Dihydropyranones, formation

The polymer-bound Mn and Cr complexes were used as catalysts for epoxidations of six phenyl-substituted olefins with m-CPBA/NMO and for dihydropyranone formation from the Danishefsky diene and aldehydes. There are several remarkable features of the novel immobilized salens ... 

Further studies by Bode and co-workers have shown that enolate formation from a-chloroaldehydes and subsequent reaction with 4-oxo-enoates or unsaturated a-ketoesters 232 generates dihydropyranones 233 in excellent diastereo- and enantio-selectivities, and with impressively low catalyst loadings [90], This work has been extended to the generation of enolate equivalents from bisulfite adducts of a-haloaldehydes 234 under aqueous conditions (Scheme 12.50) [91]. 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

The compounds covered in this section include dihydropyranones, tetrahydropyranones and their benzologues (dihydrocoumarins, chromanones and isochromanones). The area of greatest interest is undoubtedly the chromanones because of their relationship to a number of natural products and presumably also because of their ease of formation, stability and value as precursors of other heterocycles. Tetrahydropyran-2-ones comprise one of those nebulous areas of heterocyclic chemistry and usually feature in text books as 5-lactones under derivatives of hydroxy acids. 

Formation of the isochroman system is considered to trigger the synthesis of the dibenzopyran (17, X = H2) by the acid catalysed cyclisation of c/s-enediynes (16, X = H2). In a similar manner, the carboxyl function in (16, X = O) promotes cylisation to a dihydropyranone derivative which is followed by a Myers cycloaromatisation to the dibenzopyranone (17, X = O) (95TL9165). 

The origin of dihydropyran 123 can be traced to the known dihydropyranone 124, derived from commercially available acetylacetaldehyde dimethylacetal 125. Although the oxygen at C4 of dihydropyran 123 is not present in the natural product, its role was to facilitate a stereocontrolled epoxidation reaction as well as the stereoselective formation of the Q-C-glycoside. Its presence also... 

Subsequently, the same group reported a synthetically useful protocol to stereospecific synthesis of syn- and a/rti-dihydropyranones containing a stereogenic trifluoromethyl substituent through NHC-catalyzed redox het-ero-Diels-Alder reactions of either E- or Z-p-trifluoromethyl enones with a-aroyloxyaldehydes. Kinetic experiments revealed the formation of 0-acylated enolate species when an achiral precatalyst was used in these reactions, accounting for the difference in reactivity observed compared with a chiral precatalyst. The measurement of a positive KIE suggests that deprotonation of the NHC-aldehyde adduct to form the Breslow intermediate is kinetically significant (Scheme 7.84). 

Biju and co-workers developed an NHC-catalyzed reaction of 2-bromoenals with heterocyclic C—H acids, leading to the formation of coumarin/quinoli-none-fused dihydropyranone/dihydropyridinone derivatives. The reaction proceeds via the generation of a,p-unsaturated acylazolium intermediates. Moreover, the authors also presented the results on the enantioselec-tive version of this reaction (4 examples with up to 93% yield and 86% ee) (Scheme 7.103). 

Ye and co-workers [30] ingeniously replaced the enals by bromoenals and used a M-heterocyclic carbene (NHC) as chiral organocatalyst for the formation of the corresponding dihydropyranones in a formal enantioselective [3-1-3] annulation reaction (Scheme 16.14). Similarly, Scheldt s group [31] reported the synthesis of optically active bi- or tricyclic dihydropyranones by an NHC-catalyzed domino intramolecular Michael/acylation sequence. 

Optically active dihydropyranones were synthesized by Smith and co-workers [43] by a highly stereoselective chiral isothiourea-catalyzed intermolecular Michael/lactonization cascade from arylacetic acids and p,7-unsaturated a-ketoesters (Scheme 16.21). This strategy is based on the generation of chiral enolate directly from carboxylic acid activated by the in situ formation of a mixed anhydride and the organocatalyst. 

Intramolecular alkoxycarbonylation leading to lactone formation was the key step during the construction of the dihydropyranone ring of precursor 60 of marine... 

Reaction of a chiral A-heterocyclic carbene catalyst and a,/ -unsaturated aldehyde gives , -unsaturated acyl azolium that participates in enantioselective annulation via a Coates-Claisen rearrangement that invokes the formation of a hemiacetal before a sigmatropic rearrangement to give dihydropyranone products (Scheme 14)7 ... 

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