19 Novel Stereoselective Synthesis of the Spiroketal Structure Using Pd(II)-catalyst and Application to the Synthesis of Spirofungin B
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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 1,11-dihydroxyundece-9-en-5-one derivatives using palladium (II) catalyst via unstable hemiacetal intermediates, in which cyclization occurs without activation of the allylic alcohol to afford spiroketal structures. Stereoselective Tandem Cyclization using Pd (II)-catalyst Treatment of 1,11-dihydroxy-7-phenylundec-9-en-5-one (11) with 10mol% palladium (II) bis(acetonitrile) dichloride in THF afforded 6,6-membered spiroketal 12 in 62% yield as a single stereoisomer. To demonstrate the synthetic potential of this method, we have synthesized a natural product having spiroketal moiety. Synthetic study of Spirofungin B using Pd (II) catalyst Spirofungin B is a polypropionate-type antibiotic isolated from Streptomyces violaceusniger Tu 4113. Now we show a synthesis of spirofungin B using the tandem cyclization of dihydroxy ketone 27 as a key reaction. Retrosynthetic fragmentation of spirofungin B affords three segments. Firstly, we synthesized the key intermediate 17 from (Z)-2-butene-1,4-diol (Scheme 6). The aldehyde segment 19 and sulfone segment 24 was prepared from 17, respectively (Scheme 7,8). The cyclization precursor 27 was prepared by using Julia coupling reaction between aldehyde segment 19 and sulfone segment 24 (Scheme 9). The key tandem cyclization of 27 was achieved successfully by treatment with PdCl_2(PhCN)_2 at room temperature to give segment B (Scheme 10). Segment C was synthesized from alcohol ent-17 by Takai reaction (Scheme 11). Finally, the segment B was introduced to dibromoolefin 32, and 32 was coupled with the segment C by Suzuki-Miyaura coupling to afford the desired(Z,E)-diene 33 (Scheme 12). Studies on the connection of 33 and the segment A to construct the whole structure of spirofungin B are now underway.
