Calcium(II)- and Triflimide-Catalyzed Intramolecular Hydroacyloxylation of Unactivated Alkenes in Hexafluoroisopropanol

Abstract

We report an efficient intramolecular hydroacyloxylation of unactivated alkenes, offering a streamlined access to relevant γ-lactones, which features the utilization of either a calcium(II) salt or triflimide as a catalyst in hexafluoroisopropanol. This method could be applied to the synthesis of natural products and the late-stage functionalization of natural and bioactive molecules. Additionally, DFT computations were used to elucidate the twist of reactivity observed between the hydroamidation and hydroacyloxylation of unactivated alkenes regarding the formation of 5-and 6-membered rings.

Exploiting hexafluoroisopropanol (HFIP) in Lewis and Brønsted acid-catalyzed reactions

“…particularly effective to yield the desired compounds from unsaturated carboxylic acids (Scheme 29). 50 This method could be applied to the synthesis of natural products and to the postfunctionalization of natural and bioactive compounds. However, in the presence of an electron-withdrawing group (EWG) in the position of the carboxylic acid, the reaction had to be performed with HNTf2 as a catalyst.…”

Modular Synthesis of 9,10-Dihydroacridines through an ortho-C Alkenylation/Hydroarylation Sequence between Anilines and Aryl Alkynes in Hexafluoroisopropanol

“…In the past years, HFIP has become a prominent solvent in organic synthesis due to its combination of atypical properties, including strong H-bond donating ability, low nucleophilicity, redox stability, and mild acidity . It allowed us to achieve reactions that were unlikely to take place in traditional organic solvents, ,, emphasizing that, when HFIP was associated with a Lewis acid or a Brønsted acid, the acidity of the corresponding combination could be considerably boosted to even activate unreactive substrates such as highly deactivated styrenes. Recently, we applied this principle to the ortho -C alkylation of anilines with alkenes, which relies on a concerted-like mechanism that is fostered by the presence of HFIP and prevents common regioselectivity issues associated with this type of process (Scheme c).…”

Ca(NTf2)2/HFIP‐Mediated Direct and Mild Rearrangement of Cyclopropyl Carbinols to E‐Homoallylic Triflimides

“…Mechanistic studies further revealed that the introduction of hexafluoroisopropanol (HFIP) [9] could dramatically increase the acidity of the system via the formation of H‐bonding interactions with Ca(NTf 2 ) 2 , thereby facilitating the subsequent transformations even with highly electronically deactivated substrates [10] . By virtue of the established calcium catalysis, a variety of challenging transformations such as arylation, [10d,e] aza‐Piancatelli reaction, [10a,f] hydroacyloxylation, [10c] hydroamidation [10b] have been well addressed thus far. With our efforts, more recently we have also developed an ortho ‐C‐alkenylation/hydroacyloxylation sequence to assembly phthalides benefit from this Ca(NTf 2 ) 2 /HFIP co‐catalytic system [10h] .…”