Highly enantioselective propargylic hydroxylations catalyzed by chloroperoxidase
Highly enantioselective propargylic hydroxylations catalyzed by chloroperoxidase
复制标题
DOI：
10.1021/ja983612g
复制
发表时间：
1999-02-03
影响因子：
15
通讯作者：
Hager, LP
中科院分区：
文献类型：
--
作者：
Hu, SH;Hager, LP
手性丙叉醇是复杂分子，特别是生物活性化合物对映体选择性合成的重要构件。1丙叉醇的不对称合成一般有两种策略：(A)醛的不对称烯基化反应2和(B)对乙酰酮的化学计量或催化还原反应。然而，制备光学纯的炔丙醇的最直接的步骤是炔烃的不对称羟基化。到目前为止，还没有一种有效和通用的催化剂来实现这种方法。4氯过氧化物酶(CPO)是血红素酶家族中用途最广、效率最高的氧化催化剂。5自三十多年前发现CPO以来，已描述了大量的CPO催化的反应。CPO催化卤代反应，6，7醇的氧化成醛，8醛成酸，9烷基胺的脱烷基化，10酚的二聚，11和胺氧化成亚硝基化合物。12具体来说，CPO催化几个对映选择性氧化反应：烯烃的环氧化，13烯丙基和苄基的羟基化，9和亚磺化。14关于乙炔的酶促氧化的报道很少。15我们现在报道了一种由CPO催化的新的氧化反应--立体选择性丙叉羟基化。在适当的条件下，16 CPO催化多种未官能化和官能化的炔烃的对映选择性羟基化反应，得到手性丙叉醇。过氧化氢和叔丁基氢过氧化氢(TBHP)均可作为该反应的终端氧化剂。当使用过氧化氢作为氧化剂时，将其缓慢加入反应混合物中，以使CPO的强大过氧化氢酶活性降至最低。当使用TBHP时，直接向反应介质中加入2当量的TBHP即可开始氧化。
Chiral propargylic alcohols are important building blocks for the enantioselective synthesis of complex molecules, in particular, biologically active compounds. 1 There are two general strategies for the asymmetric synthesis of propargylic alcohols:(a) enantioselective alkynylation of aldehydes2 and (b) stoichiometric or catalytic reduction of acetylenic ketones. 3 However, the most direct procedure for the preparation of optically pure propargylic alcohols would be the asymmetric hydroxylation of alkynes. Until now an effective and versatile catalyst for this approach has not been available. 4Chloroperoxidase (CPO) is the most versatile and efficient oxidation catalyst in the heme enzyme family. 5 Since the discovery of CPO more than three decades ago, 6 a large number of CPO-catalyzed reactions have been described. CPO catalyzes halogenation, 6, 7 the oxidation of alcohols to aldehydes, 8 aldehydes to acids, 9 dealkylations of alkylamines, 10 dimerization of phenols, 11 and oxidation of amines to nitroso compounds. 12 In particular, CPO catalyzes several enantioselective oxidation reactions: epoxidation of alkenes, 13 allylic and benzylic hydroxylations, 9 and sulfoxidations. 14 There are very few reports concerning the enzymatic oxidation of acetylenes. 15 We now report a new oxidation reaction catalyzed by CPO, stereoselective propargylic hydroxylations. Under appropriate conditions16 CPO catalyzes the enantioselective hydroxylation of a variety of unfunctionalized and functionalized alkynes yielding chiral propargylic alcohols. Both hydrogen peroxide and tert-butyl hydroperoxide (TBHP) can serve as the terminal oxidant in this reaction. When hydrogen peroxide is used as the oxidant, it is added slowly to the reaction mixture to minimize the potent catalase activity of CPO. When TBHP is used, the oxidation is started by adding 2 equiv of TBHP directly to the reaction medium.