Development of organochalcogen-catalysts as a sustainable concept for the selective amination and halogenation of unsaturated hydrocarbons in the context of the bioinspired synthesis of medicinally relevant drugs

有机硫属元素催化剂的开发作为在医学相关药物的仿生合成背景下不饱和烃的选择性胺化和卤化的可持续概念

• 批准号: 255037315
• 负责人: Professor Dr. Alexander Breder
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/255037315?language=en
• 关键词: Development; organochalcogen; catalysts; sustainable; concept

The goal of the postulated research program is the development of an organochalcogen-based catalysis concept (chalcogen = S, Se) for the stereo- and chemoselective, oxidative nitrogenation and halogenation of simple alkenes. As a consequence, catalytic methods arising from this campaign are expected to serve as linchpin operations in endeavors toward syntheses of medicinally relevant natural products and analogs thereof. The program is subdivided into three parts: A) On the basis of mechanistic investigations the rational development of two novel classes of chiral diaryldisulfide and -selenide catalysts as well as thio- and selenoamide catalysts for the stereoselective construction of C-N and C-halogen bonds is proposed. Regarding the postulated dichalcogenides, the conceptual focus lies on the design of an unprecedented catalyst architecture, which is expected to allow for both an efficient stereoinduction as well as substrate turnover. B) Catalysts resulting from part A will be applied in a number of asymmetric transformations, such as oxidative allylic aminations and aminocyclizations of olefins. Moreover, investigations will include oxidative allylic halogenations, dihalogenations, and halo(carbo)cyclization reactions of alkenes and polyenes. In particular, development of the latter transformation will set the basis for the total synthesis of halogenated cyclic natural products. C) In order to demonstrate the general utility of the postulated chalcogen-catalysis concept, a concise and redox-economic synthesis of the labdane alkaloids haterumaimide L and M is proposed. Key-step in this endeavor is a bioinspired, asymmetric halocarbocyclization, which is expected to provide rapid access to a common intermediate that on its part should give rise to either of the target compounds.

假设的研究计划的目标是发展的有机硫族元素为基础的催化概念（硫族元素= S，硒）的立体和化学选择性，氧化氮化和卤化的简单烯烃。因此，预期由该活动产生的催化方法在努力合成药用相关天然产物及其类似物中充当关键操作。该计划被细分为三个部分：A）在机理研究的基础上，提出了两类新的手性二芳基二硫化物和-硒化物催化剂以及硫代和硒代酰胺催化剂用于立体选择性构建C-N和C-卤键的合理开发。关于假定的二硫属化物，概念上的重点在于设计一个前所未有的催化剂架构，这是预计将允许一个有效的立体诱导以及基板营业额。B）由A部分得到的催化剂将用于许多不对称转化，例如烯烃的氧化烯丙基胺化和胺环化。此外，研究将包括氧化烯丙基卤化，二卤化和烯烃和多烯的卤（碳）环化反应。特别是，后者的转化的发展将为卤代环状天然产物的全合成奠定基础。C）为了证明假定的硫族元素催化概念的一般效用，提出了拉布拉多生物碱haterumaimide L和M的简洁且氧化还原经济的合成。这一奋进的关键步骤是生物启发的不对称卤代碳环化，预计将提供快速获得共同中间体的途径，该中间体本身应产生任何一种目标化合物。

项目成果

Synthesis of (+)-Greek Tobacco Lactone via a Diastereoablative Epoxidation and a Selenium-Catalyzed Oxidative Cyclization.

• DOI: 10.1021/acs.orglett.7b00484
• 发表时间: 2017-03
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Stefan Leisering;Iker Riaño;Christian Depken;Leona J Gross;Manuela Weber;D. Lentz;R. Zimmer*;C. Stark;Alexander Breder;M. Christmann

Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant.

• DOI: 10.1021/acs.orglett.6b01130
• 发表时间: 2016-06
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: S. Ortgies;Christian Depken;Alexander Breder

Oxidative Alkene Functionalizations via Selenium-π-Acid Catalysis

• DOI: 10.1021/acscatal.7b01216
• 发表时间: 2017-09-01
• 期刊: ACS CATALYSIS
• 影响因子: 12.9
• 作者: Ortgies, Stefan;Breder, Alexander
• 通讯作者: Breder, Alexander