This invention introduces a novel approach for distal C-H functionalization using attachable- and-detachable transient directing groups (TDGs). Traditional covalently attached external auxiliaries (directing groups, DGs) required additional steps for introduction and removal, making the process cumbersome. The TDGs described herein form reversible imine linkages, enabling efficient and selective distal C-H activation and functionalization. A specifically designed biphenyl pyrimidine-based TDG overcomes the challenge of proximal C-H activation and promotes selective distal C-C bond formation amidst multiple chemically equivalent C-H bonds.
Figure (1) General scheme illustrating the transient directing group strategy for distal C–H functionalization, covering substrate, intermediate, and final product (Formula I to III).
Current methods for C-H functionalization in organic synthesis predominantly rely on covalently attached external auxiliaries, known as directing groups (DGs). While effective, these DGs necessitate additional steps, including the introduction of the DG prior to C-H activation and its removal post-functionalization. This increases the complexity, time, and cost of the synthetic process. Furthermore, achieving selective distal C- H functionalization is particularly challenging due to the tendency of proximal C-H bonds to undergo activation, leading to less precise modifications.
- Attachable-and-Detachable TDG: Utilizing a biphenyl pyrimidine-based transient directing group (TDG) via reversible imine formation, the invention enables selective distal C-H functionalization, eliminating the need for additional steps to introduce or remove traditional directing groups.
- Overriding Proximal Activation: Through strategic TDG design, the invention effectively circumvents the inherent bias toward proximal C-H activation, facilitating selective distal C-C bond formation, even in the presence of multiple chemically equivalent C-H bonds.
- Template Design: The invention's template design effectively addresses electronic and steric biases, facilitating remote C-C bond formation with exceptional selectivity, marking a significant advancement in synthetic methodologies.
- Selective Reactivity: The reaction sequence ensures selective reactivity towards distal C-H bonds, overcoming the challenges posed by the presence of multiple chemically equivalent C-H bonds.
For the transition-metal-catalyzed cross-electrophile coupling method, the prototype details would include:
- Input Materials: Various electrophiles and nucleophiles as reactants, including organic halides, organometallic reagents, and transition-metal catalysts such as palladium or nickel complexes. Solvents like acetonitrile, toluene, acetone, or THF might also be used.
- Components: The method may involve the use of specific ligands such as palladacyclic complexes as precatalysts. Specific bases, like hydrides or fluorides, and transition metals like Ni and Pd might be employed.
- Dimensions: For a laboratory-scale prototype, the dimensions would depend on the equipment used, typically involving standard laboratory glassware and reaction vessels.
- Performance Metrics: Key performance metrics would include reaction yield, selectivity, reaction time, and scalability. The prototype would be evaluated based on its ability to efficiently catalyze cross-electrophile coupling reactions under various conditions, providing high yields of the desired products.
The technology has been demonstrated and validated in lab environment.
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The method's efficiency reduces the environmental footprint by minimizing waste generation and energy consumption. Additionally, its versatility accelerates the development of pharmaceuticals, agrochemicals, and materials, fostering innovation and economic growth.
- Pharmaceuticals: Enables efficient synthesis of complex drug molecules, facilitating drug discovery and development processes.
- Agrochemicals: Streamlines the production of crop protection agents and fertilizers, enhancing agricultural productivity and sustainability.
- Materials Science: Facilitates the synthesis of advanced materials used in electronics, coatings, and catalysts, contributing to technological advancements and product innovation.
Geography of IP
Type of IP
201921053680
464317