Download or read book The Development and Application of Magnesium Amide Bases in Asymmetric Synthesis written by Linsey S. Bennie and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Extending Applications of Magnesium Amide Bases in Asymmetric Synthesis and a Mild and Selective N debenzylation Method written by Natalie R. Monks and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expansion of the application of readily available chiral magnesium-bisamides was the overall focus of the majority of this study. Comparing a structurally simple C2-symmetric magnesium bisamide and a chelating magnesium bisamide, a range of cyclobutanone substrates have been desymmetrised. Early studies employed the chlorotriethylsilane electrophile, however, efficiency of the processes with the chosen base system with cyclobutanone substrates was low. When the alternative electrophile, diphenylphosphoryl chloride, was utilised, however, a drastic improvement in both reactivity and selectivity was achieved. Optimisation of the reaction conditions with both a C2-symmetric magnesium bisamide and a chelating magnesium bisamide revealed selectivities of up to 99:1 er for the enantioenriched enol phosphate products. Furthermore, it was found that no additives are required within this novel base system and the deprotonation can be performed at a more elevated temperature of -40 °C whilst maintaining high selectivity. This efficient desymmetrisation was applied to a range of cyclobutanone substrates and seven novel enol phosphate products were formed in enantioselectivities between 76:24 and 99:1er, with the majority producing ratios greater than 89:11 er. Further application of a C2-symmetric magnesium bisamide was also sought by employing this base reagent within the synthetic route towards the natural product (+)-(S)-Sporochnol A. To this end, a scalable pathway towards a novel 4,4-disubstituted cyclohexanone was devised. The asymmetric deprotonation of this intermediate, utilising a C2-symmetric magnesium bisamide, subsequently embedded the all carbon quaternary stereocentre required within the natural product. Trapping the resulting chiral enolate with diphenylphosphoryl chloride furnished the desired enol phosphate in 88:12 er, which is an excellent level of enantioselectivity for a substrate of this type at a reaction temperature of -78 °C. Furthermore, the utility of the enol phosphate product was highlighted through a palladium-catalysed cross-coupling reaction with a Grignard reagent. Although completion of the synthesis of (+)-(S)-Sporochnol A was not achieved, the key asymmetric deprotonation and subsequent cross-coupling step were successful and high yielding. An additional study was the development of an improved method for the oxidation of secondary N-benzylamines. The application of DIAD as a means to oxidise secondary N-benzylamines, followed by a subsequent hydrolysis step has been employed to afford debenzylated free amines. This oxidation methodology has thus been applied to a range of amine substrates as an improved, mild, and selective method for benzyl deprotection. High yields of the free amines were obtained and the reaction proved to be tolerant of other functional groups and heteroatoms. Moreover, when an enantiopure secondary N-benzylamine was deprotected, the free primary amine remained optically pure, proving that these mild conditions do not interfere with other functionality within the molecule.
Download or read book The Asymmetric Synthesis of Enol Phosphates and Their Application in Total Synthesis written by Muralikrishnan Rajamanickam and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The synthesis of a wide range of highly valuable enol phosphate products has been carried out. The use of carbon centred magnesium bases, previously developed in the group has allowed the formation of kinetic enol phosphate products under room temperature conditions. By applying specific quench conditions such as the reverse addition quench condition yields up to 95% were obtained while using di-tertbutylmagnesium base. Interestingly acetophenone derivatives required the use of di-mesitylmagnesium base to access the corresponding enol phosphate compounds. Such enol phosphates can also be obtained under an enantioenriched fashion with the use of chiral magnesium bisamide bases. Previously studied C2- and pseudo C2-symmetric magnesium amide bases were synthesised and the process optimised to obtain up to 95% yield and 95:5 of selectivity on the benchmark substrate. A novel co-addition quench protocol was developed to access high reactivity and selectivity at mild temperature conditions (-20 °C).The high stability of enol phosphate products allowed a detailed study of the chiral magnesium amide bases. Such study allowed the development of a practical methodology towards chiral alkyl-magnesium amide bases allowing similar results to chiral magnesium bisamide bases with half the amount of chiral amine. Further investigations of the reactive species in solution through DOSY NMR techniques were also carried out. Finally the sum of knowledge gained through synthesis and application of enolphosphates allowed the total synthesis of a natural product (+)-Sporochnol. The key transformation of the synthesis consisted on the desymmetrisation of a prochiral ketone to generate an enantioenriched enol phosphate followed by a Kumada cross coupling reaction.The novel Kumada coupling reaction was initially developed for the synthesis of (+)-Sporochnol. With the success encountered in such methodology we further developed the reaction, which, ultimately allowed the cross coupling of unactivatedenol phosphate compounds with alkyl Grignard reagents at room temperature using commerically available and air stable PEPPSI catalysts.
Download or read book The Development and Application of Magnesium Base mediated Transformations written by Tina Weber and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The exploration of magnesium bases has been the focus of this programme. Utilising the readily prepared Mes2Mg as a base reagent in a slight excess of 1.5 mol, efficient mediation of the Shapiro reaction has been achieved. A range of easily accessible aryl tosylhydrazones, bearing electron-neutral or -donating substituents, delivered excellent levels of selectivity in electrophilic quench, up to 97:3 (E:H), in conjunction with yields up to 90 % of the corresponding disubstituted alkenes. With only 1.05 equivalents of Weinreb amides as electrophiles, yields as high as 77% could be obtained. Efforts to utilise more demanding dialkyl tosylhydrazones were of limited success. Mechanistic investigations and attempts to trap key intermediates revealed a substantial lack of reactivity of the carbon-centred base at ambient temperatures and below. Further utilisation of the in situ generated vinyl magnesium species within Kumada-type cross-coupling reactions was also briefly explored. Preliminary studies, employing iron(III) chloride as a catalyst and TMEDA as an additive, delivered up to 32% yield of the desired alkylated product. Initial investigations into the efficacy of Mes2Mg in Wittig reactions were focused on the formation of a non-stabilised phosphonium ylide and subsequent reaction with acetophenone. These studies furnished an unusually high E-selectivity of 4:1 (E:Z), albeit in low yields of the alkene product. The conversion of phosphonium salts bearing electron-withdrawing groups delivered yields of up to 93%. Extension of the methodology studies utilising magnesium base reagents within the synthesis of the natural product (-)-mucosin was targeted. Efficient preparation of two main fragments, the bicyclic core and the allylic side chain, furnished the desired compounds in 51 % and 41 % yield, respectively. In the key step, enantioselective deprotonation of the meso-ketone using a chiral magnesium bisamide produced the enol silane in excellent 92:8 selectivity and up to 87% yield. Reaction of the silylenol ether with the allylic bromide delivered the desired keto ester in a 70 % yield. As an alternative for the alkylation step, utilisation of Tsuji-Trost allylation chemistry was explored. Completion of the natural product focused at first on the reduction of the ketone moiety and subsequent installation of a bromide leaving group. Extensive 1H-NMR studies on the alcohol intermediate validated the proposed route towards (-)mucosin. Introduction of the final nbutyl side chain was attempted using a range of stoichiometric and catalytic organocuprate-based protocols. A second strategy towards (-)mucosin was devised, concentrating on alkylation of the ketone moiety instead of hydride reduction. However, the hindered position within the molecule prevented the nbutyl group introduction and the completion of the natural product in both routes.
Download or read book Novel Applications of Magnesium Base Systems in Preparative Organic Chemistry and Asymmetric Synthesis written by Peter Katai and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Magnesium Amide Bases and Amido Grignards written by Chih-Hung Lee and published by . This book was released on 1990 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Writing For Academic Journals written by Murray, Rowena and published by McGraw-Hill Education (UK). This book was released on 2013-09-01 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book unravels the process of writing academic papers. It tells readers what good papers look like and how they can be written.
Download or read book The Development and Application of Chiral Magnesium Amides and New Addition oxidation Processes written by James John Crawford and published by . This book was released on 2005 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Writing for Academic Journals 4e written by Rowena Murray and published by McGraw-Hill Education (UK). This book was released on 2019-11-16 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive guide to writing journal articles addresses all the stages and recurring challenges, from targeting a journal to dealing with reviewer feedback. Drawing on many years of running ‘Writing for Publication’ workshops, Murray explores not only style and structure but also behaviours and emotions. As a key component of both research courses and careers, this timely text also addresses the struggle to make time for high quality academic writing and how to ensure a writing-life balance. Examining a variety of approaches, relevant to many different academic disciplines, this core text demystifies and defines writing practices and makes this form of high-stakes academic writing seem manageable. Writing for journals has never been more competitive, and writers, researchers, practitioners and students need expert guidance on productive practices and ways of maintaining focus and motivation, which Murray provides. This latest edition is completely updated and more relevant than ever for clinicians, practitioners and students. "This book was already a classic, but the update makes it even more useful. From finding time to write, doing a short literature review and identifying scam journals, Rowena Murray provides an excellent, concise and accessible companion for writing academic journal papers, which is appropriate for both students and working academics." Associate Professor Inger Mewburn, Director of Research Training, The Australian National University, Australia “Rowena Murray has approached publishing in a journal with scientific rigour. Following this book’s recommendations will make it impossible to find a convincing excuse for failure to publish. She herself writes with a high level of artisanal skill; this book is fast paced, stylish and highly readable. Her own extensive experience in supporting journal article writers tempers this book with the credibility of a seasoned veteran. Best of all, there is a wealth of wisdom here—in advising on how to publish, Murray is also advising on how to live a satisfying life as a writer.” Associate Professor Susan Carter, University of Auckland, New Zealand “In Writing for Academic Journals (4th edition), Rowena Murray’s voice is direct, down-to-earth and wise. Drawing on a depth of practical experience as both published author and writing teacher, she conveys the message that, yes, publishing in academic journals is demanding, but it’s also very possible. And that once you are successful, there is still much to be learned from reading books like this one and hanging out with others in writing groups and workshops. To that end, the book is a trove of tips and techniques helpful to all who pursue the challenging craft of (good) academic writing.” Barbara Grant, Associate Professor in the School of Critical Studies in Education at the University of Auckland, New Zealand, and author of Academic writing retreats: A facilitator's uide
Download or read book Flexible Access to an Array of Enantiomerically enriched Oxabisipidines and Their Use as Chiral Ligands in Asymmetric Synthesis written by Laura Goldie and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A broad series of optically-enriched oxabispidine scaffolds incorporating a range aryl, heteroaryl, and alkyl side arms has been successfully prepared, utilising an optically-pure common oxazine intermediate and commercially available aldehydes. In efforts towards establishing efficient access to such molecules, a fully optimised route, which is amenable to the preparation of the optically-pure oxazine on a multigram scale, has been developed. In addition to the development of a general trifluoromethanesulfonic acid-activated intramolecular Mannich-type cyclisation protocol, which is accommodating to a wide range of aldehyde substrates, alternative conditions have also been developed for more challenging substrates. More forcing conditions utilising p-toluenesulfonic acid at elevated temperatures have been utilised for highly electron-rich aldehyde substrates, whereas the employment of a benzotriazole additive was required for enolisable alkyl aldehyde substrates. In addition to the broad range of bicyclic oxabispidines prepared under the conditions described, a more synthetically challenging and structurally complex tricyclic derivative has also been successfully prepared. Further to the investigations into the scope of the developed approach to the construction of such scaffolds, efforts to confirm the proposed Mannich-type cyclisation mechanism, both experimentally and computationally, are disclosed. Additionally, a number of NMR studies have been performed to confirm the stereochemistry of the family of oxabispidine derivatives. With a library of enantiomerically-enriched oxabispidines in hand, manipulation of the nitrogen functionalities was undertaken to allow the preparation of further oxabispidine derivatives, which could have potential applications as ligands in asymmetric synthesis, as well as derivatives of interest to pharmaceutical industry partners. Following this work, a programme of research centred on the utilisation of oxabispidine scaffolds within the arena of magnesium-mediated asymmetric deprotonation processes was undertaken. Initial investigations focused on the use of the phenyl-substituted bis-secondary oxabispidine, with studies into the formation of both the corresponding magnesium bisamide and lithium amide species. Such endeavours indicated that the chiral amine species must be introduced as the bis-HCl salt. Investigations into the use of such amide base species in the deprotonation of 4-tert-butylcyclohexanone to generate the corresponding enantioenriched enol phosphate product were undertaken. Whilst under lithium-mediated conditions, promising levels of enantioselectivity could be achieved (73:27 er at -78°C), only poor to moderate yields of the desired product were attained. Similarly poor reactivity was observed with the corresponding magnesium-amide base counterpart, with no improvement in the selectivity of the deprotonation process. Altering the substituent of the oxabispidine scaffold to incorporate a more electron-donating group, and therefore a potentially more reactive magnesium amide, did not lead to the desired increase in yield. Furthermore, with a view to increasing the reactivity of the oxabispidine magnesium amide system, the employment of Nmethylated oxabispidine derivatives, bearing both phenyl and methyl side arms, was studied to allow the generation of chelating alkyl magnesium amides. As with previous oxabispidine-derived magnesium amides, these base systems were screened in the deprotonation of 4-tert-butylcyclohexanone, but again only poor yields of the enol phosphate product were recovered (≤ 25% yield at room temperature) with no significant enantioselectivity being observed, despite significant experimental efforts.
Download or read book Development of Chiral Base Mediated Asymmetric Synthetic Methodology and Applications in Synthesis written by Gillian Sharples and published by . This book was released on 2001 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Alkaline Earth Metal Compounds written by Sjoerd Harder and published by Springer. This book was released on 2013-07-20 with total page 282 pages. Available in PDF, EPUB and Kindle. Book excerpt: The series Topics in Organometallic Chemistry presents critical overviews of research results in organometallic chemistry. As our understanding of organometallic structure, properties and mechanisms increases, new ways are opened for the design of organometallic compounds and reactions tailored to the needs of such diverse areas as organic synthesis, medical research, biology and materials science. Thus the scope of coverage includes a broad range of topics in pure and applied organometallic chemistry, where new breakthroughs are being achieved that are of significance to a larger scientific audience. The individual volumes of Topics in Organometallic Chemistry are thematic. Review articles are generally invited by the volume editors.
Download or read book Preparation and Use of Chiral Lithium Amide Bases in Organic Synthesis written by S. K. Rahman and published by . This book was released on 1988 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Catalysis in Asymmetric Synthesis written by Vittorio Caprio and published by John Wiley & Sons. This book was released on 2009-03-09 with total page 409 pages. Available in PDF, EPUB and Kindle. Book excerpt: Asymmetric synthesis has become a major aspect of modern organic chemistry. The stereochemical properties of an organic compound are often essential to its bioactivity, and the need for stereochemically pure pharmaceutical products is a key example of the importance of stereochemical control in organic synthesis. However, achieving high levels of stereoselectivity in the synthesis of complex natural products represents a considerable intellectual and practical challenge for chemists. Written from a synthetic organic chemistry perspective, this text provides a practical overview of the field, illustrating a wide range of transformations that can be achieved. The book captures the latest advances in asymmetric catalysis with emphasis placed on non-enzymatic methods. Topics covered include: Reduction of alkenes, ketones and imines Nucleophilic addition to carbonyl compounds Catalytic carbon-carbon bond forming reactions Catalytic reactions involving metal carbenoids Conjugate addition reactions Catalysis in Asymmetric Synthesis bridges the gap between undergraduate and advanced level textbooks and provides a convenient point of entry to the primary literature for the experienced synthetic organic chemist.
Download or read book American Doctoral Dissertations written by and published by . This book was released on 1999 with total page 848 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Index to Theses with Abstracts Accepted for Higher Degrees by the Universities of Great Britain and Ireland and the Council for National Academic Awards written by and published by . This book was released on 2008 with total page 676 pages. Available in PDF, EPUB and Kindle. Book excerpt: Theses on any subject submitted by the academic libraries in the UK and Ireland.
Download or read book Superbases for Organic Synthesis written by Tsutomu Ishikawa and published by John Wiley & Sons. This book was released on 2009-01-26 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: Guanidines, amidines and phosphazenes have been attracting attention in organic synthesis due to their potential functionality resulting from their extremely strong basicity. They are also promising catalysts because of their potential for easy molecular modification, possible recyclability, and reduced or zero toxicity. Importantly, these molecules can be derived as natural products – valuable as scientists move towards “sustainable chemistry”, where reagents and catalysts are derived from biomaterial sources. Superbases for Organic Synthesis is an essential guide to these important molecules for preparative organic synthesis. Topics covered include the following aspects: an introduction to organosuperbases physicochemical properties of organic superbases amidines and guanidines in organic synthesis phosphazene: preparation, reaction and catalytic role polymer-supported organosuperbases application of organosuperbases to total synthesis related organocatalysts: proton sponges and urea derivatives amidines and guanidines in natural products and medicines Superbases for Organic Synthesis is a comprehensive, authoritative and up-to-date guide to these important reagents for organic chemists, drug discovery researchers and those interested in the chemistry of natural products.
