Oxidative cyclization based on reversing the polarity of enol ethers and ketene dithioacetals. Construction of a tetrahydrofuran ring and application to the synthesis of (+)-nemorensic acid
Oxidative cyclization based on reversing the polarity of enol ethers and ketene dithioacetals. Construction of a tetrahydrofuran ring and application to the synthesis of (+)-nemorensic acid
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DOI：
10.1021/ja026739l
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发表时间：
2002-08-28
影响因子：
15
通讯作者：
Moeller, KD
中科院分区：
文献类型：
--
作者：
Liu, B;Duan, SQ;Moeller, KD
已经检验了氧化环化反应在构建四氢呋喃环中的效用。在这些实验中，发现醇亲核试剂是烯醇醚和烯酮二硫缩醛基团产生的自由基阳离子中间体的有效捕获剂。醇捕获基团的反应性似乎位于烯醇醚和烯丙基硅烷捕获基团的反应性之间。发现源自烯醇醚氧化的环化反应的立体化学结果受立体电子因素控制。这些环化反应的实用性通过用于合成芳樟醇氧化物和罗通地辛的关键四氢呋喃结构单元的合成来说明。由烯酮二硫缩醛的氧化引发的环化反应导致更高水平的立体选择性。这些反应的立体化学结果显示是由涉及较大乙烯酮缩醛基团的空间因素引起的。通过完成(+)-海莫酸的不对称合成，证明了利用乙烯酮二硫缩醛衍生的自由基阳离子进行环化的合成效用。最后，该反应被证明与酰胺亲核试剂的使用和内酯产物的直接形成相容。
The utility of oxidative cyclization reactions for the construction of tetrahydrofuran rings has been examined. In these experiments, alcohol nucleophiles were found to be effective traps for radical cation intermediates generated from both enol ether and ketene dithioacetal groups. The reactivity of the alcohol trapping group appeared to lie between that of an enol ether and an allylsilane trapping group. The stereochemical outcome of cyclization reactions originating from the oxidation of an enol ether was found to be controlled by stereoelectronic factors. The utility of these cyclization reactions was illustrated with the synthesis of a key tetrahydrofuran building block for the synthesis of linalool oxide and rotundisine. Cyclization reactions triggered by the oxidation of a ketene dithioacetal led to far greater levels of stereoselectivity. The stereochemical outcome of these reactions was shown to arise from steric factors involving the larger ketene acetal group. The synthetic utility of cyclizations utilizing ketene dithioacetal derived radical cations was demonstrated by completing an asymmetric synthesis of (+)-nemorensic acid. Finally, the reactions were shown to be compatible with the use of an amide nucleophile and the direct formation of a lactone product.