Quantitative Modeling of Bis(pyridine)silver(I) Permanganate Oxidation of Hydantoin Derivatives: Guidelines for Predicting the Site of Oxidation in Complex Substrates

被引：19

作者：

Bischoff, Amanda J. ^{[1
]}

Niemeyer, Zachary L. ^{[1
]}

Sigman, Matthew S. ^{[1
]}

Movassaghi, Mohammad ^{[2
]}

Nelson, Brandon M. ^{[2
]}

机构：

[1] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA

[2] MIT, Dept Chem, Cambridge, MA 02139 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2017年 / 139卷 / 43期

基金：

美国国家科学基金会;

关键词：

H BOND FUNCTIONALIZATION; CONCISE TOTAL-SYNTHESIS; ENANTIOSELECTIVE TOTAL SYNTHESES; FREE-ENERGY RELATIONSHIPS; EPIPOLYTHIODIKETOPIPERAZINE ALKALOIDS; ASYMMETRIC CATALYSIS; GENERAL-APPROACH; CHIRAL ANION; IN-VIVO; PREPARING EPIDITHIODIOXOPIPERAZINES;

D O I：

10.1021/jacs.7b09541

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The bis(pyridine)silver(I) permanganate promoted hydroxylation of diketopiperazines has served as a pivotal transformation in the synthesis of complex epipoly-thiodiketopiperazine alkaloids. This late-stage C-H oxidation chemistry is strategically critical to access N-acyl iminium ion intermediates necessary for nucleophilic thiolation of advanced diketopiperazines en route to potent epipolythiodiketopiperazine anticancer compounds. In this study, we develop an informative mathematical model using hydantoin derivatives as a training set of substrates by relating the relative rates of oxidation to various calculated molecular descriptors. The model prioritizes Hammett values and percent buried volume as key contributing factors in the hydantoin series while correctly predicting the experimentally observed oxidation sites in various complex diketopiperazine case studies. Thus, a method is presented by which to use simplified training molecules and resulting correlations to explain and predict reaction behavior for more complex substrates.

引用

页码：15539 / 15547

页数：9

共 111 条

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