title: Reduction of tertiary phosphine oxides with DIBAL-H.
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.
authors.affiliation: Department of Chemical Development, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, USA. cbusacca@rdg.boehringer-ingelheim.com
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.forename: Ravinder
authors.initials: R
authors.lastname: Raju
authors.forename: Nelu
authors.initials: N
authors.lastname: Grinberg
authors.forename: Nizar
authors.initials: N
authors.lastname: Haddad
authors.forename: Paul
authors.initials: P
authors.lastname: James-Jones
authors.forename: Heewon
authors.initials: H
authors.lastname: Lee
authors.forename: Jon C
authors.initials: JC
authors.lastname: Lorenz
authors.forename: Anjan
authors.initials: A
authors.lastname: Saha
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D010087:Oxides; D010720:Phosphines; C035719:diisobutylaluminum