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.

Tetramethyldisiloxane: A Practical Organosilane Reducing Agent

“…62 The reduction of phosphine oxides 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 has proven to be a somewhat difficult process with one method employing hexachlorodisilane as the reductant. 63,64 Aluminum hydrides, 65 SmI 2 /HMPA, 66 Cp 2 TiCl 2 /Mg, 67 and Bi/TiO 2 68 have also been used. None of these address the practical scalable approaches demanded by industry.…”

Tris[4-(trifluoromethyl)phenyl]phosphine

“…Si(OEt) 3 [RuCl 2 (p-cymene)] 2 (2.5 mol %) P(4-CF 3 -C 6 H 4 ) 3 (15 mol %) HCO 2 Na (30 mol %) dioxane, 100 ºC, 20 h (14)…”

“…Hulshof and coworkers reported that the reaction of 1-octanol in the presence of Ru 3 (CO) 12 (5 mol %) and TTPP (17 mol %) with tolane (200 mol %) as hydrogen acceptor in p-xylene at 100 • C for 4 h gave 1-octanal in 60% yield (eq 18). 13 p-xylene 100 °C, 4 h Ru 3 (CO) 12 (5 mol %) P(4-CF 3 -C 6 H 4 ) 3 (17 mol %) Final Notes. Tris [4-(trifluoromethyl)phenyl]phosphine has been widely used as an electron-deficient phosphine ligand in the transition metal-catalyzed cross-coupling, oxidative crosscoupling, catalytic alkene functionalization, and oxidation of alcohols.…”

“…1 Tris [4-(trifluoromethyl)phenyl]phosphine (TTPP) was also prepared by the reduction of the phosphine oxides with diisobutylaluminum hydride (DIBAL-H). 3 Purification: the pure TTPP was obtained by sublimation at 75 • C (0.1 Torr) or by column chromatography on silica using petroleum ether as eluent followed by recrystallization from ethanol. 1 Carbostannylation of Alkynes with 1,2-Dienes.…”

Highly efficient reduction of tertiary phosphine oxides and sulfides with amine-assisted aluminum hydrides under mild conditions

“…Among many reducing agents silanes and aluminum hydrides remain the reagents of choice for reduction of phosphine oxides [17][18][19][20][21][22][23][24][25].…”