Synthesis and [3,3]-sigmatropic rearrangements of 5-(pentafluorosulfanyl)-pent-3-en-2-ol, its homologues, and trifluoromethyl analogues

Abstract

The synthesis of aliphatic (pentafluoro-λ⁶-sulfanyl)(SF₅)-substituted compounds is more challenging than that of the related CF₃-substituted analogues. Previous investigations of [3,3]-sigmatropic rearrangements of γ-SF₅-substituted allylic alcohols failed to yield 3-SF₅-substituted carboxylic acid derivatives. Herein, we present the synthesis of a series of 1-SF₅-alk-1-en-3-ols and our efforts to apply them in Johnson–Claisen, ester enolate-Claisen, and Ireland–Claisen rearrangements. Unfortunately, these reactions failed to include the 1-SF₅-substituted 1,2-double bond, although successful reactions of analogous CF₃-allylic alcohols were reported. Further experiments revealed that bulkiness rather than electronic properties of the SF₅ group prevented [3,3]-sigmatropic rearrangements. Indeed, the introduction of a competing second vinyl group into the system (1-SF₅-penta-1,4-dien-3-ol) confirmed that a Johnson–Claisen rearrangement was successful (92% yield of methyl 7-SF₅-hepta-4,6-dienoate) with incorporation of the unsubstituted 4,5-double bond while the 1-SF₅-substituted 1,2-double bond remained unchanged. Efforts to apply 1-(SF₅CF₂)-substituted 1,2-double bond systems, which are similar to CF₃ analogues in steric requirements, in Johnson–Claisen or ester enolate-Claisen rearrangements failed because of the instability of the SF₅CF₂ substituent under various reaction conditions. On the other hand, when the SF₅ group was separated from the reaction center by a CH₂ group instead (5-SF₅-pent-3-en-2-ol), Johnson–Claisen rearrangements using six orthoesters provided the target 2-substituted 3-(CH₂SF₅)-hex-4-enoates in 55–76% yields as ∼1 : 1 mixtures of diastereomers. As an example to demonstrate the utility of these products, methyl 3-(CH₂SF₅)-hex-4-enoate was reduced, and the formed alcohol was oxidized to the aldehyde. Finally, initial experiments showed that the synthetic sequence developed for SF₅ compounds is also applicable for analogous CF₃-substituted allylic alcohols (5-CF₃-pent-3-en-2-ol) and their Johnson–Claisen rearrangement.