Chapter 26 Reactions of Interest in Medicinal Chemistry

Abstract

Publisher Summary Various literatures in organic chemistry have already established significant reactions that are quite useful in medicinal chemistry. There are 70 odd transforms that can offer more convenient access to important functional arrays because they lead to moieties. The discussion includes many useful organic processes, such as “Asymmetric Syntheses,” “New applications of Malononitrile in Organic Synthesis,” “Intramolecular Ene Reaction in Organic Synthesis,” “α-Sulfenylated Carbonyl Compounds in Organic Synthesis,” etc. A new method for transposition of carbonyl groups starts by interception of the intermediate from tosyl hydrazone decomposition with Me 3 SiCl. Another new method for dehydrogenation of carbonyl compounds consists of conversion to their pyridine-2-sulfide derivatives, followed by oxidation (MCPBA), and by mild heat. This chapter also discusses the recent development of dienes incorporating latent functionality has greatly expanded the utility of Diels Alder approaches to synthesis of complex molecules. Pyrolytic scission of cyclobutenes leads to a diene that promises to be useful in a Diels Alder approach to catechols. Heating of the silyl derivative of the acyloin product from dimethyl glutarate in the presence of dienophiles affords adducts of the transient diene. A general procedure has been developed for the preparation of 1,4-di-hydrothiophene-3-carboxylates starting from acetaldehyde-2-thiol. The unprotected carbonyl group can be condensed with anions to afford products that give substituted phenylacetic acid derivatives on aromatization. A versatile nonFriedel–Crafts approach to naphthols is provided by condensation of the toluic acid sulfoxide with substituted acrylates or methyl vinyl ketone. Sequential conjugate addition and acylation of the first formed anion leads to tetralone. A related scheme that leads to hydroxytetralones involves reaction of the anion from a phthalide (LDA) with an unsaturated ester. This reaction too involves a conjugate addition-acylation sequence.