Structure and Reactivity of Indolylmethylium Ions: Scope and Limitations in Synthetic Applications

Abstract

Eight substituted aryl(indol-3-yl)methylium tetrafluoroborates 3(a-h)-BF4 and three bis(indol-3-yl)methylium tetrafluoroborates 3(i-k)-BF4 have been synthesized and characterized by NMR spectroscopy and X-ray crystallography. Their reactions with π-nucleophiles 8(a-j) (silylated enol ethers and ketene acetals) were studied kinetically using photometric monitoring at 20 °C. The resulting second-order rate constants were found to follow the correlation log k(20 °C) = sN(N + E), in which nucleophiles are characterized by the two solvent-dependent parameters N and sN, and electrophiles are characterized by one parameter, E. From the previously reported N and sN parameters of the employed nucleophiles and the measured rate constants, the electrophilicities of the indol-3-ylmethylium ions 3(a-k) were derived and used to predict potential nucleophilic reaction partners. A discrepancy between published rate constants for the reactions of morpholine and piperidine with the (2-methylindol-3-yl)phenylmethylium ion 3h and those calculated from E, N, and sN was analyzed and demonstrated to be due to a mistake of the value reported in the literature.

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

“…[77] Recently we were also exploring, in collaboration with Dr. Barbero in Turin, other stabilized carbenium ions, [78] which were also studied by Mayr. [79] Again the electrophilicity was perfectly suitable for reactivity and for allowing the isolation of these stable carbenium ions.…”

Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives

“…Recently, highly stabilized indoleninium ions 6 have been prepared, isolated, and characterized by direct condensation of arylaldehydes and indoles in the presence of non‐nucleophilic counteranions 9. Structural investigations and related kinetic studies of these ions in reactions with nucleophiles have also been reported 10. Apart from the aforementioned exceptions, intermediates 4 and 6 are generally too unstable to be isolated and therefore the elimination–addition process is generally carried out in a single synthetic operation.…”

“…[9] Structural investigations and related kinetic studies of these ions in reactions with nucleophiles have also been reported. [10] Apart from the aforementioned exceptions, intermediates 4 and 6 are generally too unstable to be isolated and therefore the elimination-addition process is generally carried out in a single synthetic operation. The viability of this strategy depends on several factors, including the reactivity of electrophile 2 in the former F-C reaction and the aptitude of ZH to act as a good leaving group under different reaction conditions.…”

Brønsted acid-catalyzed regioselective reactions of 2-indolylmethanols with cyclic enaminone and anhydride leading to C3-functionalized indole derivatives

“…2 In this context, indolylmethanols have been recognized as a class of privileged building blocks for the synthesis of indole derivatives because this type of reactants can transform into highly reactive intermediates with resonance structures of carbocation, vinyliminium and delocalized cation in the presence of an acid, which have a tendency to be attacked by nucleophiles (Nu) and thus perform substitutions or cyclizations (Scheme 1). [3][4][5][6][7][8][9][10] However, most of the transformations employed 3-indolylmethanols as reactants since they can easily convert into vinyliminium intermediates, [3][4][5][6][7] which could even be isolated under some reaction conditions. 3,8 Thus, numerous 3-indolylmethanol-invovled transformations such as substitutions, 4 [3+2], 5 [3+3] 6 and [4+3] 7 cyclizations have been developed rapidly and well-established (eq.…”

“…[3][4][5][6][7][8][9][10] However, most of the transformations employed 3-indolylmethanols as reactants since they can easily convert into vinyliminium intermediates, [3][4][5][6][7] which could even be isolated under some reaction conditions. 3,8 Thus, numerous 3-indolylmethanol-invovled transformations such as substitutions, 4 [3+2], 5 [3+3] 6 and [4+3] 7 cyclizations have been developed rapidly and well-established (eq. 1).…”