Reactions proceed through SN1 when rearrangement yields a stable carbocation
the verdict
SUPPORTED
the evidence backs this
refutedsupported
the weight of evidence
3 sources for · 0 against
Reference literature establishes that carbocation intermediates in SN1 reactions can rearrange to form more stable carbocation structures before proceeding to products.
The modular and selective synthesis of dialkyl ethers, particularly sterically congested variants, remains a longstanding challenge in drug discovery and medicinal chemistry. Hindered alkyl ethers are especially desirable given their prevalence in bioactive natural products and favorable physicochemical properties. Classically, dialkyl ether synthesis relies on nucleophilic substitution strategies; however, SN2 reactions are fundamentally limited by steric congestion at the transition state, while SN1 pathways proceed through promiscuous carbocation intermediates prone to elimination, rearrangement, and loss of stereogenic information. Herein, we report a radical-based paradigm for general dialkyl ether synthesis enabled by an underutilized heteroatom homolytic substitution (het-SH2) mechanism. This mechanistic paradigm overcomes the intrinsic limitations of classical polar substitution chemistry by leveraging carbon-centered radicals generated under mild conditions that are insensitive to steric congestion in the bond-forming transition state. Utilizing a titanium-based catalytic platform in combination with visible-light photoredox catalysis, we demonstrate the efficient coupling of carboxylic acid-derived redox-active esters with alcohols across a broad range of substitution patterns, including 3°–2°, 3°–1°, 2°–2°, and 2°–1° architectures. This strategy grants access to dialkyl ether chemical space largely inaccessible through conventional approaches, including sterically
2. The cation may transfer a proton to a base, giving a double bond product. 3. The cation may rearrange to a more stable carbocation, and then react by mode #1 or #2. SN1 and E1 reactions are respective examples of the first two modes of reaction. The second step of alkene addition reactions proceeds by the first mode, and any of these three reactions may exhibit molecular rearrangement if an initial unstable carbocation is formed. The carbocation intermediate in electrophilic aromatic substitution (the benzenonium ion) is stabilized by charge delocalization (resonance) so it is not subject to rearrangement. In principle it could react by either mode 1 or 2, but the energetic advantage of reforming an aromatic ring leads to exclusive reaction by mode 2 (ie. proton loss). Contributors
- William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry
- The cation may transfer a beta-proton to a base, giving an alkene product. - The cation may rearrange to a more stable carbocation, and then react by mode #1 or #2. Since the SN1 and E1 reactions proceed via the same carbocation intermediate, the product ratios are difficult to control and both substitution and elimination usually take place. Having discussed the many factors that influence nucleophilic substitution and elimination reactions of alkyl halides, we must now consider the practical problem of predicting the most likely outcome when a given alkyl halide is reacted with a given nucleophile. As we noted earlier, several variables must be considered, the most important being the structure of the alkyl group and the nature of the nucleophilic reactant. The nature of the halogen substituent on the alkyl halide is usually not very significant if it is Cl, Br or I. In cases where both SN2 and E2 reactions compete, chlorides generally give more elimination than do iodides, since the greater electronegativity of chlorine increases the acidity of beta-hydrogens.
Everything we examined (3) — 2 independent sources
This check searched the claim as stated. It did not run a separate search for evidence against it.