Cyanation of aryl halides

There are several methods available for the cyanation of aryl halides. However, a common problem with many of the more traditional methods is that they are very toxic# One method to full fill these criteria has been around for a while (Weissman S A et al., J. Org. Chem.2005, 70, 1508-1510.)

  Figure: Ligand-free, palladium-catalyzed cyanation of aryl halides. 

Potassium hexacyanoferrate(II) has been used as a cyanide source. This result increases the list of metal-catalyzed reactions that can be performed without ligand.

This method's advantage is obvious; in contrast to other cyanating agents, potassium hexacyanoferrate(II) is less poisonous# and can be handle without special precaution due to the slow release of cyanide ions. Additionally, it significantly improved catalytic productivity compared to know procedures achieved previously.

#( KCN is extremely toxic (LDL0(oral, human) =2.86mg Kg-1 and develop HCN on contract with acidic water. K4[Fe(CN)6]­ is non-toxic and used in the food industry for metal precipitation in wine. Also, it has been used as an anti-agglutinating auxiliary for NaCl (table salt). It is soluble in water without decomposition. Schareina T et al, Chem Commun., 2004, 1388-1389.)

Myers Asymmetric Alkylation

Psuedoephedrine is a chiral auxiliary used for the synthesis of enantiomerically enriched carboxylic acid, aldehyde, alcohol and ketones.

Both enantiomers of pseudoephedrine are inexpensive and can be N-acylated in high yields to generate its tertiary amides. In the presence of lithium chloride, the enolates of the corresponding pseudoephedrine amides undergo diastereoselective alkylations with a wide range of alkyl halides.

Advantages of using pseudoephedrine as chiral auxiliary,

• Enolate of pseudoephedrine amide undergoes efficient and high diastereoselective alkylation with a wide variety of alkyl halides,

• High enantiomerically enriched carboxylic acids, alcohols, aldehydes, and ketones, and

• Large scale/ Preocess application ( low cost of the auxiliary, the crystallinity of starting materials and products, no requirement of carcinogenic solvents.) 

Ref: Myers, A.G. et al., J. Am. Chem. Soc., 1997, 119, 6496.

Racemic Switch

A racemic switch or chiral switch is the redevelopment in the single-enantiomer form of a drug that was first approved as a racemates (racemic mixture). Sometimes, the pharmaceutical activity of a racemic mixture is present only in one enantiomer, and the other is inactive, or the other enantiomer has an undesired activity from the first.

Omeprazole

For exmaple, Omeprazole is an Antiulcer drug (AstraZeneca) marketed in the U.S. as a racemic drug in 1995. It s a racemic mixture of R-omeprazole and S-omeprazole. Since its patent ran out in 2002 and the pharmacological activity lies in (S)-enantiomer, the company has patented now (S)-omeprazole named as esomeprazole.