title: Simple access to highly functional bicyclic γ- and δ-lactams: origins of chirality transfer to contiguous tertiary/quaternary stereocenters assessed by DFT.
abstract: This paper describes the synthesis of both polysubstituted oxazolo-pyrrolidinones and -piperidinones by a domino process. The methodology is based on the reaction between hydroxyl halogenoamides and Michael acceptors, which leads efficiently to bicyclic lactams. The process is compatible with unsymmetrical electron-withdrawing groups on the Michael acceptor, which allows the formation of two contiguous and fully controlled tertiary and quaternary stereocenters. In the case of tetrasubstituted Michael acceptors, two adjacent quaternary stereocenters are formed in good yield. Starting from (R)-phenylglycinol derived amides results in the formation of enantioenriched bicyclic lactams in low to good yields and with high levels of stereoselectivity, thus greatly increasing the scope and interest of this strategy. The origins of chirality transfer and diastereoselectivity were studied by DFT calculations and have been attributed to a kinetic control in one of the last two steps of the reaction sequence. This selectivity is dependent upon both the substituents on the Michael acceptor and the sodium cation chelation.
authors.affiliation: Laboratoire de Chimie, URCOM, EA 3221 - FR CNRS 3038, Université du Havre, UFR Sciences et Techniques, 25 rue Philippe Lebon, 76058 Le Havre cedex (France), Fax: (+033) 2-32-74-43-91.
authors.forename: Ronan
authors.initials: R
authors.lastname: Le Goff
authors.forename: Arnaud
authors.initials: A
authors.lastname: Martel
authors.forename: Morgane
authors.initials: M
authors.lastname: Sanselme
authors.forename: Ata Martin
authors.initials: AM
authors.lastname: Lawson
authors.forename: Adam
authors.initials: A
authors.lastname: Daïch
authors.forename: Sébastien
authors.initials: S
authors.lastname: Comesse
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007769:Lactams; D010080:Oxazoles; D010880:Piperidines; D011760:Pyrrolidinones
keywords: DFT; bicyclic lactams; diastereoselectivity; domino reactions; quaternary stereocenter