Mannich and O-Alkylation reactions of tetraalkoxyresorcin[4]arenes. The use of some products in ligand assisted reactions

The measurement of the pKa of a racemic tetramethoxyresorcin[4]arene explains the failure to obtain good yields in attempted Mannich reactions of tetraalkoxyresorcin[4]arenes under classical reaction conditions. The failure is related to the lack of adequate concentrations of iminium ions that results from the reduced acid strength of tetraalkoxyresorcin[4]arenes as compared to parent octahydroxyresorcin[4]arenes. However, the preparation of a series of Mannich bases derived from racemic tetraalkoxyresorcin[4]arenes was accomplished using aprotic reaction conditions, including microwave assisted reactions, and using pre-formed iminium ion intermediates. In the case of reactions using chiral bis(aminol)ethers, the reactions gave mixtures of diastereoisomers that were separated by flash chromatography. The absolute configurations of the enantiomerically pure tetrabenzoxazine derivatives were established as (P,R,S) or (M,S,R), in some cases by Xray crystallographic analysis, and by a comparison of nuclear magnetic resonance spectroscopic data. The alkylation of racemic tetramethoxyresorcin[4]arenes was achieved in reactions using an excess of N-(R)-(+)-α-methylbenzyl-2-bromoacetamide in acetonitrile containing potassium carbonate. Enantioselective ligand-assisted reactions of aromatic aldehydes are reported using dialkylzinc reagents both in the absence and presence of terminal alkynes.