1,5-anti stereocontrol in the boron-mediated aldol reactions of beta-alkoxy methyl ketones: the role of the formyl hydrogen bond.
1,5-anti stereocontrol in the boron-mediated aldol reactions of beta-alkoxy methyl ketones: the role of the formyl hydrogen bond.
复制标题
硼介导的β-烷氧基甲基酮羟醛反应中的1,5-反立体控制：甲酰基氢键的作用。
DOI：
10.1021/jo701849x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
J. Goodman
中科院分区：
文献类型：
--
作者：
R. Paton;J. Goodman
某些类型的β-烷氧基甲基酮的硼介导的羟醛缩合反应显示出与非手性醛的显著高水平的立体诱导，优先导致1，5-反相关的立体中心。由于在乙酸酯羟醛缩合反应中通常观察到低水平的不对称诱导，这具有很大的合成效用，并且已成功地用于许多聚酮化合物天然产物的全合成。我们已经研究了烷氧基保护基团（OMe，OPMB，PMP缩醛，四氢吡喃，和OTBS）存在于硼烯醇化物上的远程1，5-立体诱导的水平和意义的影响，使用密度泛函理论计算（B3 LYP/6- 31 G **）。我们的预测的非对映选择性的竞争羟醛过渡结构的比较是在良好的定性和定量协议与实验报道的值。我们的结论是，未取代的硼烯醇化物的硼羟醛缩合反应进行通过船形过渡结构，其中稳定的甲酰基氢键之间存在的烷氧基氧和醛质子。正是这种相互作用导致优先形成的1，5-反加成物，通过最小化的β-烷基基团和硼上的配体之一之间的空间相互作用。在甲硅烷基醚的情况下，由于保护基团的大小和将电子密度提供给相邻硅原子的贫电子氧原子，没有观察到这种内部氢键的偏好。我们表明，这种立体化学模型也适用于合理化的1，4-syn立体选择性硼羟醛反应涉及某些α-手性甲基酮。这些详细的结果可以概括为一个构象图，可以用来预测立体感。
The boron-mediated aldol reactions of certain types of beta-alkoxy methyl ketone show remarkably high levels of stereoinduction with achiral aldehydes, leading preferentially to 1,5-anti related stereocenters. Given the low levels of asymmetric induction usually observed in acetate aldol reactions, this is of great synthetic utility and has been used successfully in the total synthesis of a number of polyketide natural products. We have investigated the effects of the alkoxy protecting group (OMe, OPMB, PMP acetal, tetrahydropyran, and OTBS) present in the boron enolate on the level and sense of remote 1,5-stereoinduction, using density functional theory calculations (B3LYP/6-31G**). Our predictions of diastereoselectivity from comparison of the competing aldol transition structures are in excellent qualitative and quantitative agreement with experimentally reported values. We conclude that the boron aldol reactions of unsubstituted boron enolates proceed via boat-shaped transition structures in which a stabilizing formyl hydrogen bond exists between the alkoxy oxygen and the aldehyde proton. It is this interaction that leads to preferential formation of the 1,5-anti adduct, by minimizing steric interactions between the beta-alkyl group and one of the ligands on boron. In the case of silyl ethers, the preference for this internal hydrogen bond is not observed due to the size of the protecting group and the electron-poor oxygen atom that donates electron density into the adjacent silicon atom. We show that this stereochemical model is also applicable in rationalizing the 1,4-syn stereoselectivity of boron aldol reactions involving certain alpha-chiral methyl ketones. These detailed results may be summarized as a conformational diagram that can be used to predict the sense of stereoinduction.
影响因子：
5.2
作者：
Arefolov, A;Panek, JS
通讯作者：
Panek, JS