Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions

• Published in: Organic & biomolecular chemistry 2006-01, Vol.4 (22), p.4193-4205
• Main Authors: Booker, James E M, Boto, Alicia, Churchill, Gwydion H, Green, Clive P, Ling, Matthew, Meek, Graham, Prabhakaran, Jaya, Sinclair, David, Blake, Alexander J, Pattenden, Gerald
• Format: Article
• Language: English
• Subjects: Crystallography, X-Ray; Cyclization; Heterocyclic Compounds, 4 or More Rings - chemical synthesis; Heterocyclic Compounds, 4 or More Rings - chemistry; Models, Molecular; Molecular Structure; Oxazoles - chemical synthesis; Oxazoles - chemistry; Stereoisomerism
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b609604b

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).