Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• Koert et al. in the racemic synthesis of the bisindole alkaloid (rac)-cladoniamide G (103, Scheme 17) [33]. The synthesis started with benzaldehyde 97 and indole 99 which were converted to the indole building blocks 98 and 100, respectively. These were connected to bisindole 101, which reacted with

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• also achieved the first catalytic asymmetric construction of axially chiral 3,3’-bisindole scaffolds 49 bearing both axial and central chirality by employing the CPA-14-catalyzed asymmetric addition reaction of 2-substituted 3,3’-bisindoles 47 to isatin-derived 3-indolylmethanols 48. The isatin-derived

• 3-indolylmethanols and 2-substituted 3,3’-bisindole substrates bearing different substituents afforded the axially chiral 3,3’-bisindole scaffolds 49 in moderate to high yields (up to 98%) and with excellent stereoselectivities (all >95:5 dr, >99% ee, Scheme 16). Moreover, the introduction of a

• bulky group into the ortho-position of prochiral 3,3’-bisindoles allowed the synthesis of new members of axially chiral biaryls (3,3’-bisindole derivatives) bearing both axial and central chirality in high yields and excellent stereoselectivities. Moreover, this methodology represents a new strategy for

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• catalytic and uncatalytic synthetic strategies adopted for the synthesis of the non-ionic (non-metallic) versions of these important molecules till date. Keywords: bisindole; heteroatom; indole; selenide; sulfide; Introduction Indole can be considered as a “prodigy” in the family of nitrogen-based

• gave a mixture of the mono and bis isomers (5 and 6, respectively) in fair to excellent yields (Scheme 2a). Increasing the amount of iodine led to less unreacted starting material 1, and increased formation of the bisindole product 6. An almost quantitative conversion of 1 was observed with a high

• -mediated reaction of bisindole derivative 32 with Ph2SiCl2 (33, Scheme 5b) [56]. The dissociation of the indole C-2–Si bond upon UV light excitation generates a hole transport layer (HTL) in these materials, facilitating the optical activity [57]. In 1996, Frenzel reported the synthesis of bis(indol-3-yl

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• reaction was also applied to a diamine (Scheme 5). When 1,3-diaminopropane was used, the bisindole 6g was isolated in 46% yield. Interestingly, the mixed indolone/indole compound 9 was also obtained as a side product. However, no traces of the bisindolone derivative were detected. We then succeeded in

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• 7{1}), with two of them as main components. A white solid fell out of solution, which was collected by filtration and washed with cold ethanol. NMR and HRMS analysis showed that it corresponded to the bisindole derivative 8{1,1,1}. The remaining crude reaction mixture was purified by column

• –8) greatly favored the formation of bisindole triad 8{1,1,2}, while EtOH at room temperature produced an optimal (circa 1:1 w/w) mixture of 8{1,1,2} and 9{1,2,1} (Table 1, entry 1), and reflux accelerated the process without affecting the w/w ratio (Table 1, entry 2). The reaction time was notably

• Table 1 as a guide, an adaptation of entry 3 was chosen to obtain a library of diversely substituted bisindole triads 8. Since coumarin 7 remained unreacted in this approach the examples described in Figure 1 were performed by employing a 2:1 ratio of precursors 1 and 6, respectively, in the absence of

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• constitute a unique group of terpenoid bisindole natural products [1] sharing a linear cyclopenta[f]indole tricyclic partial structure. The cyclopenta[f]indole system also occurs as partial structure of the nodulisporic acids [2], the shearinines [3][4][5][6] and janthitrems [7][8][9][10]. While work has

• , which was synthesized via Heck reaction with but-3-en-2-ol (5, 89%) in the presence of LiCl, inspired by a procedure by Camp and coworkers [36]. Propargyl bisindole 7 was obtained after conversion of 4 (2 equiv) to the magnesium acetylide (iPrMgCl in THF) and Grignard reaction with ketone 6. Due to the

• be separated by HPLC due to a reisomerization upon concentration of the fractions. When bisindole 8 was subjected to AlCl3, no cyclization product was observed and only deprotection occurred. This was somewhat surprising, because treatment of 6-prenoylindole with AlCl3 in 1,2-dichlorobenzene at 150

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

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

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• -carbenoid in the C3-position of N-methylindole followed by elimination of bromide. The conjugated iminium ion is a very good electrophile and can undergo an electrophilic aromatic substitution in the C3-position of N-methylindole to form the bisindole product. Conclusion We have developed a mild and

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• ]. Treatment of indole 14 with SmI2 afforded the cyclic bisindole 15 and, after silica column chromatography, its elimination product cyclopentene 16. On the TLC only the tertiary alcohol 15 and full consumption of the starting material were observed. Product 15 was converted quantitatively to cyclopentene 16

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• explored the alternative option to the target cyclophane 1 involving the bisindolization followed by RCM (Figure 1, Route B). To design aza-polyquinanes, we reported several bisindole derivatives starting with diketones under conditions of a low melting reaction mixture [38][39][40]. Based on this insight

• , diketone 3 was subjected to a double Fischer indolization with 1-methyl-1-phenylhydrazine under conditions of a low melting reaction mixture to generate the bisindole derivative 5. It is interesting to note that conventional conditions (AcOH/HCl) for Fischer indolization were not successful with systems

• related to 3. Later, the bisindole derivative 5 was subjected to RCM in the presence of Grubbs’ 2nd generation catalyst to deliver the desired product 1 in good yield (Scheme 2). The sulfur atom present in the bisolefin 3 is more accessible for coordination with the Grubbs’ catalyst. Whereas in case of

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

A new approach for the synthesis of bisindoles through AgOTf as catalyst

• Jorge Beltrá,
• M. Concepción Gimeno and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2014, 10, 2206–2214, doi:10.3762/bjoc.10.228

• approach for this interesting and appealing reaction. Keywords: Ag(I); aldehydes; bisindole; catalysis; indole; Introduction Indole is an interesting structural motif present in more than 3000 isolated natural products and embedded in many biological systems [1][2][3]. Although this field has attracted a

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ozonolysis and acid-promoted cyclization afforded (+)-41 and (−)-41 in an overall yield of 60% and 46%, respectively. For the synthesis of staurosporinone (30) and its 3,4-dimethoxybenzyl (DMB)-protected derivative 45, a ruthenium-catalyzed C–H insertion/electrocyclization cascade using 2,2’-bisindole 44 and

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• -alkenylindoles in an atmosphere of molecular oxygen provided dihydroindoloazocine compounds that are key intermediates in the total synthesis of the austamide derivatives and the okaramine family of polycyclic bisindole alkaloids [73][74]. Enantioselective synthesis of vinyl-substituted tetrahydro-β-carbolines

pH-Responsive chromogenic-sensing molecule based on bis(indolyl)methene for the highly selective recognition of aspartate and glutamate

• Litao Wang,
• Xiaoming He,
• Yong Guo,
• Jian Xu and
• Shijun Shao

Beilstein J. Org. Chem. 2011, 7, 218–221, doi:10.3762/bjoc.7.29

• conjugated bisindole skeleton. A less strong shoulder peak at 500 nm is related to its intermolecular hydrogen bonding interaction and disappears on the addition of a small quantity of a polar protic solvent such as CH3OH or H2O to the solution. In the presence of 0–0.10 mL H2O, the intensity of the band at

• shaken carefully, the upper organic phase turned yellow, while the aqueous phase became colorless. This suggests that protonation is reversible. Conclusion In conclusion, bis(indolyl)methene, containing a conjugated bisindole skeleton, provides an easy-to-make, simple and efficient chromogenic-sensing

Synthesis of indolo[3,2-b]carbazole-based new colorimetric receptor for anions: A unique color change for fluoride ions

• Ajit Kumar Mahapatra,
• Giridhari Hazra and
• Prithidipa Sahoo

Beilstein J. Org. Chem. 2010, 6, No. 12, doi:10.3762/bjoc.6.12

• derivatives exhibit important biological activities [41]. Therefore, there has been great interest in the synthesis of bisindole compounds both naturally occurring and totally synthetic. As an extension of our work [42] on supramolecular chemistry, we now report a simple and new indolocarbazole-based