Hypervalent Bromine for Novel Synthesis

用于新型合成的高价溴

• 批准号: EP/X021742/1
• 负责人: Thomas Wirth
• 金额: $ 26万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX021742%2F1
• 关键词: Hypervalent; Bromine; Novel; Synthesis

A highly efficient and sustainable route to cyclic and chiral *3-bromane synthesis and their synthetic utilization has been proposed by the application of electric current. The use of electrons as reagent in such transformations would replace the use of stoichiometric toxic reagents and unwanted by-product formation and thereby increase the yield and the potency of the process. Owing to the enhanced reactivity of bromanes over iodanes would make the resulting *3-bromanes a versatile reagent for the fluoroalkylation reactions under milder reaction conditions. The synthesized fluoroalkyl-*3-bromane will be characterised by the various spectroscopic techniques. First time, the stereoselective fluoroalkylation strategies will be disclosed by using asymmetric *3-bromane salts. The reactivity of the chiral bromane salts will also be evaluated by accessing divergent chiral environment. The application of cyclic *3-bromanes will be demonstrated by the late stage fluoroalkylation at the primary and secondary benzylic sites. The successful outcome of the benzylic fluoroalkylation strategy will be further extended to the benzylic fluoroalkylation of commercially available drug molecules under flow conditions. Finally, the challenging aspect of microreactor technology would be incorporated for an automated self-optimization in late stage modification of peptides as well as reaction of captopril, a widely used antihypertensiondrug, via isotopic fluoroalkylation and alkynylation with the aid of HPLC and quantitative LC-MS. Detailed mechanistic studies for the generation of cyclic and chiral *3-bromane as well as their synthetic utilization in pharmaceutically useful molecule synthesis will be performed with spectroscopic evidences.

通过应用电流，提出了一种高效且可持续的环状和手性*3-溴烷合成及其合成利用的路线。在此类转化中使用电子作为试剂将取代化学计量有毒试剂的使用和不需要的副产物的形成，从而提高该过程的产率和效力。由于溴烷相对于碘烷的反应性增强，使得所得的*3-溴烷成为在较温和的反应条件下进行氟烷基化反应的通用试剂。合成的氟烷基-*3-溴烷将通过各种光谱技术进行表征。将首次公开使用不对称*3-溴烷盐的立体选择性氟烷基化策略。手性溴烷盐的反应性也将通过进入不同的手性环境来评估。环状*3-溴烷的应用将通过初级和次级苄基位点的后期氟烷基化来证明。苄基氟烷基化策略的成功结果将进一步扩展到流动条件下市售药物分子的苄基氟烷基化。最后，微反应器技术的挑战性方面将被纳入肽的后期修饰以及卡托普利（一种广泛使用的抗高血压药物）反应中的自动自我优化，通过同位素氟烷基化和炔基化，借助 HPLC 和定量 LC-MS 。将利用光谱证据对环状和手性*3-溴烷的生成及其在药用分子合成中的合成利用进行详细的机理研究。

项目成果

Hypervalent Halogen Compounds in Electrochemical Reactions: Advantages and Prospects

• DOI: 10.1002/adsc.202300412
• 发表时间: 2023-07-04
• 期刊: ADVANCED SYNTHESIS & CATALYSIS
• 影响因子: 5.4
• 作者: Winterson，Bethan;Bhattacherjee，Dhananjay;Wirth，Thomas
• 通讯作者: Wirth，Thomas