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DMSO / K2CO3 Terminal Alkyne Synthesis.

A recent report by Cheng, Jia, and Kuang (1) of Tongji University is a useful – and pleasantly straightforward- addition to the methods available for alkyne synthesis.

terminal-alkyne-11

The Terminal Alkyne Synthesis of Kuang et Al. (1)

The alkyne functionality is crucial to modern methods (Sonogashira coupling, ’Click’ chemistry, methathesis reactions) and terminal alkynes can be prepared in a handful of ways.  These include the Colvin Rearrangement (addition of lithiated TMS diazomethane to aldehydes), the mechanistically related Gilbert-Seyferth Reaction (dimethyl diazomethyl phosphonate addition to aldehydes), and the Corey-Fuchs olefination (2)with subsequent dehydrohalogenation. In most cases the reagents required for these reactions are relatively exotic.  Kuang and coworkers further point out some limitations of these reaction: low temperatures and strong bases are required.

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An alkyne synthesis you may not have seen before. Do you know the mechanism? (3)

Their reaction has some nice features:

 

  • Garden-variety cinnamic acids are easily converted to the required 2,3-dibromopropionic acids. These starting materials are inexpensive This is done via bromination in chloroform, under thermal or photochemical means (4).
  • Strong base is not required. The E2 trans elimination of HBr is mediated with (mild) potassium carbonate. Base sensitive functional groups are less susceptible than in other alkyne-forming reactions.The authors also suggest that other carbonate salts (Cs2CO3) work, also.
  • The overall scope of the reaction is broad (although it was only demonstrated for aryl 2,3-dibromoacids). Examples were provided for unfunctionalized and electron-rich ring substituents on the aromatic ring (yields of > 83%); halogenated rings (>90%); and interestingly sterically congested (i.e. ortho-substituted ring) examples (>91%). Good yields were seen for dibromoarene starting materials and pyridine analogues (98 and 72% respectively). The reaction is also tolerant of electron withdrawing ring substituents and examples are provided (p-nitro, p-CF3, p-CO2Me).

A summary of their reaction conditions follows:

Combined were anti-3-aryl-2,3-dibromopropanoic acid (0.5 mmol) , potassium carbonate (1.5 mmol) in DMSO (5 mL). The mixture was stirred at 115°C for 12 hours, when it was cooled and extracted with ether / water (15 / 20 mL, three portions). The organic extracts were combined, dried over sodium sulfate, and the residue obtained post evaporation of the extarction solvent was purified via column chromatography (silica gel / hexanes eluant).

 

Artie McKim.

(1) Cheng, X.; Jia, J.; Kuang, C. Chin. J. Chem. 201129, 2350-2354; Org. Process Res. Dev. 201216, 526.
(2) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 197213, 3769–3772
(3) See the enjoyable Chem. Commun. 2002, 1555-1563 to read about the ‘Abidi Reaction’. Suggested by Problem 11 of the on-line Harvard practice problem set.
(4) Kim, S.H. ;Wei, H.X.; Willis, S.; Li, G. Synth. Commun. 199929, 4179.

 

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