The School of Chemistry, The University of Manchester, Manchester, M13 9PL, UK.
Org Biomol Chem. 2012 Sep 14;10(34):6995-7014. doi: 10.1039/c2ob25992c. Epub 2012 Jul 25.
The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to complete diastereoselective syntheses of (±)-patulolide C 1 and (±)-epipatulolide C 40. (5Z)-3,7-syn-7-(2-Trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was prepared from the tin(iv) chloride promoted reaction of 4-(2-trimethylsilylethoxy)methoxypent-2-enyl(tributyl)stannane 16 with acrolein (1,5-syn : 1,5-anti = 96 : 4). An Ireland-Claisen rearrangement of the corresponding benzoyloxyacetate 21 with in situ esterification of the resulting acid using trimethylsilyldiazomethane gave methyl (4E,7Z)-2,9-anti-2-benzyloxy-9-(2-trimethylsilylethoxy)methoxydeca-4,7-dienoate 22 together with 10-15% of its 2,9-syn-epimer 26, the 2,9-syn- : 2,9-anti-ratio depending on the conditions used. An 88 : 12 mixture of esters was taken through to the tert-butyldiphenylsilyl ether 38 of (±)-patulolide C 1 together with 6% of its epimer 39, by reduction, a Wittig homologation and deprotection/macrocyclisation. Following separation of the epimeric silyl ethers, deprotection of the major epimer 38 gave (±)-patulolide C 1. The success of 2,3-Wittig rearrangements of allyl ethers prepared from (5Z)-3,7-syn-7-(2-trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was dependent on the substituents on the allyl ether. Best results were obtained using the pentadienyl ether 56 and the cinnamyl ether 49 that rearranged with >90 : 10 stereoselectivity in favour of (1E,5E,8Z)-3,10-syn-1-phenyl-10-(2-trimethylsilylethoxy)methoxyundeca-1,5,8-trien-3-ol 50. This product was taken through to the separable silyl ethers 38 and 39, ratio 7 : 93 by regioselective epoxidation and alkene reduction using diimide, followed by deoxygenation, ozonolysis, a Wittig homologation and selective deprotection/macrocyclisation. Deprotection of the major epimer 39 gave (±)-epipatulolide C 40.
三溴化锡促进的 7-羟基-7-苯基庚-2-烯基（三丁基）锡烷 11 与苯甲醛的反应得到了非对映异构的 1,8-二苯基辛-3-烯-1,8-二醇 12 的混合物，因此开发了间接方法用于脂肪族 1,8-立体控制，以完成（±）-patulolide C1 和（±）-epipatulolide C40 的非对映选择性全合成。（5Z）-3,7-syn-7-（2-三甲基硅基乙氧基）甲氧基辛-1,5-二烯-3-醇 17 是由锡（IV）氯化物促进的 4-（2-三甲基硅基乙氧基）甲氧基戊-2-烯基（三丁基）锡烷 16 与丙烯醛（1,5-syn：1,5-anti = 96：4）反应得到的。相应的苯甲酰氧基乙酸酯 21 的爱尔兰-克莱森重排，用三甲基硅基重氮甲烷原位酯化生成的酸，得到甲基（4E，7Z）-2,9-anti-2-苄氧基-9-（2-三甲基硅基乙氧基）甲氧基癸-4,7-二烯酸酯 22，同时还得到 10-15%的 2,9-syn-异构体 26，2,9-syn-：2,9-anti-的比例取决于使用的条件。通过还原、Wittig 同系化和脱保护/大环化，将 88：12 的酯混合物转化为（±）-patulolide C1 的叔丁基二苯基硅醚 38，同时还有 6%的其差向异构体 39。分离差向异构体的硅醚后，对主要差向异构体 38 进行脱保护，得到（±）-patulolide C1。（5Z）-3,7-syn-7-（2-三甲基硅基乙氧基）甲氧基辛-1,5-二烯-3-醇 17 制备的烯丙基醚的 2,3-Wittig 重排的成功取决于烯丙基醚上的取代基。使用戊二烯基醚 56 和肉桂基醚 49 得到最好的结果，它们的重排具有 >90：10 的立体选择性，有利于（1E，5E，8Z）-3,10-syn-1-苯基-10-（2-三甲基硅基乙氧基）甲氧基十一-1,5,8-三烯-3-醇 50。该产物通过区域选择性环氧化和使用二亚胺进行烯烃还原，得到可分离的硅醚 38 和 39，比例为 7：93，然后进行脱氧、臭氧分解、Wittig 同系化和选择性脱保护/大环化。对主要差向异构体 39 进行脱保护，得到（±）-epipatulolide C40。
