Selective derivatisation of resorcarenes: Part 7. The reason for the diastereoselectivity of Mannich reactions with chiral amines

Abstract

The formation of tetrakis(benzo-3,4-dihydro-1,3-oxazines) 2 by condensation of resorcarenes 1 with various primary amines and an excess of formaldehyde is not only regioselective but, in the case of (R)- or (S)-1-phenylethylamine and their para-substituted (Br, Me) derivatives, also completely diastereoselective. The reaction with the structurally similar (R)-1-aminoindane and (S)-1-(1-naphthyl)ethylamine, on the other hand, produced only a slight excess of one of the two possible epimers 2 and with (R)-1-cyclohexylethylamine no diastereoselectivity was found at all. The presence and the ratio of both diastereomeric structures can be clearly determined by NMR spectroscopy. Inspection of partly converted reaction mixtures suggests that the preferred crystallisation of one of the epimers is responsible for the diastereoselectivity observed in the case of 1-phenylethylamines and not an entirely diastereoselective reaction. The identity of 3, a cyclic triamine obtained as a side product of the Mannich reaction with (R)-1-aminoindane, was established by single crystal X-ray structure analysis.