The vinylogous Mukaiyama aldol reaction (VMAR) allows efficient access to larger segments for complex natural product synthesis, primarily polyketides, through the construction of vicinal hydroxyl and methyl groups as well as di and tri-substituted double bonds in one single operation. In this review, we will highlight stereoselective protocols that have been used in natural product synthesis and cluster them into the four groups that can be obtained from different silyl ketene acetals or enol ethers. At the beginning, an overview on different stereoselective VMARs is presented; disregarding their applications in total syntheses.
The Kobayashi aldol reaction has become a prominent transformation in polyketide syntheses. This methodology takes advantage of the directing effects of the Evans auxiliary and allows the stereoselective incorporation of a four carbon segment with two additional methyl branches establishing an anti-relationship between the two newly formed chiral centers. So far this transformation was restricted to anti-aldol products. We present here a modified protocol that provides the corresponding aldol product with high syn-selectivity.
The impressive biological profile of secondary metabolites isolated from strains of Sorangium cellulosum prompted us to initiate synthetic studies on kulkenon, also isolated from Sorangium cellulosum. The synthesis features a syn-selective vinylogous Kobayashi aldol reaction, recently developed by us, and a ring-closing intramolecular Heck reaction as the pivotal transformations. Comparison of the NMR spectra of the authentic and synthetic material revealed that the proposed configuration had to be revised. A combination of molecular modeling and NOE experiments was used to propose the revised configuration, which was confirmed by a new synthesis.
The reaction of (1E,3Z) ketene N,O‐acetal (I) with various aldehydes proceeds with complete syn‐selectivity to afford products with aliphatic, aromatic and unsaturated substituents.
Structure Elucidation and Total Synthesis of Kulkenon. -A combination of molecular modeling and NOE experiments is used to establish the revised configuration of (I) which is confirmed by its synthesis having a syn-selective vinylogous Kobayashi aldol reaction and an intramolecular Heck reaction as pivotal transformations. -(SYMKENBERG, G.; KALESSE*, M.; Angew. Chem., Int. Ed. 53 (2014) 7, 1795-1798, http://dx.
Die beeindruckenden biologischen Aktivitäten von Sekundärmetaboliten, die von Myxobakterien der Stämme von Sorangium cellulosum isoliert wurden, haben uns veranlasst, das ebenfalls aus Sorangium cellulosum isolierte Kulkenon zu synthetisieren. In unserer Synthese waren die von uns entwickelte syn-selektive vinyloge Kobayashi-Aldolreaktion und eine Ringschluss-Heck-Kupplung die entscheidenden Transformationen. Allerdings mussten wir nach der Synthese beim Vergleich der Spektren von authentischer und synthetischer Probe feststellen, dass es sich nicht um identische Verbindungen handelte. Mithilfe einer Kombination aus computergestützten Modellierungen und NOE-Experimenten gelang es uns schließlich, einen überarbeiteten Strukturvorschlag für Kulkenon zu machen und mit einer erneuten Synthese zu bestätigen. Abbildung 2. Konformationen und Konfigurationen der C14/C15-Untereinheit (20) und der C24/C25-Untereinheit (21) von Kulkenon; Kopplungskonstanten 3 J H,H und 2,3 J H,C [Hz] in Klammern. Abbildung 3. Signifikante NOESY-Korrelationen für authentisches Kulkenon und Verbindung 2.Abbildung 4. Die C18-C24-Bereich von authentischem Kulkenon und Verbindung 2. Schema 5. Revidierte Synthese von Kulkenon. a) 6, TiCl 4 , CH 2 Cl 2 , À78 8C, 82 %, > 20:1 d.r.; b) 3 HF·NEt 3 , MeCN, 40 8C, 25 % zwei Stufen. DMF = Dimethylformamid.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.