Asymmetric aldol additions with titanium enolates of acyloxazolidinethiones: Dependence of selectivity on amine base and Lewis acid stoichiometry
Asymmetric aldol additions with titanium enolates of acyloxazolidinethiones: Dependence of selectivity on amine base and Lewis acid stoichiometry
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DOI：
10.1021/ja9716721
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发表时间：
1997-08-20
影响因子：
15
通讯作者：
Tabet, EA
中科院分区：
文献类型：
--
作者：
Crimmins, MT;King, BW;Tabet, EA
不对称羟醛加成反应由于其在碳-碳键的不对称构建中的重要性而成为合成和机理研究的热点。特别地，Evans二烷基硼三氟甲磺酸酯介导的羟醛缩合反应是用于制备高对映体纯度（通常> 250：1非对映体选择性，即> 99%ee）的β-羟基酸及其衍生物的公认且有用的方法。1钛2 -4和锡5金属中心也被证明是有效的，在创建良好有序的过渡态羟醛反应。本文报道了利用钛-（IV）酰基恶唑烷硫酮的烯醇化物制备高非对映体纯度的“Evans”或“非Evans”合成醇醛产物的研究，方法是简单地改变刘易斯酸的化学计量和胺碱的性质.已对钛-（IV）酰基恶唑烷硫酮的烯醇化物进行了研究，但它们的选择性低于硼烯醇化物. 2-5典型的非对映选择性为88-96% de，但用R1-不饱和醛观察到低得多的选择性（对于巴豆醛，顺式A：顺式B加反式为60：40）.此外，为了实现合理的反应速率和良好的转化水平，必须使用过量的醛（2-5当量）。因此，钛烯醇化物与昂贵的或合成制备的醛的使用是禁止的。钛烯醇化物的选择性降低可能是多个机械途径同时操作的结果。[4]硼烯醇化物（和钛烯醇化物）的过渡态1被提出，得到“Evans”合成羟醛产物。6如果氯离子丢失，钛烯醇化物也可以通过2英寸进行。
Asymmetric aldol additions have been the subject of intense synthetic and mechanistic study because of their importance in the asymmetric construction of carbon-carbon bonds. In particular, the Evans dialkylboron triflate mediated aldol reaction is a well accepted and useful method for the preparation of-hydroxy acids and their derivatives in high enantiomeric purity (generally> 250: 1 diastereoselectivity, ie> 99% ee). 1 Titanium2-4 and tin5 metal centers have also been shown to be effective in creating well-ordered transition states for aldol reactions. We report here our studies on the use of titanium-(IV) enolates of acyloxazolidinethiones for the preparation of either the “Evans” or “non-Evans” syn aldol products in high diastereomeric purity by simply changing the stoichiometry of the Lewis acid and the nature of the amine base.Titanium enolates of the Evans acyl oxazolidinones have been examined, but they are less selective than the boron enolates. 2-5 Typical diastereoselectivities are 88-96% de, but much lower selectivities are observed with R,-unsaturated aldehydes (60: 40 syn A: syn B plus anti, for crotonaldehyde). Also, to achieve reasonable reaction rates and good levels of conversion, excess aldehyde (from 2-5 equiv) must be employed. 2 Therefore, the use of the titanium enolates with expensive or synthetically prepared aldehydes is prohibitive. The reduction in selectivity with titanium enolates is potentially the result of multiple mechanistic pathways operating simultaneously. 4 The transition state 1 has been proposed for the boron enolate (and the titanium enolate) to give the “Evans” syn aldol product. 6 If chloride ion is lost, the titanium enolate can also proceed through 2 in