Mild LiOMe-Catalyzed Trifluoromethylation of Carbonyl Compounds
Santhosh Reddy Naini1, Venumadhav Janganati1, Arun D R Shada1
1TCG GreenChem, Inc., 701 Charles Ewing Blvd, Ewing, New Jersey 08628, United States.
Abstract:
We report a mild lithium methoxide (LiOMe)-catalyzed protocol for the trifluoromethylation of aldehydes, acyclic and cyclic ketones, and α,β-unsaturated carbonyl compounds. This method avoids the use of fluorinated or strong bases that promote enolization, offering broad functional group tolerance, including silyl, Boc, Cbz, nitrile, and benzyl groups, enabling its application to diverse complex substrates. Additionally, LiOMe catalyzes the diastereoselective addition of CF3 to chiral keto esters derived from (1R,2S)-1-(methylamino)-2,3-dihydro-1H-inden-2-ol, affording products with diastereomeric ratios up to 84:16.
Related Concept Videos
Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
Carboxylic Acids to Methylesters: Alkylation using Diazomethane
Amides to Amines: LiAlH4 Reduction
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Acid Halides to Alcohols: LiAlH4 Reduction
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
Multiple Halogenation of Methyl Ketones: Haloform Reaction


