Catalytic Environmentally Friendly Protocol for Achmatowicz Rearrangement

Abstract

The increasing interest in Achmatowicz rearrangement in organic synthesis calls for a more environmentally friendly protocol since the most popular oxidants m-CPBA and NBS produced stoichiometric organic side product (m-chlorobenzoic acid or succinimide). Mechanism-guided analysis enables us to develop a new catalytic method (Oxone/KBr) for AchR in excellent yield with K2SO4 as the only side product, which greatly facilitates the purification. This protocol was integrated with other transformations, leading to a rapid access to the highly functionalized dihydropyranones.

Enantioselective total synthesis of decytospolide A and decytospolide B using an Achmatowicz reaction

“…24,25 Achmatowicz reaction with oxone in the presence of NaHCO 3 in a mixture (4:1) of THF and water at 23 °C for 30 min smoothly converted 10 to the corresponding dihydropyranone hemiacetal ( 9 ). 26 The resulting hemiacetal was initially subjected to reduction with Et 3 SiH and TFA at −45 °C for 3 h. This resulted in a mixture of dihydropyranone 14 and a small amount of alcohol 8 . Further optimization of the reaction with an excess of BF 3 •OEt 2 at −45 °C for 3 h provided alcohol 8 as the exclusive product in 47% yield over 2-steps.…”

Asymmetric Total Syntheses of (−)-Hedycoropyrans A and B

“…It was noted that the E / Z selectivity was significantly affected by the solvent (THF: E / Z = 5/1), instead of the counterion of the base. Sharpless asymmetric dihydroxylation of 6 with AD mix-β provided the requisite vicinal diol 7 (94% ee by HPLC), which underwent smoothly Achmatowicz rearrangement under our catalytic condition [KBr (cat.) and oxone] to provide 9 in 78% yield after immediate double acetylation.…”

Alkyne-Forming Furan Fragmentation: A General Method to Convert Furans into Alkynoic Acids

“…1 Furthermore, they are readily accessible and highly reactive, making them one of the most versatile synthons in organic synthesis. 2 For example, furans can be readily oxidized by reagents such as singlet oxygen, 3 m-CPBA, 4 NBS, 5 Oxone-KBr, 6 etc. to access a number of valuable four-carbon building blocks, depending on the substitution pattern.…”

“…Mechanistically, endoperoxide (6), derived from a [4+2] cycloaddition between furan 5 and singlet oxygen, is the key intermediate that gives rise to the classic four-carbon building blocks 1-4. 1,7 In principle, a formal retro-[3+2] fragmentation of 6 via two C-C bond cleavages might also be possible in the presence of a suitable driving force, which…”