To understand the generality of this directed site-selective hydrogenation, the substrate scope was explored (Fig. ). Remarkably, for all the substrates tested, only the arene adjacent to the DG was hydrogenated. Besides simple phenyl group, para, ortho, and meta-substituted ones all gave the corresponding hydrogenated products in excellent yield as the cis-isomer selectively (c2-c14). Besides simple alkyl substituents, diverse functional groups, such as trifluoromethyl (c7), silyl (c8), ketone (c9), ester (c10), phenyl (c11 and c12), furyl (c13) and alkenyl (c14) groups, can be tolerated. Interestingly, the less stable cis products were still obtained predominantly with those containing an epimerizable stereocenter, e.g., α to ketones and esters (c9 and c10). The much more reactive alkene moieties can survive (c14 and c15) in this reaction likely because they are further away from the DG. Other reducible functional groups, including benzyl ether (c16), benzimidazole (c17), nitrile (c18), quinoline (c19), naphthalene (c20, c28, and c29), and aryl bromide (c27), were found compatible. In addition, different substituents and substitution patterns on the phenol ring were also examined. Replacing the C6-methyl group on the phenol with a small fluorine atom still afforded the desired products (c21 and c22) in excellent yields, though the trans-reduction minor isomer was observed in these cases. The C6-ethyl-substituted or C5, C6-disubstituted phenols also worked well (c23-c25). The C4 substituent is not necessary for the desired reactivity (c26). In the presence of a C5substituent, the C6-substituent can be omitted (c28 and c29). Double saturation was achieved using the 2,6-diphenyl substrate (c30). In addition to phenols, both α-and β-naphthol-derived substrates delivered the desired products (c31 and c32). Moreover, the ortho furyl-substituted phenol provided the corresponding tetrahydrofuran-derived product (c33) efficiently. In the attempt of further broadening the substrate scope, a distance effect was observed regarding the directing efficiency (Fig. ). While the addition of one methylene spacer between the targeted aryl group and the phenol core still afforded the desired product (c34) in good yield, further extending the linker (c35) led to no conversion of the starting material (for additional challenging examples, see Supplementary Materials, section 8). Gratifyingly, the phosphinite DG can also be derived from ketone substrates (Fig. ). The α-aryl substituted tetralone substrates, though showing a competing deoxygenation side reaction (see Supplementary Materials, Table ), still afforded the desired products (c36, c37) after employing a Lewis acid additive. Beyond phenols and ketones, the use of the di-t-butyl-alkyl phosphine as the substrate was equally efficient, implying that the oxygen functional group in the substrates is not critical for the directing effect. Efforts have been made to gain preliminary understanding of the reaction mechanism. Most ruthenium-catalyzed arene hydrogenation reactions involve heterogeneous or colloidal catalysts 8b,8e,9b,9e , which are generally not effective to interact with DGs. Our control experiments nevertheless suggest that this directed saturation reaction is likely catalyzed by a homogeneous ruthenium complex. First, the mercury poisoning experiments showed that the reaction was unaffected by adding mercury metal, which usually inhibits nanoparticle-catalyzed reactions (Fig. ) . Next, a "hot filtration" test 14 was conducted: the reaction mixture was filtered through a 200 nm PTFE (polytetrafluoroethylene) filter after 2 hours and 6 hours of the reaction, respectively, and the filtrate was allowed to continue to react until the end of the reaction time (Fig. ). In both tests high yields were obtained, which is consistent with a homogeneous catalysis reaction. Moreover, small-angle X-ray scattering (SAXS) was employed to determine whether nanoparticles were formed during the reaction . The reaction mixture was tested at the beginning of the reaction, after 8 hours, and at the end of the reaction, and no nanoparticles were detected (see Supplementary Materials, Section 9). Altogether, these experiments indicate that this directed arene hydrogenation reaction unlikely involves heterogeneous catalysts.