One-Step Synthesis of delta-Lactones Having Biological Activity by Remote Carbonylation

远程羰基化一步合成具有生物活性的δ-内酯

• 批准号: 06453137
• 负责人: RYU Ilhyong
• 金额: $ 0.58万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06453137/
• 关键词: delta-lactone; carbon monoxide; saturated alcohol; radical carbonylation; lead tetraacetate; remote functionalization; 1,5 hydrogen shift; alkoxy radical

In this work, a novel straightforward method for the synthesis of delta-lactones has been pursued. Taking advantage of the lead tetraacetate-induced oxidation of alcohols, a novel delta-lactone synthesis from saturated alcohols and CO was achieved. This remote carbonylation is quite general for primary and secondary alcohols whose delta-carbons are primary or secondary. In case of an alcohol having both primary and secondary delta-carbons, carbon monoxide is incorporated at the secondary carbon in a 24 : 1 ratio. The reaction sequence can be successfully applied to a one-step synthesis of a carpenter bee sex pheromone starting from commercially available, optically pure (R)-(-)-2-hexanol and carbon monoxide. On the other hand, attempted reaction of a 1,2-diol type substrate resulted in beta-fragmentation rather than carbonylation. This suggests that for an application of this remote carbonylation to the synthesis of mevalonolactone, beta-hydroxy group should be introduced after constructing the key delta-lactone skeleton.

在这项工作中，一个新的直接的方法合成的δ-内酯已被追求。利用四乙酸铅诱导的醇氧化反应，实现了饱和醇与CO反应合成δ-内酯的新方法。这种远程羰基化对于δ碳为伯或仲的伯醇和仲醇是相当普遍的。在具有伯和仲δ-碳的醇的情况下，一氧化碳以24：1的比例在仲碳处结合。该反应顺序可成功地应用于从市售的光学纯（R）-（-）-2-己醇和一氧化碳开始的木蜂性信息素的一步合成。另一方面，1，2-二醇型底物的尝试反应导致β-断裂而不是羰基化。这表明，如果将这种远程羰基化应用于甲羟戊酸内酯的合成，则应在构建关键的δ-内酯骨架后引入β-羟基。

项目成果

Ilhyong Ryu: "Tandem radical reactions of carbon monoxide, isonitriles, and other ragent equivalents of geminal radical acceptor/radical precursor" Chemical Reviews. 96. 177-194 (1996)

Ilhyong Ryu：“一氧化碳、异腈和其他成芽自由基受体/自由基前体的试剂等价物的串联自由基反应”化学评论。

Kiyoto Nagahara: "Rate constants for addition of a primary alkyl radical to carbon monoxide" Journal of Organic Chemistry. 60. 7384-7385 (1995)

Kiyoto Nagahara：“伯烷基自由基加成一氧化碳的速率常数”有机化学杂志。

Shinji Tsunoi: "Free-radical carbonylation using a Zn(Cu) induced reduction system" Synlett. 1249-1251 (1995)

Shinji Tsunoi：“使用 Zn(Cu) 诱导还原系统进行自由基羰基化”Synlett。

柳日馨: "A n+1 Strategy for Mecrocylkastion Based on free-Radical carbonylation" Synlett. 643-646 (1994)

Yanagi Hikaru：“基于自由基羰基化的 n+1 甲基化策略”Synlett 643-646 (1994)。

Shinji Tsunoi: "Carbonylation of cyclobutanols by way of oxidative ring cleavage with LTA" Synlett. 1009-1012 (1994)

Shinji Tsunoi：“通过 LTA 氧化环裂解对环丁醇进行羰基化”Synlett。