Stronger Brønsted acids

The hetero Diels-Alder reaction is one of the most important methods for the synthesis of heterocycles. In this article an overview is given for the period since 1989 describing the reaction of heterobutadienes such as oxabutadienes, thiabutadienes, azabutadienes, diaazabutadienes, nitroso-alkenes and nitroalkenes as well as of heterodienophiles such as carbonyls, thiocarbonyls, imines, iminium salts, azo- and nitroso compounds. In addition, several other less common hetero Diels-Alder reactions such as cycloadditions of thiaazabutadienes, oxaazabutadienes, dioxabutadienes, dithiabutadienes, oxathiabutadienes, diazaoxabutadienes as well as the use of N-sulfinyl-phosphaalkynes and other dienophiles are mentioned. A main point of discussion is the stereoselectivity of the reactions and the preparation of enantiopure compounds either using dienes and dienophiles carrying a chiral auxiliary or employing chiral Lewis acids. A point stressed is the synthesis of natural products using hetero Diels-Alder reactions leading to carbohydrates, alkaloids, terpenes, antibiotics, mycotoxins, cytochalasans, antitumor agents and several other classes of natural products.

Hetero diels-alder reactions in organic chemistry

In an age when organic chemists have shown that even the most complex natural and unnatural products can be synthesized,1-3 the emphasis of synthetic chemistry is shifting to how they can be assembled in a truly practical fashion.4-6 A pressing challenge facing organic chemists, therefore, is to advance new processes that are not only efficient, selective, and high yielding, but that are also environmentally friendly.7,8 Historically, the metric of reaction success has been the yield. Although yields will remain imperative, alternative measures are the ‘greenness’ of a reaction, or E factor,9 and the volume productivity.10 The E factor, introduced by Sheldon,9 is defined as the ratio of weight waste to weight product while the volume productivity is the grams product per liter of reaction medium. The E factor for many pharmaceuticals has been estimated to exceed 100.11,12 The largest contributors to the magnitude of E factor are organic solvents, many of which are ecologically harmful and require expensive remediation.

As global environmental legislation becomes stricter, consideration of environmental concerns must be addressed at early stages of product development. By doing so, project cost reduction of 50% or more have been realized.13 Although steps toward sustainability can be made by reusing solvents, rarely is recycling accomplished with complete efficiency. An alternative strategy to reduce the E factor of reactions and their impact on the environment is to conduct them under solvent-free conditions.11,14-16 Among the benefits of solvent-free processes are cost savings, decreased energy consumption, reduced reaction times, and a large reduction in reactor size and capital investment. As a result, introduction of solvent-free reactions, including solvent-free polymerizations,14,17-20 radical additions,14,21-24 ionic reactions,25-31 solid state reactions15,32-34 and photochemical reactions15,35-37 has increased steadily in recent years. Solvent-free catalytic enantioselective reactions, however, have received much less attention.

The paucity of catalytic asymmetric solvent-free reactions is not unexpected. Catalyst efficiency and enantioselectivity is frequently highly sensitive to the nature of the solvent.38 Examples in which a catalyst can generate enantiomeric products with high levels of enantioselectivity in different solvents have been reported.39 Moreover, enantioselectivities are often dependent on catalyst concentrations. Consequently, two of the most important variables for catalyst optimization, solvent properties and concentration, are eliminated under solvent-free conditions. Furthermore, under solvent-free conditions the reaction medium will change as reagents and substrates are converted to products. The impact of such changes is currently unpredictable, complicating reaction development. We believe that these limitations have dissuaded many investigators from considering solvent-free catalytic asymmetric reactions. The potential environmental benefits and the economic incentive, however, have created significant demand for such processes.

In response to these challenges, an increasing number of research groups are developing asymmetric catalysts for use under solvent-free or highly concentrated reaction conditions. The results of these studies have been mixed. In some cases, catalysts that demonstrate excellent enantioselectivity and activity under standard solvent conditions exhibit lower selectivity in the absence of solvent. In contrast, other catalysts react with excellent levels of enantioselectivity and greatly increased activity, enabling significant reductions in catalyst loading under solvent-free conditions.

The potential advantages of asymmetric catalysis under solvent-free and highly concentrated reaction conditions have inspired this review. In turn, it is hoped that a comprehensive compilation of reports in this area will stimulate further investigations into solvent-free catalytic asymmetric reactions.

A significant body of research has been published concerning solvent-free organic synthesis and the subject has been reviewed.10,11,14,15,40 Solvent-free asymmetric catalysis, however, is a relatively new area and we are not aware of reviews devoted to this topic. This review will cover small molecule catalyzed enantioselective reactions under solvent-free or highly concentrated reaction conditions up to the end of 2006. Additionally, we will include reactions of enantioenriched substrates with enantioselective catalysts in which the diastereoselectivity is catalyst controlled (not substrate controlled). We define solvent-free reactions as those employing less than five equivalents of one reagent with respect to the substrate. The definition of highly concentrated reaction conditions used herein is those that utilize less than 5 equivalents of solvent with respect to the substrate.

Despite amazing advances in chemistry database coverage, technology, and search engines, there are no straightforward ways to search the literature for ‘highly concentrated catalytic asymmetric reactions’. Even reactions performed in the absence of solvent do not always contain the key words ‘solvent-free.’ The citations included herein come from extensive literature searches, scouring experimental sections and supporting information, and personal knowledge. Nonetheless, our apologies are extended to those who have made contributions in this area but whose work we missed.

/pdf/a-green-chemistry-approach-to-asymmetric-catalysis-solvent-zbtx2vex2w.pdf

A Green Chemistry Approach to Asymmetric Catalysis: Solvent-Free and Highly Concentrated Reactions

1. Intoduction 4348 2. Oxolane Macrodiolides 4348 2.1. Pamamycin 607 (1) 4348 2.1.1. Thomas Total Synthesis20 4349 2.1.2. Lee Total Synthesis28 4351 2.1.3. Metz Total Synthesis35 4353 2.1.4. Kang Total Synthesis41 4354 2.2. Amphidinolide X (2) 4356 2.2.1. Fürstner Total Synthesis59 4356 3. Oxane/Oxene Macrodiolides 4359 3.1. SCH 351448 (3) 4359 3.1.1. Lee Total Synthesis71 4359 3.2. Swinholide A (4) 4360 3.2.1. Paterson Total Synthesis82 4360 3.2.2. Nicolaou Total Synthesis83 4360 4. Cyclic Acetal Macrodiolides 4362 4.1. Cycloviracin B1 (5) 4362 4.1.1. Fürstner Total Synthesis96 4363 4.2. Glucolipsin A (6) 4366 4.2.1. Fürstner Total Synthesis117 4366 5. Cyclic Hemiketal Macrodiolides 4368 5.1. Boromycin (7) 4368 5.1.1. White Total Synthesis123 4368 5.2. Tartrolon B (8) 4369 5.2.1. Mulzer Total Synthesis130 4370 5.3. Debromoaplysiatoxin (9) and Aplysiatoxin (10) 4373 5.3.1. Kishi Total Synthesis142 4373 6. Conclusions 4375 7. Acknowledgments 4375 8. References 4375

/pdf/total-synthesis-of-oxacyclic-macrodiolide-natural-products-bq2vfw4hed.pdf

Total Synthesis of Oxacyclic Macrodiolide Natural Products

Chiral Brønsted Acid Catalyzed Enantioselective Aza-Diels–Alder Reaction of Brassard's Diene with Imines

Reactions of ketene acetals-14 The use of simple mixed vinylketene acetals in the annulation of quinones

Regiospecific syntheses of quinones using vinylketene acetals derived from unsaturated esters

Synthese des methoxy-1 bis-[trimethylsiloxy]-1,4 butadienes-1,2 (I). Par reaction de (I) avec des chloronaphtoquinones-1,4 synthese de methyl-2 quinizarine, islandicine, digitopurpone et erythroglaucine

New reagents for the regiospecific synthesis of naturally occurring quinizarins

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Jacques Savard

Author Tools

Chat about Author

Papers

Reactions of ketene acetals-14 The use of simple mixed vinylketene acetals in the annulation of quinones

Regiospecific syntheses of quinones using vinylketene acetals derived from unsaturated esters

New reagents for the regiospecific synthesis of naturally occurring quinizarins