Rotaxanes with dynamic mechanical chirality: Systematic studies on synthesis, enantiomer separation, racemization, and chiral-prochiral interconversion

Abstract

Dynamic mechanical chirality of [2]rotaxane consisting of a C _s symmetric wheel and a C _2v symmetric axle is discussed via the synthesis, enantiomer separation, racemization, and chiral-prochiral interconversion. This [2]rotaxane is achiral and/or prochiral when its wheel locates at the center of the axle, but becomes chiral when the wheel moves from the center of the axle. These were proved by the experiments on the enantiomer separation and racemization. The racemization energy of the isolated single enantiomers was controlled by the bulkiness of the central substituents on the axle. Furthermore, the chiral-prochiral interconversion was achieved by relative positional control of the components. The present systematic studies will provide new insight into mechanically chiral interlocked compounds as well as the utility as dynamic chiral sources.

Keywords: chiral-prochiral interconversion; dynamic mechanical chirality; enantiomer separation; mechanical chirality; prochiral; racemization; rotaxane.

FIGURE 1

(A) Mechanically chiral [2]rotaxane consisting of an unsymmetrical wheel and an symmetrical axle. (B) Generation of co-conformational dynamic mechanical chirality in [2]rotaxane consisting of a C _s symmetric wheel and a C _2v symmetric axle.

FIGURE 2

Chiral-prochiral interconversion and energy diagrams of (A) 1-RH, (B) 1-R (see also Scheme 1 and Figure 5A and Supplementary Figure S50) and (C) axially chiral 1,1′-binaphtyl derivatives for comparison.

SCHEME 1

Synthesis of 1-H₂ , rac-1-Rs, and 1-RH (See the Supplementary Materials for details).

FIGURE 3

(A) ¹H NMR spectra of 1-H ₂ , rac-1-Me, rac-1-Et, rac-1-Ac and rac-1-Bz (400 MHz, in CDCl₃ at 298 K for 1-H ₂ and at 333 K, rac-1-Me, and in DMSO-d ₆ at 373 K for rac-1-Et, at 417 K for rac-1-Ac and rac-1-Bz, see also Scheme 1 for the assignments of protons). (B) Partial VT-¹H NMR spectra of rac-1-Me (400 MHz, CDCl₃, 213–333 K). (C) Mobility and energy diagram of rac-1-Me.

FIGURE 4

(A) Enantiomer separations of rac-1-R and racemization of 1-R-a and 1-R-b. (B) Chiral HPLC profiles (CHIRALPAK IA^®) of rac-1-Et (at 333 K), rac-1-Ac (at 283 K), and rac-1-Bz (at 283 K). The determination of the rate constant of mechanostereoinversion by dynamic HPLC method was shown in Supplementary Figures S43–S45 and Supplementary Table S2. Absolute structures of mechanically chiral rotaxanes could not be determined. (C) CD and UV spectra of 1-Et-a/b, 1-Ac-a/b and 1-Bz-a/b (0.1 mM, CHCl₃, 263 K). (D) CD decay profiles of 1-Et-a (at 273 K), 1-Ac-a (at 313 K) and 1-Bz-a (at 373 K) (0.1 mM, CHCl₃, 275 nm). (E) Energy diagrams of 1-Rs.

FIGURE 5

(A) Protonation and deprotonation of the nitrogen moiety of 1-R and 1-RH. Absolute structures of mechanically chiral rotaxanes could not be determined. (B) ¹H NMR spectra (400 MHz, CDCl₃) of 1-H ₂ (298 K), 1-Me (213 K) and 1-MeH (298 K). (C) ¹H NMR spectra (400 MHz) of 1-H ₂ (CDCl₃, 298 K), 1-Et (DMSO-d ₆, 413 K) and 1-EtH (CDCl₃, 298 K). (D) Chiral structural changes of 1-Rs and 1-RHs. (E) CD and UV spectra of 1-Et-a and 1-EtH (0.1 mM, CHCl₃, 263 K). (F) UV absorption intensity profiles at 275 nm and (G) CD decay profiles at 275 nm of 1-Et-a during the protonation by TFA (red profiles, 0.1 mM, CHCl₃, 263 K). As a reference, the UV and CD profiles of 1-Et-a without addition of TFA are shown [blue profiles, in (F) and (G)]. Since simple racemization of 1-Et-a occurs without addition of TFA, UV spectrum did not change [(F), blue] and CD intensity decreased much slower than that with addition of TFA [(G), blue].