Based on these promising results, we extended our catalytic protocol for the reduction of unprotected functionalized pyridines (Scheme 3). The resulting piperidines are key saturated heterocyclic scaffolds often encountered in the synthesis of top-selling drugs. Simple and methyl-substituted pyridines, including 4-methoxypyridine, were well tolerated and efficiently reduced, thus providing the piperidines 75-80 in high yields. Halide-containing pyridines are extremely challenging molecules for this type of transformation due to competing hydrodehalogenation pathways. Applying our optimal reaction conditions, 4-chloro and 4-bromopyridine rings were selectively reduced and gave access to the corresponding piperidines 81 and 82 in moderate yields. The reaction was also amenable with pyridines bearing -OH, -CF3, -NH2, -NMe2, -CH2NH2, and -CH2OH at 4-position, thus giving the corresponding piperidines 83-88 in satisfactory to good yields upon isolation. Gratifyingly, 4-substituted pyridines with morpholine, pyrrolidine, and piperidine were capable of chemoselectively reducing the pyridine core, affording the desired products in high yields (89-91), which implies great promise for this approach in applications in clinical studies. Interestingly, para-substituted pyridines comprising potential functional groups (-Ph, -PhCl, -PhBr, -PhF, -PhCF3, -OArOCF3) under standard conditions were selectively transformed to the respective functionalized tetrahydropyridines in excellent yields (92-97) that are hitherto difficult to access therefore opening up new possibilities for synthetic and medicinal applications, thus highlighting the sustainability of our current catalysis. Notably, compound 97 is a vital intermediate for the production of delamanid, which is an antibiotic medicine used to treat multidrug-resistant tuberculosis in adults. The aromatic reduction of pyrazine-to-piperazine is seldom reported in the literature despite the potential applications of piperazine motifs in medicinal chemistry. To our delight, our Ti-catalyzed protocol could be further extended to simple and alkyl-substituted pyrazines, affording the corresponding piperazines in high yields (98-102), which are hard to prepare by other methods. Pyrrole also proved to be compatible with this reaction, furnishing the corresponding pyrrolidine in a 73% isolated yield (103). It is worth mentioning that the F(sp 3 ) carbon fraction has been improved along with the functional group persistence in all the products as shown in Scheme 3. Scheme 3. Substrate scope for the reduction of functionalized pyridines under optimized conditions. [a] Reaction conditions: 0.5 mmol of quinoline, 3 equiv. NH3•BH3, 10 mol % Cp2TiCl2, 1.0 equiv of NaOMe, 3 mL of dry THF in 21 mL sealed tube and stirred at 120 °C for 24 h, isolated yields. Reaction conditions: 0.5 mmol of quinoline, 5 equiv. NH3•BH3, 10 mol % Cp2TiCl2, 1.0 equiv of NaOMe, 3 mL of dry THF in 21 mL sealed tube and stirred at 120 °C for 24 h, isolated yields.