Selective access to constitutionally identical, orientationally isomeric calix[6]arene-based [3]rotaxanes by an active template approach

Abstract

Tris(phenylureido)calix[6]arene is endowed with unique properties that make it a valuable macrocyclic component for the synthesis of mechanically interlocked molecules. Its three-dimensional and intrinsically nonsymmetric structure is kinetically selective toward two processes: (i) in apolar media, the threading of bipyridinium based axle-like components takes place exclusively from the upper rim; (ii) S_N2 alkylation reactions of a pyridylpyridinium precursor engulfed in the cavity occur selectively at pyridylpyridinium nitrogen atom located at the macrocycle upper rim (active template synthesis). Here we exploit such properties to prepare two series of [3]rotaxanes, each consisting of three sequence isomers that arise from the threading of two identical but nonsymmetric wheels on a symmetric thread differing only for the reciprocal orientation of the macrocycles. The features of the calix[6]arene and the active template synthetic approach, together with a careful selection of the precursors, enabled us to selectively synthesise the [3]rotaxane sequence isomers of each series with fast kinetics and high yields.

Fig. 1. Graphical representation of the synthesis of [2]rotaxanes based on a calix[6]arene wheel (CX), for the sake of simplicity represented as a yellow cartoon, and bipyridinium (viologen) axles using either the passive (a) or the active (b) template synthesis.

Fig. 2. Schematic representation of the [3]rotaxane orientational isomers object of this study. The labels UU, UL and LL stand for upper–upper, upper–lower and lower–lower, and denote which rims of the two calixarene wheels are proximal in the rotaxane. The tosylate counteranions have been omitted for clarity.

Scheme 1. Reagents and conditions: (i) Ph₂CHCOCl, Et₃N, DCM, rt, 8 h; (ii) 4,4′-bipy (2 eq.), CH₃CN, reflux, 24 h; (iii) 4,4′-bipy (2.5 eq.), CH₃CN, reflux, 24 h; (iv) 1,12-dibromododecane (5 eq.), CH₃CN, reflux, 7 d; (v) 4a,b, CH₃CN, sealed tube, 100 °C, 7 d. In the cartoons of the [3]rotaxane structures, the counteranions have been omitted for clarity.

Fig. 3. ¹H NMR stack plot (400 MHz, CDCl₃) of (a) wheel CX, (b) [3]rotaxane R6UU, and (c) dumbbell 7a. For solubility reasons, spectrum (c) was taken in CD₃OD. The most representative resonances are labelled according to the molecular sketches placed above the stack plot, while their complexation induced shifts are indicated with solid lines; the unlabeled signals marked with an asterisk in the spectrum (b) belong to a rotamer of R6UU in the partial cone (paCo) conformation; see text and ESI for further details.

Fig. 4. ¹H NMR stack plot (400 MHz, CDCl₃) of the [3]rotaxanes sharing dumbbell 7a, isolated from the supramolecular-assisted reactions {A–C} of Scheme 1, and corresponding to (a) R6UU, (b) R6UL and (c) R6LL, respectively. The U and L subscript labels of the spectrum (b) indicate that the corresponding protons' chemical shifts coincide with those found for the UU and LL orientational isomers, respectively. In the sketch of the three [3]rotaxanes on the left, the tosylate counteranions have been omitted for clarity.

Fig. 5. Expansion of a 2D ROESY spectrum (400 MHz, CDCl₃, ROESY SL = 200 ms) of R6UU. Analysis of the cross-peaks shows the spatial proximity between the protons of the internal C12 alkyl chain (α–δ) and those of the phenylurea groups (b and c) present at the upper rim of the calix[6]arene macrocycles (for the full spectrum, see ESI†).

Fig. 6. Cyclic voltammograms of dumbbell 7a (black line; 1 × 10⁻⁴ M) and [3]rotaxane R6UU (red line, 2 × 10⁻⁴ M) in CH₂Cl₂ at room temperature. A 100-fold excess of TBAPF₆ was employed as supporting electrolyte.