A titanium naphtholate approach for the synthesis of analogues of griseusin A

The synthesis of analogues of the spiroketal-containing pyranonaphthoquinon e antibiotic griseusin A 1 is described. The key disconnection focused on h ydroxyalkylation of naphthol 21 with aldehyde 12. Aldehyde 12 was prepared from oxazolidinone 5 and (R)-aldehyde 6. Aldol condensation of oxazolidinon e 5 with aldehyde 6 using tin(II) triflate and tetramethylethylenediamine a fforded adduct 8 with the required 2',3'-anti 3',5'-syn stereochemistry as the major product. Aldol adduct 8 was then converted into aldehyde 12. The titanium naphtholate generated from naphthol 21 using (TiCl3OPr)-Pr-i then afforded alcohol 26 upon addition of aldehyde 12. Oxidation of alcohol 26 a fforded ketone 29 which underwent acetylation to acetate 31. Conversion of naphthol acetate 31 into naphthoquinone 33 followed by addition of 2-(trime thylsilyloxy)furan effected furofuran annulation to a 1 : 1 inseparable mix ture of adducts 34. Ceric ammonium nitrate oxidative rearrangement of this mixture of adducts produced lactol 35 which underwent cyclization to a 3.2 : 1 mixture of spiroketals 36a and 36b wherein epimerization at C-3' had oc curred.