New Methods for Green Organic Synthesis

绿色有机合成新方法

• 批准号: RGPIN-2017-04272
• 负责人: Ollevier, Thierry
• 金额: $ 2.55万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685698
• 关键词: New; Methods; Green; Organic; Synthesis

Our proposal focuses on the development of iron and bismuth-derived Lewis acids as green catalysts. Their use in synthetic chemistry needs to be further developed because they are environmentally benign, relatively nontoxic and economic in comparison to other metals. The objective of our research is the development of new synthetic methods, with emphasis on catalytic and enantioselective procedures for the straightforward preparation of molecules of pharmaceutical interest. Catalytic asymmetric processes are indispensable for producing enantiomerically enriched compounds in modern organic synthesis, providing more economical and environmentally benign processes than methods requiring stoichiometric amounts of chiral reagents. Our results will lead to new tools for the preparation of molecules of biological interest. These studies will contribute to the development of new green synthetic methods using environmentally friendly and more economical Lewis acid catalysts.******A first part of our proposal deals with the development of new chiral iron complexes for the enantioselective insertion reaction of diazo compounds into the SiH bond of silanes and the CH bond. Firstly, an enantioselective insertion reaction will be developed using Fe salts with C2-symmetric chiral ligands. Consequently, the enantioselective insertion reaction of Fe carbenoid vinyl intermediates into the SiH bond will be studied. The enantioselective synthesis of chiral allyl silanes is indeed of prime importance. The subsequent allylation reaction of carbonyl compounds using the synthesized enantio-enriched allyl silanes will be undertaken. Secondly, silanes will be used in the enantioselective hydrosilylation reaction of ketones catalyzed by iron salts and the above-selected chiral ligands. Various silanes will be employed in combination with a wide selection of Fe salts and chiral ligands. New chiral iron N-heterocyclic carbene (NHC) catalysts will be prepared and evaluated.******A second part of our proposal will focus towards the development of an efficient catalytic system for the epoxidation and dihydroxylation of alkenes. A bioinspired non-heme iron complex capable of efficient oxidation of alkenes will be developed. Initial evidence showed that the previously prepared FeIIBolm's ligand complexes would have the appropriate geometry and electronics to work as oxidation catalysts. The asymmetric oxidation of sulfides using various iron chiral complexes will be studied as well.******A third part of our research program will be devoted to the use of Bi-derived Lewis acids. These Bi complexes will be first used as catalysts for the enantioselective crotylation reaction. BiIII-derived heterobimetallic complexes will be prepared and used as catalysts for selected enantioselective reactions.

我们的建议侧重于开发铁和铋衍生的Lewis酸作为绿色催化剂。它们在合成化学中的应用需要进一步开发，因为与其他金属相比，它们是环境友好、相对无毒和经济的。我们的研究目标是开发新的合成方法，重点是直接制备药物分子的催化和对映选择性程序。在现代有机合成中，催化不对称过程对于合成富含对映体的化合物是必不可少的，与需要化学计量比的手性试剂的方法相比，它提供了更经济和环境友好的过程。我们的结果将导致新的工具来制备生物感兴趣的分子。这些研究将有助于开发使用环境友好和更经济的Lewis酸催化剂的新的绿色合成方法。*我们的建议的第一部分涉及开发新的手性铁配合物，用于重氮化合物在硅烷的SiH键和CH键上的对映选择性插入反应。首先，利用含C2对称手性配体的铁盐进行对映体选择性插入反应。因此，我们将研究铁卡宾类乙烯基中间体在SiH键上的对映选择性插入反应。手性烯丙基硅烷的对映选择性合成确实是非常重要的。随后将使用合成的富含对映体的烯丙基硅烷进行羰基化合物的烯丙化反应。其次，硅烷将用于铁盐和上述手性配体催化酮的不对称硅氢化反应。各种硅烷将与广泛选择的铁盐和手性配体结合使用。将制备和评价新型手性铁N-杂环卡宾(NHC)催化剂。*我们建议的第二部分将集中于开发一种有效的催化体系，用于烯烃的环氧化和二羟基化。将开发一种生物启发的非血红素铁络合物，能够有效地氧化烯烃。初步证据表明，先前制备的FeIIBolm配体络合物将具有适当的几何结构和电子结构，可以用作氧化催化剂。我们还将研究各种铁手性络合物对硫化物的不对称氧化。*我们的研究计划的第三部分将致力于铋衍生Lewis酸的使用。这些铋配合物将首次用作对映体选择性巴豆基化反应的催化剂。将制备BiIII衍生的异双金属配合物，并将其用作选择性对映选择性反应的催化剂。