The Final Stereogenic Unit of [2]Rotaxanes: Type 2 Geometric Isomers

Abstract

Mechanical stereochemistry arises when the interlocking of stereochemically trivial covalent subcomponents results in a stereochemically complex object. Although this general concept was identified in 1961, the stereochemical description of these molecules is still under development to the extent that new forms of mechanical stereochemistry are still being identified. Here, we present a simple analysis of rotaxane and catenane stereochemistry that allowed us to identify the final missing simple mechanical stereogenic unit, an overlooked form of rotaxane geometric isomerism, and demonstrate its stereoselective synthesis.

Figure 1

(a) Schematic demonstration that the C_2(x)(11) symmetry operation of a non-interlocked ring corresponds to the notional process of inverting the relative ring orientations in a [2]catenane; hence, any ring for which C_2(x) is a symmetry operation cannot give rise to conditional mechanical stereoisomers. (b) Conversion of a D_4h symmetric structure to rings of C_4v, C_4h, and S₄ symmetry, which we propose to be representative of the complete set of oriented (C_nh and S_2n) and facially dissymmetric (C_nv) building blocks of catenane stereochemistry, by the addition of simple vectors (± refer to vectors projecting up/down, respectively, perpendicular to the plane of the ring).

Figure 2

(a) Complete set of catenane mechanical stereogenic units that can be constructed from the archetypal rings identified (Figure 1) and their relationship with the (b) mechanical stereogenic units of rotaxanes via a notional ring-opening-and-stoppering operation, including the newly identified “type 2” rotaxane mechanical geometric unit. The vectors shown characterize their stereochemistry and their relationship to the components that gives rise to them defines the stereogenic unit.

Figure 3

(a) Comparison of the MGI-2 and MPC stereogenic units highlighting the common challenge of selectively threading of an oriented ring onto an oriented or facially dissymmetric axle, respectively. (b) Retrosynthesis of the MGI-2 stereogenic unit using a direct AT-CuAAC approach. The forward reaction proceeds via two possible diastereomeric intermediates (one shown). Although one of the half-axle units is chiral, this is symmetrized in the forward reaction, and the same achiral, diastereomeric mixture is produced whether the starting material is enantiopure or racemic.

Scheme 1. Poorly Selective Direct AT-CuAAC Synthesis of Type 2 Rotaxane Geometric Isomers 5 via Chiral Diastereomers 4

Reagents and conditions: (i) 1 (1 equiv), 2 (1.1 equiv), (S)-3 (1.1 equiv), [Cu(CH₃CN)₄]PF₆ (0.97 equiv), ⁱPr₂EtN (2 equiv). (ii) TFA, CH₂Cl₂, rt, 1 h. ^bDetermined by ¹H NMR analysis of the crude reaction product. Ar = 3,5-di-^tBu-C₆H₃.

Scheme 2. Chiral Interlocking Auxiliary Synthesis of MGI-2 Rotaxanes 10 and 11

Reagents and conditions: (i) 1 (1 equiv),6 (1.1 equiv), (S)-7 (1.1 equiv), [Cu(CH₃CN)₄]PF₆ (0.99 equiv), ⁱPr₂Et (2 equiv), CH₂Cl₂, rt, 16 h. (ii) PhB(OH)₂, Pd(PPh₃)₄, K₂CO₃, acetone-ⁱPrOH-H₂O (2:1:1), 60 °C, 3 h. (iii) K₂CO₃, CH₂Cl₂-MeOH, rt, 3 h. (iv) TFA, CH₂Cl₂, rt, 1 h. ^bDetermined by ¹H NMR analysis. Ar = 3-CO₂Me-5-Ph-C₆H₃.

Figure 4

Partial ¹H NMR (400 MHz, CDCl₃, 298 K) spectra of (a) (Z_m)-11 (92% de), (b) (Z_m,S_co-c)-10 (94% de), (c) 10 (16% de, obtained by a direct AT-CuAAC coupling, see Supporting Information Section 4), and (d) (E_m,S_co-c)-10 (92% de) (e) (E_m)-11 (94% de). Peak assignment and colors are the same as shown in Scheme 2.

Scheme 3. Co-Conformational Exchange between the Enantiomeric Co-Conformations of Rotaxane (Z_m)-11 Highlighting the Different Stereochemical Labels that Can Be Applied to Fully Assign Their Absolute Stereochemistry

Ar = 3-CO₂Me-5-Ph-C₆H₃.