Synthesis of (Z)-β-halo α,β-unsaturated carbonyl systems via the combination of halotrimethylsilane and tetrafluoroboric acid

Abstract

A procedure for the stereoselective synthesis of β-halovinyl derivatives via a conjugate addition of HX to ynones has been developed.

Metal-Free Transfer Hydrobromination of C–C Triple Bonds

“…Different electron-withdrawing groups were tested, and α,β-unsaturated ketone, carboxylic acid, and amide 6a−c reacted in good yields to afford 7a−c with moderate to high diastereocontrol. 14 Electronic modification of the aryl ring in amide 7c was possible but with eroded Z/E ratios (6d−f → 7d−f); an electron-rich βnaphthyl group was tolerated as well (6g → 7g). The doublebond isomers could be separated by flash chromatography in all these cases.…”

“…The stronger acid Tf 2 NH was necessary as a result of the intrinsically electron-poor nature of the substrates. Different electron-withdrawing groups were tested, and α,β-unsaturated ketone, carboxylic acid, and amide 6a – c reacted in good yields to afford 7a – c with moderate to high diastereocontrol . Electronic modification of the aryl ring in amide 7c was possible but with eroded Z / E ratios ( 6d – f → 7d – f ); an electron-rich β-naphthyl group was tolerated as well ( 6g → 7g ).…”

One-Pot Synthesis of (Z)-β-Halovinyl Ketones via the Cascade of Sonogashira Coupling and Hydrohalogenation

“…Recently, Xu and co-workers reported an atom-economical method for the regio-and stereoselective hydrohalogenation of ynones and ynamides using DMPU/HX (X = Br or Cl) reagents. Paixão and co-workers reported the regioselective synthesis of (Z)-β-halo α,β-unsaturated carbonyl systems via combination of halotrimethylsilane and tetrafluoroboric acid (da Silva et al, 2019). Ynones used in these hydrohalogenation methods are usually not commercially available.…”

Chemoselective Bromination of Dienoates

“…Halogenated α, -unsaturated carbonyl bearing compounds are versatile building blocks. [2][3][4] Being polyfunctional substrates these compounds have found a wide range of applications in organic synthesis. It is not surprising that very often they use as initial reagents in a one-pot fashion cascade assembly of bioactive and pharmaceutical compounds as well as analogs of natural substances.…”

“…Halogenated α,β‐unsaturated carbonyl bearing compounds are versatile building blocks . Being polyfunctional substrates these compounds have found a wide range of applications in organic synthesis.…”