Abnormal Claisen rearrangements of tetronates and stereoselective ring opening of intermediate spirocyclopropanes

A journey towards natural licochalcone E: From isolation to asymmetric total synthesis

“…Mechanistically, a homodienyl [1,5]-sigmatropic hydrogen shift of licochalcone A (1) would form a spirocyclopropane intermediate, which would undergo a [1,5]-homosigmatropic rearrangement to give licochalcone E (6) as shown in Scheme 4. This type of abnormal Claisen rearrangement is well known and is often observed in the Claisen rearrangement of g-alkyl substituted allyl ethers, which is complicated by the abnormal rearrangement leading to isomeric mixture (Schobert et al, 2001).…”

3‐Functionalized Tetronic Acids From Domino Rearrangement/Cyclization/Ring‐Opening Reactions of Allyl Tetronates

“…Tetronates 1 were in turn readily available from a domino addition/intramolecular Wittig alkenation between the corresponding α-hydroxyallyl esters and the phosphorus ylide Ph 3 PϭCϭCϭO. We have also communicated [7] that the 3-(spirocyclopropyl)dihydrofuran-2,4-diones 2 with residues R 3 bearing α-hydrogen atoms, though not isolable, are likely intermediates in the so-called ''abnormal'' Claisen rearrangements of allyl tetronates. Here we report on new evidence for this assumption, on the scope of ring-opening reactions of stable derivatives of 2 with O-, N-, S-and C-nucleophiles, and on a domino [3,5]-sigmatropic rearrangement/cyclization reaction of a penta-2,4-dienyl tetronate to give a furano [4,3-b]dihydrooxepine.…”

“…General Information: Tetronate 1a, [8] [8] 1-hydroxycyclohexanecarboxylic acid [14,15] and tetronate 9b [7] were prepared by literature procedures. All other starting compounds were purchased from Aldrich and used as such without further purification.…”

“…[1Ϫ6] We have recently reported an expeditious synthesis of the 3-[(syn-1Ј-methyl-2Ј-alkoxy)alkyl]tetronic acids 3 from allyl tetronates 1. [7] An unusual thermal domino ClaisenϪConia rearrangement [8] of 1 furnished the 3-(spirocyclopropyl)dihydrofuran-2,4-diones 2, which were isolable in cases of residues R 3 lacking α-hydrogen atoms and which could be selectively ring-opened with water or alcohols to give 3 (Scheme 1). Tetronates 1 were in turn readily available from a domino addition/intramolecular Wittig alkenation between the corresponding α-hydroxyallyl esters and the phosphorus ylide Ph 3 PϭCϭCϭO.…”

“…Ring opening of the 5-phenyl derivative 2b (R 1 ϭ H, R 2 ϭ R 3 ϭ Ph) with methanol, for instance, gave the corresponding tetronic acid 3c in 65% yield. From earlier single-crystal Xray structural analyses [7] of tetronic acids 3 with R 3 ϭ Ph, we know that vicinal coupling constants 3 J(1Ј-H/2Ј-H) of ഠ 2Ϫ4 Hz are indicative of a syn configuration of the stereocentres in the side chain at C-3. Accordingly, compounds 3Ϫ5 were also formed exclusively in syn configurations, which can be explained in terms of a selective attack of the nucleophile on the benzylic carbon atom in the intact threemembered ring from the face of the adjacent methyl group.…”