Biomimetic enantioselective synthesis of β,β-difluoro-α-amino acid derivatives

Although utilization of fluorine compounds has a long history, synthesis of chiral fluorinated amino acid derivatives with structural diversity and high stereoselectivity is still very appealing and challenging. Here, we report a biomimetic study of enantioselective [1,3]-proton shift of β,β-difluoro-α-imine amides catalyzed by chiral quinine derivatives. A wide range of corresponding β,β-difluoro-α-amino amides were achieved in good yields with high enantioselectivities. The optically pure β,β-difluoro-α-amino acid derivatives were further obtained, which have high application values in the synthesis of fluoro peptides, fluoro amino alcohols and other valuable fluorine-containing molecules.

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers

We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton shift of CF3-containing propargylic or allylic alcohols to afford the corresponding a,b-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF3 group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst.

Reaction of Lithiated Propargyl Ethers with Carbonyl Compounds – A Regioselective Route to Furan Derivatives

The deprotonation of 3-aryl-substituted alkyl propargyl ethers with n-butyllithium provides an ambident anion that reacts with carbonyl compounds to provide mixtures of γ-substituted products with alkoxyallene substructure and of α-substituted propargyl ethers. The ratio of the two product types strongly depends on the solvent: in diethyl ether the γ-substituted products predominate whereas the more polar tetrahydrofuran favors the α-adducts. The primary addition products undergo 5-endo-trig or 5-endo-dig cyclizations under various reaction conditions to afford isomeric furan derivatives. The highest selectivity in favor of α-substituted products was achieved by employing a MOM-protected propargyl ether. During the protonation step no evidence for a proton shift leading to an isomeric allenyl anion was found. A brief mechanistic discussion tries to rationalize the observed regio­selectivities.

Organocatalytic asymmetric tandem α-functionalization/1,3-proton shift reaction of benzylidene succinimides with β-trifluoromethyl enones

A bifunctional thiourea-catalyzed asymmetric tandem α-functionalization/1,3-proton shift reaction of benzylidene succinimides with β-trifluoromethyl enones has been developed.

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

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.