Efficient Multicomponent Active Template Synthesis of Catenanes

Abstract

We describe a simple and high yielding active template synthesis of [2]catenanes. In addition to mechanical bond formation using a single premacrocycle bearing an azide and alkyne moiety, our method is also suitable for the co-macrocyclization of readily available bis-alkyne and bis-azide comonomers and even short alkyne/azide components which oligomerize prior to mechanical bond formation.

Weak functional group interactions revealed through metal-free active template rotaxane synthesis

“…Active template synthesis [24][25][26][27][28][29][30][31][32][33][34][35] , in which a macrocycle accelerates a strand-forming reaction through the ring cavity, does not require strong pre-association of the starting materials. Although most active template syntheses have been developed from transition metal catalyzed reactions [24][25][26][27][28][29][30][31][32][33][34][35] , a metal-free active template system was recently discovered 36,37 in which the addition of primary amines to electrophiles can be significantly accelerated through crown ethers 37 and related macrocycles 36 by stabilization of the reaction transition state [38][39][40][41][42][43] . The reaction of a primary amine and an electrophile in the presence of a crown ether was found 37 to form [2]rotaxanes by metal-free active template Nalkylation, aza-Michael addition or N-acylation.…”

An Auxiliary Approach for the Stereoselective Synthesis of Topologically Chiral Catenanes

“…We recently reported an improved 25 , 26 active-template 27 Cu-mediated azide-alkyne cycloaddition 28 , 29 (AT-CuAAC) 30 methodology for the synthesis of sterically crowded catenanes in excellent yield. 31 We selected this methodology to demonstrate our proposed chiral auxiliary approach to topologically chiral catenanes because diastereomeric small crowded molecules, in which the topological and covalent elements of stereochemistry are held in close proximity and thus interact strongly, are a priori more likely to be separable. The required precursors, azide or alkyne pre-macrocycle ( R )- 1 (which contains a fixed stereogenic center derived from an enantiopure amino acid) and macrocycles 2 32 were synthesized in a straightforward manner from readily available building blocks (see Supplemental Information ).…”

Chirality in rotaxanes and catenanes

“…Although it has not previously been highlighted, in a similar manner to co-conformational mechanical planar chirality, it is possible to produce enantiomers with the symmetry properties of topologically chiral catenanes even without meeting the requirement of two C n h oriented rings. 155 When a catenane is formed from an oriented C n h ring (principle axis perpendicular to the macrocycle plane) and a C 2v un-oriented macrocycle (principle axis in the plane of the macrocycle), its co-conformation will be achiral whenever the oriented ring lies on the mirror plane of its partner ( Fig. 72a ).…”