Pyrones => aldehydes

Among the important processes taking place when sucrose is heated is cara-melization. Caramel is actually a very complex mixture. Some constituents are volatile, such as furan derivatives, pyrones, aldehydes, and low molecular weight carboxylic acids, and these account for 10% of the mass.340 The main constituents of the nonvolatile component have also been identified these include... 

Carbon-heteroatom double bonds can also participate in this reaction. These include both carbonyl compounds (Scheme 11.37) and imines (Scheme 11.38). Addition to aldehydes is co-catalysed by tin(II) or indium(III) salts. Under these conditions, tetrahydrofiirans are obtained. The presence or absence of the co-catalyst can also switch the reaction from one mode to another (Scheme 11.39). An indium cocatalysed cycloaddition to a 7-pyrone aldehyde 11.117 was used in a synthesis of aureothin 11.122 and A-acetylaureothamine 11.123 (Scheme 11.40). Cross-metathesis of the exo-cyc ic alkene 11.118 allowed a subsequent Suzuki coupling with a gem-dibromide 11.120 that showed the expected selectivity (Section 2.1.4.2). This reaction required the use of thallium ethoxide as the Lewis base to suppress the formation of side products. A Negishi coupling completed the synthesis of aureothin 11.122. Reduction and acylation of the nitro group yielded A-acetylaureothamine 11.123. The latter compound is active digainst Helicobacter pylori, a bacterium behind stomach ulcers. 

The synthesis of a large number of y-pyrones and y-pyranols from enamines has been brought about through the use of a wide variety of bifunctional molecules. These molecules include phenolic aldehydes (126,127), phenolic Mannich bases (128), ketal esters (129), and diketene (120-132). All of these molecules have an electrophilic carbonyl group and a nucleophilic oxygen center in relative 1,4 positions. This is illustrated by the reaction between salicylaldehyde (101) and the morpholine enamine of cyclohexanone to give pyranol 102 in a quantitative yield (127). 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

It has been shown22 that the reaction of the diene 4 with aldehydes RCHO in the presence of a catalyst prepared from (R)-BHMOL (33) and Ti(OPr-i)3, which affords the dihydro-y-pyrones 35 in good yields and high ee, proceeds by a two-step sequence via the open-chain adducts 34, which cyclize to the products on treatment with trifluoroacetic acid (equation 20). 

Early example of Cinchona alkaloid catalyzed Diels-Alder of 2-pyrone and a, 3-unsaturated aldehyde... 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

A facile one-pot synthesis of furopyrans takes place with aromatic aldehydes, cyclohexyl isocyanide, and 4-hydroxy-6-methyl-2-pyrone in the presence of a solid support such as Montmorillonite K-10 (Equation 62) <2005SC535>. The solvent-free reaction, which is enhanced by microwave irradiation, proceeds much more rapidly under these conditions than by conventional methods <2002TL2293>. The one-pot, three-component reaction is also reported to take place rapidly using water as solvent <2004M589>. 

The condensation of 6-substituted 4-hydroxypyrones with 1-cyclohexenecarboxaldehydes in the presence of L-proline gives the initial 1,2-addition addition product of the pyrone with the aldehydes, followed immediately by a 67t-electrocyclic process to give substituted oxopyrano[4,3-/ ][l]benzopyrans <1997JOC6888>. 

Aldehyde 63 (950 mg, 2 mmol) and anhydrous ZnBr2 (450 mg, 2 mmol) in dry THF (10 mL) were stirred at room temperature for 1 h. To the homogeneous solution was added diene 62 (1.3 g, 4 mmol), and the reaction mixture was stined at room temperature for 48 h. TFA (1 mL) was then added, and after an additional 5-min stirring, the solution was partitioned between EtjO (30 mL) and a saturated NaHCOj solution (30 mL). The organic layer was dried (MgS04), and concentrated in vacuo. Flash chromatography (hexanes-EtOAc, 6 4) of the residue afforded an unseparable mixture (2 1) of pyrones 64a and 64b (800 mg, 60%) as an oil. 

BSB451). Metalated enamines (in the a-methyl group) easily react with aldehydes, and the new enamines thus formed undergo an intramolecular cyclization giving 2-pyrone derivatives (84T733) (Scheme 41). 

Cyclocondensation of dioxygenated 1,3-dienes with aldehydes. In the presence of ZnCl2 in benzene or BP3 etherate in ether, this diene 1 undergoes cyclization with a wide variety of aldehydes to afford 2,3-dihydro-y-pyrones (equation I). The products... 

The palladium [Pd(Ph3)4]-catalysed 3 + 3-cycloaddition of trimethylenemethane with azomethineimines produced hexahydropyridazine derivatives under mild conditions (40 °C).171 The Lewis acid-catalysed formal oxa-[3 + 3]-cycloaddition of a,f+ unsaturated aldehydes with 6-methyl-4-hydroxy-2-pyrone, 1,3-diketones, and viny-logous silyl esters yielded a variety of pyrones at room temperature.172 Croton-aldehyde has been converted to 6-hydroxy-4-methylcyclohex-l-enecarboxaldehyde by an enantioselective 3 + 3-cycloaddition catalysed by proline. This methodology was used in the synthesis of (—)-isopulegol hydrate, (—)-cubebaol, and (—)-6-hydroxy-4-methylcyclohex-l-ene-1-methanol acetate, an intermediate in the total synthesis of the alkaloid magellanine.173... 

Phosphine-catalysed annulation between aldehydes (RCHO) and ethyl allenolate (H2C=C=CHC02Et) gives 6-substituted 2-pyrones (52), proceeding via a zwitterionic (g) enolate.201 The product is derived from the -intermediate, which is favoured by the use of sterically demanding trialkylphosphines, such as tri(cyclopentyl). However, overdoing the phosphine bulk with, for example, the tri(r-butyl) derivative gives no yield. 

In the total synthesis of nalanthalide, the crucial coupling of the 7-pyrone moiety with the diterpenoid core was achieved by lithium halogen exchange of 3-bromo-2-methoxy-5,6-dimethyl-4/7-pyran-4-one 353 and addition of the resulting 3-lithio-7-pyrone 354 to aldehyde 355 to produce 356 in an impressive 87% yield (Scheme 53) <2005OL3745, 2006TL3251>. 

The HDA reaction allows for rapid access to chiral six-membered heterocyclic structures that serve as valuable intermediates in organic synthesis. The first highly enantioselective HDA reaction promoted by a chiral hydrogen bond donor was reported from the Rawal laboratory. While investigating the cycloaddition reactions of amino-siloxy diene 115, it was observed that this diene was exceptionally reactive to heterodienophiles, and underwent HDA reactions with various aldehydes at room temperature, even in the absence of any added catalyst (Scheme 6.14). Subsequent treatment of the intermediate cycloadducts (116) with acetyl chloride afforded the corresponding dihydro-4-pyrones (117) in good overall yields [101]. Further studies of this reaction revealed a pronounced solvent effect,... 

The mechanism of the conversion of 4-pyrone to 4-pyridone involves an initial Michael reaction followed by ring-opening. Tautomerisation of enol 9.25 to aldehyde 9.26, followed by cyclisation, affords 4-pyridone 5.23. 

Hundreds of compounds have been identified in the volatile flavor components of processed foods. Hydrocarbons, alcohols, ethers, aldehydes, ketones, acids, acid anhydrides, esters, aromatic, lactones, pyrones, furans, pyridines, pyrroles, n-alkylpyrrole-2-aldehydes, pyrazines, sulfides, disulfides, thiols, thiophenes, thiazoles, trithiolanes, thialdine. ..etc. 

Food, flavors consist of numerous compounds, none of which alone is characteristic of specific food. Classes of compounds which emcompass food flavors are - hydrocarbons (aliphatic, ali-cyclic, aromatic) carbonyls (aldehydes, ketones) carboxylic acids, esters, imides, anhydrides alcohols, phenols, ethers alkylamines, alkylimines aliphatic sulfur compounds (thiols, mono-, di- and tri-sulfides) nitrogen heterocyclics (pyrroles, pyrazines, pyridines) sulfur heterocylics (thiophenes, thiazoles, trithiolane, thialidine) and oxygen-heterocyclics (lactone, pyrone, furan). Discussion will be limited to striking developments in heterocyclics. 

Bicyclic a-pyrans and -pyrones. The Ni(0)-catalyzed reaction of an aldehyde with a terminally dialkyl-substituted 1,7-octadiyne results in bicyclic a-pyrans. This reaction is highly dependent on the length of the chain connecting the triple bonds and on the presence of the terminal substituents. 

Dimethoxyoxetanes.1 In the presence of ZnCl2, this ketal reacts with 0-hydroxy aldehydes to give 2,2-dimethoxyoxetanes, which can be converted into 4-hydroxy-3-methyl-8-lactones and 5,6-dihydro-2-pyrones. In one case, an optically active lactone was obtained in 80% ee from an optically active y-hydroxy aldehyde. 

The protected keto-aldehyde (4) has also been converted, in several steps, into the dihydro-y-pyrones (11) and (12). A Birch reduction of the pyrone (11) with lithium in liquid ammonia afforded ( )-elaeokanine E (13) as the only product. A similar reduction of the epimeric pyrone (12) gave a product that is not identical with elaeokanine D, and it is considered to be ( )-epielaeokanine D (14).4... 

The reaction of N-(terf-butoxycarbonyl)leucinal 2-41 a by Danishefsky et al. with l-methoxy-3-trimethylsilyloxy-l,3-butadiene 2-10 gave the pyrones 2-42 and 2-43 with an induced diastereoselectivity of 9 1 in favour of the syn-com-pound in the presence of Eu(hfc)3 [96]. Later Garner [97] used a N-Boc-serine derived aldehyde 2-41 b and Danishefsky s diene 2-10. In both cases a chelation-control forming a complex between the nitrogen and the oxygen could explain the obtained selectivity. In the presence of HMPA chelation is minimized to give a higher extent of the anfi-product 2-43 (Fig. 2-12) [97]. 

A clear two step formation of a pyrone by an enantioselective Mukaiyama-aldol and acid catalysed aldol dihydropyrone annulation using aliphatic and aromatic aldehydes and l-methoxy-3-trimethylsilyloxy-l,3-butadiene in the presence of a tryptophan-derived oxazaborolidine was described by Corey et al. [115]. The resulting pyrone which could be assigned as a formal Diels-Alder adduct was obtained with a 67-82% ee and 57 -100% yield. 

Reactions with aldehydes. 3-Hydroxypyridine and formaldehyde give 2-hydroxymethyl-3-hydroxypyr-idine. Pyrones can be chloromethylated, e.g., 145 146. Under VilsmeierHaack conditions, pyrimidinones are converted into 5-formylchloropyrimidines for example, 147 gives the aldehyde 148. 

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