Earth Abundant Metal Catalyzed Borylations

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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.