Boron–Heteroatom Addition Reactions via Borylative Heterocyclizations
- Author(s): Tu, Kim Ngan Thi
- Advisor(s): Blum, Suzanne A
- et al.
Organoboron compounds and heterocycles are powerful building blocks and precursors for organic synthesis, including for drug discovery, and for agrochemical and material synthesis. The common strategy for the synthesis of borylated heterocycles involves two separate synthetic steps: first, synthesis of the heterocyclic core, and second, borylation of the core through established methods such as transition metal-catalyzed C–H or C–X activation/borylation or lithiation/borylation. The alternative syntheses of O- and N-heterocycles via borylative cyclization are developed and reported herein. These reactions provide access to heterocyclic core and install boron in one synthetic step, with complementary bond disconnections, regiochemistry, and functional-group compatibility to current methods. Mechanistic and kinetic studies for direct oxyboration (Chapter 2) were investigated to understand the role of gold catalyst and byproduct NaCl. The syntheses of borylated isoxazoles and dihydrofurans via gold-catalyzed direct oxyboration reactions or uncatalyzed conditions (Chapter 3 and 4, respectively) followed. The mechanism of the gold-catalyzed reaction is proposed to proceed via addition of B–O σ bonds to Au(I)-activated C–C π bonds to afford cyclization, followed by transmetalation of the organogold intermediate to achieve the desired borylated heterocycles. Finally, a copper-catalyzed direct aminoboration reaction was discovered, which affords borylated pyrazoles (Chapter 5). These methods provide low-cost, alternative routes to borylated heterocycles that can be further functionalized via metal-catalyzed cross-coupling reactions.