Enantioselective Synthesis of Trifluoromethyl α,β-Unsaturated δ-Lactones via Vinylogous Aldol-Lactonization Cascade

Abstract

The novel vinylogous aldol-lactonization cascade of alkylidene oxindole with trifluoromethyl ketones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of alkylidene oxindoles for the preparation of enantioenriched trifluoromethylated α,β-unsaturated δ-lactones.

Synthesis of (Trifluoromethyldiazirinyl)phenylboronic Acid Derivatives for Photoaffinity Labeling

“…(4-Formylphenyl)boronic acid pinacol ester 1 was treated with 1.5 equivalents of CF 3 TMS in the presence of K 2 CO 3 (30 mol%) in DMF at room temperature, with slightly larger amounts of reagent and catalyst to construct the 2,2,2-trifluoro-1-phenylethan-1-ol derivative, 10 followed by acid hydrolysis to afford a low yield of 2 (Figure 3, entry 1). Excess CF 3 TMS improved the chemical yield slightly (entries 2 and 3).…”

Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones

“…Additionally, although more sterically hindered ethyl‐derivative 3 o proved to be unreactive, the cyclic‐analogue, namely the indenyl‐derived Meldrum's acid 3 p , was transformed into the corresponding tetracyclic product 5 pa in 75 % ee (64 % yield). Subsequently, we wondered whether this Meldrum's acid‐based platform 3 a could react with other ketones, known as good starting materials for the efficient enantioselective vinylogous synthesis of 5,6‐dihydropyran‐2‐ones 1 [7, 8a–e,g–i] . However, in our case, we expected to extend the chemical diversity with the formation of isomeric and non‐racemic 3,6‐dihydropyran‐2‐one architectures 5 .…”

Recent Developments in Enantioselective Organocatalytic Cascade Reactions for the Construction of Halogenated Ring Systems

“… [98] This reaction, catalyzed by a quinidine‐derived squaramide catalyst ( C22 ), was the first asymmetric method described to produce these compounds, and it was also the first example of intramolecular amide C−N bond cleavage and lactonization of 3‐hydroxyoxindoles with 3‐trifluoroethylidene oxindoles. It builds on Bencivenni's report on a vinylogous aldol‐lactonization cascade of alkylidene oxindole in which oxindole amide C−N bond cleavage was judiciously utilized in the construction of highly substituted lactones (vide infra) [99] …”

“…Fluorinated six‐membered rings could be obtained by another formal Diels–Alder reaction, namely by a vinylogous aldol‐lactonization cascade between alkylidene oxindoles 137 and trifluoromethyl ketones 138 which led to the enantioselective synthesis of trifluoromethyl α,β‐unsaturated δ‐lactones 139 . This work was developed by Bencivenni, as mentioned above [99] . In the presence of a bifunctional tertiary amine catalyst C36 , C–N bond cleavage occurred, and the desired unsaturated lactones were obtained.…”

“… Synthesis of trifluoromethyl α,β‐unsaturated δ‐lactones by a vinylogous aldol‐lactonization cascade [99] …”