Domino Reactions with Fluorinated Five-membered Heterocycles – Syntheses of Trifluoromethyl Substituted Butenolides and γ-Ketoacids

Summary. A new approach to trifluoromethyl substituted butenolides and their thioanalogues is described starting from 2-fluoro-3-trifluoromethylfurans and -thiophenes, respectively. The reaction sequence includes three steps – nucleophilic displacement reaction, Claisen, and finally Cope rearrangement – which can be run as domino reaction. A modification of the domino reaction (transesterification instead of Cope rearrangement) provides a concise access to α-trifluoromethyl-γ-ketoacids.     

Hexafluoroacetone as a Protecting and Activating Reagent. Regioselective Esterification of Aspartic, Malic, and Thiomalic Acid

Summary. Hexafluoroacetone reacts with -functionalized ,-dicarboxy acids like aspartic, malic, and thiomalic acid to give exclusively five-membered lactones. The -carboxylic groups remain unaffected and can be derivatized separately. They can be linked i.a. to orthogonal protecting groups or multivalent alcohols like pentaerythritol to give synthetically valuable building blocks.     

Partially Fluorinated Heterocycles from 4,4-Bis(trifluoromethyl)-hetero-1,3-dienes via C–F Bond Activation – Synthesis of 2-Fluoro-3-(trifluoromethyl)furans

An efficient synthesis of 2-fluoro-3-(trifluoromethyl)furans was developed. Keystep of the reaction sequence is a [4 + 1] cycloaddition reaction of tin(II)chloride to 4,4-bis(trifluoromethyl)-1-oxabuta-1,3-dienes. At elevated temperatures the tin heterocycles are transformed into 1-aryl-4,4-difluoro-3-(trifluoromethyl)but-3-en-1-ones which on treatment with sodium hydride in dry DMF give 2-fluoro-3-(trifluoromethyl)furans. The single fluorine bound to C-(2) can be readily replaced by various N-, O-, S-, and C-nucleophiles and dinucleophiles.     

A new strategy for solid-phase depsipeptide synthesis using recoverable building blocks

The technique of choice for synthesis of small-scale depsipeptides is on a solid support. However, if expensive monomers have to be incorporated, solid-phase synthesis can quickly turn out to be unattractive because of its low atom economy. Herein, we describe a new type of recoverable and reuseable alpha-hydroxy acid building block for solid-phase synthesis and its application in the synthesis of a number of small cyclic depsipeptides. [structure: see text]