Thieme Chemistry Journal Awardees - Where are They Now? A General One-Step Synthesis of Alkynes from Enolisable Carbonyl Compounds

Abstract

Terminal and internal acetylenes were obtained in good to excellent isolated yields from carbonyl compounds by converting the carbonyl functionality into the enol nonaflate intermediate followed by elimination to give the C-C triple bond. The one-pot transformations were uniformly induced by phosphazene bases combined with mildly electrophilic nonafluorobutane-1-sulfonyl fluoride. The method is the most general among those reported to date as it applies to both acyclic ketones and aldehydes. Only moderate kinetic regioselectivity in favour of alk-1-yne achieved from methyl n-alkyl ketone represents a limitation of the method. In all the other instances, individual acetylenic products were obtained.

Key words

alkynes - eliminations - regioselectivity - nonafluoro­butane-1-sulfonyl fluoride - phosphazene bases

References and Notes

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• 10 Commercially available as a 2 M solution in THF, pK _a = 33.49 in MeCN, see: Schwesinger R. Schlemper H. Hasenfratz C. Willaredt J. Dambacher T. Breuer T. Ottaway C. Fletschinger M. Boele J. Fritz H. Putzas D. Rotter HW. Bordwell FG. Satish AV. Ji GZ. Peters EM. Peters K. von Schnering HG. Walz L. Liebigs Ann. Org. Bioorg. Chem.  1996,  7:  1055 
• 11 Recently, we reported an efficient procedure for purification of NfF which was employed in synthesis of enol nonaflates from aldehydes and cyclic ketones, see: Vogel MAK. Stark CBW. Lyapkalo IM. Synlett  2007,  2907 
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• 14a

  Typical Procedure for the Synthesis of Alkynes from Enolisable Carbonyl Compounds - 4-Phenyl-but-1-yne (2c) from 4-Phenyl-butyraldehyde (1c)
  The P₁-base (1.031 g, 3.30 mmol, 2.2 equiv) was added in one lot to the vigorously stirred mixture of 4-phenyl-butyraldehyde (0.222 g, 1.50 mmol) and NfF (0.544 g, 1.80 mmol, 1.2 equiv) in DMF (1.5 mL) at -10 ˚C. The reaction mixture was allowed to warm up to 20 ˚C for the following 2 h. The three-way tap was replaced by a glass stopper with a Teflon sleeve, and the reaction mixture was stirred in a tightly closed flask for 20 h at ambient temperature (complete conversion, NMR control). The reaction mixture was placed on the top of the column and eluted with hexane. Removal of hexane in vacuum (from 200 mbar to 15 mbar, bath at ambient temperature, no heating) furnished pure 4-phenyl-but-1-yne (2c, 0.169 g, 87% yield) as clear colourless liquid. ^¹H NMR (270 MHz, CDCl₃): δ = 1.97 (t, ⁴ J = 2.7 Hz, 1 H, HCº), 2.48 (td, ^³ J = 7.6 Hz, ⁴ J = 2.7 Hz, 2 H, CH₂CºC), 2.84 (t, ^³ J = 7.6 Hz, 2 H, CH₂Ph), 7.19-7.33 (m, 5 H, Ph). ^¹³C (67.9 MHz, CDCl₃): δ = 20.5 (CH₂CºC), 34.8 (CH₂Ph), 68.9 (HCºC), 83.8 (CºCH), 126.3 (CH _p ), 128.4 (CH _o and CH _m ), 140.4 (C _i ).

• 14b ^¹H NMR is consistent with that described in the literature, see: Uno H. Sakamoto K. Semba F. Suzuki H. Bull. Chem. Soc. Jpn.  1992,  65:  210 
• 15 Identified by matching the NMR data with those described in literature: Baird MS. Hussain HH. Nethercott W.
  J. Chem. Soc., Perkin Trans. 1  1986,  1845 

16

The high cost of the phosphazene bases represents a drawback of our protocol. We thank the referees for the respective comments. The manuscript describing a new straightforward method for the synthesis of P₁-bases is currently in preparation.