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Dialkyl ether synthesis through heteroatom homolytic substitution
This approach overcomes steric limitations in classical SN2 reactions by accessing a vast chemical space inaccessible through conventional polar nucleophilic substitution, facilitating late-stage diversification for complex pharmaceutical scaffolds.
A radical-based heteroatom homolytic substitution mechanism enables the selective synthesis of sterically congested dialkyl ethers using titanium and visible-light photoredox catalysis.
- Utilizes an underutilized heteroatom homolytic substitution (het-SH2) mechanism to bypass the sterically congested transition state of SN2 reactions.
- Employs a titanium-based catalytic platform combined with visible-light photoredox chemistry for efficient coupling across various alkyl architectures including 3°–1°.
- Provides access to dialkyl ether bioisosteres such as BCP ethers that are otherwise difficult or impossible to synthesize via standard methods.