A [4 + 4] 2-pyridone approach to taxol. 3. Stereocontrol during elaboration of the cyclooctane.
A [4 + 4] 2-pyridone approach to taxol. 3. Stereocontrol during elaboration of the cyclooctane.
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DOI：
10.1021/jo005532c
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发表时间：
2000-09
期刊：
影响因子：
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通讯作者：
Y. G. Lee;K. Mcgee;J. Chen;D. Rucando;S. Sieburth
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文献类型：
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作者：
Y. G. Lee;K. Mcgee;J. Chen;D. Rucando;S. Sieburth
通过四碳系链连接的2-吡啶酮分子内光环加成反应（6-[4-（1,2-二氢-1-甲基-2-氧-3-吡啶基）-4-[[（1,1-二甲基乙基）++ +二甲基硅基]氧]丁基]-4-甲氧基-1,3-二甲基-2(1H)-吡啶酮）得到一个具有四个新的立体中心的四环产物。这个[4 + 4]反应的非对映选择性完全由系链的一个立体碳控制。用四氧化锇处理光产物，烯烃转化为二醇，烯醇醚转化为α -羟基酮，立体控制由附近的内酰胺决定，内酰胺阻断每个烯烃的一个面。烯丙基溴化镁加成到酮上也会产生一个单一的非对映体，但出乎意料的是，这个产物是由于亲核试剂接近酮的最受阻面而产生的。在模型系统中对该反应的研究发现，烯丙基亲核试剂是独特的，非烯丙基试剂沿着预期的、最小阻碍的路径接近。这种不同的加成可能是烯丙基亲核试剂与附近的酰胺配位的结果。因此，酰胺既可以作为空间屏蔽物，也可以作为导向基团。光环加成、顺式羟基化和亲核加成三个步骤构建了环辛烷的季碳和紫杉醇八元环上五个立体中心中的四个。
Intramolecular photocycloaddition of 2-pyridones connected through a four-carbon tether (6-[4-(1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-4-[[(1,1-dimethylethyl)++ +dimethylsilyl]oxy]butyl]-4-methoxy-1,3-dimethyl-2(1H)-pyridinone) yields a single tetracyclic product with four new stereogenic centers. The diastereoselectivity of this [4 + 4] reaction is fully controlled by a stereogenic carbon of the tether. Treatment of the photoproduct with osmium tetraoxide transforms the alkene to a diol and the enol ether to an alpha-hydroxy ketone, with stereocontrol dictated by nearby lactams that block one face of each alkene. Allylmagnesium bromide addition to the ketone also yields a single diastereomer, but unexpectedly this product results from approach of the nucleophile to the most-hindered face of the ketone. Study of this reaction in a model system has found the allylic nucleophile to be unique, with nonallylic reagents approaching along the expected, least-hindered path. This contrasteric addition likely results from coordination of the allylic nucleophile to the nearby amide. The amide can therefore act either as a steric shield or as a directing group. The three steps of photocycloaddition, cis-hydroxylation, and nucleophilic addition constructs both quaternary carbons of the cyclooctane and four of the five stereogenic centers found in the eight-membered ring of Taxol.