Coupling-isomerization synthesis of chalcones.
The Sonogashira coupling of electron-deficient (hetero)aryl halides 1 and (hetero)aryl or alkenyl 1-propargyl alcohols 2 does not terminate at the stage of the expected internal propargyl alcohols, but rather gives rise to the formation of alpha,beta-unsaturated ketones 3 with a variety of acceptor substituents. This new domino reaction, a coupling-isomerization reaction (CIR), can be rationalized as a sequence of rapid Pd/Cu-catalyzed alkynylation followed by a slow amine-base-catalyzed propargyl alcohol-enone isomerization. Performing the CIR in deuterated protic solvents or with a selectively deuterated propargyl alcohol revealed that the base-catalyzed isomerization step proceeds through a formal 1,3-H shift with minimal H/D exchange with the surrounding solvent. Additionally, 19F NMR kinetic measurements on the isomerization step with the fluorinated propargyl alcohol 4 r support the mechanistic rationale.
Braun
Roland U
RU
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
Ansorge
Markus
M
Müller
Thomas J J
TJ
D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D047188:Chalcones / Q000138:chemical synthesis*; D003300:Copper / Q000737:chemistry; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D020005:Propanols / Q000737:chemistry
D000475:Alkenes; D000480:Alkynes; D000588:Amines; D047188:Chalcones; D006846:Hydrocarbons, Halogenated; D020005:Propanols; D010165:Palladium; D003300:Copper; C028255:propargyl alcohol