title: Catalytic Z-selective olefin cross-metathesis for natural product synthesis.
abstract: Alkenes are found in many biologically active molecules, and there are a large number of chemical transformations in which alkenes act as the reactants or products (or both) of the reaction. Many alkenes exist as either the E or the higher-energy Z stereoisomer. Catalytic procedures for the stereoselective formation of alkenes are valuable, yet methods enabling the synthesis of 1,2-disubstituted Z alkenes are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and of allylic amides, used until now only in E-selective processes. The corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. These transformations, promoted by catalysts that contain the highly abundant and inexpensive metal molybdenum, are amenable to gram-scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. The utility of this method is demonstrated by its use in syntheses of an anti-oxidant plasmalogen phospholipid, found in electrically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant KRN7000.
authors: Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
authors: Simon J
authors: SJ
authors: Meek
authors: Robert V
authors: RV
authors: O'Brien
authors: Josep
authors: J
authors: Llaveria
authors: Richard R
authors: RR
authors: Schrock
authors: Amir H
authors: AH
authors: Hoveyda
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D000975:Antioxidants / Q000378:metabolism; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D004987:Ethers / Q000737:chemistry; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry; D010955:Plasmalogens / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000276:Adjuvants, Immunologic; D000475:Alkenes; D000577:Amides; D000975:Antioxidants; D001688:Biological Products; D004987:Ethers; D005699:Galactosylceramides; D010955:Plasmalogens; D008982:Molybdenum; C103873:KRN 7000