The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• -specificity and functional integration achieved in a first protocellular scenario may be modest, but it is important that both kinetic control and spatial control mechanisms are included in the equation from the beginning, so that they can complement each other in their development. For an interesting bottom

• avenues in the field of systems chemistry [1][2]. For instance, although kinetic control mechanisms must play a central part in the explanation, dynamic kinetic stability [63] is not the answer (because replication is not all what matters for evolution, chemical or biological). It is probably too early to

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• -organisation of life, which, in turn, allows an assessment of semi-quantitative constraints on systems and environments from which life could evolve. Keywords: dynamic kinetic stability; kinetic control; origins of life; self-organisation; Introduction Although it is mostly understood in historic terms, the

• thermodynamic data. Indeed, there are many examples in which product formation is controlled by kinetics (reactions under kinetic control, corresponding to the situation in Figure 2), rather than by thermodynamic stabilities. In fact the presence of kinetic barriers is actually a requirement for the system to

• held far from equilibrium through the energy-fuelled supply of reactive units. Kinetic control. In many chemical reactions leading to different products, the final composition is determined by the height of the kinetic barriers corresponding to transition states (TS‡1 and TS‡2) rather than by the

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

• substitution ratio is typical of substitutions on naphthalene under kinetic control that tend to favor the alpha C–H bonds due better resonance stabilization effects [53]. Importantly, we note the alpha protons are slightly more acidic than the beta protons [54]. The mechanism of Cu catalyzed coupling

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• is reflected in the distribution products by a decrease of the endo-endo isomer (kinetic control product) jointed to an increase of the endo-exo (thermodynamic control product). Influence of catalyst surface We have seen that the DAR between cyclopentadiene and p-benzoquinone takes place thermally

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• of the lithiated N-Boc-N’-alkylpiperazines with sec-BuLi and TMEDA at −78 °C, the reaction was warmed up to −30 °C with addition of a chiral ligand. The chiral ligand coordinates with the racemic lithiation product to give a diastereomeric mixture which can be resolved under thermodynamic or kinetic

• control with electrophilic quench by a variety of electrophiles. After evaluating a few chiral diamino-alkoxide ligands, ligand 24 was identified as a superior choice. As shown in Figure 7, the result was not optimal with only 30–75% of the desired α-substituted products being obtained and the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• -matched transition state (TS6) that allows a kinetic control of the second reaction. The enantioselective addition of indoles 2 to α,β-unsaturated acyl phosphonates 24, a) screening of different catalysts and b) optimized conditions using catalyst ent-4. Study of aliphatic β,γ-unsaturated α-ketoesters 26

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• geometries and their relative stability. In this way, we could propose various robust arrangements that could be fully stable within the simulation time at room temperature, suggesting that different metastable states could coexist together with the thermodynamically most stable ones and that kinetic control

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• aCD interactions in the nucleation stage, and give insights on the structure of the embryonic building blocks of the aCD’s supramolecular nanosystems. We also note that in the case of a kinetic control of aggregation taking place by sequential interaction of further aCD, the nature of these embryonic

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• of hazardous or unstable products. Furthermore smaller volumes with higher surface areas enable faster heat removal and better temperature control to limit unwanted side reactions. Further kinetic control is achieved with reactant concentrations, feed rates, mixing regime and residence time resulting

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• polymers are thermodynamically less stable than cyclic carbonates, a kinetic control must be attained to direct the reaction to the polymeric products. To selectively lower the activation barrier towards polycarbonates, a rational development of suitable catalysts is essential. This current study aims to

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• azoloazine with high chemo- and regioselectivity [11][13][14][15]. In particular, three-component heterocyclizations involving 3-amino-1,2,4-triazoles or 4-substituted 5-aminopyrazoles yielded either 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidine-6-carboxamides under ultrasonication at room temperature (kinetic

• control) or 4,7-dihydroazolo[1,5-a]pyrimidine-6-carboxamides at reflux in an applicable solvent (thermodynamic control), respectively (Scheme 1). The behavior of the reaction of 5-aminopyrazoles containing substituents in the position 3 is influenced by the structure of aminoazoles and aldehydes, giving

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• File 1 for full details). Over the course of this work we have found that the lithiations are best performed at −78 °C and at a concentration of 0.15 M with either 5 or 6 equivalents of alkyllithium. Higher temperatures unsurprisingly resulted in poorer diastereoselectivity, pointing to kinetic control

Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting from rings of pseudo-polyrotaxane

• Kazuaki Kato,
• Katsunari Inoue,
• Masabumi Kudo and
• Kohzo Ito

Beilstein J. Org. Chem. 2014, 10, 2573–2579, doi:10.3762/bjoc.10.269

• polymerization proceeded properly only when robust hydrogen bonds formed between α-CDs were dissociated using a basic catalyst. Since the dissociation also induced dethreading, kinetic control of the polymerization and dissociation were crucial for producing graft polyrotaxanes. Consequently, this three-step

• base prevents hydrogen bond formation between the α-CDs. Meanwhile, prevention of the hydrogen bond formation is necessary for the α-CDs to access the monomers. Therefore, the kinetic control of both the dissociation of the hydrogen bonds and the polymerization is necessary. A stepwise increase in the

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• 3 is formed under kinetic control, diene 2 being thermodynamically more stable. With regard to the addition of selenium dihalides to bis(acetylene) 1, the reaction mechanism should follow a similar course, consisting of the formation of a selenonium ion of type 10 rather than the addition of 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

• protocol of Tunney and Stille starting from silylphosphines has been modified by Chan, Bergman and Toste to be enantioselective by using a [Pd(Et-FerroTANE)] catalyst. P-stereogenic phosphine boranes 111 and 112 were synthesized by arylation of racemic silylphosphines 110 under dynamic kinetic control

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• . Although analogous isomerizations of similar compounds at respective C-2, C-3 centers have been described, we present here parallel isomerizations on both chiral centers under kinetic control. cis-Silybins were obtained by the chemoenzymatic separation methods mostly due to the sensitivity of new cis

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• diastereomer as a racemic mixture. Under kinetic control, inverse-electron demand aza-Diels–Alder as well as normal Diels–Alder reactions are known to favour endo products since the endo approach maximizes secondary orbital overlap [42]. The “boat-type” transition state favours an endo orientation (“inside of

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• bed. Moreover, the nitration of toluene with 90 wt % nitric acid using a microreactor was found almost entirely preceded under kinetic control. However, with only nitric acid as the nitrating agent, the nitrotoluenes were generated in a low yield. The formation of water adversely affected the

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• can be formed under kinetic control. The third possibility is the geminal or branched (b) isomer which is usually formed where a cationic intermediate forms that facilitates migration of the σ-Pd–C bond from the terminal alkenic 1-position to the 2-position. In the majority of publications, the

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• lower temperatures (−40 °C) under kinetic control the Felkin–Anh product is predominant. At higher temperatures (−15 °C) the nucleophilic addition occurs via a thermodynamically more stable transition state that resembles the chelation control TS. These results are interesting as this is the first time

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• substrate 4, we have reached to a conclusion that its initial lithiation would occur at both vinylic sites and the following reactions with appropriate electrophiles would proceed under kinetic control where equilibration of the resultant lithiated species might be effective if the capture of electrophiles

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• the initial diorganophosphanyl radical (Scheme 7). The high E selectivity is attributable to kinetic control of the homolytic substitution, where R2P–PR2 preferentially approaches the vinyl radical from the roomier side. Although the transformation looks useful to construct an (E)-1,2

Enhancement of efficiency in organic photovoltaic devices containing self-complementary hydrogen-bonding domains

• Rohan J. Kumar,
• Jegadesan Subbiah and
• Andrew B. Holmes

Beilstein J. Org. Chem. 2013, 9, 1102–1110, doi:10.3762/bjoc.9.122

• under isodesmic kinetic control. The formation of interconnected nanostructures by 2, as observed in the AFM experiments, also leads to the interpretation of the 1H NMR self-association data as the formation of one-dimensional chains of 2. One possible mode of self-complementary interaction leading to

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• stereochemically retentive, while carbolithiation is syn selective. The reactions begin with an asymmetric carbolithiation, in which the (−)-sparteine-complexed organolithium attacks the Re enantiotopic face of the alkene to form a stereodefined organolithium formed under kinetic control. On the other hand, the