) [23]. When the reaction proceeded via a linear transition state, the reaction would be proposed to involve six competing transition state models (model A–F) as shown in Scheme 5. All these have steric repulsion but only the model B could be

• reductive Mannich-type reaction. Reaction of 2k and 1A and the configuration of Int A. The synthesis of syn-β-lactams using a reductive Mannich-type reaction. Previous results using β-substituted α,β-unsaturated esters. A new synthetic route for ezetimibe. Effect of the Lewis acid addition. Transition-state

• model without Lewis acid. Transition-state model with Lewis acid. Rh-catalyzed Mannich-type reaction using various α,β-unsaturated esters. Examination of the reaction conditions using a pilot reaction. Supporting Information Supporting Information File 580: Experimental details, characterization of the

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• though they don’t translate exactly into the t1/2 values, the heights of the calculated barriers correlate well with the experimentally observed half-lives. The release of N2 is an endothermic reaction that produces the free carbene, and according to Hammond’s postulate the transition state is closer in

• the vacant p-orbital on the carbene carbon affects the electronic structure of the transition states. The halocarboethoxy carbenes are also more stabilized than the carbene generated from EDA. The energy gain from the transition state to the free carbene is 18–20 kcal/mol for X = F, Cl and Br, but

• compounds (left) and stabilized (R’ = alkyl, R = H, alkyl) diazo esters (right). a) The decay of 2b in toluene-d8 at 35 °C. b) The plot of log(Δ[2b]) vs time. Transition-state energies (kcal/mol) for the release of N2 and formation of the singlet carbenes. The corresponding triplet carbenes are displayed to

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• ) ≈ 13:4. The antiperiplanar lone pair hypothesis (ALPH) proposes that the axial anomer of 4 constitutes the major conformer in solution [28], perhaps affording some stereoelectronic advantage to an early transition state which appears operative in the case of such acid-catalysed processes [29]. The

• flattening of the 1,3-dioxolane ring. For 16 this affords an energetically accessible conformer 16c which resembles the planar geometry anticipated for the transition state (Scheme 1), and should therefore be entropically favoured following the principle of least molecular motion. To confirm whether there

• the anti rotamer 16c would lead to a more rapid elimination of methanol after protonation, consistent with an earlier transition state [29]. Compound 5, which does not have such an accessible flattened ring conformation cannot access this lower entropy trajectory and hence reacts more slowly

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• through the efficient formation of pseudo-intramolecular transition state A. Intermediate B reacted with maleimide 2a to form Cu-pyrrolidine intermediate C. H-HMDS then reacted with the latter to regenerate the chiral CuHMDS and release the product to complete the catalytic cycle. The result obtained by

Ring-whizzing in polyene-PtL₂ complexes revisited

• Oluwakemi A. Oloba-Whenu,
• Thomas A. Albright and
• Chirine Soubra-Ghaoui

Beilstein J. Org. Chem. 2016, 12, 1410–1420, doi:10.3762/bjoc.12.135

• (dpe)+ as shown from a side view, 10, in Figure 3. The transition state for shifting Pt(dpe) from one C–C bond to another passes through a geometry very close to η 3, as shown by 11. Here b2 interacts with e”S and along the reaction path a combination of the e” degenerate set. The essential features

• F6C6–Pt(dpe), 17 in Figure 6 agrees well with the experiment. The issue is whether the transition state for ring whizzing favors the interaction between e1g and b2 shown from a top view in 18 or 19. Extended Hückel calculations favored the former [20][21]. Our present day calculations, however, favor

• 19. The structure is shown in 20. Special care was taken to search for a transition state where the Pt(dpe) group was rotated by 90° but none was found. The activation barrier was computed to be 7.4 kcal/mol. Reinhold, McGrady and Perutz [46] obtained a barrier of 6.4 kcal/mol for the same molecule

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• (CO)5…E-3]. Hence, this hydrogen atom shift is coupled with a W–C(carbene) bond dissociation. The turn over frequency (TOF) of catalytic cycles can be estimated from the energies of the TOF-determining transition state (TDTS) and the TOF-determining intermediate (TDI) [65]. The given energy difference

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• the reaction of the Cu(I) catalyst and ethynylstibane 1. Complex A coordinates with an organic azide to give complex B. Cyclization proceeds via a vinylidene-like transition state C to give 5-stibanotriazole 3. To test the reactivity of 5-stibanotriazole 3a was treated with hydrochloric acid, halogens

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type

• hydroxy group are arranged trans to each other irrespective of the configuration of the third stereogenic center at the bridgehead. A transition-state model that rationalizes this observation is depicted in Scheme 9. We propose a four-center interaction of the carbonyl moiety with the carbon–palladium

• bond in the transition state (TS) and due to this highly ordered arrangement only a boat-like transition state with a pseudo-equatorial position of the methoxycarbonyl group seems to be possible. The rigid benzene backbone further restricts the flexibility of the system. This model explains the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• . Acylation of the hydroxy group of quinidine resulted in complete loss of enantioselectivity, suggesting that hydrogen-bonding contacts between the catalyst’s hydroxy group and the substrate are important for organizing the transition state. Using catalytic quinine (25) the pseudo-enantiomer of the quinidine

• the chiral catalyst can bind and organize the transition state. Many examples of conjugate addition–enantioselective protonation have been reported using carbon and sulfur nucleophiles, conversely relatively few examples have been reported using amines as nucleophiles. Sodeoka and co-workers have

• acroleins. Luo and Cheng’s proposed mechanism and transition state. Shibasaki’s enantioselective addition of 4-tert-butyl(thiophenol) to α,β-unsaturated thioesters. Shibasaki’s application of chiral (S)-SmNa3tris(binaphthoxide) catalyst 144 to the total synthesis of epothilones A and B. Shibasaki’s

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• anhydrous EtOH as the solvent were found to be critical for achieving high yields and enantioselectivities. However, only 33% ee was obtained for 5-methylisatin under the same conditions. A plausible transition-state model was proposed and examined by DFT calculations, in which malonic acid formed two

• the corresponding R-/S-organocatalyst, respectively. The stereoselectivity could be explained by the transition state proposed. The R-enamine formed from the corresponding R-catalyst and 1,1-dimethoxyacetone attacked the isatin substrate from the Re face, thus affording the R-enantiomer. In 2014, the

• situ, giving the corresponding products with 93–99% ee. This modified protocol was also extended to electron-rich heteroarene substrates. Interestingly, hexafluoroisopropanol (HFIP) was found to be able to improve the enantioselectivity significantly. The authors also proposed a possible transition

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• C–D bond insertion was seen for either substrate (e.g., compare 35 to 36, Y = D, X = OMe). Adams proposed that a late transition state must be operative for insertion, and so the isotope effect was not pronounced. Doyle expanded the scope of the potential bridged products through the use of

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• -mediated carbenoid insertion reaction into C(sp3)–H bonds in more detail using the relationship between the transition-state structures and their corresponding free energies obtained by DFT investigation (Scheme 8) [12]. The insertion step primarily consists in the formation of the metal carbenoid 29 by

• the interaction of the diazo compound 28 and the dirhodium complex 27. In sequence, the reaction proceeds through the transition state TS-30 to release N2, and yields the carbenoid 31. The divalent carbon attached to the rhodium atom starts to interact with the hydrogen of the C(sp3)–H bond of the

• compound 32 to form the van der Waals complex 33 which undergoes through the transition state TS-34 to the product of the carbenoid insertion reaction 35, regenerating the dirhodium complex 27. In 2009, Davies and coworkers reported a DFT investigation of the relationship between the electronic

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• with benzaldehyde (PhCHO) is followed by the exergonic first aldol addition showing a small activation barrier of 1.82 kcal mol−1 via a half−chair like transition state (TS-C-A1), which is in accord with the anti-selective aldol addition of titanium enolates [53][54]. TS-C-A1 leads to the formation of

• anti-aldolate A1, possessing ΔGrel of −6.60 kcal mol−1. In the next step, A1 is attacked by a second enolate at higher temperature via the bicyclic transition state TS-A1-A2 (ΔGrel = 4.18 kcal mol−1) with a chair–chair conformation. In the last step, intramolecular cyclization with a relative TS energy

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• over the decades [1][2][3][4][5][6][7][8]. Mechanistically, the C(sp3)–H bond insertion reaction is considered to follow a concerted reaction pathway with a three-center two electron transition state (Scheme 1). Since late transition metals, typically Rh(II) complexes, are most commonly employed as the

• allylic and benzylic sites and those at the α-position of oxygen or nitrogen, show high activity because of the stabilization of the partial positive charge developed in the transition state of the metal–carbene C–H bond insertion process. Such type of intramolecular metal–carbene C–H insertions shows