TMSCN/DBU-Mediated Facile Redox Transformation of α,β‑Unsaturated Aldehydes to Carboxylic Acid Derivatives

Redox transformation of an α,β-unsaturated aldehyde to a carboxylic acid derivative by means of a combination of TMSCN and DBU was investigated. In addition to the wide use of the carboxylic acid derivatives provided by this reaction, temperature-dependent control of the kinetic or thermodynamic protonation pattern was found to selectively switch the stereochemistry of the acyl group in the product

Direct Synthesis of Azaheterocycles from N-Aryl/Vinyl Amides. Synthesis of 4-(Methylthio)-2-phenylquinazoline and 4-(4-Methoxyphenyl)-2-phenylquinoline

A flame-dried, 300-mL three-necked round-bottomed flask equipped with a 3.0 cm footballshaped stir bar, rubber septum, and low temperature thermometer is charged with benzanilide (1) (Note 1) (6.02 g, 30.5 mmol, 1 equiv), sealed under an argon atmosphere, and fitted with an argon inlet. Anhydrous dichloromethane (Note 2) (60 mL) followed by 2-chloropyridine (Note 3) (5.76 mL, 6.97 g, 61.4 mmol, 2.01 equiv) is added via syringe, and the heterogeneous mixture is vigorously stirred and cooled to <−70 °C (dry-ice–acetone bath, internal temperature). After 10 min, trifluoromethanesulfonic anhydride (Note 4) (Tf[subscript 2]O, 5.60 mL, 9.39 g, 33.3 mmol, 1.09 equiv) is added via syringe over 5 min at <−65 °C (internal temperature). After 15 min, the reaction flask is warmed to 0 °C (ice–water bath). After 5 min, the deep red solution becomes homogeneous and a solution of thiocyanic acid methyl ester (2) (Note 1) (2.52 mL, 2.67 g, 36.5 mmol, 1.20 equiv) in anhydrous dichloromethane (40 mL) is added via cannula over 5 min at 5–6 °C (Note 5). After 10 min, the cold bath is removed, and the reaction mixture is allowed to warm to 23 °C. After 2.5 h, triethylamine (Note 2) (10.0 mL, 7.26 g, 71.7 mmol, 2.35 equiv) is added via syringe over one min. The resulting mixture is concentrated with a rotary evaporator (20 mmHg, 30 °C). The remaining deep red oil is purified by flash column chromatography (Note 6) to afford quinazoline 3 (6.15 g, 80%) as an off-white solid (Note 7).National Institute of General Medical Sciences (U.S.