Scheme 6. Plausible Reaction ProcessOrganic Letters pubs.acs.org/OrgLett Letterhttps://doi.org/10.1021/acs.orglett.5c02584Org. Lett. 2025, 27, 8934−89408938
Annotation #1 - FACT:
This is an example of a nucleophilic addition reaction, in which, the sulfur acts as a nucleophile and attacks an electrophilic carbon on 1a, and this displaces Br, which is a LVG and can hold negative charge well
Scheme 3. Synthesis of Medium-Sized and Macrocyclic Thioethers
Annotation #3 - QUESTION
How does increasing the ring size, such as utilizing larger carbon rings, impact availability of electrophilic centers and stability, therefore how does that impact the speed and likelihood of intramolecular cyclization to occur in this reaction?
Table 1. Optimization of the Reaction Conditionsaentry additive (equiv) solvent T (°C) yield (%)b1 none DMSO 80 592 none DMF 80 703 none DMA 80 734 none MeCN 80 695 none toluene 80 206 none THF 80 477 none dioxane 80 238 NaI (0.2) DMA 80 689 KI (0.2) DMA 80 6610 none DMA 60 6211c none DMA 80 73aReaction conditions: 1a (0.20 mmol, 1.0 equiv), 2a (0.22 mmol, 1.1 equiv), solvent (2 mL), 12 h. bIsolated yields. cNo light.Organic Letters pubs.acs.org/OrgLett Letterhttps://doi.org/10.1021/acs.orglett.5c02584Org. Lett. 2025, 27, 8934−89408935
Annotation #2 - CONNECT:
In Table 1, as shown below, there is the utilization of a variety of solvents such as DMSO, DMF, and THF. As known about nucleophilic substitution reactions, especially ones that are SN2, the utilization of polar, operatic solvents for this reaction increases reaction rates and increases yield amount, as seen with the high yields using DMA and DMF.