Cyclochiral conformers of resorcin[4]arenes stabilized by hydrogen bonds

Abstract

Cyclochiral resorcinarenes, that maintain their cyclochirality by means of hydrogen bonds, were synthesized by a sequence of reactions involving the Mannich reaction, removal of the N,O-acetal bridge and subsequent N-substitution with an RCO group. During this study it was found that ethyl nitroacetate is a mild and very efficient agent for N,O-acetal bridge removal. The resulting resorcinarenes 4a–j exist in cyclochiral/inherently chiral kite conformations (resembling 4-bladed propellers) that are stabilized by eight hydrogen bonds (in both solid state and solution). It is shown that the cycloisomerization process is characterized by the relatively high racemization barrier (14.6–18.5 kcal mol⁻¹ as determined by 2D EXSY) and thus it can be concluded that the transformation of one cycloconformer into the other requires the simultaneous rupture of all eight hydrogen bonds. For derivatives with additional stereogenic centers two cyclodiastereoisomeric conformations were detected (diastereomeric excess in the range of 72% up to >95%). The experimental results are additionally supported by AM1 semi-empirical calculations.