Mechanistic Insight into the Formal [1,3]-Migration in the Thermal Claisen Rearrangement

Abstract

The thermal formal [1,3]-sigmatropic shift of allyl aryl ethers has been studied in depth experimentally with the aid of the density functional theory (DFT) calculations of the B3LYP function. Three mechanistic possibilities, referred to as the radical, ionic, and concerted mechanisms, have previously been put forth to explain the thermal [1,3]-rearrangement process. However, the intercrossing and radical trapping experiments indicate the rearrangement is an intramolecular process. The computational studies reveal that the concerted C[1,3]-sigmatropic shift suffered from a higher energetic barrier to allow the rearrangement to proceed under the conditions used. However, a tandem O[1,3]-sigmatropic shift with a configuration inversion of the oxygen atom and [3,3]-sigmatropic shift (the Claisen rearrangement) is the most likely pathway for the formal [1,3] rearrangement. Furthermore, the rearrangement experiments with a designed optically active substrate and O[1,3]-sigmatropic shift examples verify the new cascade rearrangement. In addition, computational and experimental studies indicate that water molecule assists the proton shift during the isomerization. The combined methods provide the new insight into the mechanism of the thermal formal [1,3]-migration in the Claisen rearrangement and the novel O[1,3]-sigmatropic shift as well.

Synthesis of 1,2,4,5-tetrasubstituted imidazoles using 2,6-dimethylpyridinium trinitromethanide {[2,6-DMPyH]C(NO2)3} as a novel nanostructured molten salt and green catalyst

“…Because of the appropriate symmetry of these compounds via 1,3-aryl sigmatropic symmetry, 30,31 almost half of the signals were observed in 1 H NMR and 13 C NMR spectra (Scheme 3).…”

Catalytic Enantioselective 1,3‐Alkyl Shift in Alkyl Aryl Ethers: Efficient Synthesis of Optically Active 3,3′‐Diaryloxindoles

“…In our attempt to work out afeasible solution, areport by Tu rnbull and co-workers on the thermal and acid-catalyzed rearrangement of 3-aryloxy-2-oxindolesc aught our attention. [13] Surprisingly,despite the synthetic utility of [1,3] alkyl shifts of alkyl aryl ethers, [14] to date,n oc atalytic enantiose-lective variant has been reported (Scheme 1b). [15] Thec hallenges for the enantioselective alkyl shift in alkyl aryl ethers, as we identified, stems from the following reasons:The chiral catalyst must 1) avoid ac oncerted [1,3] alkyl shift, [16] 2) be active enough to facilitate the CÀOb ond cleavage,a nd 3) participate in akey enantiodescriminating step.Herein, we report first catalytic enantioselective [1,3] alkyl shift in alkyl aryl ethers using chiral Brønsted acids to deliver enantioenriched 3,3'-diaryloxindoles (Scheme 1c).…”

“…When we examined other chiral phosphoric acids, B1, C1,and D1,r educed enantioselectivities were obtained (entries 8-10). Thereafter as hort solvent screen was evaluated (entries [11][12][13][14]. Unfortunately,a ni ncrease in the enantioselectivity was not observed.…”

Catalytic Enantioselective 1,3‐Alkyl Shift in Alkyl Aryl Ethers: Efficient Synthesis of Optically Active 3,3′‐Diaryloxindoles

“…[13] Surprisingly,despite the synthetic utility of [1,3] alkyl shifts of alkyl aryl ethers, [14] to date,n oc atalytic enantiose-lective variant has been reported (Scheme 1b). [13] Surprisingly,despite the synthetic utility of [1,3] alkyl shifts of alkyl aryl ethers, [14] to date,n oc atalytic enantiose-lective variant has been reported (Scheme 1b).…”

“…Ther eaction fruitfully led to the formation of the rearranged product 2a when (S)-A1 (TRIP) was used as catalyst, albeit in low yield and enantioselectivity (entry 1). Thereafter as hort solvent screen was evaluated (entries [11][12][13][14]. Next, the slightly more acidic phosphoric acid A3 pleasingly delivered 2a in 83 % yield and 54 % ee (entry 3).…”