REDUCTlON

1. Reduction of Carbonyl Compounds

2. Reducing Agents

1) Reduction of Carbonyl Compounds

Most reductions of carbonyl groups are now done with reagents that transfer a hydride ion.

A large number of reducing agents have become available that provide chemo-, stereo-, and enantioselectivity in reduction.

Since formation of a new stereogenic center during carbonyl group reduction may require either relative or absolute stereocontrol, the use of chiral reducing agents has become a popular means for controlling the stereochemical outcome of reductions.

a) A chemoselective reagent reacts selectively with one functional group in the presence of other functional groups.

b) In a regioselective reaction, the reagent adds at only one of two possible regions.

c) A stereoselective reaction leads to the exclusive or predominant formation of one of several possible stereoisomeric products.

d) In a stereospecijic reaction, a given substrate isomer leads to one product while another stereoisomer leads to the opposite stereoisomeric product

e) A prochiral center is a trigonal carbon of C=O and C=C that is not a stereogenic center but can be made chiral by addition reactions.

A stereogenic carbon atom (chiral center, chiral atom, asymmetric atom) is bound to four different groups and thus generates chirality.

Note that a molecule may possess a molecular chirality without having a stereogenic center.

Stereoisonzers have the same molecular formula, but their atoms have a different spatial arrangement - a different configuration.

Stereoisomers are classified as :

a) Enantiomers: When the isomers are mirror images of each other and cannot be superimposed mirror images

b) Diastereoisomers: When the isomers are not mirror images of each other (this includes alkene E, Z isomers). Diastereoisorners possess different physical and chemical properties.

2) Reducing Agents:

The majority of reductions of carbonyl compounds and nitriles with nucleophilic reducing agents, such as M[AlH4] and M[BH4], proceed via nucleophilic transfer of a hydrogen atom with two electrons called a "hydride" from the reducing agent to the carbonyl or cyano carbon.

The rate of reduction and the chemoselectivity of a reducing agent toward a given substrate depends on factors.

2.1) Allurninurn Hydrides :

Lithium Aluminum Hydride-LiAlH4 :

Lithium aluminum hydride (LAH) is a powerful reducing agent but is not very chemoselective.

It must be used in nonprotic solvents such as Et2O or THF; is.

The reagent is usually used in excess, with only three hydrides of LiAlH4 being utilized.

The reduction of esters to primary alcohols and the reduction of amides to amines requires two hydrides, whereas reduction of carboxylic acids to primary alcohols consumes three hydrides.

The reactivity of LAH may be changed by the addition of dialkyl amines.

Aliphatic and aromatic carboxylic esters are reduced to the corresponding aldehydes by LAH in the presence of diethylamine at room temperature.

2.2) Lithium Tri-alkoxyaluminum Hydride, Li[ALH(OR)3] :

The reactivity and selectivity of LAH can be modified and tolerate by replacing three of its hydrides with t-brxtoxy or ethoxy or methoxy or iso-propoxy group.

This type of reagents are less reactive but more selective than LAH for the regeoselectivity and stereoselectivity.

2.3) Lithium tri-t-butoxyaluminium hydride :

Reduces aldehydes and ketones to the corresponding alcohols and reduces acid chlorides to aldehydes.

Epoxides, esters, carboxylic acids, tert-amides, and nitriles are only slowly, reduced.

Thus, the reagent can be used for chemoselective reduction.

2.4) Lithium triethoxyaluminum hydride :

It is a more powerful reagent which reduces tertamides and nitriles to the corresponding aldehydes.

2.5) Sodium Bis(2-methoxyethoxy)aluminum Hydride- Na[AIH2(OCH2CH20CH3)2] or Red-Al :

Sodium Bis(2-methoxyethoxy)aluminum Hydride- Na[AIH2(OCH2CH20CH3)2] Sodium bis(2-methoxyethoxy)aluminum hydride, or Red-Al is a versatile, commercially available reducing agent.

It is thermally more stable than LAH and may be used in aromatic hydrocarbon as well as in ether solvents.

Overall, the reducing properties of Red-A1 are similar to those of LAH (reductions of aldehydes, ketones, esters, etc.)