Highly Efficient p-Toluenesulfonic Acid-Catalyzed Alcohol Addition or Hydration of Unsymmetrical Arylalkynes

Abstract

Under a catalytic amount of PTSA in aqueous or alcoholic media, activated unsymmetrical arylalkynes 1 undergo regioselective water or alcohol addition to afford successfully carbonyl compounds 2 in good to excellent yields. This new environmentally metal-free procedure, which afforded only Markovnikov adducts, is characterized by the mildness of acidic conditions and the excellent regio- and chemoselectivity.

unsymmetrical arylalkyne - hydration - PTSA - ketone - alcohol addition - water

References

1a Hudrlik PF. Hudrlik AM. The Chemistry of Carbon-Carbon Triple Bond   Part I:  John Wiley and Sons; New York: 1978. 

1b Larock LC. Leong WW. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.269 

2a Kagan HB. Marquett A. Jacques J. Bull. Soc. Chim. Fr.  1960,  1979 

2b Budde WL. Dessy RE. J. Am. Chem. Soc.  1963,  85:  3964 

2c Olah GA. Meidar D. Synthesis  1978,  671 

2d Matsuo K. Urabe K. Izumi Y. Chem. Lett.  1981,  1315 

2e Amiet G. Hügel HM. Nurlawis F. Synlett  2002,  495 

2f Nishizawa M. Skwarczynski M. Imagawa H. Sugihara T. Chem. Lett.  2002,  12 

3a Tokunaga M. Wakatsuki Y. Angew. Chem. Int. Ed.  1998,  37:  2867 

3b Alavarez P. Basetti M. Gimeno J. Mancini G. Tetrahedron Lett.  2001,  42:  8467 

3c Taqui Khan MM. Halligudi SB. Shukla S. J. Mol. Catal.  1990,  58:  299 

3d Setty-Fichman M. Sasson Y. Blum J. J. Mol. Catal. A: Chem.  1997,  126:  27 

3e Pal M. Parasuraman K. Gupta S. Yeleswarapu KR. Synlett  2002,  1976 

3f Hiscox W. Jennings PW. Organometallics  1990,  9:  1997 

3g Hartman JW. Hiscox WC. Jennings PW. J. Org. Chem.  1993,  58:  7613 

3h Baidossi W. Lahav M. Blum J. J. Org. Chem.  1997,  62:  669 

3i Israelsohn O. Vollhardt KPC. Blum J. J. Mol. Catal. A: Chem.  2002,  184:  1 

3j Fukuda Y. Utimoto K. J. Org. Chem.  1991,  56:  3729 

3k Mizushima E. Sato K. Hayashi T. Tanaka M. Angew. Chem. Int. Ed.  2002,  41:  4563 

3l Vasudevan A. Verzal MK. Synlett  2004,  631 

3m Damiano JP. Postel M. J. Organomet. Chem.  1996,  522:  303 

4a Smith JM. Stewart HW. Roth B. Northey EH. J. Am. Chem. Soc.  1948,  70:  3997 

4b Allen AD. Chiang Y. Kresge AJ. Tidwell TT. J. Org. Chem.  1982,  47:  775 

4c Menashe N. Reshef D. Shvo Y. J. Org. Chem.  1991,  56:  2912 

4d Menashe N. Shvo Y. J. Org. Chem.  1993,  58:  7434 

5 Tsuchimoto T. Joya T. Shirakawa E. Kawakami Y. Synlett  2000,  1777 

6a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 

6b Alami M. Ferri F. Linstrumelle G. Tetrahedron Lett.  1993,  34:  6403 

7

Typical Procedure for the PTSA-Catalyzed Hydration of Unsymmetrical Arylalkynes: To a stirred solution of 1a (162 mg, 1 mmol) in 2 mL of absolute EtOH, was added pTSA monohydrate (38 mg, 0.2 mmol). The mixture was heated at reflux for 5 h, diluted with H₂O and extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous Na₂SO₄. After removal of the solvent under vacuo, the crude product was purified by column chromatography on silica gel (CH₂Cl₂) to afford 196 mg (94%) of 2b as a yellow oil. 3-Ethoxy-1-(4-methoxy-phenyl)propan-1-one (2b): ¹H NMR (270 MHz, CDCl₃): δ = 7.89 (2 H, d, J = 8.9 Hz), 6.87 (2 H, d, J = 8.9 Hz), 3.79 (2 H, t, J = 6.8 Hz), 3.78 (3 H, s), 3.47 (2 H, q, J = 7.0 Hz), 3.14 (2 H, t, J = 6.7 Hz), 1.14 (3 H, t, J = 7.0 Hz). ¹³C NMR (67.5 MHz, CDCl₃): δ = 196.7, 163.3, 130.2, 130.0, 113.5, 66.3, 65.8, 55.2, 38.4, 14.9. 1-(4-Aminophenyl)-6-hydroxyhexan-1-one (2f): ¹H NMR (270 MHz, CD₃OD): δ = 7.75 (2 H, d, J = 8.8 Hz), 6.63 (2 H, d, J = 8.8 Hz), 3.55 (2 H, t, J = 6.4 Hz), 2.87 (2 H, t, J = 7.6 Hz), 1.80-1.20 (6 H, m). ¹³C NMR (67.5 MHz, CD₃OD): δ = 201.5, 153.6, 132.1, 126.8, 114.3, 62.3, 38.6, 33.5, 26.7, 26.1. 1-(2-Methoxyphenyl)hexan-1-one (2k): ¹H NMR (270 MHz, CDCl₃): δ = 7.61 (1 H, dd, J = 7.6 Hz, J = 1.8 Hz), 7.45-7.30 (1 H, m), 7.00-6.85 (2 H, m), 3.84 (3 H, s), 2.92 (2 H, t, J = 7.5 Hz), 1.75-1.55 (2 H, m), 1.35-1.25 (4 H, m), 0.87 (3 H, t, J = 6.9 Hz). ¹³C NMR (67.5 MHz, CDCl₃): δ = 202.9, 158.1, 132.8, 129.9, 128.7, 120.4, 111.4, 55.2, 43.5, 31.4, 23.9, 22.3, 13.7.

8 For a review see: Swaminathan S. Narayanan KV. Chem. Rev.  1971,  71:  429 

9a Tzalis D. Koradin C. Knochel P. Tetrahedron Lett.  1999,  40:  6193 

9b Hartman JW. Sperry L. Tetrahedron Lett.  2004,  45:  3787 

9c For a review, see: Alonso F. Beletskaya IP. Yus M. Chem. Rev.  2004,  104:  3079