Chapter 25. Reactions of Interest in Medicinal Chemistry

Abstract

This chapter describes various synthetic procedures for reaction of interests in medicinal chemistry. A stable storable hydroborating and reducing agent which is liquid at room temperature is provided by dimethylsulfide-borane. An excellent reagent for the oxidation of Schiff bases to oxaziridines, nitrogen-containing aromatic heterocycles to N -oxides, and nitrosamines to nitramines is t-amylhydroperoxide with MOCl 5 . T1(NO 3 ) 3 is useful for (1) the degradation of monoalkylacetylenes to carboxylic acids containing one less carbon atom, (2) synthesis of acyloins from dialkylacetylenes, and (3) synthesis of methyl arylacetates from acetophenones. The acetylenic linkage in compounds containing both double and triple bonds can be protected as the acetylene–dicobalt hexacarbonyl complex by treatment with cobalt carbonyl. A single-step reductive elimination of epoxides to olefins with Zn–Cu couple in ethanol has been described. Sulfoxides, including the conformationally restricted thioxanthine sulfoxide, are quantitatively deoxygenated with NaBH 4 -CoCl 2 in 95% ethanol. A one-step four-carbon homologation leading to a variety of 4-alkyl-2-buten-1-ols is provided by reaction of 1,3-butadiene monoxide with primary or secondary trialkylboranes in the presence of catalytic amounts of O 2 or other free-radical initiator.