A Catalytic Method for the Reduction of Secondary and Tertiary Phosphine Oxides

Abstract

TMDS has been found to be an efficient hydride source for the reduction of tertiary and secondary phosphine oxides using a catalytic amount of Ti(Oi-Pr)₄. All classes of tertiary phosphine oxides, such as triaryl, trialkyl, and diphosphine, were effectively reduced.

phosphorus - reductions - titanium - hydrosiloxane - phosphine oxides

References and Notes

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2b Berthod M. Saluzzo C. Mignani G. Lemaire M. Tetrahedron: Asymmetry  2004,  15:  639 

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3b Engel R. The Reduction of Quinquevalent Phosphorus to the Trivalent State   Engel R. Marcel Dekker, Inc.; New York: 1992. 

4a LiAlH₄, see: Henson PD. Naumann K. Mislow K. J. Am. Chem. Soc.  1969,  91:  5645 

4b LiAlH₄/CeCl₃, see: Imamoto T. Takeyama T. Kusumoto T. Chem. Lett.  1985,  1491 

4c LiAlH₄/MeOTf, see: Imamoto T. Kikuchi S.-I. Miura T. Wada Y. Org. Lett.  2001,  3:  87 

Alane (AlH₃) prepared in situ by addition of concd H₂SO₄ to a solution of LiAlH₄ in THF, see:

4d Griffin S. Heath L. Wyatt P. Tetrahedron Lett.  1998,  39:  4405 

4e Bootle-Wilbraham A. Head S. Longstaff J. Wyatt P. Tetrahedron Lett.  1999,  40:  5267 

4f DIBAL-H for sec-phosphine oxides: Busacca CA. Lorenz JC. Grinberg N. Haddad N. Hrapchak M. Latli B. Lee H. Sabila P. Saha A. Sarvestani M. Shen S. Varsolona R. Wei X. Senanayake CH. Org. Lett.  2005,  7:  4277 

4g Phosphine boranes can be obtained by treatment of the reaction mixtures with borane-THF or directly by reduction of phosphine oxides with borane in THF. For the reduction of tertiary phosphine oxides, see: Köster R. Morita Y. Angew. Chem., Int. Ed. Engl.  1965,  4:  593 

4h For the reduction of secondary phosphine oxides, see: Stankevic M. Pietrusiewicz KM. Synlett  2003,  1012 

4i Phosphine boranes could be obtained directly from phosphine oxides by using a mixture of LiAlH₄/NaBH₄/CeCl₃, see: Imamoto T. Oshiki T. Onozawa T. Kusumoto T. Sato K. J. Am. Chem. Soc.  1990,  112:  5244 

5a HSiCl₃: Horner L. Balzer WD. Tetrahedron Lett.  1965,  21:  1157 

5b HSiCl₃/NR₃: Cremer SE. Chorvat RJ. J. Org. Chem.  1967,  32:  4066 

5c PhSiH₃: Marsi KL. J. Org. Chem.  1974,  39:  265 

5d Ph₂SiH: McKinstry L. Livinghouse T. Tetrahedron  1994,  50:  6145 

5e Me₃SiCl/LiAlH₄: Kyba EP. Liu ST. Harris RL. Organometallics  1983,  2:  1877 

6

Trichlorosilane: fp -13 °C, bp 31 °C; phenylsilane: fp 8 °C, bp 120 °C; diphenylsilane: fp 98 °C, bp 97 °C.

7 Deleris G. Dunogues J. Calas R. Bull. Soc. Chim. Fr.  1974,  3-4:  672 

8 Naumann K. Zon G. Mislow K. J. Am. Chem. Soc.  1969,  91:  7012 

9 Timokhin BV. Kazantseva MV. Blazhev DG. Rokhin AV. Russ. J. Gen. Chem.  2000,  70:  1310 

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12 Handa Y. Inanaga J. Yamaguchi M. J. Chem. Soc., Chem. Commun.  1989,  298 

13a Phosphine oxides have been reduced using stoichiometric amount of MgCp₂TiCl₂ in boiling THF: Mathey F. Maillet R. Tetrahedron Lett.  1980,  21:  2525 

13b Phosphine oxides have been reduced using two equiv of Schwartz reagent: Zablocka M. Delest B. Igau A. Skowronska A. Majoral J.-P. Tetrahedron Lett.  1997,  38:  5997 

14 Berk SC. Buchwald SL. J. Org. Chem.  1992,  57:  3751 

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16 Lawrence NJ. Drew MD. Bushell SM. J. Chem. Soc., Perkin Trans. 1  1999,  3381 

(EtO)₃SiH should be used properly since it is volatile and is known to cause blindness. Furthermore, incident using this product have been reported, see ref. 12 in:

17a Berk SC. Kreutzer KA. Buchwald SL. J. Am. Chem. Soc.  1991,  113:  5093 

17b Berk SC. Buchwald SL. J. Org. Chem.  1993,  58:  3221 

18 PMHS has already been used to reduce tertiary phosphine oxides neat at 280-300 °C, see: Fritzsche H. Hasserodt U. Korte F. Friese G. Adrian K. Arenz HJ. Chem. Ber.  1964,  97:  1988 

19

SAFETY: TMDS is quite stable and not generally considered as a hazardous material, but under specific conditions, TMDS can generate high volumes of hydrogen gas in acid and basic conditions. Thus, all the necessary precautions for the safe handling of flammable gases should therefore be observed as mentioned in MSDS. Although TMDS proved to be stable up to 250 °C in a glass vessel, small exothermic reactions were observed with metallic ones. Furthermore, the use of glassware always gives rise to significantly higher conversion than the use of metal-containing reactors. This is probably due to the low stability of the titanium hydride intermediate. Further studies are being done to confirm this.

20

Ace pressure tube Aldrich Ref. Z181099. We have checked that under those conditions the internal pressure does not exceed 1.2 bar.

21

CAUTION: The TMDS remaining in the filtrate must be destroyed by slow addition of a 3 M alcoholic solution of KOH at r.t. TMDS decomposes on contact with bases, forming hydrogen.

22

General Procedure for the Reduction of dppe, dppp, and dppb Oxides
In a 30 mL sealed tube with a magnetic stirrer were placed the diphosphine (2.32 mmol) and methylcyclohexane (5 mL). Then, TMDS (1.03 mL, 5.8 mmol, 2.5 equiv) was added to the reaction vessel followed by Ti(Oi-Pr)₄ (0.07 mL, 0.23 mmol). The flask was heated at 100 °C. After 7 h, the ³¹P NMR analysis showed the complete conversion of the starting reagent. The heterogeneous mixture was cooled at 0 °C, filtrated over porous glass and washed with 4 × 5 mL of pentane. The resulting white solid was dried under vacuum, yielding the desired compound.
1,2-Bis(diphenylphoshino)ethane(dppe): yield 95%, mp 161 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.32 (20 H, m), 2.13-2.08 (4 H, m). ³¹P NMR (81 MHz, CDCl₃): δ = -11.3.
1,3-Bis(diphenylphosphino)propane(dppp): yield 91%, mp 63 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.39-7.33 (8 H, m), 7.30-7.28 (12 H, m), 2.21 (4 H, t, J = 7.5 Hz), 1.71-1.55 (2 H, m). ³¹P NMR (81 MHz, CDCl₃): δ = -16.3.
1,4-Bis(diphenylphosphino)butane(dppb): yield 95%, mp 135 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.44-7.34 (8 H, m), 7.33-7.30 (12 H, m), 2.04 (4 H, t, J = 7.5 Hz), 1.62-1.54 (4 H, m). ³¹P NMR (81 MHz, CDCl₃): δ = -14.9.

23 Takaya H. Akutagawa S. Noyori R. Org. Synth., Coll. Vol. VIII  1993,  65-69:  57 

( S )-2,2′-Bis(diphenylphosphino)-1,1′-binaphtyl (BINAP)

24a

In a tube with a magnetic stirrer was placed (S)-BINAP oxide (1.44 g, 2.2 mmol, 1 equiv) in 5 mL of methylcyclohexane. To this heterogeneous mixture was added TMDS (0.97 mL, 5.5 mmol, 2.5 equiv) and Ti(Oi-Pr)₄ (70 µL, 0,22 mmol, 0.1 equiv). The tube was sealed and the mixture stirred and heated at 100 °C overnight. The hetero-geneous mixture was cooled at 0 °C and filtrated over porous glass, washing 4 to 5 times with cold pentane. The resulting white solid was dried under vacuum, yielding 1.26 g (92% yield, ee >98%). ¹H NMR (300 MHz, CDCl₃): δ = 7.93 (2 H, d, J = 8.5 Hz,), 7.88 (2 H, d, J = 8.1 Hz), 7.51 (2 H, d, J = 8.5 Hz), 7.39 (2 H, t, J = 7.9 Hz), 7.24-7.10 (20 H, m), 6.95 (2 H, dd, J = 8.1 Hz), 6.89 (2 H, d, J = 8.5 Hz). ³¹P NMR (81 MHz, CDCl₃): δ = -14.3. [α]_D ²⁵ -224 (c 0.365, benzene); lit. [α]_D ²⁵ -229 (c 0.31, benzene). The ee was determined after oxidation with H₂O₂ according to ref. 24b. Chiral column [Daicel Chiralpak AD, 0.46 cm ∅ × 25 cm, 254 nm UV detector, r.t., eluent 75:25 (n-heptane-2-PrOH), flow rate 0.5 mL/min], t _R = 14.25 min for S and 18.3 for R.

24b Sekar G. Nishiyama H. J. Am. Chem. Soc.  2001,  123:  3603 

25

General Procedure for the Reduction of Trialkylphosphine Oxides
In a 50 mL dried round-bottomed flask fitted with a magnetic stirrer and a condenser were placed the phosphine oxide (5.2 mmol) and methylcyclohexane (5 mL). Then, TMDS (1.14 mL, 6.5 mmol, 1.25 equiv) and Ti(Oi-Pr)₄ (154 µL, 0.52 mmol) were added to the reaction vessel. The heterogeneous mixture was stirred at 100 °C under an argon atmosphere. After 10 h, ³¹P NMR analyses showed the complete conversion of the starting reagent. The mixture was cooled down to 0 °C and 1 M BH₃·THF (10.4 mL, 10.4 mmol, 2 equiv) was added dropwise to the solution. The mixture was allowed to warm to r.t. and stirred for 1 h. The solution was again cooled down to 0 °C and a 3 N alcoholic KOH solution (10 mL) was added dropwise to the reaction vessel (caution: abundant foaming). After gas formation has subsided, the resulting heterogeneous mixture was stirred at 50 °C under an argon atmosphere for 2 h. After cooling, the mixture was washed with H₂O (2 × 5 mL), a 10% aq solution of HCl (5 mL), and a sat. aq solution of NaHCO₃ (5 mL). The resulting solution was dried upon MgSO₄ and concentrated under vacuum, yielding a pale liquid containing only pure phosphine borane.
Tri-n-octylphosphine-borane (TOPB): yield 90%. ¹H NMR (300 MHz, CDCl₃): δ = 1.61-1.20 (42 H, m), 0.95-0.81 (9 H, m). ³¹P NMR (81 MHz, CDCl₃): δ = 15.6.
Tri-n-butylphosphine-borane (TBPB): yield 95%. ¹H NMR (300 MHz, CDCl₃): δ = 1.54-1.35 (18 H, m), 0.90 (9 H, t, J = 7.1 Hz). ³¹P NMR (81 MHz, CDCl₃): δ = 15.6.

26

General Procedure for the Reduction of Secondary Phosphine Oxides
In a 50 mL dried round-bottomed flask fitted with a magnetic stirrer and a condenser were placed secondary phosphine oxide (2 mmol) and methylcyclohexane (5 mL). Then, TMDS (0.44 mL, 2.5 mmol, 1.25 equiv) and Ti(Oi-Pr)₄ (59 µL, 0.2 mmol) were added to the reaction vessel. The heterogeneous mixture was stirred at 100 °C under an argon atmosphere overnight. After 10 h, ³¹P NMR analyses showed the complete conversion of the starting reagent. The mixture was cooled down to 0 °C and 2 M BH₃·DMS (3 mL, 6 mmol, 3 equiv) was added dropwise to the solution. The mixture was allowed to warm to r.t. and stirred for 2 h. The crude material was concentrated under vacuum and purified by flash chromatography EtOAc-cyclohexane (5:95) to give the product as a white solid.
Diphenylphosphine-borane: yield 85%. ¹H NMR (300 MHz, C₆D₆): δ = 7.44-7.38 (4 H, m), 6.98-6.88 (6 H, m), 5.85 (1 H, d, J = 378 Hz), 2.40-1.36 (3 H, br m). ³¹P NMR (81 MHz, C₆D₆): δ = 2.9.
Bis(4-methoxyphenyl)phosphine-borane: yield 89%. ¹H NMR (300 MHz, CDCl₃): δ = 7.57 (4 H, dd, J = 8.9, 2.3 Hz), 6.96 (4 H, d, J = 8.7 Hz), 6.23 (1 H, d, J = 378 Hz). ³¹P NMR (81 MHz, CDCl₃): δ = -1.54.