Enantioselective Access to Tetrahydroxanthones via Copper-bis(oxazoline)-Catalyzed [4 + 2] Cycloaddition

Abstract

Highly enantioselective access to tetrahydroxanthone compounds was achieved through copper-bis(oxazoline)-catalyzed [4 + 2] cycloaddition of chrom-4-one dienophiles and Danishefsky’s diene. Oxo-dihydroxanthone (enone) adducts, containing a quaternary stereocenter, are generated in up to 98% yield and 89% ee. Cycloadducts are utilized in the synthesis of tetrahydroxanthones, featuring a novel organotin-mediated quasi-Krapcho decarboxylation of β-keto esters, with retention of stereochemistry. Tetrahydroxanthone is a versatile intermediate to a diverse array of biologically relevant, saturated xanthones.

Transition‐Metal Catalyzed [4+2]‐Cycloaddition Reactions: A Sexennial Update

“…[150] Attard et al in 2023 reported the synthesis of biologically relevant tetrahydroxanthone analogues 156 by copper-bis(oxazoline)-catalyzed [4 + 2] cycloaddition followed by an organotin-mediated quasi-Krapcho decarboxylation of β-keto esters (Scheme 42). [151] Initially, chrom-4-one dienophiles 153 and Danishefsky's diene 154 afforded oxo-dihydroxanthone (enone) adducts 155 containing a quaternary stereocenter in good yields and high enantiomeric excess. The cycloadduct 155 were utilized in the synthesis of 156 with retention of stereochemistry.…”

Synthesis of 2-amino-9H-chromeno[2,3-d]thiazol-9-ones with anti-inflammatory activity via cascade reactions of 2-amino-3 iodochromones with amines and carbon disulfide

“…Chromones are also useful building blocks for constructing diverse and complex heterocycles. 10–17 Among the chromone containing scaffolds, tricyclic chromone fused heterocycle compounds are quite important. Some of the tricyclic compounds are recurrent drugs or drug candidates, for example, the anti-inflammatory and anti-allergic drug amlexanox ( 1 ), 18 the anti-tubercular compound 2 , 19 the antimicrobial compound 3 , 20 and the antitumor compounds 4 (ref.…”

The Asymmetric Synthesis of Polycyclic Tetrahydroxanthone via the Cascade Reaction of Alkene‐Substituted 1,3‐diketones and Alkenyloxindoles

“…[5] For instance, the groups of Shibasaki [6] and Feng [7] reported independently efficient chiral Lewis acid-catalyzed enantioselective vinylogous additions using 2-ester-activated chromones as electrophilic donor, which is followed by Dieckmann cyclization to produce the tetrahydroxanthone-type natural products (Scheme 1a). In addition, the 3-EWG-activated chromones were also successfully applied in [4 + 2] annulation through chiral Lewis acid catalysis, [8] trienamine catalysis, [9] phosphine catalysis [10] to access various structurally diverse tetrahydroxanthones (Scheme 1b). Chi and co-workers reported the cascade reaction of chromone dienones with β-methyl enals promoted by N-heterocyclic carbene (NHC) to provide chiral hydroxanthone skeleton.…”