On the susceptibility of organic peroxy bonds to hydride reduction

Article abstract of DOI:10.1021/jo050139y

Reduction of organic molecules that contain a peroxy bond is broadly considered as a "risky" and uncertain operation when cleavage of the peroxy linkage is not desired. For this reason, such reduction steps are normally avoided at the planning stage of the synthesis when possible. As a natural consequence, the information in the literature about the susceptibility of organic peroxy bonds to reducing species is scant. In this work the tolerance of organic peroxy bonds to some common hydride reductants was examined systematically for the first time. Using reduction of ester group to alcohol as a probe, LiAlH₄, LiAlH(O^tBu)₃, LiBHEt ₃, and LiBH₄ were found to be significantly better than other reductants examined when taking into consideration both the completeness of the reduction of ester groups and the peroxy bond survival rate. LiBH ₄ appeared to be the most suitable reductant for the reduction under discussion, not only because of the high reduction yields/excellent compatibility with peroxy bonds, but also because of the advantages in practical aspects. The results disclosed herein may (hopefully) provide a handy reference for dealing with reduction of other peroxy bond-containing molecules in the future.