title: Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions.
abstract: In model studies towards the quaternary centre at the heart of diazonamide A (early structure 2; revised structure 1), cyclisations of the alkene-substituted iodoaryls 4, 13, 18 and 23, under Heck reaction conditions, were shown to lead to the corresponding benzodihydrofuran 5, benzofuranone 14 and the oxindoles 19 and 24 respectively, in 50-80% yield. Further manipulation of the benzodihydrofuran 5 then led to the intermediates 30, 33 and 39, which make up parts of the oxazole-indole heterocyclic core in diazonamide A. Attempts to perform a corresponding 13-exo-trig Heck cyclisation from the precursor 46a, prepared from 44 and 45, leading to 47 were not successful. A similar outcome was obtained during attempts to effect Heck cyclisations from the ester 57 and the related ether 59. Treatment of the chromene-substituted iodoaryl 62 with Pd(OAc)2, PPh3 and Ag2CO3 led to the spirocycle 64 as a crystalline solid. X-Ray crystal structure analysis established that the quaternary centre in 64 had the same configuration as that present in diazonamide A (1).
authors.affiliation: School of Chemistry, The University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: James E M
authors.initials: JE
authors.lastname: Booker
authors.forename: Alicia
authors.initials: A
authors.lastname: Boto
authors.forename: Gwydion H
authors.initials: GH
authors.lastname: Churchill
authors.forename: Clive P
authors.initials: CP
authors.lastname: Green
authors.forename: Matthew
authors.initials: M
authors.lastname: Ling
authors.forename: Graham
authors.initials: G
authors.lastname: Meek
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: David
authors.initials: D
authors.lastname: Sinclair
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blake
authors.forename: Gerald
authors.initials: G
authors.lastname: Pattenden
mesh_terms: D018360:Crystallography, X-Ray; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408862:diazonamide A