Synthesis of Trifluoromethyl Ketones via Tandem Claisen Condensation and Retro-Claisen C–C Bond-Cleavage Reaction

Abstract

A highly efficient, operationally simple approach to trifluoromethyl ketones has been developed that builds on the use of a tandem process involving Claisen condensation and retro-Claisen C-C bond cleavage reaction. Enolizable alkyl phenyl ketones were found to react readily with ethyl trifuoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones, which were quite different from the general Claisen condensation products, β-diketones. This procedure uses readily available starting materials and can be extended to the preparation of perfluoroalkyl ketones in excellent yield.

1,5‐Diketones Synthesis via Three‐Component Cascade Reaction

“…On the basis of earlier studies and our results,2,4a,d,8 we propose a possible mechanism for the cascade reaction (Scheme ). The first step is the oxidation of N , N ‐dicyclohexylmethylamine 1f with TBHP affording an iminium ion A , which undergoes a Mannich reaction with trifluoromethyl β‐diketone to generate a Mannich base B .…”

Isotope labelling by reduction of nitriles: Application to the synthesis of isotopologues of tolmetin and celecoxib

“…The iodinated celecoxib analogue 14 was prepared in a twostep process (Scheme 3). 20,21 Condensation of the iodoacetophenone 10 with ethyl trifluoroacetate 11 gave the 1,3-dicarbonyl 12, which cyclised regioselectively with the hydrazine 13 to give the iodinated intermediate 14.…”

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodiumS-organyl sulfurothioates under basic conditions

“…Although detailed mechanisms for these reactions remain to be elucidated, the literature has clearly demonstrated that many transformations involving β-keto esters are dependent on the strength and concentration of the base [56][57][58][59][60][61][62][63][64]. Therefore, based on the above results and on the information from the literature, we propose the following mechanism for the synthesis of 3 (Scheme 4) [56][57][58][59][60] and 4 (Scheme 5) [61][62][63][64]: We believe that initially, an acidic hydrogen atom bonded to the methylene group between the two carbonyl groups in the β-keto ester 1 is removed by a HO − anion to generate the stabilized carbanion intermediate A.…”

“…Although detailed mechanisms for these reactions remain to be elucidated, the literature has clearly demonstrated that many transformations involving β-keto esters are dependent on the strength and concentration of the base [56][57][58][59][60][61][62][63][64]. Therefore, based on the above results and on the information from the literature, we propose the following mechanism for the synthesis of 3 (Scheme 4) [56][57][58][59][60] and 4 (Scheme 5) [61][62][63][64]: We believe that initially, an acidic hydrogen atom bonded to the methylene group between the two carbonyl groups in the β-keto ester 1 is removed by a HO − anion to generate the stabilized carbanion intermediate A. The carbanion then attacks the most available sulfur atom of the sodium S-organyl sulfurothioate 2 to produce the keto−enol tautomers B, C, and D. Subsequently, when 4 equiv of NaOH (concentrated solution) are used, the most electron-deficient carbonyl group experiences a quick attack by the HO − anion, generating the unstable tetrahedral intermediate ion E, the breakdown of which leads to a negatively charged 2-organylthioacetate stabilized by both a carbonyl group and the sulfur atom.…”