Synthesis of Alkyl-Substituted Pyridines by Directed Pd(II)-Catalyzed C–H Activation of Alkanoic Amides

Abstract

Reactions sensitive to air or moisture were carried out under a positive pressure of argon using standard Schlenk techniques. All solvents were reagent grade or better. Dry tetrahydrofuran and dichloromethane were obtained from a MBRAUN MB-SPS 800 solvent purification system. Other dry solvents were obtained from Acros and Sigma-Aldrich and used without further purification. Solvents used for workup and column chromatography were distilled prior to use. Other chemicals were purchased from Sigma-Aldrich, Alfa Aesar, TCI Europe and Acros Organics and were used without further purification. Flash Chromatography was performed on silica gel 60 (Merck, 230-240 mesh). Thin-layer Chromatography (TLC) was performed on Merck silica gel 60 F254 plate. 1 H, 13 C and 19 F NMR spectra were collected using a Bruker AV-400 or a Bruker AV-360 NMR spectrometer. Measurements were done at ambient temperature. 1 H NMR chemical shifts are referenced to the residual hydrogen signals of the deuterated solvent, and the 13 C NMR chemical shifts are referenced to the 13 C signals of the deuterated solvent. 31 F NMR chemical shifts are reported as received. The NMR data are reported in ppm. Abbreviations used in the description of NMR data are as follows: s, singlet; d, doublet; t, triplet; dd = doublet of doublets; dt = doublet of triplets; ddd = doublet of doublet of doublets; m, multiplet; bs, broad singlet. IR spectra were recorded on a a JASCO IR-4100 (ATR) spectrophotometer. Mass spectra were recorded on a Thermo Finnigan LTQ FT (HRMS-ESI) or a Thermo Sientific LTQ Orbitrap XL (HRMS-ESI).