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

The synthesis of aliphatic (pentafluoro-lambda(6)-sulfanyl)(SF5)-substituted compounds is more challenging than that of the related CF3-substituted analogues. Previous investigations of [3,3]-sigmatropic rearrangements of gamma-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 similar to 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.

Automated summary

The steric hindrance of the SF5 group hindered the [3,3]-sigmatropic rearrangement reactions. The use of 1-SF5-alk-1-en-3-ols failed to successfully incorporate the 1-SF5-substituted 1,2-double bond in Johnson-Claisen, ester enolate-Claisen, and Ireland-Claisen rearrangements.