Nicholas reactions in the construction of cyclohepta[de]naphthalenes and cyclohepta[de]naphthalenones. The total synthesis of microstegiol.
The application of the Nicholas reaction chemistry of 2,7-dioxygenated naphthalenes in the synthesis of cyclohepta[de]napthalenes and in the synthesis of (±)-microstegiol (1) is presented. The substitution profile of Nicholas monosubstitution (predominantly C-1) and disubstitution reactions (predominantly 1,6-) on 2,7-dioxygenated napthalenes is reported. Application of a 1,8-dicondensation product and selected C-1 monocondensation products to the construction of cyclohepta[de]naphthalenes by way of ring closing metathesis and intramolecular Friedel-Crafts reactions, respectively, is described. Deprotection of the C-7 oxygen function to the corresponding naphthol allows tautomerization to cyclohepta[de]naphthalene-1-ones upon seven-membered-ring closure in most cases, and replacement of the C-2 oxygen function in the naphthalene by a methyl group ultimately allows the synthesis of (±)-microstegiol.
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, N9B 3P4, Canada.
Rafiq A
RA
Taj
James R
JR
Green
D002384:Catalysis; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013237:Stereoisomerism; D044024:Tetralones / Q000737:chemistry*
D009281:Naphthalenes; D044024:Tetralones; C555846:microstegiol