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.
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]
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 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) |
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]
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]
Trifluoroacetic acid, often used in these reductions, is a strong, corrosive acid. Some hydrosilanes are pyrophoric.
An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.
Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula NaBH4. It is a white crystalline solid, usually encountered as an aqueous basic solution. Sodium borohydride is a reducing agent that finds application in papermaking and dye industries. It is also used as a reagent in organic synthesis.
The Wolff–Kishner reduction is a reaction used in organic chemistry to convert carbonyl functionalities into methylene groups. In the context of complex molecule synthesis, it is most frequently employed to remove a carbonyl group after it has served its synthetic purpose of activating an intermediate in a preceding step. As such, there is no obvious retron for this reaction. The reaction was reported by Nikolai Kischner in 1911 and Ludwig Wolff in 1912.
The Hiyama coupling is a palladium-catalyzed cross-coupling reaction of organosilanes with organic halides used in organic chemistry to form carbon–carbon bonds. This reaction was discovered in 1988 by Tamejiro Hiyama and Yasuo Hatanaka as a method to form carbon-carbon bonds synthetically with chemo- and regioselectivity. The Hiyama coupling has been applied to the synthesis of various natural products.
The Corey–Itsuno reduction, also known as the Corey–Bakshi–Shibata (CBS) reduction, is a chemical reaction in which a prochiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol. The oxazaborolidine reagent which mediates the enantioselective reduction of ketones was previously developed by the laboratory of Itsuno and thus this transformation may more properly be called the Itsuno-Corey oxazaborolidine reduction.
Polymethylhydrosiloxane (PMHS) is a polymer with the general structure [−CH3(H)Si−O−]. It is used in organic chemistry as a mild and stable reducing agent easily transferring hydrides to metal centers and a number of other reducible functional groups. A variety of related materials are available under the following CAS registry numbers 9004-73-3, 16066-09-4, 63148-57-2, 178873-19-3. These include the tetramer, copolymers of dimethylsiloxane and methylhydrosiloxane, and trimethylsilyl terminated materials.
Chloroplatinic acid (also known as hexachloroplatinic acid) is an inorganic compound with the formula [H3O]2[PtCl6](H2O)x (0 ≤ x ≤ 6). A red solid, it is an important commercial source of platinum, usually as an aqueous solution. Although often written in shorthand as H2PtCl6, it is the hydronium (H3O+) salt of the hexachloroplatinate anion (PtCl2−
6). Hexachloroplatinic acid is highly hygroscopic.
Organosilicon chemistry is the study of organometallic compounds containing carbon–silicon bonds, to which they are called organosilicon compounds. Most organosilicon compounds are similar to the ordinary organic compounds, being colourless, flammable, hydrophobic, and stable to air. Silicon carbide is an inorganic compound.
Hydrosilylation, also called catalytic hydrosilation, describes the addition of Si-H bonds across unsaturated bonds. Ordinarily the reaction is conducted catalytically and usually the substrates are unsaturated organic compounds. Alkenes and alkynes give alkyl and vinyl silanes; aldehydes and ketones give silyl ethers. Hydrosilylation has been called the "most important application of platinum in homogeneous catalysis."
Hydrosilanes are tetravalent silicon compounds containing one or more Si-H bond. The parent hydrosilane is silane (SiH4). Commonly, hydrosilane refers to organosilicon derivatives. Examples include phenylsilane (PhSiH3) and triethoxysilane ((C2H5O)3SiH). Polymers and oligomers terminated with hydrosilanes are resins that are used to make useful materials like caulks.
Luche reduction is the selective organic reduction of α,β-unsaturated ketones to allylic alcohols with sodium borohydride (NaBH4) and lanthanide chlorides, mainly cerium(III) chloride (CeCl3), in methanol or ethanol. The Luche reduction can be conducted chemoselectively toward ketone in the presence of aldehydes or towards α,β-unsaturated ketones in the presence of a non-conjugated ketone.
In organic chemistry, carbonyl reduction is the organic reduction of any carbonyl group by a reducing agent.
Enantioselective ketone reductions convert prochiral ketones into chiral, non-racemic alcohols and are used heavily for the synthesis of stereodefined alcohols.
The dehydrogenative coupling of silanes is a reaction type for the formation of Si-Si bonds. Although never commercialized, the reaction has been demonstrated for the synthesis of certain disilanes as well as polysilanes. These reactions generally require catalysts.
Copper hydride is inorganic compound with the chemical formula CuHn where n ~ 0.95. It is a red solid, rarely isolated as a pure composition, that decomposes to the elements. Copper hydride is mainly produced as a reducing agent in organic synthesis and as a precursor to various catalysts.
Metal-catalyzed C–H borylation reactions are transition metal catalyzed organic reactions that produce an organoboron compound through functionalization of aliphatic and aromatic C–H bonds and are therefore useful reactions for carbon–hydrogen bond activation. Metal-catalyzed C–H borylation reactions utilize transition metals to directly convert a C–H bond into a C–B bond. This route can be advantageous compared to traditional borylation reactions by making use of cheap and abundant hydrocarbon starting material, limiting prefunctionalized organic compounds, reducing toxic byproducts, and streamlining the synthesis of biologically important molecules. Boronic acids, and boronic esters are common boryl groups incorporated into organic molecules through borylation reactions. Boronic acids are trivalent boron-containing organic compounds that possess one alkyl substituent and two hydroxyl groups. Similarly, boronic esters possess one alkyl substituent and two ester groups. Boronic acids and esters are classified depending on the type of carbon group (R) directly bonded to boron, for example alkyl-, alkenyl-, alkynyl-, and aryl-boronic esters. The most common type of starting materials that incorporate boronic esters into organic compounds for transition metal catalyzed borylation reactions have the general formula (RO)2B-B(OR)2. For example, bis(pinacolato)diboron (B2Pin2), and bis(catecholato)diborane (B2Cat2) are common boron sources of this general formula.
Ionic hydrogenation refers to hydrogenation achieved by the addition of a hydride to substrate that has been activated by an electrophile. Some ionic hydrogenations entail addition of H2 to the substrate and some entail replacement of a heteroatom with hydride. Traditionally, the method was developed for acid-induced reductions with hydrosilanes. Alternatively ionic hydrogenation can be achieved using H2. Ionic hydrogenation is employed when the substrate can produce a stable carbonium ion. Polar double bonds are favored substrates.
Ugi’s amine is a chemical compound named for the chemist who first reported its synthesis in 1970, Ivar Ugi. It is a ferrocene derivative. Since its first report, Ugi’s amine has found extensive use as the synthetic precursor to a large number of metal ligands that bear planar chirality. These ligands have since found extensive use in a variety of catalytic reactions. The compound may exist in either the 1S or 1R isomer, both of which have synthetic utility and are commercially available. Most notably, it is the synthetic precursor to the Josiphos class of ligands.
Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula [(C5H5)2TiCl]2. It is an air sensitive green solid. The complex finds specialized use in synthetic organic chemistry as a single electron reductant.
The Mukaiyama hydration is an organic reaction involving formal addition of an equivalent of water across an olefin by the action of catalytic bis(acetylacetonato)cobalt(II) complex, phenylsilane and atmospheric oxygen to produce an alcohol with Markovnikov selectivity.