2.4.6- Trisubstituted-2//-pyrans, reaction with

The distribution of charge in the resonance forms (28)-(31) suggests that nucleophiles may attack at C-2, C-4 or C-6 (or at C-2 or C-4 in 1-benzopyrylium cations, and at C-l, C-3 or C-4a in 2-benzopyrylium ions) but they most commonly add at C-2 for example, attack by cyanide ion gives a 2//-pyran (37) which exists partly or wholly as the acyclic isomer (38). Steric and electronic effects in the reactants probably have a role in determining the course of the reaction of trisubstituted pyrylium salts with nucleophiles. A mixture of both 2H- and 4H-pyrans is sometimes produced, for example, from methoxide ion and 2,4,6-triphenylpyrylium perchlorate (39) no acyclic product was detected in this reaction... 

Other 4,5,6-trisubstituted pyran-2-ones are readily accessible from the Re-catalysed reaction of 3-substituted propynoates with 1,3-dicarbonyl compounds. The intermediate enolic adduct can sometimes be isolated (Scheme 24) <07T11803>. 

The synthesis began with Prins qrchzation of the symmetric vinylo-gous ester 273, prepared from heptadienol 272, followed by hydrolysis of the resulting trifluoroacetate and benzylation, to afford the desired 2,6-cis-tetrahydropyran 274 with 92 8 diastereoselection at C5 [113], By this novel desymmetrization, 2,4,6-all-ci5 trisubstituted pyran was efficiently provided. Boron-enolate aldol reaction, as Carreira did, of the methyl ketone 274 with aldehyde 275 gave hydroxy ketone 271 as a single isomer. In contrast to Car-reira s result, samarium-catalyzed intramolecular Tishchenko reduction [114]... 

A 2,4)6-trisubstituted 2H or 4/f) pyran (38, R = R = Ph) was reported to result in low yield by catalytic reduction of 2,4,6-triphenyl-pyrylium salts by oxidation or by treatment with concentrated sulfuric acid it regenerated the triphenylpyrylium cation. There was no subsequent confirmation of this reaction. The reduction of pyrylium salts with sodium borohydride affords 1,5-diones by way of 4H-pyrans and 2,4-dien-l-ones by way of 2H-pyrans. ... 

The amount of a given isomer in reaction mixtures is affected by substitution patterns of the starting pyrylium ions and by the structure of a reagent, in accordance with quantum chemical interpretations using various LCAO-MO methods.201-2028 Almost all additions to 2,6-disubstituted pyrylium ions occur at position 4 to give 4//-pyrans. Unsubstituted or 2,4,6-trisubstituted substrates may be attacked, on the other hand, at a or y positions providing 2H- and/or 4//-pyrans. Limited information on tetrasubstituted and penta-substituted pyrylium ions leads to the conclusion that the former afford AH-pyrans, whereas the latter tend to be attacked by nucleophiles only at positions 2 or 6. 

The reactions of 3,5,6-trisubstituted 2-pyrones 317 with MeMgl lead to mixtures containing about 13% 2//-pyrans 318.305... 

It has been found (72BSF707) that in general the reaction of methylmagnesium iodide with 2,4,6-trisubstituted pyrylium salts leads to 2//-pyrans. However, as the bulk of the 2-and 6-substituents increases, minor amounts of 4//-pyrans are formed. When the pyrylium salt is unsubstituted at C-4, significant quantities of the 4//-pyran are produced, along with the corresponding 2//-pyran and unsaturated ketones. It appears that substituents in the 3- and 5-positions of the pyrylium salts have little effect on the course of the reaction. 

In 2006, the Bode group documented NHC-catalyzed highly enantiose-lective 1-oxodiene Diels-Alder reactions of a broad range of enones with racemic a-chloroaldehydes as the dienophile precursors. This process affords a diverse set of highly enantioenriched 3,4,6-trisubstituted dihydro-pyran-2-ones from readily available starting materials under mild conditions (room temperature, 1.5 equiv. of NEtj, 6 h). The use of readily accessible racemic a-chloroaldehydes as enolate precursors greatly expands the scope of enantioselective NHC-catalyzed Diels-Alder reactions. It also makes possible, for the first time, asymmetric annulations with exceptional enantiose-lectivity under reliable eonditions with less than 1 mol% of a chiral NHC catalyst (Scheme 7.77). 

Waldmann and coworkers " (Scheme 7.12) described the enantioselective synthesis of a library of 2,4,6-trisubstituted tetrahydropyrans by an oxa-Diels-Alder reaction. The corresponding pyrane ring is prevalent in a number of natural products. To access it stereoselectively with a solid-phase synthesis strategy, cycloaddition reaction of Danishefsky s diene 59 with resin-bound aldehydes 58 was carried out in the presence of 5 mol% of the chromium catalyst 63. After the release of resin, the product (61) was... 

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