Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• equiv) in DMF solution and ICI as the promoter (3 equiv) in n-PrOH and was subjected to an oxidative 1,2-aryl migration. The reaction is carried out in a coiled reactor at 90 °C and 1 min residence time. The outlet stream is subjected to an alkaline solution of 2-mercaptoethanol, which quenched the ICI

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• corresponding 7-D-pyrazolopyridine 7. When ethyl propiolate (2c) was used 2,7-dideuteropyrazolo[1,5-a]pyridine 8 was formed along with monodeuterated product 9. The deuterium atom may appear in position 2 of compound 8 in two different ways (Scheme 2). The first one includes deuterium atom migration from

• 3a -> 2 hydrogen atom migration is a highly exothermic process. However, the formation of 11 is probably kinetically unfavorable due to the prohibited 1,3-hydrogen shift. Thus, no NMR signals corresponding to 11 were found in the reaction mixture before oxidation. Another possible way of deuterium

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• absence of other salts the lithium salt is relatively stable. This phenomenon was explained by the formation of a dinuclear methoxy-bridged borate intermediate [C6F5B(OMe)2–(μ-OMe)–B(OMe)2C6F5]− (B) followed the migration of both the aryl and the methoxy groups. If Li+ and [C6F5B(OMe)3]− form a contact

• ion pair (solution of Li[C6F5B(OMe)3] in CH2Cl2), such migration of −OMe and its subsequent elimination is hindered [42]. In the case of pentafluorophenyltrifluoroborates the similar conversion does not occur even with Li[C6F5BF3] in DME (contact ion pairs) due to the higher Lewis acidity of C6F5BF2

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• followed by 1,5-hydrogen migration involving the o-alkyl substituent. 1,5-Diradicals 102 were formed as a result of elimination of acid HX from 1,4-diradicals 101. Finally, 1,5-diradicals 102 underwent cyclization to give 1-indanones 103 in good yields and 2-alkylidene benzo[c]furan derivatives 104 as

• , next alkenylrhodium 165 were formed as intermediates as a result of dehydration and β-H elimination followed by hydrorhodation, respectively. Then, rhodium 1,4-migration, alkylrhodation and finally rhodium elimination led to 1-indanones 162 via intermediates 166 and 167. Abicoviromycin (168) is an

• to a mixture of 1,2-dihydroisoquinolines 236 and substituted 1-indanone derivatives 237 via alkoxy group migration in 16 and 57% yields, respectively (Scheme 66) [95]. 2 Construction of the 6-membered ring The titles of subsections in this chapter contain names of the 1-indanone precursors which

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

• /toluene (1:1) and toluene giving 20%, 63% and 75% of olefin isomerization (from NMR and GC), respectively, for each solvent [34]. This isomerization was attributed to the translocation of the tertiary radical intermediate to a more stable allyl radical leading to the double bond migration. This

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

• hydroxyphenylbenzimidazole and a topotecan derivative increases from 2 to 4 [32] and from −3 to 6 [31], respectively, upon migration from water solution into CB[7]. In contrast, it was demonstrated that the photoacidity of 2-naphthol is completely suppressed when it is complexed to CB[7] because the hydroxy functionality is

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

• the galactose derivative 2 (Scheme 1). The reaction gave a 56% yield of 3 as a 1:1 mixture of α- and β-glucosides. Migration of a TBS group to the acceptor alcohol 2 was observed as a byproduct (10%). Attempts of glycosylating 2 with the thioglycoside or the corresponding glycosyl halides were

• banyaside. TES-protected glycosylimidates were also employed in the synthesis of antitumor saponins which contained partially acylated oligosaccharides. The TES groups could be removed by comparatively mild treatment with fluoride without hydrolysis or migration of O-acyl groups [10]. This strategy has also

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• (triflic) acid (CF3SO3H) as the Lewis acid catalyst to yield 4-isobutylpropiophenone (2). Once this is complete a solution of di(acetoxy)phenyl iodide (PhI(OAc)2) and trimethyl orthoformate (TMOF) in methanol (MeOH) is added to the reaction mixture in order to induce a 1,2-aryl migration to produce the

Effects of solvent additive on “s-shaped” curves in solution-processed small molecule solar cells

• John A. Love,
• Shu-Hua Chou,
• Ye Huang,
• Guilllermo C. Bazan and
• Thuc-Quyen Nguyen

Beilstein J. Org. Chem. 2016, 12, 2543–2555, doi:10.3762/bjoc.12.249

• properties, which unfortunately results in s-shaped J–V curves and poor performance. We show that this is due to non-ideal phase separation, specifically a preferential migration of the electron acceptor to the bottom anode interface. This can, however, be mitigated through appropriate processing, using a

Protonated paramagnetic redox forms of di-o-quinone bridged with p-phenylene-extended TTF: A EPR spectroscopy study

• Nikolay O. Chalkov,
• Vladimir K. Cherkasov,
• Gleb A. Abakumov,
• Andrey G. Starikov and
• Viacheslav A. Kuropatov

Beilstein J. Org. Chem. 2016, 12, 2450–2456, doi:10.3762/bjoc.12.238

• coordination sites should cause an equalization of the proton constants on the p-phenylene group in the case of a fast process. In fact, we have not found any evidence of such migration, at least accessible for an observation in the EPR timescale. The lack of a substantial temperature dependence of the shape

Solvent-free, visible-light photocatalytic alcohol oxidations applying an organic photocatalyst

• Martin Obst and
• Burkhard König

Beilstein J. Org. Chem. 2016, 12, 2358–2363, doi:10.3762/bjoc.12.229

• test tube. Subsequently, the rotating glass rod is pressed into the test tube, which leads to vertical migration of the reaction mixture and the formation of a film between the inner wall of the test tube and the glass rod. The reaction is carried out by rotation and irradiation with the LEDs from the

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• nucleophilic 1,2-migration of aryl (Ph) or alkyl (Me) group R2 occurs, producing α-oxoketene D. The latter interacts with N–H-group of the aminoester 1 to give acylamides 6a–c. Predominance of the Wolff rearrangement over typical carbenoid reactions (N–H-insertion, etc.) in the case of diazodicarbonyl

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

• summarize systematically related and different features of these reactions, compares their mechanisms, and assesses the prospects of their application. By definition, a rearrangement is a migration of an atom or a group of atoms from one atom to another within the same molecule [189]. In contrast, a

• as rearrangements of peroxides can give both isomeric and non-isomeric compounds either containing a peroxy group or without the latter. In most cases, a rearrangement involves the migration or cleavage of the peroxide group in an intermediate molecule, and the stability of the latter is responsible

• binds to the carbonyl group of ketone 1 to form the tetrahedral intermediate 3 which is referred to as the Criegee intermediate. The next step involves the concerted migration of the R2 group to the peroxide oxygen atom, resulting in the formation of ester 4 and carboxylic acid 5 (Scheme 2). The ability

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

• ; density functional theory (DFT); hapototropic rearrangements; HOMO–LUMO interactions; polyene-ML2 complexes; ring-whizzing; Introduction Polyene–transition metal complexes were found to undergo fluxional rearrangements as early as 1956 with the preparation of Cp2Fe(CO)2 [1]. The migration of an MLn unit

• thought [20] that migration of an ML2 unit from one ring to another would involve an η3 structure where Pt would bond to C(1), C(9) and C(8). For the carbon numbering system please see 48. Bonding between b2 ML2 and the b1g MO would be retained. Unfortunately this is not quite the entire story. One of the

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• ) with barely visible traces of mono-polyamide conjugate (line 6, e). Lines 5d and 6d are visible by UV-shadowing bands of electrophoresis migration marker xylene cyanol that is absent in other gels. Mass-spectrometry analysis confirmed the identity of the products obtained (Table S3 in Supporting

• arrows indicate positions: a and c – initial alkyne-modified oligonucleotides, b and e – 1:1 conjugates TFO:polyamide, f – 1:2 conjugate TFO-polyamide, d – visible migration marker xylene cyanol. Electrophoresis analysis of reaction mixtures in 20% denaturing polyacrylamide gel after TINA-TFO-MGB

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

• -ylidene)(pentacarbonyl) W(CO)5(12) (Scheme 1f) [53]. In principle, the formation of imines from NH carbene complexes can occur by three conceivable fundamental pathways. The first pathway starts with the dissociation of the carbene followed by a 1,2-H shift at the free carbene (elimination–migration). The

• second one operates via a hydrogen atom shift at the coordinated carbene followed by dissociation of the resulting imine (migration–elimination). A third conceivable pathway could start with CO loss, followed by H atom migration. To the best of our knowledge, the mechanism of the imine formation from NH

• carbene complexes is not yet established. In the absence of a base, the bulky diferrocenylcarbene complex Cr(CO)5(E-2) is stable even in refluxing toluene and hence, a simple migration–elimination or elimination–migration reaction is not anticipated in this case. We report here the heavier tungsten

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

• [2,3,4-kl]acridines (the core structure of plakinidine C) from enaminones and 3-indolyl-3-hydroxyoxindoles through a cascade ring-opening/recyclization/methyl migration sequence (Scheme 61) [78]. The reactions proceeded well in MeCN in the presence of catalytic I2 (30 mol %) under an O2 atmosphere

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ]. The resulting disruption of protein–(glycosamino)glycan interactions had important biomedical consequences such as reduced selectin-mediated tumor cell adhesion [12][13], suppressed selectin-mediated leukocyte migration [11][14][15], reduced angiogenesis [3], or inhibition of tumor growth by decreased

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• may expect such a barrier in the tautomerization (probably catalyzed by water) which forms the zwitterion by proton migration from the neutral imine. The experimental results on Strecker degradation have been summarized in a rule that says that the most efficient promoters have a structure of the type

• ). We therefore expected that kinetic effects during the tautomerizations might be responsible for the observed selectivity and checked the interconversion pathways between the tautomers 7–11 which differ only in the position of one proton. Such a proton migration must of course be catalyzed, and water

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

• in bringing the issue of dynamic effects to a wide audience [46]. The question addressed in this work was ostensibly simple: is the mechanism of dehydration/alkyl migration of a protonated alcohol a concerted or stepwise process? The IRC for the process revealed a concerted mechanism (Figure 5, blue

• and co-workers [55]. Additionally, replacing R in Figure 5 with a non-methyl substituent opened up the possibility of the formation of two different products resulting from migration of different alkyl groups (tertiary carbocation products A and B in Figure 5). While these differences led to results

• preorganization of the substrate into a conformation that disfavors the 1,2-hydride shift actually promotes miltiradiene formation. Finally, when dynamics trajectories were initiated from the region of the 1,6-proton transfer transition state associated with proton migration to the si face of the C=C double bond

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• medical school, research was one of my pursuits from freshman year throughout my undergraduate career. The project entailed the use of variable-temperature NMR to measure the dynamics of ligand migration in trimetallic osmium clusters [22][23]. Dr. Rosenberg was an inspirational figure, and his pursuit

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• ]. The trityl group in myo-11 and scyllo-11 was cleaved without acetyl migration using FeCl3 [47] to afford myo-12 and scyllo-12 in good yields. The primary hydroxy groups can be easily converted into fluorine by action of DAST in dichloromethane in less than 5 minutes to give myo-13 and scyllo-13 in 95

• /or acetate migration. By reducing the reaction time to 15 minutes the byproducts formation could be lowered to 10% and myo-2 was obtained in 45% isolated yield. It is worthy to note that 41% of the starting material was recovered. At this stage, the fluorination was tested using DAST [48] on myo-20

• show any fluorine incorporation. Various types of compounds resulting from the migration of the tertiary acetate to the primary position, elimination reaction or cyclization were identified depending on the experimental procedure. From these results, the fluorination was finally investigated on myo-22

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• migration, as reported previously, gave mycothiol 1 [23][24]. Conclusion We demonstrated a MSH synthesis using an anomerization reaction through endocyclic cleavage in the presence of a weak Lewis acid. Murphy also reported the utility of the anomerization of glucuronic acid for preparing 1,2-cis-linked

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• [18][19], decarboxylative alkenylation of cycloalkanes with aryl vinylic carboxylic acids [20][21], trifluoromethylthiolation [22], thiolation [23][24], alkenylation [25][26], dehydrogenation−olefination and esterification [27][28], radical addition/1,2-aryl migration [29], cascade alkylation

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• promoting the migration of its acetalic H atom in a hydride-like manner. As result, we have disclosed a variety of tandem processes initiated by [1,5]- and [1,4]-hydride shifts from the acetalic carbon atom toward electrophilic molecular fragments [19][20][21][22][23][24][25][26][27]. Thus, we have reported

• products, it seems reasonable to hypothesize that the conversions 3 → 5 + 6 are initiated by an H migration from the acetalic carbon toward the fulvene substructure. If this migration is a [1,4]-hydride shift to the exocyclic C4 carbon atom of the fulvene fragment, as initially postulated, this step

• geometries of both transition structures TS1-A and TS1-B, more specifically to the distance between the two carbon atom termini of the H migration, shorter in TS1-B (2.63 Å) than in TS1-A (2.67 Å). Therefore, TS1-B is earlier than TS1-A. The geometry of TS1-B also accounts for its greater conjugation as the