Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

Abstract

The stereoselective formation of quaternary carbon centers is one of the most challenging tasks in organic chemistry and can only be achieved using methods which employ some form of carbon ± carbon bond forming reaction. [1] One of the most straightforward methods for the formation of carbon ± carbon bonds is the alkylation of an enolate with an alkyl halide and, fluoride ions were 1 to 2 mm. The protonation constant of fluoride in water is: log K HF/F 3.15. NMR Measurements: 1 H NMR spectra were recorded on a Bruker AM500 spectrometer at 500 MHz. Binding constants were obtained by NMR titrations of L with fluoride from 25 measurements in D 2 O at pD 5.0 AE 0.1. Initial concentrations were [L] 0 2 mm and titrations were performed using aliquots from a 20 mm stock solution of NaF. A solution of the sodium salt of [2,2,3,3-D 4 ]-3-(trimethylsilyl)propionic acid (TPS) in D 2 O in a capillary tube was used as an external reference. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. All spectra were recorded at room temperature. The association constants K s were calculated by fitting f to d obs (consisting of several independent NMR signals) with a 1:1 association model using Sigma Plot software. Equations (1) and (2) were used, where L is the ligand and A À is the anion, and the error limit in K is less than 10 %:The Job×s plot was performed by examining different concentration ratios of L and NaF in D 2 O at pD 5.0 AE 0.1, while maintaining the total concentration of the ligand plus NaF at 10 mm. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. NMR measurements were recorded at room temperature.