Pyran, electrocyclic reactions

Photochemically induced electrocyclic reactions in 2/f-pyrans have been discussed in preceding sections. Ring cleavage has been reported on irradiation of cannabinol in ethanol to give the alkene (238)189 details of the... 

With hydroxide anions (or with water at pH >5) pyrylium salts form pseudobases 16 (2-hydroxy-2//-pyrans) that tautomerize to acyclic 3-penten-l,5-diones 17 via a thermally allowed electrocyclic reaction. Most ring transformation reactions of pyrylium salts involve a similar ring-opening. 

A review of the use of electrocyclic reactions in synthesis has been presented" and of asymmetric electrocyclic reactions that result in diastereo- or enantio-selectivity selection as a consequence of the influence of a chiral component, be it substrate or catalyst, on the electrocyclic bond-forming process." Computational studies of 0 electrocyclic ring-opening reactions of 2-pyrone and 6-fluoro-2-pyrone are pseudoper-icyclic 6-fluoro-2-pyranol are a borderline case and 2-pyranol, pyran, and 6-fluoro pyran reactions are pericyclic in character." ... 

Analogous to the opening of 1,3-cyclohexadiene is the electrocyclic reaction of ring opening of 2H-pyrans XXVI->XXVII ... 

Recently, in the course of studies directed towards the total synthesis of saudin, the Stoltz group developed a tandem Stille-oxa-electrocyclization reaction to access substituted pyran systems (56 + 57 —> SS) ". ... 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

The same authors extended the [2 + 2 + 2]-cycloaddition methodology to the use of highly electron-deficient tricarbonyl compounds such as ketomalonates (Equation (33)).360 In that particular case, the reaction does not stop at the initial stage of 277-pyrans 164. Instead, a thermally induced electrocyclic ring opening occurred to form the corresponding cyclopentenes 165 as final product. 

A related 1,7-cyclization has been invoked to account for the formation of diazepine 292 from the electrophilic diazoalkane substitution reaction of ethyl diazoacetate and dimethyl diazomethylphosphonate, with the 2,4,6-trimethylpyr-ylium salt 289 (337) (Scheme 8.70). While the expected 4-(diazomethyl)-47/-pyran 290 could be isolated (20-22%), the 2-substituted isomer 291 was not. It was proposed that this latter species underwent 671-electrocyclic ring opening followed... 

Examples of photochemically induced im electrocyclizations in oxygen-containing systems are relatively rare. 2//-Phenanthro[9,10-h]-pyran-4-carboxamides (16), for example, have been obtained in this way by irradiation of dienones (17).17 Similarly, the a-pyran (18) is formed on irradiation of ( )-//-ionone (19)18 a triplet excited state is believed to be involved and the reaction proceeds via the Z-isomer (20). The reverse process involving ring opening is more common and can lead to a wide variety of photochemically derived products. Thus, the products of irradiation of 2,2-dimethylchromene... 

A three-component one-pot coupling of 2,6-dimethylphenyl isocyanide, methyl 2,4-dioxopentanoate and alkynoic esters leads to the isatin-like compounds (or fused pyrans) 20 (Scheme 5). The reaction proceeds by initial formation of the zwitterionic intermediate 21, which is protonated by methyl 2,4-dioxopentanoate. Attack of the newly generated nucleophile then forms the intermediate 22. The pyrrolidinone ring is formed upon loss of methanol and electrocyclization then occurs to afford the desired 2//-pyrans (Scheme 5) <2005S1049>. 

The electrocyclization of 5-oxo-2,4-pentadienal (89) to pyran-2-one (90) is an example of a psendopericyclic reaction. As shown in Fignre 4.21, the disrotatory electrocyclization of 88 occurs with a closed loop of the p-orbitals in the transition state. On the other hand, the electrocyclization of 89 has no such closed loop. Rather, two orbital disconnections interchange the role of bonding and nonbonding orbitals. 

Spiro-cyclobutene derivatives prepared from the intramolecular Wittig reaction of DMAD with ethyl oxo-(2-oxocycloalkyl)ethanoates yield cycloalka[6]pyrans via a thermal electrocyclic ring-opening - ring-closing sequence (Scheme 1) <03X2001 >. 

Electrocyclic opening of (di)bromocyclopropanes containing internal nucleophilic groups under silver(I), or mercury(II) assistance at 25 °C provides a route to vinyl-substituted lactones, pyrans, and tetrahydrofurans in good to excellent yields, e.g. formation of 35, 37, and 39. = These reactions are related to thermolytic versions. 

Among the reactions of 4i/-pyran, a few ring transformations are of synthetic interest. For instance, the triphenyl-4-benzyl-47/-pyran 1 isomerizes on irradiation to give 2-benzyl-2//-pyran 2 which, on addition of HCI, is converted quantitatively into 1,2,3,5-tetraphenylbenzene 4, The transformation into the benzene system probably occurs by an electrocyclic O/C-2 opening of compound 2 to give the dienone 3, followed by intramolecular aldol condensation ... 

When aldehydes were employed in place of CO2 in the cyclization reactions, the formation of dienones was observed. These are presumed to be formed by the electrocyclic ring opening of the proposed pyran intermediate (Figure 13.33) [78]. 

Takeshita s [54] synthesis of sesquiterpenoid sativene relies on a high-pressure Diels-Alder reaction of 2H-pyran-2-one 142 (methyl coumalate) as diene component with 2 -dimethylcydohexadiene 143 (Scheme 35). Cycloadduct 144 was obtained stereospecifically as the cxo-isomer and decarbonylated to intermediate 145. Its electrocyclization and further transformations in three S5mthetic steps complete synthesis of sativene. 

Finally, the spontaneous electrocyclic ring opening of pyran derivatives (obtained by a vinylogous aldol reaction between vinyl malononitriles and aldehydes) into dienamides is to be mentioned in this section [97]. 

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