Cycloaddition pyridinium betaines

Despite the lack of success in the attempts at intramolecular cycloaddition with substrates 83 and 91, a moderately promising outcome was observed for the nitroalkene substrate (98, Scheme 1.10c). Heating a dilute solution of oxido-pyridinium betaine 98 in toluene to 120 °C produced a 20 % conversion to a 4 1 mixture of two cycloadducts (110 and 112), in which the major cycloadduct was identified as 110. While initially very encouraging, it became apparent that the dipolar cycloaddition reaction proceeded to no greater than 20 % conversion, an outcome independent of choice of reaction solvent. Further investigation, however, revealed that the reaction had reached thermodynamic equilibrium at 20 % conversion, a fact verified by resubmission of the purified major cycloadduct 110 to the reaction conditions to reestablish the same equilibrium mixture at 20 % conversion. 

Cycloadditions of betaines are not restricted to electron-deficient alkenes. Pyridinium-3-olates also react with conjugated olefins (e.g., styrenes) and with electron-rich olefins (e.g., ethyl vinyl ether). In the latter case, the betaine LUMO/alkene HOMO interaction becomes dominant and reaction is only observed with pyridinium-3-olates having a low-energy LUMO... 

In the [ 8+n2] cycloaddition of the bromoketene 6.402 to the pyridinium betaine 6.401 giving the lactone 6.403, the oxygen atom has the highest coefficient in the HOMO, and the next highest is the pyridinium 2-position, which is the other site of attack when the group R is not large 892... 

The reaction of trichloro-1.2.4-triazine with norbornene is followed by loss of N to give an intermediate dihydropyridine which reacts with a second molecule of alkene to yield (28).36 The presence of 2-alkyl or -aryl substituents in pyridinium betaines leads to the formation of a substantial proportion of reverse-orientation products in cycloadditions to unsymmetrical alkenes (e. g. (29) - (30)). 40... 

N-SulfonyIcarbamyloxypyridinium betaines from sulfonylisocyanates. Pyridine N-oxide in abs. benzene mixed with p-toluenesulfonyl isocyanate in the same solvent whereupon an exothermic reaction precipitates the product l-(p-toluenesulfonylcarbamyloxy)pyridinium betaine. Y 90%. — No 1,3-dipolar cycloaddition occurs. 

The first example of a stable pyridinium yhde of type 80 is the pyridinium phenacylide (80, A = CH2COPh), obtained from the N-phenacylpyridinium ion (79, A = CH2COPh) by deprotonation with Na2C03 [97]- The reactivity of the pyridinium betaines is determined by their electron distribution (80a-c). Thus, they can be smoothly alkylated or acylated at the N-substituent ( 81) as 1,3-dipoles, they undergo dipolar cycloadditions with activated alkynes or alkenes [98] for example, the sequence 80 —> 82 83 establishes an efficient principle of indolizine synthesis (cf. p. 154). 

In an Initio study of the tautomerism of 2- and -hydroxy-pyridines, 4 -hydroxypyridine was calculated to be 2.4 kcal/mol more stable than 4-pyridone. 2-Pyridone was calculated to be 0.3 kcal /mol more stable than 2-hydroxypyridine and this is in good agreement with experimental values obtained from tautomeric studies in the gas phase.A study of the bromination of the 2-pyridone/2-hydroxypyridine system has revealed that reaction occurs via the principal "one" tautomer at pH<6 and via the conjugate anion at pH>6. Attack on the "one" occurs preferentially at the 3-position, whereas on the anion it probably occurs mainly at the 5-position. The facile formation of 3f5-dibromo-2-pyridone results from the comparable reactivity of the monobromopyridones at pH<1 and pH>4- Practical procedures have been reported for the preparation of 3-bromo-2-pyridone and 3,5-dibromo-2-pyridone Cycloaddition of 2-substituted pyridinium betaines with unsymmetrical alkenes gives products of mixed orientation for example, treatment of (40) with methyl... 

The ring expansion reaction of diaryl cyclopropenones and cyclopropene thiones occurring with pyridinium, sulfonium, and phosphonium enolate betaine 427268-270) is related to 1,3-dipolar cycloadditions. This process results in formation of 2-pyrones 428 by loss of pyridine (or sulfide or phosphine) and insertion of the remaining fragment C=C-0 to the C1(2)/C3 bond of the cyclopropenone ... 

In aqueous solution 3-hydroxypyridine 176 equilibrates with the mesomeric betaine 177a for which no uncharged structure can be written. Since these pyridinium-3-olates 177a undergo 1,3-dipolar cycloadditions, it is reasonable to assume that there is also a contribution of the one form 177b to the overall structure. 

Acceptor-CH-substituted pyridinium-N-betaines 15 (accessible in situ by deprotonation of the corresponding N-alkylpyridinium salts 14) undergo 1,3-dipolar cycloaddition with activated alkynes and alkenes as dipolarophiles. With alkynes, the cycloadducts (16/19) dehydrogenate spontaneously to indolizines, which are either of the 1,2,3-trisubstituted type 17 or (indicating a regioselective cycloaddition) of the 1,3-disubstituted type 18. With olefinic substrates, the presence of an oxidant for additional dehydrogenation of the primary cycloadduct (20 -> 17) is required [219] ... 

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