Enantioselective synthesis

The enantioselective synthesis is a chemical synthesis method. It aims to steer a chemical synthesis in favor of the generation of one enantiomer over another. In the synthesis of natural products , which are often chiral, enantioselective synthesis is an indispensable tool.

Enantiomers are molecules that behave like an image and a mirror image but cannot be converted into one another by rotation. In addition to their interaction with polarized light, they have the same physical properties. The enantiomers react with achiral molecules in the same way, but not with other chiral molecules. For example, ( S ) - asparagine has a bitter taste, while ( R ) -asparagine tastes sweet. ( S ) - propranolol is a β-blocker, while ( R ) -Propanolol is a contraceptive.

Furthermore, the enantioselective synthesis can be used to determine the configuration or the conformation of a molecule. Enantioselective syntheses are also useful in determining the mechanism of reactions. The enantioselective synthesis is a stereoselective synthesis and belongs to the asymmetric syntheses .

history

The first targeted asymmetric synthesis was carried out by Emil Fischer in 1894, who obtained the two epimers L - mannonic acid and L - gluconic acid in a ratio of 3: 1 via the cyanohydrin reaction of L - arabinose .

By the decarboxylation of 2-ethyl-2-methylmalonic acid , which Willy Marckwald in 1904 with brucine , an optically active alkaloid had reacted before the salt, it succeeded in optically active representation of the 2-methylbutanoic acid.

W. Marckwald defined asymmetric synthesis in 1904 as follows:

"Asymmetrical syntheses are those which generate optically active substances from symmetrically constituted compounds with the intermediate use of optically active substances, but avoiding any analytical process."

- W. Marckwald

principle

The principle is based on the shielding of enantiotopic half-spaces in transition states by sterically demanding groups such as iso- propyl groups. As a result, one enantiomer is preferentially formed. The educt must be prochiral for this. A chiral adjuvant must also be present, which may be recoverable. For example, the amino acid ( S ) -valine or the use of imino acids are suitable . The principle thus differs from that of enantioselective catalysis .

Examples

Hydrogenation of carbonyl groups

• Reduction of carbonyl groups with BINAL-H from BINOL , LiAlH ₄ and ROH
• Reduction of chiral boranes, e.g. B. Alpine borane

Alkylations

• α-Alkylation of ketones with the Enders reagents SAMP / RAMP
• Evans auxiliaries
• Bislactime ether process (Schöllkopf method): alpha-alkylation of amino acids via chiral bislactime ethers

chiral auxiliary: 2,5-diketopiperazine

literature

• Dieter Enders , Reinhard W. Hoffmann : Asymmetric Synthesis . In: Chemistry in Our Time . tape 19 , no. 6 , 1985, pp. 177–190 , doi : 10.1002 / ciuz.19850190602 .

Individual evidence

1. ^ W. Marckwald: About asymmetric synthesis . In: Reports of the German Chemical Society . tape 37 , no. 2 , 1904, pp. 1368-1370 , doi : 10.1002 / cber.19040370226 .
2. ↑ J. Martens: Induction of asymmetry by imino acids. In: Chemiker-Zeitung . No. 110, 1986, pp. 169-183.