Efficacious modification of the mitsunobu reaction for inversions of sterically hindered secondary alcohols
TL;DR: In this article, a modification of the Mitsunobu protocol for effecting stereochemical inversions of alcohols has been discovered in which use of p-nitrobenzoic acid as the nucleophilic partner results in significantly improved yields with relatively hindered substrates.
About: This article is published in Tetrahedron Letters.The article was published on 1991-06-24. It has received 320 citations till now. The article focuses on the topics: Mitsunobu reaction & Nucleophilic substitution.
Citations
More filters
TL;DR: This review concludes that Etherification without Cyclization and N-Alkylation should be considered as separate science, and the proposed treatment of Etherification with Cyclization as a separate science should be reconsidered.
Abstract: 10. Patented Literature 2616 10.1. Esterification 2616 10.2. Ether Formation 2619 10.2.1. Etherification without Cyclization 2619 10.2.2. Etherification with Cyclization 2624 10.3. N-Alkylation 2625 10.4. Other Reactions 2627 11. Summary and Outlook 2628 12. Note Added in Proof 2628 13. Abbreviations Used in This Review 2629 14. Acknowledgments 2629 15. Supporting Information Available 2630 16. References 2630
909 citations
TL;DR: Bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes.
Abstract: Exactly half a century has passed since the launch of the first documented research project (1965 Dendral) on computer-assisted organic synthesis. Many more programs were created in the 1970s and 1980s but the enthusiasm of these pioneering days had largely dissipated by the 2000s, and the challenge of teaching the computer how to plan organic syntheses earned itself the reputation of a "mission impossible". This is quite curious given that, in the meantime, computers have "learned" many other skills that had been considered exclusive domains of human intellect and creativity-for example, machines can nowadays play chess better than human world champions and they can compose classical music pleasant to the human ear. Although there have been no similar feats in organic synthesis, this Review argues that to concede defeat would be premature. Indeed, bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules (with full stereo- and regiochemistry) coded in appropriate formats, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes. The Review begins with an overview of some basic theoretical concepts essential for the big-data analysis of chemical syntheses. It progresses to the problem of optimizing pathways involving known reactions. It culminates with discussion of algorithms that allow for a completely de novo and fully automated design of syntheses leading to relatively complex targets, including those that have not been made before. Of course, there are still things to be improved, but computers are finally becoming relevant and helpful to the practice of organic-synthetic planning. Paraphrasing Churchill's famous words after the Allies' first major victory over the Axis forces in Africa, it is not the end, it is not even the beginning of the end, but it is the end of the beginning for the computer-assisted synthesis planning. The machine is here to stay.
403 citations
TL;DR: A review of progress in the MITSUNOBU this article reaction can be found in this article, with a focus on the MIT SUNOBU reaction and a review of the progress.
373 citations
327 citations
289 citations
References
More filters
165 citations
107 citations
82 citations
TL;DR: Nucleophilic substitution reactions of Hydroxysteroids using Triphenylphosphane/diethylazodicarboxylate in benzene was described in this article, where it was not possible to run this substitution process in the hitherto used solvent THF.
Abstract: Nucleophilic Substitution Reactions of Hydroxysteroids using Triphenylphosphane/diethylazodicarboxylate
Nucleophilic substitution reactions by means of the title reagent on various more or less hindered steroid alcohols with suitable nucleophils in benzene is described. It was not possible to run this substitution process in the hitherto used solvent THF. Cholestan-3α-ol (1) was transformed to the 3β-substituted products 3β-benzoyloxy-cholestane (1a) and 3β-azido-cholestane (1b). Testosterone (2) affords with the corresponding nucleophils after short heating in benzene the inverted 17α-substituted products 3a, 3b and 3c. Analogously the 17α-azido-derivative 5a arises from 17β-hydroxy-androst-3-on (4). In the presence of a ketogroup in the substrate a competitive reaction can occur as it is shown in the case of cholestan-3-on (6): the products are the en-hydrazo-dicarboxylate-steroids 7a and 7b. The sterically very hindered 11α-position in 11α-hydroxy-4-pregnen-3,20-dion (8) can be transformed also to the 11β-azide 9a. The substitution of a 6β-hydroxy group in androstane-3β, 6β, 17β-triol-3,17-diacetate (10) to the 6α-azide 11a affords the elimination product 12 as main component. Trans-diaxial vicinal diols such as cholestane-2β,3α-diol (13) give a mixture of the α- and β-oxiranes 14a and 14b.
57 citations