Reaction with pyrylium ions

Cycloaddition reactions in pyrone derivatives A and D and activated pyrones B, C, and E (Scheme 46) with pyrylium-ion character are important in synthetic methodology because the initial bicycloadducts F-J, which can have up to four contiguous stereocenters as well as variously membered rings (3, 4, 5, 6, 7, etc.), can be formed in one procedure. These bicycload-... 

Reactions of pyrylium ions with nucleophiles, which first lead to 2/f-pyrans 11 followed by ring-cleavage to the dienones 12, are important in preparative chemistry. On ring closure, which occurs with... 

Scheme 6.15 Reaction of pyrylium ions with primary amines and hydroxide anion.

This is manifest in the reactivity of 180/180-Z1 which was generated from 3-bromo-41-f-pyran (283) by /3-elimination of hydrogen bromide with KOtBu (Scheme 6.61). Whether or not this reaction was conducted in the presence of styrene or furan, the only product identified was tert-butyl 4H-pyran-4-yl ether (284). This is in line with the relationship of the intermediate to a pyrylium ion. Thus, the addition of the tert-butoxide ion to 180/180-Zj has to be expected at the 4-position with formation of the vinyl anion 285, which is then protonated to give 284. Likewise, the attack of the nucleophile is predicted at C2and C6 leading to the vinyl anions 286, which... 

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. 

However, if a tetrasubstituted pyrylium ion possessed one or two condensed six-membered carbocyclic rings, then only 4//-pyrans 191, 192, 27, and 193 are isolable (35 to 92%) after reaction with PhCH2MgCl236 or with other Grignard reagents RMgX.210... 

Interestingly, the addition of the hydride ion to benzo[c]pyrylium cations with the formation of adducts of type 107 occurs not only in reactions with lithium aluminum hydride (54JOC1533) or sodium boro-hydride (89KGS750), but also on short-time heating of the formate 30 (R1 = ME, R2 = Et, R3 = Ver, R4 = OMe) in formic acid [67ACH-(51)107] (Scheme 7). 

In the context of mechanistic studies, the electrochemical behavior and reactions with nucleophiles of 4-chloro-2,6-diphenylpyrylium and 4-chloro(bromo)flavylium have been studied <1999CHE653>. The proposed mechanism for nucleophilic substitution in halogen-substituted pyrylium and flavylium salts passes through formation of a charge-transfer complex that is converted into an ion-radical pair by simple electron transfer. Heterocyclic cleavage of the C-halogen bond occurs at the stage of the radical or the adduct from the reaction of the pyrylium salt and the nucleophile. In this study, an amine nucleophile was used however, the data are likely relevant for other types of nucleophiles as well (Scheme 5). 

The presence of a 4-(4-dimethylaminophenyl) group enhances the visible absorption differences between the pyrylium and thiopyrylium salt analogues. Thus, on reaction of 625 with hydrosulfide ion a change in hue from magenta (540 nm) to blue (580 nm) is observed this color change serves as the basis for a new chemodosimeter selective for hydrosulfide (Scheme 240) <2003JA9000>. 

The first step involves the formation of a pyridinium ion by reaction of a pyrylium ion with a primary amine the second step (dequaternization) has been studied more extensively than the first (amine + pyrylium). This important work on dequaternization deserves special mention because, besides the value for synthesis and understanding of steric acceleration, it sheds new light on the mechanism of aliphatic nucleophilic substitution (84CSR47). 

Monocyclic 1,3-oxazepines 419 can be prepared by reaction of aliphatic diazo compounds with 1,3-oxazinium perchlorates 418 (Scheme 194) <1974S187>. Tetra- and penta-phenyl-1,3-oxazepines 421 (R = H or Ph) have been obtained by the reaction of azide ion with pyrylium salts 420 (Scheme 195) <1978H(11)331>. 

An attempt to prepare 2,4,6-triphenylselenopyrylium cation (10) by reaction of the corresponding pyrylium ion 8 with Na2Se was unsuccessful (78AP170). 

The reaction has been successfully carried out also with 2,6-di-tert-butylthiopyrylium (26) and selenopyrylium (27) (87JOC2123), but not with the corresponding pyrylium ion (25), which apparently does not form a phosphonium salt with triphenylphosphine (79JOC4456). 

An interesting class of reactions are initiated by the intramolecular attack of a carbonyl group to the aUcyne to form pyrylium ions, which can react further with aUcynes to form naphthalenes by a [4 + 2] cyloaddition followed by a cycloreversion or suffer addition of external nucleophiles (equation 15). ... 

Pyrylium ions react with ammonia or primary amines to give pyridinium ions (see p. 498). Primary amines react with 1,4-diketones, with microwave irradiation, to give A -substituted pyrroles.Similar reactions in the presence of Montmorillo-nite KSF or by simply heating the components with tosic acid have been reported. 

The reactivity of pyrylium ions with azides has been discussed theoretically on the basis of extended Hiickel molecular orbital (EHMO) calculations (84T3549). As long as the pyrylium ring is hindered, the most favorable approach of the reactants corresponds to a reaction coordinate yielding azidopyrans. However, when the ring approach is free, the system can assume a geometry that allows the formation of a stable complex. 

The kinetic and equilibrium constants for the reaction of 2,6-di-/-butyl-4-R -pyrylium cations 194d-h with methoxide ion to yield the corresponding A-H and 2-H adducts 195d-h and 196d-h (Scheme 37) have been determined in MeOH at 25°C (88JOC1729). The reaction involves the... 

Pyrylium phosphonic acids (60a) have been prepared by the reaction of triethyl phosphite with pyrylium salts followed by oxidation of the product (either before or after hydrolysis) with the triphenylmethyl carbonium ion. This approach has been used to obtain the analogous thiopyrylium phos-phonates (60b) and the cyclopropene and tropylidene derivatives (61) and (62). The enamine phosphonates (63) are readily accessible from addition... 

Pyridinium ions 45 with iV-acceptor substituents also add O- and N-nucleophiles via C-2 to give 46. This is followed by ring opening, probably in an electrocyclic process, at N/C-2 resulting in the formation of 1-azatrienes 47 Zincke reaction, cf. the corresponding transformations of the pyrylium ion, see p 225) ... 

Heteroarenes show specific side-chain reactivity at heterobenzylic C-H-bonds in position 2 or 4 to the ring hetero atom. This is responsible for a large number of base-catalyzed electrophilic C-C forming processes like aldol, Claisen and Mannich reactions with appropriately substituted pyrylium and pyridinium ions, pyridines, benzazines and benzodiazines. 

Relatively little has appeared in the past year on the synthesis and reactivity of the six membered, potentially aromatic, phosphinine ring system. A route to the first C2-asymmetric phosphinine (147), derived from (+ )-camphor, has been developed from the reaction of a pyrylium salt precursor with P(TMS)3. The chiral phosphinine is a crystalline, air-stable solid and forms complexes with metal ions, therefore having some potential as a ligand in homogeneous eatalysis." A pyrylium salt-P(TMS)3 final step was also used in the synthesis of a series of 2-(2 -halo)triarylphosphinines (148), subsequently shown to form a series of tungsten(0) and rhodium(I) complexes involving coordination of the phosphorus sp lone pair to the metal." Interest has continued in studies of the coordination chemistry of phosphabarrelenes, derived from the established reactions of phosphinines... 

Addition of an ammonia source to pyrylium salts readily affords pyridine derivatives and provides a good method for the preparation of the pyridine moiety if the corresponding pyrylium salt is accessible. The carbon oxygen double bond present in the pyrylium salt is an oxonium ion however, owing to aromatic stabilization they are easily formed by a variety of methods. The reactivity of pyrylium salts toward nucleophiles makes them useful reagents for the preparation of structurally diverse heterocyclic compounds. Thus pyrylium salts afford pyridines by reaction with ammonia, pyridine-A -oxides by reaction with hydroxylamine and pyridinium salts by reaction with primary amines. 

Pyrylium salts bearing various metallo-carbonyl moieties at the para position of the heterocycle have been synthesized [99-103]. The manganese and rhenium pyrylium salts 59-60 [104] together with the chromium pyrylium ions 42, 43 and 61 [105] successfully labeled the protein BSA to afford the corresponding pyridinium adducts as evidenced by the comparison with the spectroscopic data of model pyridinium derivatives. Interestingly, the reaction can readily be monitored by UV-visible spectroscopy. 

This addition/ring-opening sequence - which in the case of the unsubstituted pyrylium ion (1, R = H) already occurs with H20-is reversible, that is, treatment of 3/4 with acid reconstitutes the pyrylium system. In the reaction of the 2,4,6-triphenylpyrylium ion (1, R = Ph) with methoxide, C-2-addition is accompanied by C-4-addition affording the methoxysubstituted 2H- and 4H-pyrans (5) and (6). 

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