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Lewis Acid Catalyzed Functional Group Transformations Using Borane-Ammonia

thesis
posted on 2024-04-11, 20:41 authored by Abdulkhaliq Atwan AlawaedAbdulkhaliq Atwan Alawaed

Borane-ammonia (BH3-NH3) has played an essential role in shaping and promoting the field of organic chemistry. However, we believe that the potential applications of BA in organic reductions have yet to be investigated. Our studies aimed to investigate BA as a reducing agent in organic reactions and to delve into the associated reduction mechanisms. In the second chapter of our research, we discovered that a combination of borane-ammonia and titanium tetrachloride (TiCl4) has been explored as a versatile system for reducing various carbonyl compounds. By using BA with a small amount of TiCl4 catalyst (10 mol%) in diethyl ether (Et2O), we reduced different aryl and alkyl ketones into secondary alcohols at room temperature in just 30 minutes. This method is much faster than traditional uncatalyzed conditions, which usually take 24 hours or more to achieve the same reduction, and it does so without impacting other functional groups. Substituted cycloalkanones are selectively reduced to the thermodynamically favored product. Our deuterium labeling experiments found that the most probable pathway involves the hydroboration mechanism involving ketones and borane-ammonia in the presence of TiCl4.


A slight variation in this chemical system can significantly impact the deoxyhalogenation process of aryl aldehydes, ketones, carboxylic acids, and esters. This process involves using a metal halide Lewis acid as a carbonyl activator, halogen carrier, and borane-ammonia. The selectivity of this process is determined by balancing the carbocation intermediate's stability with the Lewis acid's acidity. The choice of solvent and Lewis acid depends on the substituents present, and different substitution patterns have been explored. These principles have also been applied to selectively convert alcohols into alkyl halides. Furthermore, this system is used to selectively deoxygenate carbonyls of aldehydes and ketones into methyl and methylene hydrocarbons. The substituents on the benzene ring play a significant role in the deoxygenation process of carbonyl carbons in aldehydes and ketones.


In the third chapter of the study, various applications of the titanium system are examined. The TiCl4/BH3-NH3 system was used to directly reduce a range of carboxylic acids to the corresponding alcohols at room temperature with good to excellent yields. This reduction method was achieved by adjusting the stoichiometry of borane-ammonia. This process is tolerant to various potentially reactive functional groups, such as N-protected amino acids, enabling the selective reduction of acids in the presence of amides and nitriles. Further, the titanium system was used to deoxygenation aromatic and aliphatic carboxylic esters into ethers. The ratio of borane-ammonia and catalyst controls the process. This method is the first practical borane-mediated process compatible with many sensitive functional groups and can convert challenging aromatic acid esters into ethers. Using BF3–Et2O as the catalyst changes the result products, reducing the esters to alcohols instead.


In the fourth chapter of our exploration, we looked at various applications of this system that involved reducing aliphatic and aromatic nitriles to primary amines. This was achieved by using 2.0 equivalents of BH3-NH3 and a molar equivalent of TiCl4. We also found that the TiCl4/BA system in dichloroethane (DCE) under reflux temperature efficiently reduces (deoxygenates) a range of aromatic and aliphatic primary, secondary, and tertiary carboxamides. We adjusted the catalyst and reductant stoichiometry accordingly, and the resulting amines were obtained in high yields using a simple acid-base workup.

History

Degree Type

  • Doctor of Philosophy

Department

  • Chemistry

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Padinjaremadhom Ramachandran

Additional Committee Member 2

Herman O. Sintim

Additional Committee Member 3

Jianguo Mei

Additional Committee Member 4

Alexander Wei

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