A Diels-Alder-Based Total Synthesis of (-)-Kainic Acid
One of the earliest and most important examples of the Diels–Alder reaction in total synthesis was ..
The Diels-Alder reaction in total synthesis - Scripps VIVO
In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.
The transannular Diels-Alder (TADA) reaction was applied to the synthesis of the CDE ring system of nakiterpiosin (1). TADA product 28 is a key intermediate toward the total synthesis of 1.
Total synthesis confirms laetirobin as a formal Diels-Alder adduct ..
Similarly, E. J. Corey’s 1969 prostaglandin F2α synthesis is a retrosynthetic masterpiece which every aspiring organic chemist needs to study. Only a five-membered ring exists in the product, yet Corey had the vision to see that carbon atoms 6–11 (prostaglandin numbering) could form the six carbon atoms of the cyclohexene Diels-Alder product. Diels-Alder reaction of the cyclopentadiene derivative and a ketene equivalent yielded a bridged bicyclic product. Conversion to the ketone, followed by Baeyer-Villiger oxidation, gave the bridged bicyclic lactone. A few steps later, the bridged lactone had been converted into the fused lactone that we now call the Corey lactone, in homage to the organic chemistry giant.
The Diels-Alder reaction is not merely restricted to the synthetic lab; nature also enjoys a good Diels-Alder reaction from time to time. And who can forget the endiandric acids from the pericyclic chemistry unit in their graduate organic chemistry class? The unsaturated acid with seven double bonds is a naturally occurring polyene. Once formed, the molecule spontaneously undertakes three separate pericyclic reactions to form an incredible amount of molecular complexity as a single pair of enantiomers. Initial 8π conrotatory electrocyclization yields a cyclooctatriene. A 6π disrotatory electrocyclization forms a fused bicycle. Depending on which diastereomer is formed in this electrocyclization, the bicycle is in perfect orientation to perform one of two Diels-Alder reactions to form either endiandric acid B or endiandric acid C. All this occurs nonenzymatically in nature.
17/05/2002 · Abstract
First reported in 1928 by Otto Diels and his graduate student Kurt Alder, the chemists at once saw the importance of their work and wanted the exclusive rights to utilize their reaction. They write in their 1928 paper: “The possibility of synthesis of complex compounds related to or identical with natural products such as terpenes, sesquiterpenes, perhaps even alkaloids, has been moved to the near prospect. ... We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems” ( DOI: ). Fortunately for us, this exclusivity no longer applies.
Peter Vollhardt’s 1980 synthesis of estrone showcases a beautiful example of an intramolecular Diels-Alder reaction. Under thermal conditions, the benzocyclobutene undergoes a 4π electrocyclic ring opening to give an intermediate -quinodimethane—a perfectly situated and highly reactive diene. The pendant dienophile readily reacts with this diene to close the last two rings of the cholesterol framework.
Diels–Alder reaction - Wikipedia
Recent applications of the hetero Diels–Alder reaction …
22/10/2017 · The Diels-Alder (DA) reaction has been applied to the total synthesis of natural products
Salt Effects on Diels-Alder Reaction ..
05/06/2014 · The Diels-Alder (D-A) reaction is one of the most powerful reactions in organic synthesis
The Diels-Alder reaction: an update - SciELO
21/05/2015 · Total synthesis of (+)-gelsemine via an organocatalytic Diels-Alder approach
08/01/2001 · The Diels-Alder Reaction: ..
The total synthesis of (+)-gelsemine is completed in a highly enantioselective manner from readily accessible starting materials. This synthesis features an enantioselective organocatalytic Diels–Alder reaction, a formidable intramolecular aldol cyclization and a challenging intramolecular SN2 displacement. The combination of all these features resulted in exceptional overall synthetic efficiency: the enantio excess is over 99%, and the total yield is about 5%.
The Evans group has used the IMDA reaction both in total synthesis ..
Gratifyingly, the yield of the desired endo product was 47% after reduction of the aldehyde carbonyl group with sodium borohydride, and its enantio excess was determined using chiral high-performance liquid chromatography (HPLC) to be 99.7%, while the exo product was not detected. It was surprising that intermediate 3a was also produced in 30% yield. Since intermediate 3 was stable under the reaction conditions, 3a may be a result of the double-bond isomerization of the enal during the catalytic process, and the rate of the double-bond isomerization was comparable to that of the Diels–Alder cycloaddition (). Fortunately, 3a was converted into 3 with DBU (1,8-diazabicycloundec-7-ene) in refluxing toluene in 97% yield, which brought the total yield of the Diels–Alder cycloaddition to 76%. Intermediate 3 was then further selectively reduced to the hemiacetal 4 using Dibal-H at −78°C in 94% yield. The subsequent Wittig reaction furnished the methyl enol ether, which was directly treated with trimethyl orthoformate and a catalytic amount of p-toluenesulfonic acid to provide intermediate 5 and 5a (13:1) as a separable mixture in 93% combined yield. Although 5a may be used as well, it was converted into 5 by treating it with pTSOH in methylene chloride (DCM) and only 5 was used for the next step. After a conventional ozonolysis of intermediate 5 in DCM, the resulting dicarbonyl intermediate was directly treated with sodium methoxide in methanol at 0°C due to the fact that the dicarbonyl intermediate was unstable for storage. To our delight, the aldol reaction afforded the desired product 6 in 60% combined yield. However, the reaction of 6 with the methanesulfonyl chloride resulted in a complex mixture. Thus, the hydroxyketone intermediate 6 was reduced to diol 7 with sodium borohydride (97%) and the formation of disulfonate 8 with methanesulfonyl chloride was quantitative, the structure of which was confirmed through X-ray crystallographic analysis (). Treatment of intermediate 8 with DBU (1,8-diazabicycloundec-7-ene) in refluxing toluene led to the formation of alkene 9 (85%) and reduction of the Cbz protective group to methyl with lithium aluminium hydride in THF afforded 10 in 86% yield. Subsequent acid hydrolysis of the acetal with aqueous hydrochloric acid in THF provided hemiacetal 11 (96%).
Diels Alder Reaction | Organic Chemistry | Chemical …
How to cite this article: Chen, X. et al. Total synthesis of (+)-gelsemine via an organocatalytic Diels–Alder approach. Nat. Commun. 6:7204 doi: 10.1038/ncomms8204 (2014).
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