Nucleophilic Reactivities of 2‐Substituted Malonates

Abstract

Kinetics of the reactions of 2‐substituted malonate anions and 5‐substituted Meldrum's acid anions with benzhydrylium ions and structurally related quinone methides have been monitored in dimethyl sulfoxide solution at 20 °C. The resulting second‐order rate constants followed the correlation lg k(20 °C) = sN(E + N), which allowed the nucleophile‐specific parameters N and sN to be calculated for these highly stabilized carbanions and to integrate them in our comprehensive nucleophilicity scale. Given that the reactions of the benzhydrylium ions with the anions derived from 5‐aryl‐substituted Meldrum's acids did not proceed to completion, the corresponding equilibrium constants could be determined. In combination with available data for pyridines and benzoate ions, these equilibrium constants provide a direct comparison of the strengths of C‐, N‐, and O‐centered Lewis bases with respect to C‐centered Lewis acids.

Tf2O-Promoted Intramolecular Schmidt Reaction of the ω-Azido Carboxylic Acids

“…The mixture was extracted with EA (10 mL × 3), and the combined organic phase was washed with brine (10 mL × 5), dried over Na 2 SO 4 , and concentrated. The residue was purified by flash chromatography to give 9h as a yellowish oil (5.86 g, 81% yield from the diethyl malonate): known compound; R f = 0.62 (EtOAC/PE = 1/5); 1 H NMR (CDCl 3 , 400 MHz) δ 4.15–4.22 (m, 4H), 3.14 (d, J = 9.2 Hz, 1H), 2.04–2.13 (m, 1H), 1.64–1.73 (m, 5H), 1.01–1.33 (m, 11H); 13 C NMR (CDCl 3 , 100 MHz, plus APT) δ (up) 168.9 (2), 61.2 (2), 30.9 (2), 26.2, 26.1 (2), δ (down) 58.5, 38.0, 14.2 (2).…”

Amide-Phosphonium Salt as Bifunctional Phase Transfer Catalyst for Asymmetric 1,6-Addition of Malonate Esters to para-Quinone Methides

“…para -Quino methides ( p -QMs), structurally featuring a cyclohexadiene with the carbonyl group in para -conjugation with an exo methylene group, exist in a variety of natural products and pharmaceuticals, and have been known as reactive intermediates in many chemical, medicinal, and biological processes . When suitable substituents, typically electron-donating groups, are introduced onto the cyclohexadiene core, typically at α-positions, this type of compounds become stable enough for isolation, and can be handled in further operations, e.g., as a reaction component in organic synthesis. − …”

“…Since 2002, Mayr et al have published a series of reports, wherein these readily available p -QMs were employed as reference electrophiles for establishing the reactivity scale of a variety of nucleophiles including electron rich π-nucleophiles and carbanions generated from active methylene and methine compounds . Despite successful application of p -QMs to physical organic chemistry in Mayr’s works, the involvement of p -QMs in organic synthesis, particularly in asymmetric synthesis, has never been reported until recently.…”