Chiral auxiliary

An auxiliary ( lat. auxiliari = help ) in chemistry a covalently attached to a molecule group which allows a particular reaction or their stereochemical course affected. After a successful reaction, the auxiliary can be cleaved in a further step back.

Chiral auxiliaries

With the help of a chiral auxiliary can be one in and of itself is not stereoselective chemical reaction are controlled of course, that after cleavage of the auxiliary nevertheless preferred enantiomer is obtained. The best known example of a chiral auxiliary is the Evans auxiliary, which is used in the synthesis of enantiomerically pure α - Evans -alkylated carboxylic acid derivatives. Chiral auxiliaries are the auxiliaries used in the most important organic synthesis.

The operation of an auxiliary, based on the fact that the stereochemical information is brought into the molecule by attachment of a chiral group. This possible attacks on this molecule are always diastereoselective, the two products of the reaction are therefore diastereomers. Due to steric interaction ( for example shield one side of the molecule by a large substituents on the chiral auxiliary ) is formed preferentially one diastereomer. After cleavage of the auxiliary, the diastereomers are converted by loss of the stereogenic center at the auxiliary in the enantiomers.

The advantage in the use of chiral auxiliaries is in relatively easy access from the chiral pool. The now well-known and commonly used auxiliaries are well tested and found mostly very good stereoselectivity. The disadvantage is that the stereochemical information in contrast to the stereoselective catalysis must be used stoichiometrically and the auxiliary after cleavage often can not be recovered. The atom economy in the use of a chiral auxiliary in a reaction sequence is thus as a rule.

Evans auxiliaries

Structure

Evans auxiliaries are oxazolidinones. The auxiliary 2 is derived from the valine. Most frequently auxiliaries benzyl- 3 and 4 are used today, which are accessible from phenylalanine. They are named after their discoverer David Evans.

Synthesis

Evans auxiliaries are derived from amino acids. These are first reduced to amino alcohol and then condensed to the oxazolidinone.

Use

Without the use of an auxiliary of the attack of an electrophile (in this example methyl iodide ) to the enolate takes place (from the methyl ester by deprotonation with LDA generated ) non-selectively from both sides of the double bond to give ( ee = 0%) formed both enantiomers in the same proportion be.

However, instead of bringing the methyl ester of the Evans chiral auxiliary ( chiral oxazolidinone, which is bonded via an amide bond in the molecule) is done, the attack by the less hindered side of the molecule. Through the stereocenter in the Auxiliary, the reaction proceeds now diastereoselective. The two possible products of the alkylation of (forward of the top and bottom ) generates two diastereomers which can be, if necessary, separately. Only after cleavage of the auxiliary (here with LiOH/H2O2 ) obtained in enantiomerically pure form the desired product.

Enders reagent

Enders as reagent ( S )-1- amino-2- (methoxymethyl ) pyrrolidine, and ( R)-1 -amino- 2-( methoxymethyl) pyrrolidine referred to ( SAMP and RAMP ). They are derived from proline auxiliaries which can be used for the stereoselective alkylation of aldehydes ( SAMP or RAMP so-called process).

Other auxiliaries

8- phenylmenthyl Auxiliar: For auxiliary -induced diastereoselectivity in the conjugate addition of cuprates.

2.5 dimethylpyrrolidine is used among other things as auxiliary for intermolecular radical additions to acrylic acid derivatives.