Demonstration of a common concerted mechanistic pathway for the acid-catalyzed cyclization of 5,6-unsaturated oxiranes in chemical and enzymatic systems
Demonstration of a common concerted mechanistic pathway for the acid-catalyzed cyclization of 5,6-unsaturated oxiranes in chemical and enzymatic systems
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DOI：
10.1021/ja980096l
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发表时间：
1998-04-15
影响因子：
15
通讯作者：
Staas, DD
中科院分区：
文献类型：
--
作者：
Corey, EJ;Staas, DD
聚异戊二烯类化合物的手性末端环氧化物的酸催化环化是一种非常强大的合成构建，其是甾醇和三萜生物合成的关键步骤1，并且也是用于多种多环萜类化合物的对映选择性合成的越来越有用的途径。[2]虽然最近已经证明在甾醇生物合成中环氧乙烷裂解和初始环化事件是一致的，但是在环氧乙烷的非酶环化反应中环氧乙烷裂解和环化步骤的相对时间仍然不清楚。本文描述了酸催化的单环化过程如1 f 2的研究，并提供了令人信服的证据，表明这类反应是通过环氧乙烷CO裂解和CC键形成协同进行的，而不是通过离散的碳正离子如3进行的。通过GC和1HNMR分析动力学和产物，研究了饱和类似物4的反应。在作为溶剂的CDCl 3（或CHCl 3）中，在25 ℃下，用ClCH 2COOH作为催化剂3（0.1M，10当量），4的反应遵循伪一级动力学，并以指定的量生成5-7作为产物，并具有指定的产物形成的分解的伪一级速率常数。动力学测量在几个
The acid catalyzed cyclization of chiral terminal epoxides of polyprenoids is an extremely powerful synthetic construction which is a key step in sterol and triterpene biosynthesis1 and also an increasingly useful route for the enantioselective synthesis of a wide variety of polycyclic terpenoids. 2 Although it has recently been demonstrated that in sterol biosynthesis the oxirane cleavage and initial cyclization events are concerted, 1a the relative timing of the oxirane cleavage and cyclization steps in nonenzymatic cyclization reactions of oxiranes has remained obscure. This paper describes the study of acid-catalyzed monocyclization processes such as 1 f 2 and provides compelling evidence that such reactions proceed via a pathway in which oxirane CO cleavage and CC bond formation are concerted rather than via discrete carbocations such as 3.To evaluate the rate and nature of acid-catalyzed non-π-assisted reactions of 1, the reaction of the saturated analogue 4 was investigated by GC and 1H NMR analysis of kinetics and products. In CDCl3 (or CHCl3) as solvent at 25 C with ClCH2COOH as catalyst3 (0.1 M, 10 equiv), the reaction of 4 followed pseudo first-order kinetics and generated 5-7 as products in the indicated amounts and with the indicated dissected pseudo first-order rate constants for product formation. Kinetic measurements at several