DNA-encoded CH functionality via photoredox-mediated hydrogen atom transformation catalysis.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Chemistry

Background:

• Functionalization of saturated heterocycles is crucial in medicinal chemistry.
• Existing methods for α-alkylation often require harsh conditions or pre-functionalized substrates.
• Developing mild and efficient methods for C-H functionalization is a key challenge.

Purpose of the Study:

• To develop a novel photoredox-catalyzed method for the α-alkylation of N-Boc saturated heterocycles.
• To enable C(sp3)-C(sp3) bond formation using readily available starting materials.
• To create a method compatible with the construction of DNA-encoded libraries.

Main Methods:

• Utilized photoredox catalysis with hydrogen atom transfer (HAT) for catalytic activation.
• Employed DNA-linked acrylamides as alkylating agents.
• Investigated the reaction scope with various five-, six-, and seven-membered cyclic substrates.

Main Results:

• Successfully achieved α-alkylation of N-Boc saturated heterocycles.
• Demonstrated the tolerance of diverse cyclic substrates (5-, 6-, and 7-membered rings).
• Established a mild, DNA-compatible reaction condition suitable for library synthesis.

Conclusions:

• The developed photoredox-catalyzed HAT reaction provides an efficient route for α-alkylation of heterocycles.
• This method streamlines the functionalization of native C-H bonds in cyclic systems.
• The reaction is well-suited for the synthesis of DNA-encoded libraries, expanding possibilities in drug discovery.