With the above dilemma in mind, we envisioned that the SoM and SoB groups may be able to address the problem. To that end, we tested if the SoM and SoB protected cytidine, which are compounds 5a and 5b (Scheme 2), respectively, could be deprotected under non-nucleophilic conditions using fluoride. The hypothesis was that upon removal of the TBS group with fluoride, the intermediates 6a-b would undergo intramolecular cyclization to release cytidine under neutral conditions driven by the formation of the 5membered ring side products 7a-b. For the model study, compounds 5a-b were synthesized using 8a-b, respectively (see Supporting Information for the synthesis of 8a-b). They were then treated with Et3N-HF in the presence of excess Et3N at various temperatures and times. TLC analysis of the reactions found that the TBS group in 5a-b could be removed to give 6a-b almost instantly even at 0 °C. Complete conversion of 6a to cytidine could be achieved at 65 °C for 30 minutes, which are the conditions for the deprotection of 2′-OTBS in standard RNA synthesis methods. In contrast, complete conversion of 6b to cytidine, however, needed harsher conditions. The fact that 6a is easier than 6b to deprotect may be due to the electron-withdrawing effect of the methoxy group in SoM. In addition, the stereo effect of the methoxy group, which may potentially increase the frequency of collision between the hydroxyl oxygen and amide carbonyl carbon in 6a that leads to the formation of 7a, may also have contributed to the difference. Details of the studies are provided in Supporting Information (Figure ). Based on the above observations, we decided to further study the suitability of SoM for sensitive RNA synthesis by synthesizing actual RNAs.