Carbonyl reduction
Encyclopedia
Carbonyl reduction in organic chemistry is the organic reduction of any carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....

 group containing compound by a reducing agent
Reducing agent
A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...

. Typical carbonyl compounds are ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

s , aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....

s, carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

s and ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

s. A carbonyl group can be reduced to the alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

 or the oxygen atom can be removed altogether, a process called deoxygenation
Deoxygenation
Deoxygenation is a chemical reaction involving the removal of molecular oxygen from a reaction mixture or solvent, or the removal of oxygen atoms from a molecule.Classic representatives of deoxygenation are:...

. Many reducing agents are metal hydrides based on boron
Boron
Boron is the chemical element with atomic number 5 and the chemical symbol B. Boron is a metalloid. Because boron is not produced by stellar nucleosynthesis, it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the...

 and aluminum. A second important method is catalytic hydrogenation
Hydrogenation
Hydrogenation, to treat with hydrogen, also a form of chemical reduction, is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically...

. .

Metal hydride mechanism

The reaction mechanism
Reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...

 for metal hydride reduction is based on activation of the carbonyl group by the metal followed by nucleophilic addition
Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....

 of hydride. Another general system is catalytic hydrogenation
Hydrogenation
Hydrogenation, to treat with hydrogen, also a form of chemical reduction, is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically...

 by metal. LiAlH4 is more reactive than NaAlH4 because the smaller lithium cation is a better Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

. A crown ether
Crown ether
Crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups. The most common crown ethers are oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., -CH2CH2O-. Important members of this series are the tetramer , the pentamer , and the hexamer...

 reduces reactivity. Alkoxide substitution in metal hydrides increases solubility and selectivity. An example is Red-Al
Red-Al
Red-Al, or sodium bisaluminumhydride, is an organoaluminium compound with the formula NaAlH22. The name which is a trademark of Sigma-Aldrich refers to its being a Reducing aluminium compound. It is used almost exclusively as a solution in toluene, which is used as a reagent in organic synthesis...

.

Aldehyde and ketone reduction

The reaction product of the reduction of an aldehyde is a primary alcohol
Primary alcohol
A primary alcohol is an alcohol which has the hydroxyl radical connected to a primary carbon. It can also be defined as a molecule containing a “–CH2OH” group.Examples include ethanol and butanol....

 and that of a ketone a secondary alcohol. Reagents are lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...

  , diisobutylaluminium hydride
Diisobutylaluminium hydride
Diisobutylaluminium hydride, DIBAL, DIBAL-H or DIBAH, is a reducing agent with the formula 2, where i-Bu represents isobutyl...

, sodium borohydride
Sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate, is an inorganic compound with the formula NaBH4. This white solid, usually encountered as a powder, is a versatile reducing agent that finds wide application in chemistry, both in the laboratory and on a technical scale. Large amounts are...

, L-selectride
L-selectride
L-selectride is an organoborane. It is used in organic chemistry as a reducing agent, for example in the reduction of a ketone, as part of Overman's synthesis of strychnine....

, diborane
Diborane
Diborane is the chemical compound consisting of boron and hydrogen with the formula B2H6. It is a colorless gas at room temperature with a repulsively sweet odor. Diborane mixes well with air, easily forming explosive mixtures. Diborane will ignite spontaneously in moist air at room temperature...

, diazene
Diazene
Diazene, also called diimine or diimide, is a compound having the formula 2. It exists as two geometric isomers, E and Z. Diazene is also the parent member of the entire class of azo compounds with the formula 2, where R is an organyl group...

 and aluminum hydride. Sodium borohydride tolerates more functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...

s (nitro group, nitrile
Nitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

, ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

) than LiAlH4 and can also be used with water or ethanol as a solvent (LiAlH4 reacts with protic solvents). Sodium cyanoborohydride
Sodium cyanoborohydride
Sodium cyanoborohydride is the inorganic compound with the formula NaBH3. This colourless salt is widely used in organic synthesis for the reduction of imines.-Preparation and use:...

, 9-BBN
9-BBN
9-Borabicyclo[3.3.1]nonane or 9-BBN is an organoborane compound. This colourless solid is used in organic chemistry as a hydroboration reagent. The compound exists as a hydride-bridged dimer, which easily cleaves in the presence of reducible substrates...

-pyridine and tributyltin hydride
Tributyltin hydride
Tributyltin hydride is an organotin compound with the formula 3SnH. It is a colorless liquid that is soluble in organic solvents. The compound is used as a source of hydrogen atoms in organic synthesis.-Synthesis and characterization:...

 are selective for aldehydes. A method for selective ketone reduction in presence of an aldehyde is NaBH4 / cerium chloride.

In hydrogenation platinum
Platinum
Platinum is a chemical element with the chemical symbol Pt and an atomic number of 78. Its name is derived from the Spanish term platina del Pinto, which is literally translated into "little silver of the Pinto River." It is a dense, malleable, ductile, precious, gray-white transition metal...

 and ruthenium
Ruthenium
Ruthenium is a chemical element with symbol Ru and atomic number 44. It is a rare transition metal belonging to the platinum group of the periodic table. Like the other metals of the platinum group, ruthenium is inert to most chemicals. The Russian scientist Karl Ernst Claus discovered the element...

 are preferred catalysts. Specific methods are the Meerwein–Ponndorf–Verley reduction (aluminumisopropylate/isopropanol), the Bouveault–Blanc reduction (sodium metal/ethanol) and the Cannizzaro reaction
Cannizzaro reaction
The Cannizzaro reaction, named after its discoverer Stanislao Cannizzaro, is a chemical reaction that involves the base-induced disproportionation of an aldehyde lacking a hydrogen atom in the alpha position...

 (KOH induced aldehyde disproportionation)

Carboxylic acid reduction

Typical reagents for the reduction of carboxylic acids or carboxylate salts to alcohols are lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...

 , diborane
Diborane
Diborane is the chemical compound consisting of boron and hydrogen with the formula B2H6. It is a colorless gas at room temperature with a repulsively sweet odor. Diborane mixes well with air, easily forming explosive mixtures. Diborane will ignite spontaneously in moist air at room temperature...

, DIBAL and aluminum hydride. Catalytic hydrogenation and NaBH4 are ineffective.

Ester reduction

Esters (R(CO)OR') can be reduced to alcohols RCH2OH and R'OH by lithium aluminium hydride
Lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH or known as LithAl, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters,...

  and aluminum hydride. Diisobutylaluminium hydride
Diisobutylaluminium hydride
Diisobutylaluminium hydride, DIBAL, DIBAL-H or DIBAH, is a reducing agent with the formula 2, where i-Bu represents isobutyl...

 and lithium tri-t-butoxyaluminum hydride are selective for the formation of the aldehyde. Catalytic hydrogenation over copper chromite is reported.

1,4-reduction

In 1,4-reduction (also called conjugate reduction) the reaction substrate is an unsaturated carbonyl compound, an enone
Enone
An enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....

 or enal. The 1,2-reduction product (an allyl alcohol
Allyl alcohol
Allyl alcohol is an organic compound with the structural formula CH2=CHCH2OH. Like many alcohols,it is a water soluble, colourless liquid, but it is more toxic than typical small alcohols. Allyl alcohol is used as a raw material for the production of glycerol, but is used as a precursor to many...

) competes with 1,4-reduction to the saturated ketone or aldehyde. In 1,4-reduction the first step is conjugate addition of the hydride to the enolate ion followed by acidic workup forming the ketone.

1,2-reduction is found with DIBAL and 9-BBN
9-BBN
9-Borabicyclo[3.3.1]nonane or 9-BBN is an organoborane compound. This colourless solid is used in organic chemistry as a hydroboration reagent. The compound exists as a hydride-bridged dimer, which easily cleaves in the presence of reducible substrates...

 and alane
Alane
Alane may refer to:* Aluminium hydride, a chemical reagent used as a reducing agent* Alane , 1997 song recorded by Wes...

. 1,4-reduction can be accomplished with catalytic hydrogenation and by alkylmetal hydrides.

An example is the reduction of chalcone
Chalcone
Chalcone is an aromatic ketone and an enone that forms the central core for a variety of important biological compounds, which are known collectively as chalcones or chalconoids.-Chemical synthesis:...

 by tributyltin hydride
Tributyltin hydride
Tributyltin hydride is an organotin compound with the formula 3SnH. It is a colorless liquid that is soluble in organic solvents. The compound is used as a source of hydrogen atoms in organic synthesis.-Synthesis and characterization:...

 :

Conjugate reduction chalcone


An asymmetric version of this reaction has also been developed .

Asymmetric synthesis

Well known carbonyl reductions in asymmetric synthesis are the Noyori asymmetric hydrogenation
Noyori asymmetric hydrogenation
The Noyori asymmetric hydrogenation is a chemical reaction described as an asymmetric reduction of β-keto-esters.Both enantiomers of BINAP are commercially available and widely used...

 (beta-ketoester reduction /Ru/BINAP) and the CBS reduction
CBS reduction
The Corey-Itsuno Reduction, also known as the Corey-Bakshi-Shibata reduction, is a chemical reaction in which an achiral ketone is enantioselectively reduced to produce the corresponding chiral, non-racemic alcohol...

(BH3, proline derived chiral catalyst).
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