Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions.
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).
Booker
James E M
JE
School of Chemistry, The University of Nottingham, Nottingham, NG7 2RD, UK.
Boto
Alicia
A
Churchill
Gwydion H
GH
Green
Clive P
CP
Ling
Matthew
M
Meek
Graham
G
Prabhakaran
Jaya
J
Sinclair
David
D
Blake
Alexander J
AJ
Pattenden
Gerald
G
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
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408862:diazonamide A