Ether Synthesis by Acetal Reduction

• General Characteristics

The reduction of the oxonium cations generated by acidic treatment of acetals is a way to synthesize ethers.

Triethylsilane (Et₃SiH) is a reducing agent that is stable under acidic conditions and suited for this purpose. Lewis acids such as BF₃ and TMSOTf are often used to enhance the reactivity. Other known conditions include LiAlH₄-BF₃ (or AlCl₃), DIBAL-H, BH₃, and H₂/Rh-Al₂O₃/HCl.

• General References

・Tsunoda, T.; Suzuki, M.; Noyoro, R. Tetrahedron Lett. 1979, 20, 4679. doi:10.1016/S0040-4039(01)86681-8

• Reaction Mechanism

• Examples

In the reduction of benzylidenes (or p-methoxybenzylidenes) by DIBAL, the products will be mono-protected with Bn (or PMB) at the more sterically congested hydroxyl group.

Bn and PMB groups can be strategically migrated into more congested positions using oxidative acetal formation by DDQ and reductive ring opening by DIBAL.

• Experimental Procedure

• Experimental Tips

• References

• Related Books

migration of benzyl and PMB groups, Reduction of acetals, synthesis of ethers