Abstract
We recently reported the intramolecular substitution of an allyl alcohol by a heteroatom using a palladium (II) catalyst without activation of the allylic alcohol. We report here highly stereoselective intramolecular cyclization of dihydroxyketone using palladium (II) catalyst via unstable hemiacetal, in which cyclization occurs without activation of the allylic alcohol to afford spiroketal structures.1) Cascade type cyclization via hemiacetal inermediate using Pd(II) catalyst. Treatment of 1 , 11 -tetrahydropyranyloxyun dec-9-en-5-one derivatives 1 and 3 with 10 mol% palladium (II) bis(benzonitrile) dichloride in THE afforded 6,6-membered spiroketal in good yield and good stereoselecitivity.2) Synthetic studies of spirofungin A and B Spirofungin A is a polyketide-type antibiotic isolated from Streptomyces violaceusniger Tu 4113. Now we show a synthesis of spirofungin A using the cascade cyclization of ketone 12 as a key reaction. Retrosynthetic fragmentation of spirofungin A affords three segments. Firstly, we synthesized the aldehyde segment 9 from 1,3-propanediol and the sulfone segment 10 was prepared from methyl (R)-3-hydroxy-2-methylpropionate. The cyclization precursor 12 was prepared by using Julia coupling reaction between the aldehyde segment 9 and the sulfone segment 10 (Scheme 2). The key cascade cyclization of 12 was achieved successfully by treatment with PdCl_2(PhCN)_2 and Me0H at room temperature to give the spiroketal 7 and 13 (Scheme 4). Studies on the connection of the segment B and the segment A and C to construct the whole structure of spirofungin A are now underway.
