Reduction of Carbonyls to Alcohols Using Metal Hydrides

Hydrogen can be used as a nucleophile if it’s bonded to a metal in such a way that the electron density balance favors the hydrogen side. A hydrogen atom that carries a net negative charge and bears a pair of unshared electrons is called a hydride ion. How much negative charge density resides on hydrogen depends on the difference in electronegativity between hydrogen and the metal it’s bonded to.

(M = metal)

The most common sources of the hydride anion (^–:H) are lithium aluminum hydride (LiAlH₄) and sodium borohydride (NaBH₄). Note! these reagents serve as a source of hydride due to the presence of a polar metal-hydrogen bond. Because aluminum is less electronegative than boron, the Al-H bond in LiAlH₄ is more polar, thereby, making LiAlH₄ a stronger reducing agent.

General Reaction

Nucleophilic addition of a hydride anion (^–:H) to an aldehyde or a ketone gives a tetrahedral alkoxide anion intermediate, which on protonation yields the corresponding alcohol. Aldehydes produce 1^o-alcohols and ketones produce 2^o-alcohols. Both LiAlH₄ and NaBH₄ are capable of reducing aldehydes and ketones to the corresponding alcohol.

Predicting the Product of a Hydride Addition to a Carbonyl

During the reduction, the C=O double bond in the reactant becomes a C-O single bond in the product. The breaking of the C=O double bond allows for the formation of two new single bonds in the product. One will be attached to the oxygen (O-H) and one to the carbon (C-H).

Example

Mechanism for the Reduction of Carbonyls using LiAlH₄

Step 1. Nucleophilic attack to form a tetrahedral alkoxide intermediate

Step 2. Protonation to form an alcohol

Reagent	Preferred Solvents	Functions Reduced
Sodium Borohydride NaBH4	ethanol; aqueous ethanol 15% NaOH;	aldehydes to 1º-alcohols ketones to 2º-alcohols
Lithium Aluminum Hydride LiAlH4	ether;	aldehydes to 1º-alcohols ketones to 2º-alcohols carboxylic acids to 1º-alcohols esters to alcohols nitriles & amides to amines

Mechanism for the Addition of Grignard Reagents

The mechanism starts with the formation of a acid-base complex between ⁺MgX and the carbonyl oxygen. The ⁺MgBr of the Grignard reagent acts as a Lewis acid and accepts a lone pair of electrons from the carbonyl oxygen. This gives the oxygen a positive charge which correspondingly increases the partial positive charge on the carbonyl carbon increasing it susceptibility to nucleophilic attack. The carbanion nucleophile from the Grignard reagent adds to the electrophilic carbon of the acid-base complex forming a C-C bond. The two electrons of the C=O are pushed toward the carbonyl oxygen atom forming a tetrahedral magnesium alkoxide intermediate. The alkoxide intermediate is converted to an alcohol through addition of a acidic aqueous solution. The ⁺MgX ion is also converted to HOMgX.

Step 1. Lewis acid-base formation

step 2. Nucleophilic attack

Step 3. Protonation