A Chiral Macrocycle for the Synthesis of Both Mechanically Planar Chiral Rotaxanes and Catenanes in Excellent Enantiopurity

Abstract

Active-template auxiliary methodologies have previously been developed for the stereoselective synthesis of chiral interlocked molecules in which the mechanical bond provides the sole stereogenic unit. To date however, the covalent auxiliary has been included in the half-axle components (rotaxanes) or pre-macrocycle components (catenanes), and thus mechanically chiral rotaxane and catenane syntheses rely on different chiral components. Here we present a single, simple amino acid-derived macrocycle that mediates the formation of both catenanes and rotaxanes in excellent stereoselectivity. We demonstrate the flexibility of our approach through the stereoselective synthesis of all three isomers of a co-conformationally mechanically planar chiral [3]rotaxane.

A topologically chiral catenane that is not topologically chiral

“…Catenane 3 was synthesized (Fig. 2a) using an active template 17 Cu-mediated alkyne-azide cycloaddition reaction between azide/alkyne pre-macrocycle alkene (Z)-1 and chiral bipyridine macrocycle (S)-2 (98% ee) 18 . 1 H NMR analysis confirmed that catenane 3 was isolated as a single diastereomer (>96% de), consistent with the covalent stereochemistry of (S)-2 efficiently controlling the relative orientation of the bipyridine and alkene containing macrocycles 18 .…”

“…2a) using an active template 17 Cu-mediated alkyne-azide cycloaddition reaction between azide/alkyne pre-macrocycle alkene (Z)-1 and chiral bipyridine macrocycle (S)-2 (98% ee) 18 . 1 H NMR analysis confirmed that catenane 3 was isolated as a single diastereomer (>96% de), consistent with the covalent stereochemistry of (S)-2 efficiently controlling the relative orientation of the bipyridine and alkene containing macrocycles 18 . Catenane 3 also contains a coconformational geometric stereogenic unit 19 , the configuration, Eco-c, of which is controlled by the geometry of the starting pre-macrocycle, (Z)-1, and fixed in the interlocked product due to the steric bulk of the styrene and silyl ether units which prevent shuttling of the bipyridine macrocycle between the two triazole-containing compartments.…”

A topologically chiral catenane that is not topologically chiral

“…Catenane 3 was synthesized (Fig. 2a) using an active template 29 Cu-mediated alkyne-azide cycloaddition reaction between azide/alkyne pre-macrocycle alkene (Z)-1 and chiral bipyridine macrocycle (S)-2 (98% ee) 30 . 1 H NMR analysis confirmed that catenane 3 was isolated as a single diastereomer (>96% de), consistent with the covalent stereochemistry of (S)-2 efficiently controlling the relative orientation of the bipyridine and alkene containing macrocycles 30 .…”

“…2a) using an active template 29 Cu-mediated alkyne-azide cycloaddition reaction between azide/alkyne pre-macrocycle alkene (Z)-1 and chiral bipyridine macrocycle (S)-2 (98% ee) 30 . 1 H NMR analysis confirmed that catenane 3 was isolated as a single diastereomer (>96% de), consistent with the covalent stereochemistry of (S)-2 efficiently controlling the relative orientation of the bipyridine and alkene containing macrocycles 30 . Catenane 3 also contains a coconformational geometric stereogenic unit 31 , the configuration, Eco-c, of which is controlled by the geometry of the starting pre-macrocycle, (Z)-1, and fixed in the interlocked product due to the steric bulk of the styrene and silyl ether units which prevent shuttling of the bipyridine macrocycle between the two triazole-containing compartments.…”