Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

Abstract

Following to the computational expectation, our previously reported intriguing 1,3-proton shift of 4,4,4-trifluorobut-2-yn-1-ols was successfully extended to the 4,4,4-trifluorobut-2-en-1-ol system under metal-free conditions to afford the corresponding saturated ketones in high to excellent chemical yields using such a convenient and easy-to-handle base as DBU at the toluene refluxing temperature, and utilization of the corresponding optically active substrates unambiguously demonstrated that this transformation proceeded in a highly stereoselective fashion.

Preparation and Reactions of CF3‐Containing Phthalides

“…In this instance, after migration of the acidic H a in Int‐10 to the alkoxide oxygen, the resultant enolate would follow condensation with the in situ generated CF 3 C=O group to form 14a . As reported from this laboratory as well as others, it is interesting to note that H b in 14a was estimated to possess equal or higher acidity than the hydroxy proton and our computation, actually clarified that the carbanion after removal of H b is 26.4 kcal mol –1 more stable than the corresponding alkoxide where the ideal environment of the former carbanion by the nice flat conjugation system should play a significantly important role (Figure ). Energetic relationship between the intermediary enol form 15′a and the diastereomeric products, syn ‐ and anti ‐12′a led to reasonable elucidation of the exclusive formation of the latter.…”

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers

“…Presence of the electronwithdrawing CF3 group was considered to play a crucial role in activation of a proton, H a , at the allylic position of 1, and its abstraction was actually realized by the action of such a weak base as DBU under the toluene refluxing condition which resulted in the simple isomerization to the intermediates, Int-1, followed by the conversion to their keto form 2 to complete this interesting sequence. This reaction mechanism was proved by our own computation for the transition state [7] as well as by experimental employment of the deuterated substrate by the other group [8]. On the basis of this successful as well as convenient proton shift process starting from the CF3-containing allylic alcohols 1, we envisaged its interesting extension from the synthetic point of view: thus, our idea was that the bisallylic ethers 2 possibly readily synthesized by way of the O-allylation of 1 were recognized as the potential substrates for the Claisen rearrangement as long as the proton shift of 3 to 4 was possible.…”

“…Preparation of the CF3-containing allylic alcohols 1 was carried out in a stereoselective fashion following to our own developed method like 1) reactions of adequate Grignard reagents with CF3CO2Et to construct the ketones CF3-C(O)-R 1 , 2) their Horner-Wadsworth-Emmons reactions with (EtO)2P(O)CH2C(O)R 2 [14], and 3) NaBH4 reduction of the obtained ,-unsaturated ketones. Important to note is the fact that the sequences 1) and 2) could be performed without isolation of the intermediary trifluorinated ketones which allowed the possible formation of 1 even with a "small" R 1 whose isolation is usually difficult due to their low boiling points and high volatility [7,15].…”

“…It is widely understood that strategic entry of fluorine atoms or fluorinated groups to adequate molecules gave strong impact to the original character in many instances, and thus development of novel methods for the construction of a variety of such compounds has attracted significant attention of researchers working in the field of synthetic organic chemistry, material science, and biologically active compounds [1][2][3][4][5]. For this reason, we have been studying to realize facile preparation of such molecules, and recently reported an interesting proton transfer starting from both propargylic [6] and allylic alcohols [7], enabling to form diverse ,-enones and saturated ketones, respectively, just by their treatment with very convenient as well as easy-to-handle tertiary amines. The representative example for the latter was described in Scheme 1.…”

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

“…The formation of the 3-fluoroalkylated indanones as a side product may be explained based on the previous literature [ 20 , 40 ]. The reaction of Int-1 with the alkynes 1 also gives Int-2b as a regioisomeric intermediate of Int-2a , leading to the 3-fluoroalkylated cobalt alkoxide Int-3b .…”