Synthesis of four mono-functionalized α-cyclodextrin derivatives for further confirming DIBAL-H-promoted bis-de-O-methylation mechanism

Abstract

In our previous studies, a mechanism for DIBAL-H promoted regioselective bis-de-O-methylation of per-O-methylated cyclodextrin (CD) was proposed based on per-O-methylated β-CDs. As a further step to this work, four per-O-methylated α-CD derivatives (6, 7, 11, and 18) with mono functional group at the secondary rim have been designed and synthesized. Using DIBAL-H as a chemical ‘scalpel’, we found that (1) only the O-methyl at C-2A of 6 could be easily removed and (2) the O-methyl at C3B could be firstly regioselectively removed slowly, followed by a rapid removal of the second O-methyl at C2A to provide 3. Combined with our previous studies, we think that not only O-3B-methyl but also O-2A and O-3B are necessary for the formation of ‘tweezers’ during DIBAL-H promoted bis-de-O-methylation reaction of per-O-methylated CD.