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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=710958
• 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.

我们的建议集中在铁和铋衍生的刘易斯酸作为绿色催化剂的发展。它们在合成化学中的用途需要进一步开发，因为与其他金属相比，它们对环境无害，相对无毒且经济。我们的研究目标是开发新的合成方法，重点是催化和对映选择性程序，用于直接制备具有药用价值的分子。催化不对称方法是现代有机合成中制备对映体富集化合物不可或缺的方法，与需要化学计量的手性试剂的方法相比，它提供了更经济和环境友好的方法。我们的研究结果将为制备生物学感兴趣的分子提供新的工具。这些研究将有助于开发使用环境友好和更经济的刘易斯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的重氮化合物到硅烷的SiH键和CH键的对映选择性插入反应。首先，利用铁盐与C2-对称手性配体的不对称插入反应。因此，将研究Fe类卡宾乙烯基中间体到SiH键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最重要的。随后将进行使用合成的对映体富集的烯丙基硅烷的羰基化合物的烯丙基化反应。其次，硅烷将用于铁盐和上述手性配体催化的酮的对映选择性硅氢加成反应。各种硅烷将与广泛选择的Fe盐和手性配体组合使用。新型手性铁氮杂环卡宾（NHC）催化剂的制备和评价。 我们的建议的第二部分将集中在发展一个有效的催化体系的环氧化和二羟基化烯烃。将开发能够有效氧化烯烃的生物启发的非血红素铁络合物。初步证据表明，以前制备的FeIIBolm的配体配合物将具有适当的几何形状和电子作为氧化催化剂。我们也将研究不同铁手性配合物对硫化物的不对称氧化反应。 我们研究计划的第三部分将致力于使用Bi衍生的刘易斯酸。这些铋配合物将首先用作对映选择性巴豆酰化反应的催化剂。BiIII衍生的杂环化合物将被制备并用作选定的对映选择性反应的催化剂。