Metal-Catalyzed Hydroboration of Unsaturated Bonds (C=C, C=N, C=O) and Alkylation of Nitriles
Transformations of organic substrates into more valuable chemical targets is an exciting and fruitful avenue of investigation. Such transformations can be achieved using catalytic or stoichiometric reactions. Catalysts play an indispensable role in industrial chemistry; it is believed that ~80 percent of all manufactured products involved the use of catalysis at some point during synthesis. Moreover, approximately 90 percent of all industrial chemicals made worldwide use catalysts within the manufacturing process. Catalysis can be broadly divided into different categories: homogenous catalysis, heterogeneous catalysis, organocatalysis and, enzymatic catalysis. Homogenous and heterogeneous catalysis may both involve the use of metals to carry out a chemical transformation. Many organic transformations are catalyzed by precious metals; noble metals like iridium (Ir), palladium (Pd), platinum (Pt), rhodium (Rh) typically afford good regio- and stereo-selectivity. The price, scarcity, and toxicity of precious metals are motivating factors driving the use of earth-abundant metals in catalysis. The replacement of precious metals with base metals will also help reduce the cost of the end-product. The metal-catalyzed hydroboration reaction is an example of homogenous catalysis and has been well studied for 45 years. In a typical hydroboration reaction, hydrogen and boron are added across a pi-bond, most typically those found in C=C, C=N and, C=O bonds. Hydroboration can accommodate mild reagents, reaction conditions and can tolerate a variety of functional groups. The substituted boron group may also act as a ‘functional handle’ to potentially allow formation of a new C-C bond or introduce an alternative functional group such as an alcohol, amide, amine, or halogen. In the first part of this dissertation, we report the 1,4-regioselective hydroboration of N-heteroarenes using a nickel-based catalyst system. Commercially available Ni(acac)2 was used in conjunction with tricyclopentylphosphine (PCyp3) to carry out hydroboration of pyridines to afford 1,4-dihydropyridines (1,4-DHPs) with yields of up to 96%. To the best of our knowledge, our catalyst system represents the first successful example of 1,4-selectivity for para-substituted pyridines. The second part of this dissertation describes the hydroboration of alkenes using a BIAN (bis-arylimino)acenaphthene supported iron complex and hydroboration of amides using a lanthanum-based catalyst. The products obtained after the hydroboration of alkenes, i.e., alkyl boronates, can potentially be used as coupling partners in Suzuki-Miyaura chemistry. The products obtained after hydroboration of amides, i.e., amines, are important molecules in both the pharmaceutical agriculture industries. The third part of the dissertation discusses the alkylation of nitriles employing alcohols. We have utilized our well-explored BIAN ligands in conjunction with commercially available cobalt(II) chloride to carry out the transformation. α-alkylated nitriles obtained from alkylation of nitriles have a number of applications as they are essential synthons in the synthesis of several drug molecules, including isoaminile and phenylalkylamines. The final part of the dissertation deals with the hydroboration of carbonates. We disclose an operationally convenient method for the hydroboration of carbonates. Commercially available La(acac)3 was employed in the hydroboration of carbonates to afford diols and methanol as the reduction products. The results of our lanthanum-based catalytic system were compared with previously reported NaHBEt3-catalyzed hydroboration of carbonates.