Journal of Organic Chemistry 2008-02-15

Reduction of tertiary phosphine oxides with DIBAL-H.

Carl A Busacca, Ravinder Raju, Nelu Grinberg, Nizar Haddad, Paul James-Jones, Heewon Lee, Jon C Lorenz, Anjan Saha, Chris H Senanayake

Index: J. Org. Chem. 73 , 1524-1531, (2008)

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Abstract

The reduction of tertiary phosphine oxides (TPOs) and sulfides with diisobutylaluminum hydride (DIBAL-H) has been studied in detail. An extensive solvent screen has revealed that hindered aliphatic ethers, such as MTBE, are optimum for this reaction at ambient temperature. Many TPOs undergo considerable reduction at ambient temperature and then stall due to inhibition. 31P and 13C NMR studies using isotopically labeled substrates as well as competition studies have revealed that the source of this inhibition is tetraisobutyldialuminoxane (TIBAO), which builds up as the reaction proceeds. TIBAO selectively coordinates the TPO starting material, preventing further reduction. Several strategies have been found to circumvent this inhibition and obtain full conversion with this extremely inexpensive reducing agent for the first time. Practical reduction protocols for these critical targets have been developed.