CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

Methods of Asymmetric Synthesis: 15 In 1894, Emil Fischer laid the foundation of
modern asymmetric synthesis by homologation of sugars via cyanohydrins reaction. 16 An
asymmetric reaction is defined as a reaction in which a prochiral unit in an substrate
molecule is converted to a chiral unit such that the possible stereoisomers are produced in
unequal amounts. The reactants may be chiral reagents, solvents, catalysts or physical
forces such as circularly polarized light. The stereoselectivity is primarily influenced by
the chiral catalyst, reagent, or auxiliary, despite any stereogenic elements that may be
present in the substrate. The efficacy and success of an asymmetric reaction is denoted by
enantiomeric excess (ee) of the desired enantiomer, which is defined as the absolute
difference between the mole fractions of each enantiomer and is expressed in percentage.
A common strategy to achieve efficient asymmetric synthesis is to use a chiral auxiliary in
proximity to the location where the new stereogenic center is to be introduced. When the
reaction proceeds, the configuration of the new stereogenic centers being formed are
influenced by the chirality of the chiral reactant; the chiral reactant “induces” chirality at
the newly formed stereogenic centers. In some cases, a chiral solvent or a chiral catalyst is
used to induce chirality. In all cases, the existing chiral entity in the reaction (reactant or
solvent or catalyst) is involved in the transition state, resulting in diastereomeric transition
states of which the lower-energy one is favored. The known methods can be conveniently
divided into four major classes, depending on how this influence is exerted. The classes are
as follows.
a) Substrate-Controlled methods.
In this method, a chiral substrate is reacted with an achiral reagent so that the
reaction is directed intramolecularly by a stereogenic unit already present in the substrate.
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