Nucleophilicity Parameters of Pyridinium Ylides and Their Use in Mechanistic Analyses

Abstract

Kinetics of the reactions of pyridinium, isoquinolinium, and quinolinium ylides with diarylcarbenium ions, quinone methides, and arylidene malonates (reference electrophiles) have been studied in dimethylsulfoxide solution by UV-vis spectroscopy. The second-order rate constants (log k2) were found to correlate linearly with the electrophilicities E of the reference electrophiles, as required by the linear free-energy relationship log k(20°C) = sN(N + E) (J. Am. Chem. Soc. 2001, 123, 9500), which allowed us to derive the nucleophile-specific parameters N and sN for these ylides. Pyridinium substitution is found to have a similar effect on the reactivity of carbanionic reaction centers as alkoxycarbonyl substitution. Agreement between the rate constants measured for the 1,3-dipolar cycloadditions of pyridinium, isoquinolinium, and quinolinium ylides with acceptor substituted dipolarophiles (arylidenemalononitrile and substituted chalcone) and those calculated from E, N, and sN shows that the above correlation can also be employed for predicting absolute rate constants of stepwise or highly unsymmetrical concerted cycloadditions. Deviations between calculated and experimental rate constants by a factor of 10(6) were demonstrated to indicate a change of reaction mechanism.

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

“…The resulting products may then be converted into indolizines by oxidation, [8][9][10] or into indolizidines by reduction or other type of functionalization (Scheme 1). [11,12] Scheme 1.…”

Electrophilicities of 1,2‐Disubstituted Ethylenes

“…[13] log k 2 = s N (N + E) (1) We recently quantified the nucleophilic reactivities N and s N of colored pyridinium ylides 2 [14] (Table 1) and sulfonium ylides 3 [15] (Table 2) based on the kinetics of their reactions with benzhydrylium ions, quinone methides, and benzylidene malonates. [13] log k 2 = s N (N + E) (1) We recently quantified the nucleophilic reactivities N and s N of colored pyridinium ylides 2 [14] (Table 1) and sulfonium ylides 3 [15] (Table 2) based on the kinetics of their reactions with benzhydrylium ions, quinone methides, and benzylidene malonates.…”

“…[13] log k 2 = s N (N + E) (1) We recently quantified the nucleophilic reactivities N and s N of colored pyridinium ylides 2 [14] (Table 1) and sulfonium ylides 3 [15] (Table 2) based on the kinetics of their reactions with benzhydrylium ions, quinone methides, and benzylidene malonates. [14] Table 1.…”

The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts

“…These dirhodium(II) compounds are mild Lewis acids that coordinate with Lewis bases, 37 sometimes causing diminished reactivity toward diazo compounds. Isoquinolinium/pyridinium methylides are readily accessible nucleophiles of variable base strengths 38 that readily undergo [2 + 3]-cycloaddition reactions. 39 Testing the limits of stable dipoles in their reactions with metalloenolcarbenes, isoquinolinium/pyridinium methylides were treated with enoldiazoacetate 12 in the presence of dirhodium catalyst without obvious catalyst inhibition, and instead of 1,3-dipolar cyclization through [2 + 3]-cycloaddition, [3 + 3]-cycloaddition readily occurred to give substituted quinolizidines 26 in high yield and high enantioselectivity when the reaction was catalyzed by Rh 2 ( S -PTIL) 4 (Scheme 14).…”