title: Cyclic beta-amino acid derivatives: synthesis via lithium amide promoted tandem asymmetric conjugate addition-cyclisation reactions.
abstract: The product distribution upon conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide to dimethyl-(E,E)-nona-2,7-dienedioate can be controlled to give either the cyclic 1,2-anti-1,6-anti-beta-amino ester (derived from conjugate addition and intramolecular enolate cyclisation) or the acyclic bis-beta-amino ester derivative (derived from double conjugate addition) in high de. The introduction of a protected nitrogen functionality into the diester skeleton facilitates, after conjugate addition and intramolecular enolate cyclisation, the asymmetric construction of piperidines in high de; variation in the N-protecting group indicates that the highest stereoselectivity is observed with alpha-branched N-substituents. Tandem conjugate addition-aldol reactions can also be achieved stereoselectively, with lithium amide conjugate addition to epsilon- and zeta-oxo-alpha,beta-unsaturated esters giving the corresponding five and six membered cyclic beta-amino esters in high de. N-deprotection by hydrogenolysis of the products arising from these reactions furnishes a range of polyfunctionalised transpentacin and transhexacin derivatives in high de and ee.
authors.affiliation: Department of Organic Chemistry, University of Oxford, Chemical Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: David
authors.initials: D
authors.lastname: Díez
authors.forename: Sara H
authors.initials: SH
authors.lastname: Dominguez
authors.forename: Narciso M
authors.initials: NM
authors.lastname: Garrido
authors.forename: Dennis
authors.initials: D
authors.lastname: Kruchinin
authors.forename: Paul D
authors.initials: PD
authors.lastname: Price
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
mesh_terms: D000577:Amides / Q000737:chemistry*; D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008094:Lithium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009904:Optical Rotation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared
chemical_list: D000577:Amides; D000598:Amino Acids, Cyclic; D010880:Piperidines; D008094:Lithium