title: Ruthenium-catalysed synthesis of fluorinated bicyclic amino esters through tandem carbene addition/cyclopropanation of enynes.
abstract: The reaction of fluorinated 1,6- and 1,7-enynes, containing the moiety N(PG)C(CF(3))(CO(2)R), with diazo compounds in the presence of [RuCl(cod)(Cp*)] (cod=cycloocta-1,5-diene, Cp*=C(5)Me(5) , PG=protecting group) as the catalyst precursor leads to the formation of fluorinated 3-azabicyclo[3.1.0]hexane-2-carboxylates and 4-azabicyclo-[4.1.0]heptane-3-carboxylates. This catalytic transformation was applied to various protecting groups and has proved to be a selective and a general synthetic tool to form constrained proline or homoproline derivatives in good yields. Z stereoselectivity of the created alkenyl group is obtained with N(2)CHSiMe(3), whereas N(2)CHCO(2)Et favours selectively the E configuration for the same double bond. The diastereoselectivity exo/endo depends on the size of the created ring. The X-ray structures of two products have been determined, showing the stereochemistry of the compounds. The reaction can be understood by initial [2+2] addition of the Ru=CHY bond, generated from diazoalkane, with the C≡CH bond of the enyne leading to a key bicyclic ruthenacyclobutane, which promotes the cyclopropanation, rather than metathesis. This selective formation of bicyclic [n.1.0] compounds results from the ruthenium-catalysed creation of three carbon-carbon bonds in a single step under mild conditions.
authors: Laboratoire Catalyse et Organométalliques, UMR 6226-Sciences Chimiques de Rennes, CNRS-Université de Rennes 1, Campus de Beaulieu, 35042 Rennes, France.
authors: Matthieu
authors: M
authors: Eckert
authors: Solenne
authors: S
authors: Moulin
authors: Florian
authors: F
authors: Monnier
authors: Igor D
authors: ID
authors: Titanyuk
authors: Sergey N
authors: SN
authors: Osipov
authors: Thierry
authors: T
authors: Roisnel
authors: Sylvie
authors: S
authors: Dérien
authors: Pierre H
authors: PH
authors: Dixneuf
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000588:Amines / Q000138:chemical synthesis; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003500:Cyclization; D055808:Drug Discovery / Q000379:methods*; D004952:Esters / Q000138:chemical synthesis*; D005461:Fluorine / Q000737:chemistry*; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D057786:Peptidomimetics / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D000588:Amines; D001643:Bridged Bicyclo Compounds; D004952:Esters; D009942:Organometallic Compounds; D057786:Peptidomimetics; C030011:carbene; D005461:Fluorine; D012428:Ruthenium; D011392:Proline; C010983:homoproline; D008697:Methane