N-Vinyl and N-Aryl Hydroxypyridinium Ions: Charge-Activated Catalysts with Electron-Withdrawing Groups

Abstract

Charge-enhanced Brønsted acid organocatalysts with electron-withdrawing substituents were synthesized, and their relative acidities were characterized by computations, 1:1 binding equilibrium constants (K 1:1 ) with a UV−vis active sensor, 31 P NMR shifts upon coordination with triethylphosphine oxide, and in one case by infrared spectroscopy. Pseudo-first-order rate constants were determined for the Friedel−Crafts alkylations of Nmethylindole with trans-β-nitrostyrene and 2,2,2-trifluoroacetophenone and the Diels−Alder reaction of cyclopentadiene with methyl vinyl ketone. These results along with kinetic isotope effect determinations revealed that the rate-determining step in the Friedel−Crafts transformations can shift from carbon−carbon bond formation to proton transfer to the catalyst's conjugate base. This leads to an inverted parabolic reaction rate profile and slower reactions with more acidic catalysts in some cases. Electronwithdrawing groups placed on the N-vinyl and N-aryl substituents of hydroxypyridinium ion salts lead to enhanced acidities, more acidic catalysts than trifluoroacetic acid, and a linear correlation between the logarithms of the Diels−Alder rate constants and measured K 1:1 values.

Charge‐activated TADDOLs: Recyclable organocatalysts for asymmetric (hetero‐)Diels–Alder reactions

“…IR spectra were obtained with a Thermo Scientific Nicolet iS5 spectrometer with an iD5 laminated diamond attenuated total reflectance (ATR) source. Proton and 13 C NMR spectroscopy was performed with Bruker Avance 400-and 500-MHz instruments (101 and 126 MHz for 13 C). The chemical shifts were referenced at δ 5.32 and 54.0 (CD 2 Cl 2 ), δ 7.26 and 77.2 (CDCl 3 ), and δ 2.50 and 39.5 (DMSO-d 6 ) and are given in ppm.…”

“…1 H NMR (500 MHz, DMSO-d 6 ) δ 8.59 (dd, J = 2.0, 0.6 Hz, 2H), 8.50 (dd, J = 4.7, 1.7 Hz, 2H), 7.83 (dt, J = 8.0, 2.0 Hz, 2H), 7.44 (s, 2H), 7.41 (ddd, J = 8.0, 4.8, 0.8 Hz, 2H), 7.22-7.30 (m, 10H), 4.34 (s, 2H), 0.96 (s, 6H). 13…”

“…1 H NMR (500 MHz, DMSO-d 6 ) δ 8.84 (d, J = 1.7 Hz, 2H), 8.82 (dd, J = 5.6, 1.0 Hz, 2H), 8.45 (d, J = 8.3, 2H), 7.97 (dd, J = 8.3, 5.5 Hz, 2H), 7.30-7.26 (m, 4H), 7.23 (br s, 2H), 7.20-7.17 (m, 6H), 4.83 (s, 2H), 1.17 (s, 6H). 13…”

“…[8,9] Within the last decade, our group has reported several organocatalytic scaffolds with positively-charged centers that greatly increase acidity and subsequent activity. [10][11][12][13][14] This has been accomplished most often with the introduction of pyridinium motifs in place of neutral phenyl group derivatives (Figure 2). These charged aryl groups are envisioned as convenient ones for the enhancement of TADDOL hydrogen bond donor ability while maintaining some of the minimal steric bulk that is required for good stereoselectivities.…”

Effects of Brønsted acid cocatalysts on the activities and selectivities of charge‐enhanced thiourea organocatalysts in Friedel–Crafts and oxa‐Pictet–Spengler reactions

“…Positively charged centers are also known to be highly effective in increasing the activity of a variety of organocatalytic scaffolds including thioureas. [17][18][19][20] This tactic increases catalyst acidity in nonpolar and non-hydrogen bond accepting solvents more so than neutral electron-withdrawing groups such as CF 3 , CN, or NO 2 and typically leads to faster transformations. [21] Moderate to good stereoselectivities also have been achieved by cationic Brønsted acids containing chiral substituents.…”