Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• mechanistic studies suggest that catalyst F1 favours enol formation of starting material 4, thus providing a convincing rational why no base is required for this transformation [79]. Another class of easily accessible electrophilic N-transfer reagents are (aryl)-diazonium salts like compounds 41. The control

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

• were obtained with human dermal microvascular endothelial cells (HDMVEC), murine L929 fibroblasts and HeLa cells. Mechanistic studies in a cell-free system then showed that mycolactone efficiently inhibited the co-translational translocation of polypeptides into the ER, while the post-translational

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• previously reported [28]. Presumably, this reaction proceeds via azomethine ylid 6 (Scheme 3); analogous indolium ylids have been used synthetically in 1,3-dipolar cycloadditions [29] and mechanistic studies have been published on the related decarboxylation of pyridinium 2-carboxylates [30]. Fortunately, α

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• organic synthesis and medicinal chemistry. The inside of the reaction mixture has not been studied in depth, but we have begun mechanistic studies. Previous and present approaches. Substrate scope. (All of these reactions were carried out on a 2.0 mmol scale using CH3CN (2.0 mL) as a solvent.) Control

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• that these transformations proceed via a stable sulfonyl-DMAP intermediate [31][32][33][34]. Although many reported mechanistic studies reflect on the unique significance of the para-dialkylamino group [32] to the stabilization of the intermediate, DMAP was never reported to be used as the sole

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

• broad applications in studies of chemical and biochemical reaction mechanisms and metabolism pathways. Deuterium is the most common used isotopic label in mechanistic studies. Deuterated organic compounds are widely used in biological [1] and pharmacological [2][3][4][5] investigations. In the last

• intramolecular ring closure [21][22][23][24]. The importance of these cores for medical chemistry studies suggests that isotopically labeled pyrazolo[1,5-a]pyridines and triazolo[1,5-a]pyridines could be of interest. Recently, deuterium-labeled pyridinium-N-imines were applied to mechanistic studies of the

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• in the absence of theoretical or mechanistic studies. Phenylacetylene (7), 1-bromo-4-ethynyl benzene (8) and 1-ethynyl-4-nitrobenzene (9) were hydrogenated using a Pd@C catalyst with trimodal pore-size distribution [152]. The chemoselectivity to the corresponding alkene product showed to follow the

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• significantly, when compared to other reported heteroatom-doping syntheses, the fluorescence of the B-CDs was dynamically quenched by Fe3+ ions. Mechanistic studies suggested that a dynamic quenching model was prevalent at low concentrations due to interactions between Fe3+ and the CD surface, possibly

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• systems for the rapid analysis and optimization of reaction parameters and conditions. The use of this technique in mechanistic studies is also discussed. Review Commercial flow probes NMR spectroscopy is based on the absorption of radiofrequency radiation to produce absorption on the nuclear spin level

• will discuss some recent selected examples of the application of NMR reaction monitoring in flow chemistry. These examples include the design of flow systems, the use of standard NMR instruments and flow probes, the use of microcoils and finally the use of flow-NMR for kinetic and mechanistic studies

• -on-a-chip approach. Kinetic and mechanistic studies The rapid analysis produced in flow NMR can be used for the detection of reactive intermediates and consequently for studying reaction mechanisms and the rapid optimization of a chemical process. The first example was described by Nakakoshi et al

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

• followed by anion exchange. The resultant oxocarbenium/tetraphenylborate ion pair undergoes a nucleophilic attack by silyl ketene acetal, which is followed by scavenging the trimethylsilyl cation with a chloride anion to result in chlorotrimethylsilane and the product. Mechanistic studies were conducted to

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• and heteroatoms and performing mechanistic studies which will be reported in due course as a full paper. Chroman-based tetracyclic natural products 1–4 of the brazilin family and our designed, B-ring-modified analogues of brazilin 5. Assessment of the IFCEA cyclization on additional substrates (±)-6b

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• that tactics can easily be analysed and compared and similar applications can be condensed (both in the text and in the corresponding schemes). Methodology driven investigations as well as mechanistic studies are not the main focus of this review but may be mentioned in the introductory section

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

• hetero-Diels–Alder reaction. In the reaction of arylnitroso dienophiles containing a nitro group in close proximity to the reaction center, unsubstituted dienes show a higher reactivity than substituted dienes, due to steric effects. Mechanistic studies of the nitroso hetero-Diels–Alder reaction

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

• the Michael products [19] which are the dominant products in polar solvents [25]. Previous mechanistic studies by Koerner and Rickborn [25] have collected strong arguments for a fast concerted [4 + 2]-cycloaddition of the deprotonated anthrone. Michael products were shown to be secondary products of a

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• organometallic methodology, asymmetric catalysis, total synthesis, and mechanistic studies. I opted for the latter and spent my Ph.D. studying the mechanism of the Wulff–Dötz reaction [1], while at the same time gaining a broad background in methodology and synthesis (Figure 2). I had a fantastic time in

• mimic, etc), only to find out after several months of synthesis that it did not function as planned! I wanted to utilize versatile chemistry that allowed me to synthesize and evaluate the compound of interest quickly and modify it rapidly for further mechanistic studies. This led me to become a peptide

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

• . However, some of the reactions using β-substituted α,β-unsaturated esters did not afford the products or gave the products in very low yield (Scheme 2). Herein, we report an expansion for our previous reductive Mannich-type reaction and mechanistic studies for the stereoselectivity of this reaction

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

• mechanistic studies to the formation of imine E-3 are performed by NMR, IR and UV–vis spectroscopy and liquid injection field desorption ionization (LIFDI) mass spectrometry as well as by trapping experiments for low-coordinate tungsten complexes with triphenylphosphane. W(CO)5(E-2) decays thermally in a

• ) followed by detailed mechanistic studies regarding the formation of imine E-3 are presented including mass spectrometric, NMR, IR and UV–vis spectroscopic kinetic studies in combination with (TD)-DFT methods. Results and Discussion Synthesis of W(CO)5(E-2) The diferrocenyl NH carbene complex W(CO)5(E-2) is

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• -terminal dehydratase domain and a C-terminal LanC-like cyclase domain, and detailed mechanistic studies on LamM enzymes was enabled by the in vitro reconstitution of lacticin 481 synthetase, LctM [47][54][55][56]. Both class III (“LanKC” [57]) and IV (“LanL” [49]) synthetases feature three domains, where a

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• and selectivity [24] (Scheme 2a). Unfortunately, the scope of this reaction is rather limited, as this is the only example presented in the paper. Mechanistic studies performed by the same group on this system support a hydropalladation/cyclization/β-hydride elimination mechanism. Rhodium catalysis of

• lithium aluminum hydride in excellent yield. The absolute configuration of the [3.1.0] pyrrolidines was assigned by analogy to 76, which was determined to be (R,R) by single crystal X-ray crystallography. Mechanistic studies After having successfully developed this synthetic methodology, a few questions

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• temperature. In this account we disclose, in addition to full details associated with this C–H activation chemistry, additional applications of room temperature Fujiwara–Moritani reactions including a synthesis of the herbicide boscalid, as well as spectroscopic and mechanistic studies. Results and Discussion

• favorably with all known routes to this pesticide shown in Scheme 6 [86][208][209][210][211][212][213]. Mechanistic insight Although there have been a number of mechanistic studies on C–H activation reactions involving neutral palladium species [34][108][109][110][111][112][113][114][115][116][117][118][119

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

• diastereoselectivities (all >95:5 dr) and enantioselectivities (up to >99% ee, Scheme 58) [75]. Mechanistic studies showed that this cascade reaction proceeded via a vinylogous Michael addition/Friedel–Crafts process involving a dual H-bonding activation of substrates. In 2015, Wang and co-workers reported Lewis acid

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

• . Carbene cascade for fused bicycles. Cascade formation of bridged rings. Conformational effects. Hydrazone cascade reaction. Mechanistic studies. Gold carbene formation from alkynes. Au-catalyzed bridged-bicycle formation. Gold carbene/alkyne cascade. Gold carbene/alkyne cascade with C–H bond insertion

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

• is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. Keywords: C–H

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• reaction between malonitirile 184 and substituted aromatic imine 185 catalyzed by bifunctional thiourea 88 (Scheme 60) [81]. Many functional groups were tolerated, obtaining the desired densely functionalized tetrahydroquinolines 186. Additional mechanistic studies by the authors strongly suggest the

• to be employed in order to obtain spiro-dihydropyran-oxindole derivatives 231 in good to excellent yields, using catalyst 232 (Scheme 72) [91]. The mechanistic studies showed that the 3,5-bis(trifluoromethyl)phenyl group was an essential component of the thiourea catalyst. After the optimization of

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• reactions yielded highly functionalized cyclopentenes with an all-carbon quaternary center in moderate to good yields and good to excellent enantioselectivities. Further extension of the reaction reported herein and mechanistic studies are ongoing in our laboratory. Experimental General procedure for the [3