Here, we report a systematic study on catalyst optimization, reaction scope and applications of the novel Mo(VI) system to the synthesis of a bioactive oxazoline antibiotic. We began our studies by evaluating the 6-methylpicolinate ligand alongside similar catalysts in cyclodehydration of serine derivative 1 (Table ). Reaction of 1 with MoO2(acac)2 without a ligand additive resulted in a low yield of 2 (24%, entry 1) and a significant amount of dehydroalanine side product (39%). Similar results were observed when 6-methylpicolinic acid (20 mol%) and MoO2(acac)2 (10 mol%) were directly added to the reaction mixture and refluxed with the substrate (Entry 2). We hypothesized that the suboptimal yield was a result of the poor solubility of MoO2(acac)2, preventing the formation of the putative MoO2(6-MePic)2 complex. Therefore, we generated a series of catalysts by combining the bidentate ligands 3a-3m and MoO2(acac)2 in methanol and collecting the resulting solid by filtration (Entry 3 -15). Catalyst 3a was found to be the best picolinic acid-based additive for generation of oxazoline 2 with almost quantitative conversion into 2 and low or undetectable amounts of the dehydroalanine byproduct. Electron rich 3d and electron poor (3e -3f) catalysts (Entry 6 -8) were found to give 2 in slightly lowered yields. Hydroxyquinoline 3g, with a phenolate ligand, was less effective and a significant amount of alcohol 1 remained after 14 h of reaction time, which was not found in other reactions even with lower yield. Despite the similarities to 3g, menthol derivative 3h performed better, which may be due to the difference in flexibility of the ligands, solubility of the catalyst, and/or a combination of electronic factors of the anionic ligand. It is interesting to note that thiazole 3i was also very effective in promoting cyclization, despite the lower basicity of the thiazole nitrogen, thought to facilitate proton transfer in the catalysis. This was further explored with other azole-based catalysts (Entry 12 -14) with only minor changes in yield of 2. Catalyst 3m, containing the significantly less basic tetrahydrofuran ligand, gave 87% of oxazoline 2. These results show that the basicity of the neutral ligand is not a key feature of catalytic oxazoline synthesis. Interestingly, addition of 3n, which has been reported by Ishihara as an effective additive, produced 2 in a reduced yield, indicating that the second coordination site is beneficial for the overall yield and suppressed dehydroalanine formation (Entry 16). To demonstrate the utility of the optimized MoO2(6-MePic)2 system, reactions of substituted cysteines were performed (Scheme 2). The catalysis proved very effective in cyclizing Nbenzoyl dipeptides containing N-terminal cysteine (6 -8, 82-89%). The ability of the catalytic system to tolerate the relatively sensitive Fmoc protective group is highly valuable, as demonstrated in the preparation of 9 -10 in 83-95% yield. Furthermore, the C2-exomethine position of thiazolines are Reaction conditions: MoO2(6-MePic)2 (10 mol%), PhMe (10 mM, purged with N2), azeotropic reflux (CaH2 plug), heating bath 110-140 °C, 4 h.