57th Annual Report on Research 2012 Under Sponsorship of the ACS Petroleum Research Fund

During the grant period extending form September 1, 2011 to August 31, 2012 we have continued to make significant strides in our research into the dynamic self-assembly of nanoporous boronate ester macrocycles. As described in our original proposal, and updated in our project narrative of last year, our goals are to: (i) develop a fundamental understanding of how organic diols are able to undergo reversible dynamic covalent bond formation with boronic acids, giving boronate esters; and (ii) to use this understanding to create well-defined, shape-persistent boronate ester macrocycles with internal porous cavities that have dimensions on the nanoscale. While the related chemistry of infinitely periodic covalent organic frameworks (COFs) has seen significant advances since first introduced in 2005, the design of discrete covalent organic polygons has continued to be a challenge and there remain few reports of such dynamically assembled boronate ester compounds in the literature. One of, if not the greatest, difficulty in designing and synthesizing these materials has been the very limited solubility of organic oligo-catechols and oligo-boronic acids. This narrative describes the successes we’ve had in developing the synthesis of rigid polycyclic aromatic oligo-catechols and demonstrating their self-assembly with bis-boronic acids over the past year of the grant period.

To enhance the solubility of oligo-catechols we have developed new synthetic routes to the synthesis of alkyl-substituted derivatives of bis-catechols based on phenyl, phenyl-ethynyl, phenanthrene, and triphenylene backbones. By substituting target bis-catechols with two hexyloxy alkyl chains we have – for the first time – been able to synthesize derivatives of polycyclic aromatic bis-catechols that are soluble in common organic solvents (e.g. CHCl₃, CH₂Cl₂, THF, EtOAc, dioxane, etc.). Our success over the reporting period has been driven largely by the efforts of one graduate student and two undergraduate students. Through careful and systematic evaluations of a range of catechol protecting groups, transition-metal cross-coupling methodologies, and oxidative annulation strategies these students have found high-yielding and scalable routes to bis-catechols wherein the catechol moieties are oriented at angles of 0°, 120°, and 180°.

Combining these directional bis-catechols with bis-boronic acids under the appropriate conditions will enable the dynamic self-assembly of discrete, nanoporous boronate ester polygons that adopt square, rectangular, and hexagonal geometries. Indeed we have successfully demonstrated the dynamic self-assembly of discrete, shape persistent boronate ester rectangles upon combining 1,4-phenyl bis-boronic acid with either hexyloxy-substituted linear terphenyl tetraols or hexyloxy-substituted linear phenyl bis-ethynyl catechols. These assemblies have been definitively confirmed spectroscopically (¹H NMR, IR, UV/Vis) as well as spectrometrically (high-resolution MALDI mass spectrometry). The two rectangular assemblies represent the first syntheses of such discrete boronate ester polygons with well-defined nanoscale pores. These results were recently presented at the American Chemical Society National Meeting in Philadelphia, PA (poster title: “Dynamic assembly of discrete covalent organic polygons” ORGN-761). We are currently writing a manuscript describing these results and aim to submit within the month.

Building upon the first successful demonstrations of the dynamic self-assembly of discrete boronate-ester rectangles we are currently optimizing conditions for the related self-assembly of boronate-ester hexagons. The target hexagons will have internal pore diameters of roughly 2.7 nm, an approximate 1.6 nm increase in pore size relative to the rectangles. Furthermore, soluble hexagonal boronate-ester polygons will represent discrete versions of the widely studied COF-5 infinite lattice. In order to prepare soluble, discrete analogues of COF-5 required the development of new synthetic routes to triphenylene tetraols. While several methods for the synthesis of triphenylene alcohols and diols have been reported in the literature, the procedures suffered from low yields and require harsh reaction conditions. One example of the synthesis of a triphenylene tetraol has been reported in the literature, however its synthesis has only proven successful on preparative scales (typically <50 mg). Over the past 3 months we have developed a high-yielding route to triphenylene tetraols that can be easily scaled to produce gram quantities of product. Our route involves a novel combination of Pd-catalyzed coupling reactions to create a terphenyl backbone, followed by oxidative annulation using DDQ, and finally a selective deprotection of two catechol units to reveal the desired target product. Preliminary ¹H NMR results have shown the triphenylene tetraol is capable of self-assembling with 1,4-bisboronic acid, however the conditions need to be optimized as samples prepared thus far show measurable amounts of unreacted starting materials. Once optimized we will publish these results as well.

Several of the synthetic and computational methods we’ve used to design and synthesize our desired boronate-ester macrocycles have given rise to additional projects in the Northrop lab. The new synthetic route to triphenylene tetraols, for example, is currently being adapted to the preparation of new liquid crystalline materials. Knowledge gained from the boronate ester project has contributed to other studies: one involving self-assembling π-electron rich and π-electron poor materials and another involving the efficiency and kinetics of thiol-ene chemistry. The impact of the boronate ester project on these two additional areas of study has helped lead to two new publications during the reporting period. The research outlined above has significantly impacted one graduate student as well as two undergraduate students during the current reporting period. Both undergraduate students are seniors, writing senior theses, and plan to go to graduate school in chemistry. The wide range of synthetic, analytical, and computational techniques these students have acquired as a result of their involvement in research will be incredibly valuable assets to them as they enter graduate programs next year. The graduate student on the project has made excellent progress and has developed into an impressively independent researcher, capable of taking full intellectual and procedural reigns of the project. The project has also significantly impacted my independent career as we have successfully developed a new area of discrete, nanoporous boronate ester polygons and have now published 3 journal articles with two more currently in preparation.