Zirconium Metal Organic Frameworks as Heterogeneous Catalysts for Meerwein-Ponndorf-Verley Reactions

Abstract

Various zirconium-containing MOF-808 compounds have been prepared as potential catalysts for the Meerwein-Ponndorf-Verley (MPV) reduction of carbonyl compounds. Modified MOF-808 have been synthethized in which a small fraction of the trimesate ligands present in pristine MOF-808 has been replaced by dicarboxylate ligands, as a strategy to induce a controlled creation of defects. The linkers used are: isophthalate (MOF-808-IPA), 3,5-pyridinedicarboxylate (MOF-808-Pydc), 5-aminoisophthalate (MOF-808-NH2) and 5-hydroxyisophthalate (MOF-808-OH). All these compounds are highly crystalline and isoreticular with pristine MOF-808. The catalytic activity of pristine and defect engineered MOF-808 has been evaluated for MPV reactions, using cyclohexanone as model substrate. All the materials show a higher catalytic activity than that of zirconium terephthalate UiO-66 used as reference. This higher activity is attributed to the higher amount of coordinatively unsaturated Zr4+ ions in MOF-808 than in UiO-66. Moreover, MOF- 808-IPA and MOF-808-Pydc are more active than pristine MOF-808, which is due to the creation of less sterically crowded sites due to the introduction of defective dicarboyxlate linkers. A further advantage of MOF-808 over UiO-66 is the presence of a wider pore system, which allows converting bulkier substrates. To evaluate this characteristic, a bulky ketone has been used; estrone, which can enter the pores of MOF-808 but not those of UiO-66. Accordingly, MOF-808 can fully convert estrone selectively to estradiol, while UiO-66 shows barely any catalytic activity. Interestingly, when MOF- 808 is used as catalysts, a noticeable amount of the isomer 17alpha-estradiol is produced, which is difficult to obtain by other means. Therefore, the diastereoselective properties of MOF-808 for MPV reactions are interesting from the preparative point of view. In order to investigate in more detail the diastereoselective properties of MOF-808 for MPV reactions, various substituted cyclohexanones have been considered: 3-methylcyclohexanone (3MeCH), 2- methylcyclohexanone (2MeCH) and 2-phenylcyclohexanone (2PhCH). Depending on the alcohol used as reducing agent and the position of the substituent in the cyclohexanone molecule, MOF-808 selectively favors the formation of one isomer or the other with a different diastereoselectivity: 82%, 61% and 94%, respectively for 3MeCH, 2MeCH y 2PhCH. These results can be rationalized by considering the preferential formation of a given transition state in the confined space available inside the MOF pores. The energetic characteristics of the process have been analyzed by a combined use of kinetic studies and theoretical calculations. Finally, in view of the interesting properties of MOF-808 as catalyst for MPV reactions, this material has been successfully applied to the preparation of a number of challenging hydroxysteroid compounds with pharmacologic interest through a chemo-, regio- and diastereoselective reduction of the corresponding oxosteroid. In this way, it has been possible to prepare in one single reaction step the following compounds: 17alpha-estradiol, 5alpha-androstan-3beta,17alpha-diol and epitestosterone. This demonstrates the high potential of MOF-808 as a catalysts for the synthesis of high added value compounds.