Synthesis of Schiff bases on the basis of the isosteviol terpenoid

(–)‐Isosteviol as a Versatile Ex‐Chiral‐Pool Building Block for Organic Chemistry

“…Interestingly, when the reaction takes place in ethanol instead of THF, ethylamine 12b is formed as the major product. Alternatively, amines 12a can be obtained when formamides 13 (R = H, Me) are heated at reflux under basic conditions 26. Compound 13 itself is formed by heating (–)‐isosteviol or its methyl ester with excess formamide in formic acid.…”

“…Amine 12a (R = H) can subsequently be transformed into Schiff base derivative 14 by the reaction of the amine moiety with the appropriate benzaldehyde under basic conditions. A variety of substituents on the salicylaldehyde component are compatible, including a nitro or tert ‐butyl group at the para position, respectively 26. Although the individual reports do not discuss it in detail, the stereocenter at the 16‐position is not formed with good stereoselectivity, but usually as a mixture of diastereomers that are difficult to separate.…”

“…In a Curtius‐type rearrangement, the carboxylic acid moiety of 2 can be stereospecifically converted into the corresponding amine 45 (Scheme ) 26. Activation of the acid with thionyl chloride33 or phosphorus trichloride34 to give 43 and subsequent reaction with sodium azide renders the acyl azide derivative 44 .…”

“…Upon heating in benzene at reflux, Curtius rearrangement occurs to give the intermediate isocyanate. Amine 45 can then be obtained directly as the hydrochloride from the isocyanate by acid hydrolysis 26. Compound 45 can function as the starting compound for the synthesis of a variety of Schiff bases.…”

“…Despite the steric demand of the primary amine 45 , the yields of the imines are astonishingly good. The potential applications of these Schiff bases as ligands for metal complex catalysis could not be realized, however, due to the formation of insufficient quantities of complexes with, for example, vanadium acetylacetonate 26…”