title: Concise and highly stereoselective synthesis of the C20-C26 building block of halichondrins and Eribulin.
abstract: A concise, stereoselective, and scalable synthesis of the C20-C26 building block of halichondrins and Eribulin is reported. The synthesis relies on three key transformations: regiospecific Ru-catalyzed intramolecular hydrosilylation, highly stereoselective S(N)2' substitution, and selective conversion of a C-Si to C-I bond. It is carried out in a 5-pot/4-workup operation without chromatographic purification, except for filtration through a silica-gel plug, to give the C20-C26 building block (dr > 200:1; ee > 99%) in ca. 60% overall yield from epoxide 1.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
authors.forename: Mingde
authors.initials: M
authors.lastname: Shan
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kishi
mesh_terms: D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D005663:Furans / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis*; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism; D000095662:Polyether Polyketides
chemical_list: D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin