title: Alpha-phosphono lactone analogues of farnesyl pyrophosphate: an asymmetric synthesis via ring-closing metathesis.
abstract: An alpha-phosphono lactone derivative of farnesol has been prepared, in both racemic and nonracemic forms, to provide a new type of farnesyl pyrophosphate analogue. Attempted preparation of the racemic alpha-phosphono lactone through rearrangement of a vinyl phosphate derived from the parent lactone resulted in both rearrangement and lactone ring opening, revealing that the farnesyl lactone was not stable to the excess of strong base required for the rearrangement. A procedure for C-P bond formation based on generation of the lactone enolate, reaction with a P(III) reagent, and oxidation was successful in providing the racemic alpha-phosphono lactone, in part, because only 1 equiv of strong base was required. The same strategy for phosphonate synthesis then was applied to the nonracemic farnesyl lactone, prepared through a sequence including allylation of farnesal with a nonracemic borane reagent, reaction of the product alcohol with acryloyl chloride, and formation of an unsaturated lactone through ring-closing metathesis. A similar strategy gave the corresponding racemic alpha-phosphono lactam through a six-step sequence from farnesal.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Du
authors.forename: David F
authors.initials: DF
authors.lastname: Wiemer
mesh_terms: D004986:Ether; D005204:Farnesol; D005663:Furans; D007202:Indicators and Reagents; D007536:Isomerism; D007783:Lactones; D008968:Molecular Conformation; D063065:Organophosphonates; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis*; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship
chemical_list: D005663:Furans; D007202:Indicators and Reagents; D007783:Lactones; D063065:Organophosphonates; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D004986:Ether; C018674:tetrahydrofuran; D005204:Farnesol; C004808:farnesyl pyrophosphate