Assymetric Induction

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  • Topic: Stereochemistry, Asymmetric induction, Steric effects
  • Pages : 7 (2065 words )
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  • Published : May 23, 2013
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Asymmetric induction
From Wikipedia, the free encyclopedia
Asymmetric induction (also enantioinduction) in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of achiral feature present in the substrate, reagent, catalyst or environment.[1] Asymmetric induction is a key element in asymmetric synthesis. Asymmetric induction was introduced by Emil Fischer based on his work on carbohydrates.[2] Several types of induction exist. Internal asymmetric induction makes use of a chiral center bound to the reactive center through a covalent bond and remains so during the reaction. The starting material is often derived from chiral pool synthesis. In relayed asymmetric induction the chiral information is introduced in a separate step and removed again in a separate chemical reaction. Special synthons are called chiral auxiliaries. In external asymmetric induction chiral information is introduced in the transition state through a catalyst of chiral ligand. This method of asymmetric synthesis is economically most desirable. -------------------------------------------------

[edit]Carbonyl 1,2 asymmetric induction
Several models exist to describe chiral induction at carbonyl carbons during nucleophilic additions. These models are based on a combination of steric and electronic considerations and are often in conflict with each other. Models have been devised by Cram (1952), Cornforth (1959), Felkin (1969) and others. [edit]Cram's rule

The Cram's rule of asymmetric induction developed by Donald J. Cram in 1952[3] is an early concept relating to the prediction of stereochemistry in certain acyclic systems. In full the rule is: In certain non-catalytic reactions that diastereomer will predominate, which could be formed by the approach of the entering group from the least hindered side when the rotational conformation of the C-C bond is such that the double bond is flanked by the two least bulky groups attached to the adjacent asymmetric center. The rule indicates that the presence of an asymmetric center in a molecule induces the formation of an asymmetric center adjacent to it based on steric hindrance. In his 1952 publication Cram presented a large number of reactions described in the literature for which the conformation of the reaction products could be explained based on this rule and he also described an elaborate experiment (scheme 1) making his case.

The experiments involved two reactions. In experiment one 2-phenylpropionaldehyde (1, racemic but (R)-enantiomer shown) was reacted with the Grignard reagent of bromobenzene to 1,2-diphenyl-1-propanol(2) as a mixture of diastereomers, predominantly the threo isomer (see for explanation the Fischer projection). The preference for the formation of the threo isomer can be explained by the rule stated above by having the active nucleophile in this reaction attacking the carbonyl group from the least hindered side (seeNewman projection A) when the carbonyl is positioned in a staggered formation with the methyl group and the hydrogen atom, which are the two smallest substituents creating a minimum of steric hindrance, in a gauche orientation and phenyl as the most bulky group in the anti conformation. The second reaction is the organic reduction of 1,2-diphenyl-1-propanone 2 with lithium aluminium hydride, which results in the same reaction product as above but now with preference for the erythro isomer (2a). Now a hydride anion (H-) is the nucleophile attacking from the least hindered side (imagine hydrogen entering from the paper plane). In the original 1952 publication, additional evidence was obtained for the structural assignment of the reaction products by applying them to a Chugaev elimination, wherein the threo isomer reacts to the cis isomer of -α-methyl-stilbene and the erythro isomer to the trans version.

[edit]Felkin...
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