Reductions with hydrosilanes

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Reductions with hydrosilanes are methods used for hydrogenation and hydrogenolysis of organic compounds. The approach is a subset of ionic hydrogenation. In this particular method, the substrate is treated with a hydrosilane and auxiliary reagent, often a strong acid, resulting in formal transfer of hydride from silicon to carbon.[1] This style of reduction with hydrosilanes enjoys diverse if specialized applications.

Scope[edit]

Deoxygenation of alcohols and halides[edit]

Some alcohols are reduced to alkanes when treated with hydrosilanes in the presence of a strong Lewis acid. Brønsted acids may also be used. Tertiary alcohols undergo facile reduction using boron trifluoride etherate as the Lewis acid.[2] Primary alcohols require an excess of the silane, a stronger Lewis acid, and long reaction times.[3]

Skeletal rearrangements are sometimes induced.[4] Another side reaction is nucleophilic attack of the conjugate base on the intermediate carbocation.[5] In organosilane reductions of substrates bearing prostereogenic groups, diastereoselectivity is often high. Reduction of either diastereomer of 2-phenyl-2-norbornanol leads exclusively to the endo diastereomer of 2-phenylnorbornane.[6] None of the exo diastereomer was observed.

Allylic alcohols may be deoxygenated in the presence of tertiary alcohols when ethereal lithium perchlorate is employed as a source of Li+.[7]

Reductions of alkyl halides and triflates gives poorer yields in general than reductions of alcohols. A Lewis or Bronsted acid is required.[8]

Reduction of carbonyls[edit]

Aldehydes and ketones

Polymeric hydrosilanes, such as polymethylhydrosiloxane (PHMS), may be employed to facilitate separation of the reduced products from silicon-containing byproducts.[9][10]

Enantioselective reductions of ketones may be accomplished through the use of catalytic amounts of chiral transition metal complexes.[11] In some cases, the transition metal simply serves as a Lewis acid that coordinates to the ketone oxygen; however, some metals (most notably copper) react with hydrosilanes to afford metal hydride intermediates, which act as the active reducing agent.[12]

In the presence of rhodium catalyst 1 and rhodium trichloride, 2-phenylcyclohexanone is reduced with no diastereoselectivity but high enantioselectivity.[13]

Esters

Esters may be reduced to alcohols under conditions of nucleophilic activation with caesium or potassium fluoride.[14]

Aldehydes undergo hydrosilylation in the presence of hydrosilanes and fluoride. The resulting silyl ethers can be hydrolyzed with 1 M hydrochloric acid. Optimal yields of the hydrosilylation are obtained when the reaction is carried out in very polar solvents.[10]

(13)

Reduction of C=C bonds[edit]

Hydrosilanes can reduce 1,1-disubstituted double bonds that form stable tertiary carbocations upon protonation. Trisubstituted double bonds may be reduced selectively in the presence of 1,2-disubstituted or monosubstituted alkenes.[15]

Aromatic compounds may be reduced with TFA and triethylsilane. Substituted furans are reduced to tetrahydrofuran derivatives in high yield.[16]

A synthesis of (+)-estrone relies on selective hydrosilane reduction of a conjugated alkene as a key step. The ketone carbonyl and isolated double bond are unaffected under the conditions shown.[17]

Ether cleavage[edit]

Acetals, ketals, and aminals are reduced in the presence of hydrosilanes and acid. Site-selective reduction of acetals and ketals whose oxygens are inequivalent have been reported—the example below is used in a synthesis of Tamiflu.[18]

Other functional groups that have been reduced with hydrosilanes include amides,[19] and α,β-unsaturated esters[20] enamines,[21] imines,[22] and azides.[23]

Safety[edit]

Trifluoroacetic acid, often used in these reductions, is a strong, corrosive acid. Some hydrosilanes are pyrophoric.


References[edit]

  1. ^ Larson, Gerald L.; Fry, James L. (2008). "Ionic and Organometallic-Catalyzed Organosilane Reductions". Organic Reactions: 1–737. doi:10.1002/0471264180.or071.01. ISBN 978-0471264187.
  2. ^ Kraus, George A.; Molina, Maria Teresa; Walling, John A. (1986). "Reduction of cyclic hemiacetals. The synthesis of demethoxyeleutherin and nanaomycin A". Journal of the Chemical Society, Chemical Communications (21): 1568. doi:10.1039/C39860001568.
  3. ^ Gevorgyan, Vladimir; Rubin, Michael; Benson, Sharonda; Liu, Jian-Xiu; Yamamoto, Yoshinori (September 2000). "A Novel B(C6F5)3-Catalyzed Reduction of Alcohols and Cleavage of Aryl and Alkyl Ethers with Hydrosilanes †". The Journal of Organic Chemistry. 65 (19): 6179–6186. doi:10.1021/jo000726d. PMID 10987957.
  4. ^ Adlington, Merwyn G.; Orfanopoulos, Michael; Fry, James L. (August 1976). "A convenient one-step synthesis of hydrocarbons from alcohols through use of the organosilane-boron trifluoride reducing system". Tetrahedron Letters. 17 (34): 2955–2958. doi:10.1016/S0040-4039(01)85498-8.
  5. ^ Doyle, Michael P.; McOsker, Charles C. (February 1978). "Silane reductions in acidic media. 10. Ionic hydrogenation of cycloalkenes. Stereoselectivity and mechanism". The Journal of Organic Chemistry. 43 (4): 693–696. doi:10.1021/jo00398a039.
  6. ^ Carey, Francis A.; Tremper, Henry S. (January 1969). "Carbonium ion-silane hydride transfer reactions. II. 2-Phenyl-2-norbornyl cation". The Journal of Organic Chemistry. 34 (1): 4–6. doi:10.1021/jo00838a002.
  7. ^ Wustrow, David J.; Smith, William J.; Wise, Lawrence D. (January 1994). "Selective deoxygenation of allylic alcohols and acetates by lithium perchlorate promoted triethylsilane reduction". Tetrahedron Letters. 35 (1): 61–64. doi:10.1016/0040-4039(94)88162-6.
  8. ^ Barclay, L. R. C.; Sonawane, H. R.; MacDonald, M. C. (15 January 1972). "Sterically Hindered Aromatic Compounds. III. Acid-catalyzed Reactions of 2,4,6-Tri- t -butyl- and 2-Methyl-4,6-di-t-butylbenzyl Alcohols and Chlorides". Canadian Journal of Chemistry. 50 (2): 281–290. doi:10.1139/v72-041.
  9. ^ Pri-Bar, Ilan; Buchman, Ouri (March 1986). "Homogeneous, palladium-catalyzed, selective hydrogenolysis of organohalides". The Journal of Organic Chemistry. 51 (5): 734–736. doi:10.1021/jo00355a029.
  10. ^ a b Fujita, Makoto; Hiyama, Tamejiro (November 1988). "Fluoride ion-catalyzed reduction of aldehydes and ketones with hydrosilanes. Synthetic and mechanistic aspects and an application to the threo-directed reduction of .alpha.-substituted alkanones". The Journal of Organic Chemistry. 53 (23): 5405–5415. doi:10.1021/jo00258a003.
  11. ^ Larson, Gerald L.; Liberatore, Richard J. (26 July 2021). "Organosilanes in Metal-Catalyzed, Enantioselective Reductions". Organic Process Research & Development: acs.oprd.1c00073. doi:10.1021/acs.oprd.1c00073.
  12. ^ Lipshutz, Bruce H.; Noson, Kevin; Chrisman, Will; Lower, Asher (July 2003). "Asymmetric Hydrosilylation of Aryl Ketones Catalyzed by Copper Hydride Complexed by Nonracemic Biphenyl Bis - phosphine Ligands". Journal of the American Chemical Society. 125 (29): 8779–8789. doi:10.1021/ja021391f. PMID 12862472.
  13. ^ Nishiyama, Hisao; Park, Soon-Bong; Itoh, Kenji (August 1992). "Stereoselectivity in hydrosilylative reduction of substituted cyclohexanone derivatives with chiral rhodium-bis(oxazolinyl)pyridine catalyst". Tetrahedron: Asymmetry. 3 (8): 1029–1034. doi:10.1016/S0957-4166(00)86036-X.
  14. ^ Corriu, R.J.P.; Perz, R.; Reye, C. (January 1983). "Activation of silicon-hydrogen, silicon-oxygen, silicon-nitrogen bonds in heterogeneous phase". Tetrahedron. 39 (6): 999–1009. doi:10.1016/S0040-4020(01)88599-9.
  15. ^ Kursanov, D. N.; Parnes, Z. N.; Bolestova, G. I. (May 1968). "Ionic hydrogenation of anthracene and dihydroanthragene with a hydride ion donor". Bulletin of the Academy of Sciences of the USSR Division of Chemical Science. 17 (5): 1107. doi:10.1007/BF00910867.
  16. ^ Bolestova, G. I.; Parnes, Z. N.; Kursanov, D. N. J. Org. Chem. USSR (Engl. Transl.) 1979, 15, 1129.
  17. ^ Takano, Seiichi; Moriya, Minoru; Ogasawara, Kunio (March 1992). "A concise stereocontrolled total synthesis of (+)-estrone". Tetrahedron Letters. 33 (14): 1909–1910. doi:10.1016/S0040-4039(00)74175-X.
  18. ^ Federspiel, Muriel; Fischer, Rolf; Hennig, Michael; Mair, Hans-Jürgen; Oberhauser, Thomas; Rimmler, Gösta; Albiez, Thomas; Bruhin, Jürg; Estermann, Heinrich; Gandert, Carsten; Göckel, Volker; Götzö, Stephan; Hoffmann, Ursula; Huber, Gabriel; Janatsch, Günter; Lauper, Stephan; Röckel-Stäbler, Odette; Trussardi, Rene; Zwahlen, Andreas G. (July 1999). "Industrial Synthesis of the Key Precursor in the Synthesis of the Anti-Influenza Drug Oseltamivir Phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3 R ,4 S ,5 S )-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate". Organic Process Research & Development. 3 (4): 266–274. doi:10.1021/op9900176.
  19. ^ Selvakumar, Kumaravel; Harrod, John F. (2001). "Titanocene-Catalyzed Coupling of Amides in the Presence of Organosilanes To Form Vicinal Diamines". Angewandte Chemie International Edition. 40 (11): 2129–2131. doi:10.1002/1521-3773(20010601)40:11<2129::AID-ANIE2129>3.0.CO;2-2.
  20. ^ Ojima, Iwao; Kumagai, Miyoko; Nagai, Yoichiro (May 1976). "Hydrosilylation of α,β-unsaturated nitriles and esters catalyzed by tris (triphenylphosphine)chlororhodium". Journal of Organometallic Chemistry. 111 (1): 43–60. doi:10.1016/S0022-328X(00)87057-6.
  21. ^ Rosentreter, U. (1985). "Stereoselective Synthesis of all- trans -Isomers of 1,2,3,4-Tetrahydropyridines and Piperidines from Hantzsch-Type 1,4-Dihydropyridines". Synthesis. 1985 (2): 210–212. doi:10.1055/s-1985-31160.
  22. ^ Loim, N. M. (June 1968). "Ionic hydrogenation of the C=N linkage in azomethynes". Bulletin of the Academy of Sciences of the USSR Division of Chemical Science. 17 (6): 1345. doi:10.1007/BF01106312.
  23. ^ Chandrasekhar, S.; Chandraiah, L.; Reddy, Ch. Raji; Reddy, M. Venkat (July 2000). "Direct Conversion of Azides and Benzyl Carbamates to t- Butyl Carbamates Using Polymethylhydrosiloxane and Pd-C". Chemistry Letters. 29 (7): 780–781. doi:10.1246/cl.2000.780.
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