# Zirconium-Containing Metal-Organic Frameworks (MOFs) as Catalysts for Biomass Conversion
## 7 Conversion of Other Biomass-Derived Compounds
### Reduction of Carbonyl Compounds: Synthesis of Hydroxysteroids
Given the outstanding performance of MOF-808 and the large space available inside the pores, we then wanted to use it for converting very bulky substrates, such as substituted cyclohexanones [80] or estrone [23; 81]. This is a natural steroid molecule with approximate dimensions of 11.2 A \(\times\) 6.2 A \(\times\) 4.2 A. As expected, UiO-66 was completely inactive for the reduction of estrone (E1) to estradiol (E2), but both pristine and defect-engineered MOF-808 afforded the full conversion of E1 after 24 h of reaction. The reduction of the (pro-chiral) carbonyl group of E1 at position 17 can give rise to a mixture of two estradiols: 17\(\alpha\)-E2 and 17\(\beta\)-E2, as shown in Scheme 10. Interestingly, when MOF-808 was used as an MPV catalyst for the reduction of E1, the main product obtained was 17\(\alpha\)-E2, with a diastereoselectivity ratio of up to 87:13 under optimized conditions. It is worth noting that the formation of 17\(\alpha\)-hydroxy steroids from the corresponding 17-ketosteroid is, in general, challenging. Usually, the 17\(\beta\) isomer is obtained almost exclusively when NaBH\({}_{4}\) or other reducing agents are used; the steric hindrance of the 18-methyl group imposes the approaching direction of the hydride from the _anti_-face, giving rise to \(-\)CH\({}_{3}\) and \(-\)OH groups in _syn_ configuration in the final product. Therefore, when 17\(\alpha\)-OH compounds are the desired product, additional reactions are required to produce the inversion of the 17\(\beta\)-OH isomer through Mitsunobu reactions [82], involving multiple protection-deprotection steps and resulting in very low final yields. For example, [PERSON] et al. described the synthesis of a similar 17\(\alpha\)-OH steroid (5\(\alpha\)-androstane-3\(\beta\),17\(\alpha\)-diol)  
Figure 10: Reduction of estrone (E1) yields a mixture of estradiols: 17\(\alpha\)-E2 and 17\(\beta\)-E2 diastereoisomers. from the 17-ketosteroid by a four-step reaction involving reduction, toosylation, acetate substitution, and hydrolysis, with a final yield of the 17\(\alpha\) product of only 4% [83]. [PERSON] et al. introduced later a modification of this process by adding three more steps: epoxidation with peracetic acid, reduction with NaBH\({}_{4}\), and hydrolysis with NaOH, attaining a final yield of 54% [84]. [PERSON] and [PERSON] used a chiral Rh complex, yielding the 17\(\alpha\)-hydroxy-estrone-3-methyl ether in 36%, together with the 17\(\beta\)-compound in a 26% yield [85]. In sharp contrast with these poor results, the use of MOF-808 as an MPV catalyst affords a means for producing 17\(\alpha\)-E2 in 87% selectivity in one single reaction step. Moreover, we showed that the solid catalyst can be easily recovered at the end of the reaction by simple filtration or centrifugation and used in consecutive catalytic runs without losing the activity of the diastereoselectivity to the elusive 17\(\alpha\)-E2 compound for at least six catalytic cycles [81]. However, we wanted to go a step further and check if this remarkable diastereoselective synthesis of 17\(\alpha\)-E2 could also be applied to the synthesis of other 17\(\alpha\)-hydroxy steroids, as well as to address other important aspects of the reaction, such as the regio- and chemo-electivity of the MPV reduction of 17-ketosteroids over MOF-808. Scheme 11 summarizes the considered reactions and the results obtained. Similar to E1, epiandrosterone (EPIA) also bears a keto group in position 17. When this molecule was submitted to a MPV reaction under the same conditions and using the MOF-808 catalyst, we also observed the formation of the 17\(\alpha\)-OH compound as the main reaction product, thus evidencing the general applicability of the method. Moreover,we then considered androstenedione (\(\Delta^{4}\)-androstene-3,17-dione, A4) as a substrate. This compound contains two keto groups, in positions 3 and 17, as well as another easily reducible functional group, a C=C bond in position 4.