Synthesis of Enantiomerically Pure Bambus[6]urils Utilizing Orthogonal Protection of Glycolurils

Abstract

A general strategy for the synthesis of 2N,4N'-disubstituted glycoluril enantiomers on a multigram scale using orthogonal protection is reported. The use of these glycolurils is demonstrated in the synthesis of enantiomerically pure bambus[6]uril macrocycles. Moreover, the deprotection of (S)-1-phenylethyl substituents on the macrocycle was achieved, opening access to various chiral bambus[6]urils via post-macrocyclization modification strategy.

Scheme 1. Schematic Overview of the Preparation of Enantiomerically Pure Bambus[6]uril BU3via Orthogonal Protective Steps of 1a and Post-Macrocyclization Modification of BU1

Scheme 2. Synthesis of Glycolurils 1a and 1b

(a) Previously reported synthesis route.^, (b) This work.

Scheme 3. Protection of Nitrogen Atoms of Glycoluril 1a with Allyl Bromide

Scheme 4. (a) Cleavage of the (S)-1-Phenylethyl Group and (b) Reaction of 1-Phenylethan-1-ylium Cation 6 with 1,4-Dimethoxybenzene

Scheme 5. Alkylation of Glycoluril 5 followed by Cleavage of the Allyl Groups of 8a–8d

Scheme 6. Cleavage of the (S)-1-Phenylethyl Group from BU1 Resulting in BU2 and Subsequent Alkylation of BU2 into BU3a–BU3e