Rim-Differentiated C5-Symmetric Tiara-Pillar[5]arenes

Abstract

The synthesis of "rim-differentiated" C₅-symmetric pillar[5]arenes, whose two rims are decorated with different chemical functionalities, has remained a challenging task. This is due to the inherent statistical nature of the cyclization of 1,4-disubstituted alkoxybenzenes with different substituents, which leads to four constitutional isomers with only 1/16th being rim-differentiated. Herein, we report a "preoriented" synthetic protocol based on FeCl₃-catalyzed cyclization of asymmetrically substituted 2,5-dialkoxybenzyl alcohols. This yields an unprecedented 55% selectivity of the C₅-symmetric tiara-like pillar[5]arene isomer among four constitutional isomers. Based on this new method, a series of functionalizable tiara-pillar[5]arene derivatives with C₅-symmetry was successfully synthesized, isolated, and fully characterized in the solid state.

Figure 1

(a) In the Lewis acid-catalyzed oligocyclization, the reaction of asymmetrically functionalized monomer (M₁ or M₂) with formaldehyde can form two key monomeric intermediates M_A and M_B, which undergo further oligomerization. The alkoxy substituents (OR1 and OR2) can be oriented in both syn and anti fashions when two adjacent phenylene rings are connected by the CH₂ bridge. This process, after ring closure of the linear pentamers, eventually leads to the formation of four P[5] constitutional isomers (see panel b). The nearly statistical nature of this oligomerization/cyclization makes the desired tiara-P[5] (T-P[5]) with C₅ symmetry the least abundant product (∼1/16th). To circumvent this, (see panel c) our “preoriented” strategy employs monomer M_A with a hydroxymethylene handle. This handle directs the reaction to formation of all-syn linear pentamer (P_syn) in the presence of a weak Lewis acid, resulting in T-P[5] with high selectivity and yield.

Figure 2

(a) Rim-differentiated (propargyl)₅-T-P[5] 2a and the other three constitutional isomers of (propargyl)₅-P[5] isomers. HPLC chromatograms of mixtures of (propargyl)₅-P[5]isomers obtained from (b) conventional statistical and (c) our “preoriented” synthesis. (d) ¹H NMR spectrum of 2a.

Figure 3

Side and top views of X-ray solid-state structures of different tiara-pillar[5]arenes obtained by preoriented synthetic protocol, illustrated in a blend of tubular stick and space-filling representations: (a) (propargyl)₅-T-P[5] (2a), (b) (allyl)₅-T-P[5] (2b), (c) (homoallyl)₅-T-P[5] (2c), (d) (2-bromoethyl)₅-T-P[5] (2d), (e) (3-bromopropyl)₅-T-P[5] (2e), (f) (propargyl)₅(allyl)₅-T-P[5] (2f), and (g) (3-azidopropyl)₅-T-P[5] (3) [all T-[P5]s, apart from 2f, have five OCH₃ groups on the other rim]. Only one of the two enantiomeric coconformations in the solid state is shown for each compound. All hydrogens and guest molecules are omitted for clarity. Color code: alkyne, purple; allyl, magenta; azido, green; bromine, orange; carbon, gray; oxygen, red.