Author Archive

OBC Highlights: A transition metal-free strategy for the desulfonative borylation of benzyl sulfones

Compounds containing carbon-boron bonds are of high significance because they can be used as the precursors for various reactions such as 1,2-metallate rearrangements, deborylative nucleophilic addition reactions and the formation of carbon-oxygen and carbon-nitrogen bonds through hydrolysis and aminolysis respectively. Sulfones are useful for increasing the functionality of a molecule by alkylation and arylation (scheme 1), however till date there have been very few reports regarding the transformation of carbon-sulfonyl bonds to carbon-boron bonds. The transformation of sulfonyl groups to boryl groups under metal free organocatalysis is still a challenging task.

Scheme 1: Sequential functionalization of benzylic sulfones

In their recent OBC publication, Prof Cathleen M. Crudden et.al. of Queen’s University, Ontario developed a beautiful protocol for the transition metal-free desulfonative borylation of benzyl sulfones using simple pyridine derivatives as catalysts (scheme 2). They reported the borylation of cyclic sulfones to afford functionalized sulfones and sulfonamides through a sulfinate intermediate which could be trapped with electrophiles. As they chose benzhydryl phenyl sulfone (1a) as a model substrate for their optimization, they reported the formation of the desired dibenzylic boronic (2a) ester along with diphenylmethane (3a) as a by-product. By using trifluorotoluene as a solvent instead of ethereal solvents, they optimized their conditions, resulting in an enhanced formation of 2a and supressed formation of 3a.

 

Scheme 2: Pyridine-promoted desulfonative borylation of benzyl sulfones

The reaction was well tolerated by a range of benzhydryl sulfones bearing both electron-neutral and electron-rich aryl groups with good yields. Even sterically hindered ortho-substituted aryl groups also afforded the desired products with lower yields. Unfortunately, benzhydryl sulfones bearing electron-withdrawing substituents such as trifluoromethyl, esters, cyano, allyl and iodide groups were not tolerated the transformation. Crudden et. al. executed control experiments in order to understand the reaction mechanism, finding that the sulfone bearing terminal olefin did not afford any product and also that TEMPO ((2,2,6,6-Tetramethylpiperidin-1-yl)oxyl) completely inhibited borylation. Based on these observations, they proposed a single electron transfer mechanism for borylation based on the work from Tuttle and Zhang and Jiao.

In conclusion, Crudden et al. succeeded in developing a desulfonylative borylation of alkyl sulfon es through 4-arylpyridine catalysis which yields synthetically useful benzylic boron compounds.

Read their full article now.

About the Blog Writer: A. Vamshi Krishna is currently pursuing a Ph.D. in organic chemistry with Prof. D. B. Ramachary at University of Hyderabad. His research mainly focuses on asymmetric supramolecular-organocatalysis, where he synthesises highly functionalized biologically active novel scaffolds with excellent selectivities and yields. His passion for scientific writing made him become a blog writer.

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OBC Highlight: Trifluoromethylated proline analogues through highly diastereoselective formal (3+2) cycloadditions

Amino acids form the fundamental building blocks of proteins and peptides and largely control the biochemical and biophysical properties of a living organism. Incorporation of fluorine in amino acids has been an area of wide interest, because replacement of a hydrogen atom with a fluorine atom leads to a significant change in the electronic properties of a substrate and could potentially lead to a wide variation in its biological activity. The most common functional group introduced in this regard is the trifluoromethyl (-CF3) group, which provides an alternative to the -CH3 group in terms of its electronic properties. One very commonly available source of the -CF3 group is ethyl 3,3,3-trifluoromethyl pyruvate, which was utilized very elegantly by Professor Mario Waser and his group in their recent report published from the Johannes Kepler University, Linz to form α-trifluoromethylated proline derivatives, which are potentially very interesting surrogates for naturally occurring proline.

Scheme 1: Diastereoselective formal (3+2) cyclization to form α-CF3 proline derivatives

Benzyl imine derived from ethyl 3,3,3-trifluoromethyl pyruvate was treated with benzylidene indanedione (1) in the presence of LiOH to form the spirocyclic α-trifluoromethyl proline derivative 3 as the sole diastereomer (Scheme 1). It was observed that simple ammonium salts used as phase transfer catalysts could improve the conversion drastically and benzyl triethylammonium bromide (TEBAB) was found to be the best reagent for the same. This transformation exhibits a wide substrate scope with different acceptors and donors alike, while maintaining very good diastereoselectivities.

Mechanistically, the transformation is driven by the formation of the stable 2-azaallyl carbanions (4 and 4’), which by virtue of its two resonating forms could form the two different spirocyclic regioisomers 3 and 5 (Scheme 2). It was observed that the α-nucleophilic attack on the Michael acceptor 1 proceeded exclusively and there was no trace of the γ-adduct for any of the substrates. The remarkable levels of diastereoselectivity of the α-adducts adds to the ingenuity of the method.

Scheme 2: Formal (3+2) cyclization modes leading to α-CF3 proline derivatives

This is indeed a very useful and efficient method for the construction of an unprecedented class of α-trifluoromethylated proline derivatives which can easily be incorporated in peptide chains for biological studies. There is however, room for improvement in this methodology, as the efforts towards enantioselective formation of the trifluoromethylated proline derivatives were unfortunately met with failures. The authors used cinchona alkaloid derived chiral phase transfer catalysts, which resulted in unsatisfactory enantioselectivities. A successful enantioselective protocol towards the formation of fluorinated amino acids would drive this field of research even further in future.

About the blog writer: Satrajit Indu is a recent PhD graduate from Indian Institute of Technology Bombay. His doctoral work in the group of Prof. Krishna P. Kaliappan was mainly focused on the total synthesis of complex natural products and development of new catalytic methods aimed for achieving interesting chemical transformations. A keen interest in organic chemistry coupled with an urge to communicate with the scientific community has driven him to take up blog writing.

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OBC Highlight: Planarized and structurally constrained B,N-phenylated dibenzoazaborine: diversity in electronic properties

Polycyclic aromatic hydrocarbons (PAHs) containing heteroatoms have recently been grabbing the attention of scientists as they exhibit intriguing photophysical properties and can be widely used as building blocks for π-conjugated materials due to the effect of heteroatoms on the electronic properties of the system.

PAHs are often employed in OLEDs. Over the last few years, these PAHs have been synthesized in several different ways. Kawashima et.al synthesized different acene-like π-extended dibenzoborines such as compound B which show fascinating photophysical properties. More recently, Hatakeyama et.al have reported the synthesis of various PAHs that contain multiple 1,4-azaborine rings, such as compound C, which show excellent thermally activated delayed fluorescence. By investigating these types of molecules in more detail, their electronic properties can be improved to make better OLEDs.

a) Representative examples of previously reported dibenzoazaborine-based pi-conjugated compounds and b) planarized B,N-phenylated dibenzoazaborine 1 together with reference compounds 2-4

a) Representative examples of previously reported dibenzoazaborine-based pi-conjugated compounds and b) planarized B,N-phenylated dibenzoazaborine 1 together with reference compounds 2-4

a) UV-vis absorption and b) fluorescence spectra of 1 (red), 2 (blue), 3 (green) and 4 (orange) in THF.

a) UV-vis absorption and b) fluorescence spectra of 1 (red), 2 (blue), 3 (green) and 4 (orange) in THF.

In their recent OBC publication, Professor Shigehiro Yamaguchi of the Institute of Transformative Bio- Molecules, Nagoya University et al. explored in detail the relation between the structure of materials and their electronic structures. They mainly focused on the correlation between the ring-fusion mode, where two cyclic rings fused in a planar manner, and the degree of structural constraint within the dibenzoazaborine skeleton. As constraining molecules into a planar fashion can extend π-conjugation and increase chemical stability, Shigehiro planarized the B-, N- phenyl groups in dibenzoazaborine to synthesize a new family of planarized triarylboranes with a carbazole substructure, confirming this structure by single-crystal X-ray diffraction analysis. They studied the photophysical properties of 1 and compared it with compunds 2-4. Compound 1 showed an intense absorption band at λabs= 402 nm unlike compounds 2-4 which showed λabs at 389 and 371, 400, 404 and 387 nm respectively. The fluorescence spectra of compound 1 showed an intense deep blue emission with a full width at half maximum (FWHM) of 27 nm which is due to its rigid structure. The optimized structure of 1 with respect to DFT calculations matched with the experimentally determined crystal structure. They report the time dependent DFT calculations which prove compound 1 to have the highest oscillator strength (f) amongst compounds 1-4, resulting in the largest molar absorption coefficient (ε). This clearly represents that it absorbs light strongly at the given wavelength. They also studied the electrochemical properties of 1-4 using cyclic voltammetry which resulted in one reversible reduction wave irrespective of the structural constraint showing that there are no electronic effects imposed on the structural constraint.

In conclusion, Shigehiro et al. succeeded in synthesizing structurally constrained, planarized dibenzoazaborines and investigating their photophysical and electronic effects.

Read their full article at https://rsc.li/2Xw8uoA.

Blog writer description: I am A. Vamshi Krishna, pursuing a PhD in organic chemistry with Prof. D. B. Ramachary at the University of Hyderabad. My research mainly focuses on asymmetric supramolecular-organocatalysis where we synthesise highly functionalized biologically active novel scaffolds with excellent selectivity and yields. I am passionate about scientific writing.

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Organic & Biomolecular Chemistry welcomes new Associate Editor Elizabeth Krenske

New OBC Associate Editor Elizabeth Krenske

We are delighted to welcome Dr Elizabeth Krenske to the OBC team as an Associate Editor. Elizabeth is an Associate Professor at the University of Queensland, Australia, where her research focuses on the computational study of organic reactions and modelling of drug molecules and interactions.

After starting out her career in chemistry as an undergraduate at the University of Queensland, Elizabeth undertook a PhD in the field of synthetic main-group chemistry at The Australian National University’s Research School of Chemistry, under the supervision of Professor S. Bruce Wild. She spent a further two years carrying out postdoctoral research at the Australian National University, before receiving a Fulbright Scholarship and commencing postdoctoral studies at UCLA with Ken Houk. Elizabeth returned to Australia in 2009 as an Australian Research Council (ARC) Australian Postdoctoral Fellow at the University of Melbourne, and moved to The University of Queensland in 2012 as an ARC Future Fellow. She is currently an Associate Professor and Strategic Research Fellow in the University of Queensland School of Chemistry and Molecular Biosciences. To find out more about Elizabeth and her research, visit her webpage or browse some of her recent publications below.

 

Elizabeth’s recent publications:

 

The fate of copper catalysts in atom transfer radical chemistry

Polym. Chem., 2019, 10, 1460-1470

 

Asymmetric synthesis of multiple quaternary stereocentre-containing cyclopentyls by oxazolidinone-promoted Nazarov cyclizations

Chem. Sci., 2018, 9, 4644-4649

 

Synthesis of spirocyclic orthoesters by ‘anomalous’ rhodium(II)-catalysed intramolecular C–H insertions

Org. Biomol. Chem., 2018, 16, 256-261

 

Claisen rearrangements of benzyl vinyl ethers: theoretical investigation of mechanism, substituent effects, and regioselectivity

Org. Biomol. Chem., 2017, 15, 7887-7893

 

An unprecedented stereoselective base-induced trimerization of an α-bromovinylsulfone

Org. Biomol. Chem., 2017, 15, 5529-5534

 

Submit your research to Elizabeth now!
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OBC Highlight: A new atom and mass efficient synthetic route for tamoxifen

Nowadays, chemists are increasingly interested in revealing simpler methodologies for the synthesis of various drugs with high selectivity and purity. Transition metal catalysis has opened a wide window for the synthesis of different natural products and drugs with greater ease.

Z-Tamoxifen is one such drug, which is used in the treatment of breast cancer. Although there are many well-established synthetic procedures for the synthesis of Z-tamoxifen by various research groups such as T. Stiidemann et.al. and P. L. Coe et.al. etc., there are disadvantages to current methods, such as the use of multiple synthetic steps and generation of stoichiometric amounts of waste. Thus, there is a need to overcome these drawbacks.

In their recent OBC publication, Prof. Ben L. Feringa et.al. of Stratingh Institute for Chemistry, University of Groningen, Nijenborgh develop a fantastic two step protocol for the synthesis of Z-tamoxifen from commercially available starting materials. Usually, the transmetallation of anions formed by carbolithiation of (diphenyl)acetylenes with magnesium, boron, zinc or aluminium results in an active cross coupling partner, but with low atom efficiency. Here, Feringa et.al., for the first time proposed the direct cross coupling of the formed organolithium reagent with aryl halides in the presence of an active palladium nanoparticle based catalyst, cutting down the number of synthetic steps required to two, with excellent selectivities and yields. They report the thorough screening of reaction conditions such as solvent, temperature, catalyst loading etc. and explain the effect of various reaction parameters. The 0.67 atom economy and 22% RME achieved in the study is twice as good as the previously reported best protocol, and the scientists found that THF gave the desired product without encouraging any side reactions. Another advantage of this reaction is that the formed side product (lithium halide) can be easily removed.

Hence, Prof. Ben L. Feringa laid a new efficient pathway for the synthesis of biologically important Z-tamoxifen through his works.

Read their full article now.

 

About the Blog Writer: A. Vamshi Krishna is currently pursuing a PhD  in Organic chemistry with Prof. D. B. Ramachary at University of Hyderabad. His research mainly focuses on asymmetric supramolecular catalysis and organocatalysis, where he synthesises highly functionalized biologically active novel scaffolds with excellent selectivities and yields. He is passionate about scientific writing.

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Editor’s Choice: Santanu’s recommended articles

Professor Santanu Mukherjee (Indian Institute of Science, Bangalore), recently joined the Organic & Biomolecular Chemistry team as an Associate Editor. Santanu works in the field of asymmetric catalysis, with a focus on the discovery of new enantioselective transformations. His research group investigates hydrogen bonding, Lewis base and bifunctional catalysis, and more recently, he has focused on iridium-catalyzed asymmetric allylic substitution reactions.

 

To find out more about Santanu, take a look at our recent blog welcoming him to the team.

 

Santanu has picked out a selection of his personal favourite recent OBC articles which you can read now for free*

 

Santanu’s Recommended OBC Articles:

 

Catalyst-controlled positional-selectivity in C–H functionalizations

Virendra Kumar Tiwari and Manmohan Kapur

 

 

 

An enantioselective synthesis of α-alkylated pyrroles via cooperative isothiourea/palladium catalysis

W. Rush Scaggs, Toya D. Scaggs and Thomas N. Snaddon

 

Organocatalytic asymmetric synthesis of highly substituted pyrrolidines bearing a stereogenic quaternary centre at the 3-position

Soumendranath Mukhopadhyay and Subhas Chandra Pan

 

Total synthesis of incargranine A

Patrick D. Brown and Andrew L. Lawrence

 

 

 

 

Studies toward the synthesis of strevertenes A and G: stereoselective construction of C1–C19 segments of the molecules

Tapan Kumar Kuilya, Subhendu Das, Dhiman Saha and Rajib Kumar Goswami

 

Formal [4 + 2] benzannulation of 2-alkenyl indoles with aldehydes: a route to structurally diverse carbazoles and bis-carbazoles

Ankush Banerjee, Avishek Guin, Shuvendu Saha, Anushree Mondal and Modhu Sudan Maji

 

Vinylogous acyl triflates as an entry point to α,β-disubstituted cyclic enones via Suzuki–Miyaura cross-coupling

Daria E. Kim, Yingchuan Zhu and Timothy R. Newhouse

 

 

 

 

*Access is free until 28/02/2019 through a registered RSC account.

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OBC warmly welcomes Professor Anthony Davis as our new Editorial Board Chair

We are delighted to announce the appointment of Prof. Anthony Davis as the new Organic & Biomolecular Chemistry Editorial Board Chair. Tony returns to the Board after serving for many years as an Editorial Board member and we are very pleased to welcome him to his new role as Chair.

 

Tony is a Professor of Supramolecular Chemistry at the University of Bristol, with research focusing on anion recognition and transport, carbohydrate recognition, and crystal engineering. He started his chemistry career at Oxford University, obtaining both his undergraduate degree and D.Phil (in the group of Dr Gordon Whitham), followed by two years of postdoctoral work under the supervision of Prof. Jack Baldwin. He joined the group of Prof. Albert Eschenmoser in 1981, working as a Royal Society European Exchange Fellow, before becoming a Lecturer in Organic Chemistry at Trinity College, Dublin, in 1982. In September 2000, he moved to his current institution, and you can find out more about his current group on the research group webpage.

 

Tony is also a co-founder of Ziylo, a biotechnology company focusing on the development of new treatments for diabetes patients, which was recently sold to Novo Nordisk. A second company spun out of Ziylo, Carbometrics, continues to work on carbohydrate sensing.

 

Prof. Davis is the recipient of numerous awards including the Tilden Medal and the RSC Award for Physical Organic Chemistry. He has published hundreds of articles, and you can see a selection of his great work below.

 

Upon becoming Chair, Tony commented, “OBC is a cornerstone of organic chemical publishing, and I’m delighted to take on this responsibility.”

 

Read some of Tony’s latest publications:

Maltodextrin recognition by a macrocyclic synthetic lectin

Chem. Commun., 2018, 54, 8649-8652

 

Anion transport by ortho-phenylene bis-ureas across cell and vesicle membranes

Org. Biomol. Chem., 2018, 16, 1083-1087

(Included in the 2018 OBC HOT article collection)

 

Enantioselective carbohydrate recognition by synthetic lectins in water

Chem. Sci., 2017, 8, 4056-4061

 

Synthesis and evaluation of a desymmetrised synthetic lectin: an approach to carbohydrate receptors with improved versatility

Org. Biomol. Chem., 2016, 14, 1930-1933

(Included in the 2016 OBC HOT article collection)

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Introducing Professor Santanu Mukherjee, OBC Associate Editor

OBC is delighted to welcome our new Associate Editor, Professor Santanu Mukherjee, to the Editorial Board.

Santanu started his career in chemistry at R. K. Mission Residential College, Narendrapur, India, obtaining his BSc in 2000. He went on to study for his MSc in chemistry at IIT, Kanpur, 2002, before joining Professor Albrecht Berkessel at Universität zu Köln for his doctoral studies. After completing these in 2006, he worked as a postdoctoral fellow with Professor Benjamin List at Max-Planck Institut für Kohlenforschung in Mülheim an der Ruhr until 2008 and with Professor E. J. Corey at Harvard University from 2008-2010. In 2010, Santanu returned to India to join the Department of Organic Chemistry at Indian Institute of Science, Bangalore as an Assistant Professor and was promoted to Associate Professor in 2015.

His research interests focus on asymmetric catalysis, with a particular emphasis on the discovery of new enantioselective transformations, and recently, on iridium-catalyzed asymmetric allylic substitution reactions. To find out more about his research interests, you can visit the group webpage.

Santanu is a recipient of numerous recognitions and awards, and has published a large number of papers in high quality journals. Below are just a few examples of these publications:

 

Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of coumarins

Chem. Sci., 2018, 9, 5767-5772,  Edge Article

“On water” catalytic enantioselective sulfenylation of deconjugated butyrolactams

Org. Biomol. Chem., 2017, 15, 6921-6925,  Paper

Nitro-enabled catalytic enantioselective formal umpolung alkenylation of β-ketoesters

Chem. Sci., 2017, 8, 6686-6690,  Edge Article

Catalytic enantioselective cascade Michael/cyclization reaction of 3-isothiocyanato oxindoles with exocyclic α,β-unsaturated ketones en route to 3,2′-pyrrolidinyl bispirooxindoles

Org. Biomol. Chem., 2016, 14, 10175-10179,  Communication

 

Submit a manuscript for Santanu to handle today

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Bristol Synthesis Meeting 2019

Organic & Biomolecular Chemistry are proud to sponsor the 2019 Bristol Synthesis Meeting, to be held in the Victoria Rooms, University of Bristol, 9th April 2019.

The meeting boasts a fantastic line up of speakers including OBC Advisory Board members Helma Wennemers (ETH Zurich) and Ilan Marek (Technion, Israel Institute of Technology).

Registration is now open, so for the full list of speakers and to register, see the Bristol Synthesis Meeting webpage.

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OBC welcomes new Editorial Board member Corinna S. Schindler

We are delighted to introduce Assistant Professor Corinna S. Schindler as the newest member of our Editorial Board.

Originally from Schwaebisch Hall, Germany, Corinna carried out her undergraduate studies at the Technical University of Munich, completing her Diploma Thesis under the supervision of K. C. Nicolaou at the Scripps Research Institute in La Jolla. She then joined the Carreira group at ETH Zurich for her Ph.D., before accepting a postdoctoral position with Eric N. Jacobsen at Harvard University. In 2013 she moved to her current faculty as an Assistant Professor at the University of Michigan.

Over the course of her career, Corinna has worked in various areas of organometallic and organic synthetic chemistry. Currently, her research lab in Michigan focuses primarily on developing new synthetic methodologies to access biologically active structures, and you can find out more by visiting the group webpage.

Corinna has been recognized by numerous awards including the NSF Career Award, c&en’s Talented Twelve Award, the American Chemical Society Green Chemistry Institute GreenX: Rising Star Award and an Alfred P. Sloan Foundation Fellowship.

 

Read her publications, including:

Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors

Chem. Commun., 2015, 51, 8990-8993, DOI: 10.1039/C5CC02918J

Photoredox activation and anion binding catalysis in the dual catalytic enantioselective synthesis of β-amino esters

Chem. Sci., 2014, 5, 112-116, DOI: 10.1039/C3SC52265B

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