Academic literature on the topic 'Phosphonate(benzofuryl-2 o,o-dialkyl)'

Fusarisetin A 3 is an intriguing inhibitor of cell migration and invasion that is not itself cytotoxic. Ang Li of the Shanghai Institute of Organic Chemistry developed (J. Am. Chem. Soc. 2012, 134, 920) a total synthesis of (–)-fusarisetin A, demonstrating that the natural material had the absolute configuration opposite to that originally assigned. A key step in the synthesis was the highly diastereoselective cyclization of 1 to 2. The absolute configuration of 1 and so of synthetic 3 was derived from commercial citronellol, which is prepared on an industrial scale by asymmetric synthesis. To this end, the reagents 6 and 8 were required. The β-ketothio ester 6 was prepared from the Meldrum’s acid 4 and the phosphonate 8 was derived from methyl sorbate 7. The acetal of citronellal 9 was ozonized with reductive work-up to give the alcohol 10. Protection followed by hydrolysis gave the aldehyde 11, which was condensed with 8 to give the triene 12. Deprotection followed by oxidation delivered an aldehyde, which was condensed with 6 to give the Diels-Alder precursor 1. With BF3 • OEt2 catalysis, the Diels-Alder cycloaddition proceeded under mild conditions, –40oC for 40 min, leading to 2 as a single diastereomer. Comparable intramolecular Diels-Alder cyclizations with single carbonyl activation gave mixtures of diastereomers. The alcohol 13 was prepared by transesterification of 2 with trifluoroethanol. Activation with MsCl led directly to the kinetic O-alkylation product 14. Following the precedent of Trost (J. Am. Chem. Soc. 1980, 102, 2840), exposure to a Pd catalyst smoothly converted 14 into 15 as the desired diastereomer. Condensation of the ester 15 with the amine 16 gave the diene 17. Selective oxidation of the monosubstituted alkene under Wacker conditions gave the ketone, which was reduced selectively by the Luche protocol to the alcohol 18. Exposure of 18 to NaOCH3 initiated Dieckmann cyclization, leading to (–)-fusarisetin A 3.

Richard J. K. Taylor of the University of York has developed (Angew. Chem. Int. Ed. 2008, 47, 1935) the diasteroselective intramolecular Michael cyclization of phosphonates such as 2. Quenching of the cyclized product with paraformaldehyde delivered ( + )-Paeonilactone B 3. Roberto Fernández de la Pradilla of the CSIC, Madrid established (Tetrahedron Lett. 2008, 49, 4167) the diastereoselective intramolecular hetero Michael addition of alcohols to enantiomerically-pure acyclic sulfoxides such as 4 to give the allylic sulfoxide 5. Mislow-Evans rearrangement converted 5 into 6, the enantiomerically-pure core of Ethyl Deoxymonate B 7. The ellagitannins, represented by 10, are single atropisomers around the biphenyl linkage. David R. Spring of the University of Cambridge found (Organic Lett. 2008, 10, 2593) that the chiral constraint of the carbohydrate backbone of 9 directed the absolute sense of the oxidative coupling of the mixed cuprate derived from 9, leading to Sanguiin H-5 10 with high diastereomeric control. A key challenge in the synthesis of the solandelactones, exemplified by 14, is the stereocontrolled construction of the unsaturated eight-membered ring lactone. James D. White of Oregon State University found (J. Org. Chem. 2008, 73, 4139) an elegant solution to this problem, by exposure of the cyclic carbonate 11 to the Petasis reagent, to give 12. Subsequent Claisen rearrangement delivered the eight-membered ring lactone, at the same time installing the ring alkene of Solandelactone E 14. AD-mix usually proceeds with only modest enantiocontrol with terminal alkenes. None the less, Ian Paterson, also of the University of Cambridge, observed (Angew. Chem. Int. Ed. 2008, 47, 3016, Angew. Chem. Int. Ed. 2008, 47, 3021) that bis-dihydroxylation of the diene 17 proceeded to give, after acid-mediated cyclization, the bis-spiro ketal core 18 of Spirastrellolide A Methyl Ester 19 with high diastereocontrol.