:Reductions with hydrosilanes

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.{{cite journal |last1=Kraus |first1=George A. |last2=Molina |first2=Maria Teresa |last3=Walling |first3=John A. |title=Reduction of cyclic hemiacetals. The synthesis of demethoxyeleutherin and nanaomycin A |journal=Journal of the Chemical Society, Chemical Communications |date=1986 |issue=21 |pages=1568 |doi=10.1039/C39860001568}} Primary alcohols require an excess of the silane, a stronger Lewis acid, and long reaction times.{{cite journal |last1=Gevorgyan |first1=Vladimir |last2=Rubin |first2=Michael |last3=Benson |first3=Sharonda |last4=Liu |first4=Jian-Xiu |last5=Yamamoto |first5=Yoshinori |title=A Novel B(C₆F₅)₃-Catalyzed Reduction of Alcohols and Cleavage of Aryl and Alkyl Ethers with Hydrosilanes † |journal=The Journal of Organic Chemistry |date=September 2000 |volume=65 |issue=19 |pages=6179–6186 |doi=10.1021/jo000726d|pmid=10987957}}

:File:HSScope1.png

Skeletal rearrangements are sometimes induced.{{cite journal |last1=Adlington |first1=Merwyn G. |last2=Orfanopoulos |first2=Michael |last3=Fry |first3=James L. |title=A convenient one-step synthesis of hydrocarbons from alcohols through use of the organosilane-boron trifluoride reducing system |journal=Tetrahedron Letters |date=August 1976 |volume=17 |issue=34 |pages=2955–2958 |doi=10.1016/S0040-4039(01)85498-8}} Another side reaction is nucleophilic attack of the conjugate base on the intermediate carbocation.{{cite journal |last1=Doyle |first1=Michael P. |last2=McOsker |first2=Charles C. |title=Silane reductions in acidic media. 10. Ionic hydrogenation of cycloalkenes. Stereoselectivity and mechanism |journal=The Journal of Organic Chemistry |date=February 1978 |volume=43 |issue=4 |pages=693–696 |doi=10.1021/jo00398a039}} 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.{{cite journal |last1=Carey |first1=Francis A. |last2=Tremper |first2=Henry S. |title=Carbonium ion-silane hydride transfer reactions. II. 2-Phenyl-2-norbornyl cation |journal=The Journal of Organic Chemistry |date=January 1969 |volume=34 |issue=1 |pages=4–6 |doi=10.1021/jo00838a002}} None of the exo diastereomer was observed.

:File:HSStereo1.png

Allylic alcohols may be deoxygenated in the presence of tertiary alcohols when ethereal lithium perchlorate is employed as a source of Li⁺.{{cite journal |last1=Wustrow |first1=David J. |last2=Smith |first2=William J. |last3=Wise |first3=Lawrence D. |title=Selective deoxygenation of allylic alcohols and acetates by lithium perchlorate promoted triethylsilane reduction |journal=Tetrahedron Letters |date=January 1994 |volume=35 |issue=1 |pages=61–64 |doi=10.1016/0040-4039(94)88162-6}}

:File:HSScope2.png

Reductions of alkyl halides and triflates gives poorer yields in general than reductions of alcohols. A Lewis or Bronsted acid is required.{{cite journal |last1=Barclay |first1=L. R. C. |last2=Sonawane |first2=H. R. |last3=MacDonald |first3=M. C. |title=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 |journal=Canadian Journal of Chemistry |date=15 January 1972 |volume=50 |issue=2 |pages=281–290 |doi=10.1139/v72-041}}

:File:HSScope3.png

;Aldehydes and ketones

Polymeric hydrosilanes, such as polymethylhydrosiloxane (PHMS), may be employed to facilitate separation of the reduced products from silicon-containing byproducts.{{cite journal |last1=Pri-Bar |first1=Ilan |last2=Buchman |first2=Ouri |title=Homogeneous, palladium-catalyzed, selective hydrogenolysis of organohalides |journal=The Journal of Organic Chemistry |date=March 1986 |volume=51 |issue=5 |pages=734–736 |doi=10.1021/jo00355a029}}{{cite journal |last1=Fujita |first1=Makoto |last2=Hiyama |first2=Tamejiro |title=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 |journal=The Journal of Organic Chemistry |date=November 1988 |volume=53 |issue=23 |pages=5405–5415 |doi=10.1021/jo00258a003}}

:File:HSEx.png

Enantioselective reductions of ketones may be accomplished through the use of catalytic amounts of chiral transition metal complexes.{{cite journal |last1=Larson |first1=Gerald L. |last2=Liberatore |first2=Richard J. |title=Organosilanes in Metal-Catalyzed, Enantioselective Reductions |journal=Organic Process Research & Development |date=26 July 2021 |volume=25 |issue=8 |pages=1719–1787 |doi=10.1021/acs.oprd.1c00073|doi-access=free}} 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.{{cite journal |last1=Lipshutz |first1=Bruce H. |last2=Noson |first2=Kevin |last3=Chrisman |first3=Will |last4=Lower |first4=Asher |title=Asymmetric Hydrosilylation of Aryl Ketones Catalyzed by Copper Hydride Complexed by Nonracemic Biphenyl Bis - phosphine Ligands |journal=Journal of the American Chemical Society |date=July 2003 |volume=125 |issue=29 |pages=8779–8789 |doi=10.1021/ja021391f|pmid=12862472|bibcode=2003JAChS.125.8779L }}

:File:HSStereo2.png

In the presence of rhodium catalyst 1 and rhodium trichloride, 2-phenylcyclohexanone is reduced with no diastereoselectivity but high enantioselectivity.{{cite journal |last1=Nishiyama |first1=Hisao |last2=Park |first2=Soon-Bong |last3=Itoh |first3=Kenji |title=Stereoselectivity in hydrosilylative reduction of substituted cyclohexanone derivatives with chiral rhodium-bis(oxazolinyl)pyridine catalyst |journal=Tetrahedron: Asymmetry |date=August 1992 |volume=3 |issue=8 |pages=1029–1034 |doi=10.1016/S0957-4166(00)86036-X}}

:File:HSStereo3.png

;Esters

Esters may be reduced to alcohols under conditions of nucleophilic activation with caesium or potassium fluoride.{{cite journal |last1=Corriu |first1=R.J.P. |last2=Perz |first2=R. |last3=Reye |first3=C. |title=Activation of silicon-hydrogen, silicon-oxygen, silicon-nitrogen bonds in heterogeneous phase |journal=Tetrahedron |date=January 1983 |volume=39 |issue=6 |pages=999–1009 |doi=10.1016/S0040-4020(01)88599-9}}

:File:HSScope6.png

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.

{{NumBlk|:|$$

\ce{\mathit{n}-C10H21CHO} + {\color{Blue}\ce{PhMe2Si}}\ce{H ->[\ce{TBAF}][\ce{rt}] \mathit{n}-C10H21CH2O}{\color{Blue}\ce{SiMe2Ph}}

|{{EquationRef|13}}}}

:$$

\begin{array}{lr}

\ce{Solvent} & \ce{Yield}(\%) \\

\hline

\ce{CH2Cl2} & 1\\

\ce{THF} & 9\\

\ce{Me2NCOH} & 56\\

\ce{DMPU} & 89\\

\ce{HMPA} & 91

\end{array}

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.{{cite journal |last1=Kursanov |first1=D. N. |last2=Parnes |first2=Z. N. |last3=Bolestova |first3=G. I. |title=Ionic hydrogenation of anthracene and dihydroanthragene with a hydride ion donor |journal=Bulletin of the Academy of Sciences of the USSR Division of Chemical Science |date=May 1968 |volume=17 |issue=5 |pages=1107 |doi=10.1007/BF00910867}}

:File:HSScope4.png

Aromatic compounds may be reduced with TFA and triethylsilane. Substituted furans are reduced to tetrahydrofuran derivatives in high yield.Bolestova, G. I.; Parnes, Z. N.; Kursanov, D. N. J. Org. Chem. USSR (Engl. Transl.) 1979, 15, 1129.

:File:HSScope5.png

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.{{cite journal |last1=Takano |first1=Seiichi |last2=Moriya |first2=Minoru |last3=Ogasawara |first3=Kunio |title=A concise stereocontrolled total synthesis of (+)-estrone |journal=Tetrahedron Letters |date=March 1992 |volume=33 |issue=14 |pages=1909–1910 |doi=10.1016/S0040-4039(00)74175-X}}

:File:HSSynth.png

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.{{cite journal |last1=Federspiel |first1=Muriel |last2=Fischer |first2=Rolf |last3=Hennig |first3=Michael |last4=Mair |first4=Hans-Jürgen |last5=Oberhauser |first5=Thomas |last6=Rimmler |first6=Gösta |last7=Albiez |first7=Thomas |last8=Bruhin |first8=Jürg |last9=Estermann |first9=Heinrich |last10=Gandert |first10=Carsten |last11=Göckel |first11=Volker |last12=Götzö |first12=Stephan |last13=Hoffmann |first13=Ursula |last14=Huber |first14=Gabriel |last15=Janatsch |first15=Günter |last16=Lauper |first16=Stephan |last17=Röckel-Stäbler |first17=Odette |last18=Trussardi |first18=Rene |last19=Zwahlen |first19=Andreas G. |title=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 |journal=Organic Process Research & Development |date=July 1999 |volume=3 |issue=4 |pages=266–274 |doi=10.1021/op9900176}}

:File:HSScope8.png

Other functional groups that have been reduced with hydrosilanes include amides,{{cite journal |last1=Selvakumar |first1=Kumaravel |last2=Harrod |first2=John F. |title=Titanocene-Catalyzed Coupling of Amides in the Presence of Organosilanes To Form Vicinal Diamines |journal=Angewandte Chemie International Edition |date=2001 |volume=40 |issue=11 |pages=2129–2131 |doi=10.1002/1521-3773(20010601)40:11<2129::AID-ANIE2129>3.0.CO;2-2}} and α,β-unsaturated esters{{cite journal |last1=Ojima |first1=Iwao |last2=Kumagai |first2=Miyoko |last3=Nagai |first3=Yoichiro |title=Hydrosilylation of α,β-unsaturated nitriles and esters catalyzed by tris (triphenylphosphine)chlororhodium |journal=Journal of Organometallic Chemistry |date=May 1976 |volume=111 |issue=1 |pages=43–60 |doi=10.1016/S0022-328X(00)87057-6}} enamines,{{cite journal |last1=Rosentreter |first1=U. |title=Stereoselective Synthesis of all- trans -Isomers of 1,2,3,4-Tetrahydropyridines and Piperidines from Hantzsch-Type 1,4-Dihydropyridines |journal=Synthesis |date=1985 |volume=1985 |issue=2 |pages=210–212 |doi=10.1055/s-1985-31160}} imines,{{cite journal |last1=Loim |first1=N. M. |title=Ionic hydrogenation of the C=N linkage in azomethynes |journal=Bulletin of the Academy of Sciences of the USSR Division of Chemical Science |date=June 1968 |volume=17 |issue=6 |pages=1345 |doi=10.1007/BF01106312}} and azides.{{cite journal |last1=Chandrasekhar |first1=S. |last2=Chandraiah |first2=L. |last3=Reddy |first3=Ch. Raji |last4=Reddy |first4=M. Venkat |title=Direct Conversion of Azides and Benzyl Carbamates to t- Butyl Carbamates Using Polymethylhydrosiloxane and Pd-C |journal=Chemistry Letters |date=July 2000 |volume=29 |issue=7 |pages=780–781 |doi=10.1246/cl.2000.780}}

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

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Category:Organic reactions