Earth Abundant Metal Catalyzed Borylations

芳基硼酸和烷基硼酸酯在有机合成中非常重要，特别是作为Suzuki-Miyaura和c -杂原子交叉偶联、共轭加成和各种官能团转化的底物。通常，它们的制备（与三烷基硼酸盐与镁或烷基锂的反应）仅限于无活性官能团的底物，或增加昂贵的保护/去保护步骤。新开发的合成芳基硼酸盐的途径包括pd催化的烷氧二硼或烷氧硼烷试剂与芳基卤化物的交叉偶联，以及ir催化的芳香底物的ch -硼化反应。这些方法虽然有效，但有一些局限性，需要更良性、更便宜的替代品，这些替代品也可以最大限度地减少对环境有害的废物的产生。通过实验和理论研究的结合，并基于我们非常成功的环境友好型铜催化硼化方案的初步研究，包括在水中的反应，我们计划开发新的铜、铁和锌催化剂，用于将硼酸酯基团引入芳香族、杂芳香族和脂肪族底物中。我们还计划开发新的C-C键形成工艺，包括通过新的铜和铁催化的涉及烷基硼酸盐的交叉偶联反应形成sp3-sp3 C-C键。在适当情况下，将与涉及贵金属催化剂（例如钯）的现有方法进行比较，而在其他情况下，将开发全新的催化方法。动力学和机理研究将与模拟催化循环步骤的化学计量反应一起进行。我们将重点研究碳卤素键的硼化，包括1,1-二卤烷，将开发不对称β-硼化的新工艺，以及1,2-二烯的硼化，以及其他合成烯基硼酸盐的方法。最后，我们的目标是开发新的一锅、单溶剂的多步序列工艺，如硼化/Suzuki-Miyaura交叉偶联，完全由地球丰富的金属如Cu和Fe催化。

Aryl- and alkylboronic acids and esters are of great importance in organic synthesis, in particular as substrates for Suzuki-Miyaura and C-heteroatom cross-couplings, conjugate additions, and a wide variety of functional group transformations. Classically, their preparation (reaction with trialkyl borates with magnesium or lithium alkyls) is limited to substrates free of reactive functional groups, or adds costly protection/deprotection steps. Newly developed routes to arylboronates include Pd-catalyzed cross-coupling of alkoxydiboron or alkoxyborane reagents with aryl halides, and the Ir-catalyzed CH-borylation of aromatic substrates. While effective, these methods have several limitations and there is a need for more benign, cheaper alternatives, which also minimize the generation of environmentally hazardous waste. Via a combination of experimental and theoretical studies, and based on our very successful preliminary studies of environmentally friendly copper catalyzed borylation protocols, including reactions in water, we plan to develop new copper, iron and zinc catalysts for the introduction of boronate ester groups into aromatic, heteroaromatic and aliphatic substrates. We also plan to develop novel C-C bond forming processes, including the formation of sp3-sp3 C-C bonds, via new copper and iron catalyzed cross-coupling reactions involving alkylboronates. Where appropriate, comparisons will be made with existing processes involving precious metal catalysts (e.g., Pd), whereas in other cases, completely new catalytic processes will be developed. Kinetic and mechanistic studies will be performed along with studies of stoichiometric reactions which model steps in the catalytic cycles. We will focus on the borylation of carbon-halogen bonds, including 1,1-dihaloalkanes, will develop new processes for asymmetric β-borylation, as well as the diboration of 1,2-dienes, and other methods for the synthesis of allylboronates. Finally, we aim to develop new one-pot, single-solvent processes for multi-step sequences, such as borylation/Suzuki-Miyaura cross-coupling, catalyzed entirely by earth abundant metals such as Cu and Fe.