The Domino Oxa‐Michael Addition–Aldol Reaction: Access to Variably Substituted Tetrahydroxanthenones

Abstract

Tetrahydroxanthenones represent the core of many natural products, most of which exhibit interesting biological activities. In the course of our synthetic efforts towards the total synthesis of the secalonic acids, which contain two of these tricyclic units, we have investigated the influence of substituents on the one‐step domino oxa‐Michael addition–aldol reaction leading to tetrahydroxanthenones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Xanthones from Fungi, Lichens, and Bacteria: The Natural Products and Their Synthesis

“…Also in 2008, Gérard and Bräse reported the synthesis of blennolide C and some analogues, confirming the suggestion made by Krohn that this compound had the structure formerly assigned to β-diversonolic ester. In common with the group's synthesis of diversonol (Scheme ), the ABC -ring tricyclic xanthone was constructed in a single step via an efficient domino oxa-Michael-aldol reaction ,− , from a substituted salicylic aldehyde 237 (Scheme ) and 4-hydroxycyclohexenone ( 266 ), the latter of which can be accessed enantioselectively and efficiently constructed using a synthesis developed within the group . Use of the weak base imidazole delivered the tricycle in 61% yield as a 1.5:1 ratio of diastereomers.…”

“…Some novel methodologies for the synthesis of aromatic xanthones published very recently involve the CO addition of carboxylic acids to benzyne derivatives, the CAN-mediated oxidative cyclization of 2-hydroxy-2′,5′-dimethoxybenzophenones, an unusual base-promoted dimerization of 3-(1-alkynal)chromones to form 2-alkynyl xanthones, and the oxidation of xanthenes with C–H activation utilizing a chromium (III) superoxo complex . While the number of methodologies for the synthesis of hydroxanthones are far fewer in number, an effective and general one-step methodology for the synthesis of the partially reduced xanthone core has been developed via domino oxa-Michael aldol reaction of salicylaldehyde derivatives and cyclohexenones. ,− …”

A Stereoselective Approach to Functionalized Cyclohexenones

“…The yields are moderate to low, as there is a problem with the reactivity of diketone 10 in all these reactions. Under the reaction conditions, the diketone can tautomerize into 2-methylhydroquinone (12). This conversion was observed for all the reactions, even in the formation of Diels-Alder adducts 11 (see Scheme 3).…”

“…Finally, the (R)-and (S)-CBS reagents were applied to the reduction reaction, but, again, mixtures of regioisomers were obtained. Under the reaction conditions, the diketone can tautomerize into 2-methylhydroquinone (12). In every case, however, it did effect a preference for cyclohexenone 1 instead of the desired cyclohexenone 2.…”

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

“…The racemic synthesis of 2 H -chromene was reported by Bräse et al in 2005 [39–40]. A strategy based on the organocatalytic enantioselective synthesis of chiral 2 H -chromenes through tandem-oxa-Michael–aldol sequence was first reported by Arvidsson et al [41] in 2006, using diarylprolinolether as an effective organocatalyst.…”