Catalytic enantioselective intramolecular Tishchenko reaction of meso-dialdehyde: synthesis of (S)-cedarmycins

Abstract

The first successful example of a catalytic enantioselective intramolecular Tishchenko reaction of a meso-dialdehyde in the presence of a chiral iridium complex is described.

Synthesis of 1,3-Dioxepine-Fused (Tricyclic) Bispyrazoles Involved with Pyrazolone Derivatives and Dichloromethane

“…Due to the interesting structural and functional properties of benzo­[1,3]­dioxepines, more and more methods have been developed for their synthesis . The conventional benzo­[1,3]­dioxepine syntheses involved the classic transititon-metal-catalyzed cross-coupling followed by acetal formation (Scheme a-i). , An alternative to this approach would involve the acetal linkage of the two phenolic moieties followed by transition-metal-catalyzed intramolecular cross-coupling (Scheme a-ii). , These methods could be an economically inefficient and environmental harmful process due to the requirement of prefunctionalization of substrates and associated with waste production . Other methods are mainly represented by [4+3] cycloaddition to construct 1,3-dioxepane in the presence of a metal catalyst and/or an organocatalyst. ,− For example, recently, the Feng group reported the ring-opening/[4+3] cycloaddition reaction toward 4,5-dihydrobenzo­[ d ]­[1,3]­dioxepine derivatives by employing a special chiral rare-earth-metal complex catalyst (Scheme b)…”

Using α- and β-Epimerizations of cis-2,3-Bis(hydroxymethyl)-γ-butyrolactone for the Synthesis of Both Enantiomers of Enterolactone

“…Recently, we developed the first intramolecular asymmetric Tishchenko reaction of 4 and the asymmetric lactonization of 6 . In both cases, the reaction allowed for the enantioselective synthesis of γ-butyrolactone 5 . In this previous study, we reported that both enantiomers of lactone 5 can be synthesized using the same enantiomer of the catalyst by simply changing the reaction system (Scheme ).…”

“…For our synthesis of enterolactones, we investigated a process starting from lactone 5 (Scheme ). Optically pure 5 can be obtained via the recrystallization of crude 5 . Deprotection of the diphenylmethylene acetal of 5 under acidic conditions unexpectedly yielded the β-epimerized trans -diol 2 as the major product.…”

“…Next, we investigated the synthesis of (+)-enterolactone via an α-epimerization step (Scheme ). For that purpose, lactone 5 was converted to cis -diol 1 using hydrogenolysis under neutral conditions and then converted to the di-MPM ((4-methoxyphenyl)­methyl) ether, cis - 8 . Treatment of cis - 8 under basic conditions with 1,8-diazabicyclo(5.4.0)­undec-7-ene (DBU) successfully triggered an α-epimerization to furnish trans - 8 .…”

“…In other words, under basic conditions, α-epimerization via path A base and β-epimerization via path B base and path C base could cause racemization. In fact, we observed the racemization in the synthesis of cedarmycin . In the current study, we used an acidic heterogeneous catalyst (Amberlite IR-120­(H)) for the deprotection of acetal 5 in order to avoid neutralization by the base during workup (Scheme ).…”