CATALYTIC, ENANTIOSELECTIVE ALDOL ADDITION REACTIONS

我们制备了一类钛(IV)络合物的两个成员，它们催化 (0.5-2mol%)添加硅烯醇醚、烷基烯醇醚和 二烯醇转化为醛。母体络合物很容易从 Ti(OIPR)4和2-氨基-2‘-席夫碱三齿配体 羟基-1，1‘-联苯乙酯。以此为基础的配位体支架基元 联萘具有几个配基设计的显著特征：(1) 简单的合成；(2)通过缩合反应使胺容易衍生 醛和磺酰氯，因此，(3)改善 金属的整体电子和立体结构的增量变化- 配体复合体。这些功能将使我们能够全面检查 这些催化剂用于醛加成反应。 在这些初步观察的基础上，这一行动的总体目标 建议包括： (1)研究对映体选择性的羟醛加成反应 开发强大的催化、碳-碳键形成方法 硅烷基烯醇酸盐和二烯醇酸盐与醛的加成反应。 (2)扩大我们对反应参数的研究，以包括溶剂效应； 反应浓度和具有该意图的催化剂的制备方法 制定一项实用的大规模协议。 (3)开发一种以试剂为基础的催化剂，能够超越 手性醛、手性甲基酮的固有立体化学偏向-- 烯烃加成反应。 (4)深入了解催化剂的溶液结构和 催化剂-乙醛络合物的核磁共振氢谱和X射线结晶学研究。 (5)将催化过程应用于大分子乳酸菌素A的合成，以及 抗生素不是很容易从自然来源获得，但被证明具有保护作用 T淋巴母细胞来自HIV感染。 催化对映体选择性方法学的成功开发 光学活性β-羟基酯和β-羟基丁酸酯的制备 α，β-不饱和酯为化合物提供了途径 以其他方式直接获得的现代催化对映体 方法论。此外，这些光学加合物是有用的起点。 用于合成立体化学复杂结构的材料 在人类医学方面的潜在应用。我们预计，对 新型含三齿配体的钛(IV)配合物将为 相关的羰基加成反应的其他催化剂的开发。

We have prepared two members of a class of Ti(IV) complexes which catalyze (0.5-2mol%) the addition of silyl enol eithers, alkyl enol ethers, and dienolates to aldehydes. The parent complex is readily prepared from Ti(OiPr)4 and a Schiff-base tridentate ligand derived from 2-amino-2'- hydroxy-1,1'-binapthyl. A ligand scaffolding motif based on this binaphthyl possesses several salient features for ligand design: (1) facile synthesis; (2) easy derivatization of the amine by condensation with aldehydes and sulfonyl chlorides, and, consequently, (3) amenability to incremental variation in the overall electronics and sterics of the metal- ligand complex. These feature will allow us to fully examine the scope of these catalysts for aldehyde addition reactions. On the basis of these preliminary observations, the broad aims of this proposals are: (1) To study the enantioselective aldol addition process with the intent of developing powerful catalytic, C-C bond-forming methodology for the addition of silyl and alkyl enolates and dienolates to aldehydes. (2) To expand our study of reaction parameters to include solvent effects, reaction concentration, and method of catalyst preparation with the intent of developing a practical large-scale protocol. (3) To develop a reagent based catalyst that is able to override the inherent stereochemical biases of chiral aldehyde chiral methyl ketone- enolate addition reactions. (4) To gain insight into the solution structure of the catalyst and catalyst-aldehyde complex by 1H NMR spectroscopy and X-ray crystallography. (5) To apply the catalytic process to the synthesis of macrolactin A, an antibiotic not readily available from natural sources but shown to protect T-lymphoblasts from HIV infection. The successful development of a catalytic, enantioselective methodology for the preparation of optically active beta-hydroxy esters and delta-hydroxy- alpha, beta-unsaturated esters provide access to compounds that are not otherwise directly available by modern, catalytic enantioselective methodology. moreover, these optically adducts are useful starting materials for the synthesis of stereochemically complex structures with potential applications in human medicine. We anticipate that the study of novel Ti(IV) complexes with tri-dentate ligands will lay a foundation for the development of other catalysts for related carbonyl addition reactions.