NaBH4-TMEDA and a palladium catalyst as efficient regio- and chemoselective system for the hydrodehalogenation of halogenated heterocycles

A New Synthesis of Gefitinib

“…Similarly unsatisfactory results were obtained by using a combination of NaBH 4 and TMEDA under palladium catalysis. 22 However, a chemoselective conversion was finally realized by using zinc and acetic acid in the presence of tetrabutylammonium bromide (Bu 4 NBr) as an additive, a reagent combination that had previously been shown to reduce a chloropyridine substrate selectively. 23 In addition to the desired product 5, under these conditions we also observed that small amounts of 3-chloro-4-fluoroaniline were formed, which probably originated from an acid-mediated solvolysis of the quinazoline moiety.…”

Chemoselective Radical Dehalogenation and C–C Bond Formation on Aryl Halide Substrates Using Organic Photoredox Catalysts

“…The aqueous layer was extracted with CH 2 Cl 2 (3 × 20 mL) and the combined organic layers were dried over MgSO 4 , filtered, and then concentrated in vacuo. The residue was purified by column chromatography with toluene/EtOAc (gradient from 100:0 to 99:1) as the eluant to afford 13 2-(Benzoyloxy)ethyl 4-Bromobenzoate (14). A vial equipped with a magnetic stir bar and fitted with a Teflon screw cap septum was charged with 13 (47.5 mg, 0.100 mmol, 1.0 equiv), tris-acetyl-PTH (2.0 mg, 0.095 mmol, 0.05 equiv), formic acid (19 μL, 0.504 mmol, 5.0 equiv), tributylamine (120 μL, 0.504 mmol, 5.0 equiv), and DMSO (1 mL).…”

“…13,14,15,16 Our group recently reported the use of 10-phenylphenothiazine (PTH, 1) for photomediated, controlled radical polymerizations and radical dehalogenation of aryl and alkyl halides ( Figure 1). 17, 18,19 PTH was found to be a highly reducing organic photocatalyst (E 1/2 * = -2.1 V vs. SCE), with the ability to access a variety of unactivated carbon-halogen bonds that were inaccessible with previous metal-free systems.…”

“…This includes aryl–aryl bond formations as well as radical cyclizations and atom transfer radical additions. ,− Such a versatile transformation warrants the development of photocatalytic systems that can chemoselectively activate carbon–halogen bonds (C–X), giving potential for taking a single synthetic derivative bearing multiple C–X bonds and synthesizing a large library of complex targets. Currently, there are very few reports demonstrating the concept of chemoselective dehalogenations, and these are limited to metal-based nonphotocatalyzed systems. − …”

Design, synthesis and evaluation of antitumor acylated monoaminopyrroloquinazolines

“…Therefore, the previously reported compound 5 10 was chlorinated 18 with POCl 3 to generate 6 . Chloride 6 was not stable towards extensive workup and it was thus used directly without further purification for reduction by NaBH 4 in the presence of PdCl 2 (dppf)•DCM 19 to provide monoamine 7 in 16% yield. Direct coupling of 7 with NHS ester 8 at an elevated temperature (120 °C) yielded 4a in 11% yield.…”