Method for the Preparation of Derivatives of Heptiptycene: Toward Dual-Cavity Baskets

Abstract

We have developed a novel synthetic method that enables the preparation of functional derivatives of heptiptycene, i.e., cavitands with two juxtaposed cavities. The homocoupling of bicyclic dibromoalkenes is promoted by Pd(OAc)2 (10%) in dioxane (100 °C) to give cyclotrimers in 27-77% yield under optimized reaction conditions (Ph3P, K2CO3, n-Bu4NBr, N2, 4 Å MS). These dual-cavity baskets show a strong π → π* absorption at 241 nm (ε = 939,000 M(-1) cm(-1)), along with a subsequent fluorescence emission at 305 nm.

A Hexavalent Basket for Bottom‐Up Construction of Functional Soft Materials and Polyvalent Drugs through a “Click” Reaction

“…To sum up, using the newly optimized procedure, one shouldb ea ble to convert 5gof anthracene into 2.0 go fm ultivalent 4 in circa ten days (Figure 2C). This is in as tark contrast with the original protocol, [24] which on this scale (a) provides 440 milligrams of the multivalent host, (b) is more costly,a nd (c) requiresaconsiderably longert ime for completion.…”

“…[32] Both methods gave satisfactory results, albeit relatively inexpensive (BINAP)PdCl 2 was found to, under mild reaction conditions, [46] facilitate the conversion of 8 into 9 in excellent 89 %y ield ( Figure 2C). As in this transformation the reactant must undergo four consecutive reactions, the yield of each step is 97 %o na verage!T he conversion is scalable andc an be run safely on am ulti-gram scale (50 psi pressure of CO) with facile and quick purification of crude 9.T o transform 9 into 3 ( Figure 2C), we used published [24] yet somewhat modified bromination/dehydrobromination procedures. Finally,t he homocoupling of 3 was catalyzed with Pd(OAc) 2 to give dual-cavity 4 in 50 %y ield.…”

“…Some time ago, we developed a synthetic method for obtaining the dodecaester derivative of heptiptycene 4 (Figure B) in <5 % overall yield. In brief, commercially available dianhydride 2 was converted into dibromoalkene 3 in nine linear steps . Following, palladium‐catalyzed cyclotrimerization of 3 was optimized to give dual‐cavity 4 in circa 50 % yield .…”

“…[20,23] In this vein, we hereby describe an effective synthetic method for obtaining structurally unique host 1 (Figure 1) containing six terminal alkynes at the periphery of its two fused cavitands. [24] To demonstrate the utility of dual-cavity 1 as ab uildingb lock in modular synthesis, we used the highly efficient CuAAC [25] "click" reaction for conjugating six carbohydrates, PEG polymers, and aromaticsc arrying azide functional groups ( Figure 1). Since such polyvalent baskets could be designed to assemble into vesicles, [26] six recognition groups [18b] could be branching from their curved surface [27] with ap otentialu se in the preparation of functional soft materials.…”

“…Indeed, diversity‐oriented approaches or other creative solutions have been explored for developing more effective binders, yet the scope of synthetically accessible, biocompatible and topologically different structures remains limited . In this vein, we hereby describe an effective synthetic method for obtaining structurally unique host 1 (Figure ) containing six terminal alkynes at the periphery of its two fused cavitands . To demonstrate the utility of dual‐cavity 1 as a building block in modular synthesis, we used the highly efficient CuAAC “click” reaction for conjugating six carbohydrates, PEG polymers, and aromatics carrying azide functional groups (Figure ).…”