Transition-metal-free reactions of organoboranes.

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The aim of my research program is to develop novel transition-metal-free carbon-carbon (C-C) bond forming methodologies using organoboranes. The underlying theme of my proposal is an amphoteric reactivity of organoboranes. Boranes are electrophilic when neutral but nucleophilic when negatively charged. In situ generation of nucleophilic species from neutral boranes and their novel reactions are being discussed. C-C bond forming reactions involving organoboron compounds are usually associated with transition-metals that are expensive, toxic and often require the presence of sophisticated ligands. Boron is inexpensive and environmentally benign. Moreover, its low toxicity resulted in the incorporation of boron into pharmaceuticals. Proposed reactions provide “greener” alternative to the currently available protocols. The first section focuses on the development of novel C-C bond forming reactions using potassium organotrifluoroborate salts. Recently, we have discovered a single-step synthesis of ketones from acyl chlorides and trifluoroborates. We propose that in situ generated electrophilic difluoroborane interacts with a carbonyl functionality of the acyl chloride producing nucleophilic borates and electrophilic species. The reaction between newly formed nucleophilic borate and an electrophile affords propargyl ketones. Importantly, the reaction occurs in the absence of transition metals. Similarly, reactions of imines, isocyanates and aldehydes with trifluoroborates under the developed conditions are anticipated to form important functionalities such as amines, amides and alcohols respectively. The second section describes the opening of aziridinium ion with organoboronic acids and the application of the reaction to the synthesis of beta and gamma amino acids. To our knowledge, there are no literature examples of aziridinium ions reacting with organoborones. In this case, neutral boronic acids will be activated and directed to the aziridinium electrophilic center by the Lewis basic moiety present in the substrate. The establishment of stereocenters, which takes place at the early stage of the synthesis, relies on well-known epoxidation protocols. Subsequent reactions are stereospecific, which prevents epimerization of the chiral centers. Therefore, the enantiomeric purity of the starting epoxide will be translated to the final amino acid. The final section of my proposal focuses on the development of transition-metal-free reactions between gaseous carbon monoxide and organoboranes. This approach describes novel reactions based on the activation of neutral organoboranes with carbon monoxide. I propose efficient synthesis of acyl boronate esters and complex trifluroborates that are known to have great synthetic potential but difficult to prepare. In addition, novel bora-Brook rearrangements of acyl boronates are being described. Overall, outcomes of this research program will result in greater atom economy and will decrease the amount of toxic waste associated with metals in both academic and industrial settings. In addition, novel methodologies will ensure rapid access to diverse chiral molecules, which is crucial for the development of complex molecules and natural products. In summary, the proposed research program will have a significant impact on our understanding of the fundamental aspects of boron chemistry, which in turn will lead to the development of green reactions for the synthesis of compounds of biological and medicinal relevance. This program will serve as an excellent tool for the training of both graduate and undergraduate students.