Selectivity in radical alkylation of substituted pyrroles

Abstract

ABSTRACT:The theoretical study of a highly regioselective intermolecular oxidative free-radical substitution of 2-and 3-formylpyrroles that yields 2,5-and 2,3-disubstituted pyrroles, respectively, is described. A mechanistic and kinetic study was carried out using quantum chemical methods and classical transition state theory. Rate constants were obtained at 298 K and atmospheric pressure. All possible channels were considered and branching ratios were obtained. The selectivity predicted using theoretical methods agrees very-well with experimental results.

Micellized Tris(bipyridine)ruthenium Catalysts Affording Preparative Amounts of Hydrated Electrons with a Green Light‐Emitting Diode

“…As trapping reagents that avoid the formation of several cross‐coupling products, we selected mesitylacetate MesAc and N ‐methylpyrrole‐2‐carboxylate NMPCA. With the former, all ring positions except meta are occupied; with the latter, it is well known that the addition of radicals to pyrroles almost exclusively occurs at the ring position adjacent to the nitrogen atom . Proof of principle for the viability of our approach is obtained from the NMR spectra in SI‐5.3.…”

“…meta are occupied;with the latter,i tiswell known that the addition of radicals to pyrroles almoste xclusively occurs at the ring position adjacent to the nitrogen atom. [38][39][40][41][42][43] Proof of principle fort he viability of our approachi so btained from the NMR spectra in SI-5.3. In the case of MesAc, the deceleration of the traget reactionb yt he overcrowdedt rapping reagent only allows am oderate yield of the coupling product, with benzoate remaining the main product;h owever, the sterically less demanding NMPCA turns the table and approximately reverses the product distribution (Scheme3).…”

A Green‐LED Driven Source of Hydrated Electrons Characterized from Microseconds to Hours and Applied to Cross‐Couplings

“…Especially promising as coupling reagents are N ‐alkylated pyrroles, because they are very reactive towards radicals and exclusively afford 2‐substituted products; hence, even at moderate concentrations they permit effective and selective radical usage . In our strongly basic aqueous solutions, N ‐methyl‐2‐pyrrolecarboxylic acid (NMPCA) is particularly well suited for intercepting the e aq .…”

“…Especially promisinga sc oupling reagents are N-alkylated pyrroles,b ecause they are very reactive towards radicals and exclusively afford 2-substituted products;h ence,e ven at moderate concentrationst hey permit effective and selective radical usage. [25][26][27][28][29][30] In our strongly basic aqueous solutions, N-methyl-2-pyrrolecarboxylic acid (NMPCA)i sp articularly well suited for intercepting the e aq C À -generated radicals, as it combines this reactivity with excellent solubility.M oreover,i ts deprotonated carboxylate substituent increases its hydrophilicity,s uch as to ensurei ts exclusion from the micelles, in which it might otherwise interfere with the electron source. Figure 6a demonstrates the successful cross-coupling of NMPCA withC lAc as the radicalp recursor to give 5-(2-carboxymethyl)-N-methylpyrrole-2-carboxylate 1 in am oderate yield of 41 %( for the formulae of all cross-coupling products, see Scheme 1).…”

First Micelle‐Free Photoredox Catalytic Access to Hydrated Electrons for Syntheses and Remediations with a Visible LED or even Sunlight

“…Monitoring the yields of dechlorination and cross-coupling in parallela llows factoring out all the complex issues influencing the formation of the s radicals, such as catalyst stability and parasitic e À aq scavenging, because ac hloride ion is only liberated when a s radicali sb orn.H ence, the ratio of each pair of yields in Scheme 2, which for convenience has also been in-cluded in Table S2 of SI-4.2, specifies the fraction of the s radicals intercepted by the trapping reagent, with the only proviso that all end products arising through the adduct have been captured and summed. Thec ross-coupling product 6 represents the only case in point;t he pyrrole and indole derivates, which constitute the majority of trapping reagents in Scheme 2, are known to couple only in the ring position adjacent to the nitrogen; [26][27][28][29][30][31] and their substitution pattern allows no isomers, as is the case for mesityl acetate. The yield ratios so obtained exhibit ac lear dichotomy:t hey are near unity for uncharged trappingc omponents (products 1, 2, 8, 9,a nd 11) and half as large for the negatively charged ones.…”