Asymmetric synthesis of oxygen heterocycles via Pd-catalyzed dynamic kinetic asymmetric transformations: Application to nucleosides
Asymmetric synthesis of oxygen heterocycles via Pd-catalyzed dynamic kinetic asymmetric transformations: Application to nucleosides
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DOI：
10.1002/chem.200304949
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发表时间：
2003-09-22
影响因子：
4.3
通讯作者：
Kuhn, O
中科院分区：
文献类型：
--
作者：
Trost, BM;Brown, BS;Kuhn, O
外消旋丁二烯和异戊二烯单环氧化物在手性钯催化剂和硼助催化剂存在下与不饱和醇反应，分别生成3-烷氧基-4-羟基-1-丁烯和3-烷氧基-4-羟基-3-甲基-1-丁烯，在动态动力学不对称转化中具有优异的区域选择性和对映体选择性，由此起始环氧化物的两种对映体提供相同的对映体产品。对于 2-苯基丁二烯单环氧化物（很容易从苯甲酰氯和乙烯基溴化镁获得），反应通过动力学拆分进行。提出了一个使结果合理化的模型。双烯烃产品是Ru催化闭环复分解反应的理想底物。通过这种方式，五元、六元和七元氧杂环很容易获得对映体纯。这种非常简单的两步过程的价值通过使用五元环杂环形成非天然和不寻常的核苷来证明，这些核苷无法通过其他方式轻松获得。该序列涉及最初的 2,5-二氢呋喃经 Ru 催化异构化为 2,3-二氢呋喃，然后通过硒促进嘧啶或嘌呤碱基的加成。该策略的一个优点是可以轻松获得任一对映体系列，这两种对映体系列都具有重要的生物学应用。
Racemic butadiene and isoprene monoepoxide react with unsaturated alcohols in the presence of a chiral palladium catalyst and a boron co-catalyst to give 3-alkoxy-4-hydroxy-1-butene and 3-alkoxy-4-hydroxy-3-methyl-1-butene, respectively, with excellent regio- and enantioselectivity in a dynamic kinetic asymmetric transformation whereby both enantiomers of the starting epoxides provide the same enantiomeric product. In the case of 2-phenylbutadiene monoepoxide, easily available from phenacyl chloride and vinylmagnesium bromide, the reaction proceeds by kinetic resolution. A model to rationalize the result is presented. The bis-olefin products are ideal substrates for the Ru catalyzed ring closing metathesis. In this way, five-, six-, and seven-membered oxygen heterocycles are readily available enantiomerically pure. The value of this very simple two step process is demonstrated by the use of the five-membered ring heterocycles to form unnatural and unusual nucleosides that cannot be easily accessed by other means. The sequence involves a Ru catalyzed isomerization of the initial 2,5-dihydrofuran to a 2,3-dihydrofuran followed by a selenium promoted addition of a pyrimidine or purine base. One advantage of this strategy is the easy access to either enantiomeric series, both of which have important biological applications.