Synthesis of (Z)-1-Organylthiobut-1-en-3-ynes: Hydrothiolation of Symmetrical and Unsymmetrical Buta-1,3-diynes

Abstract

Hydrothiolation of 1-organylbuta-1,3-diynes and 1,4-diorganylbuta-1,3-diynes with the sodium organylthiolate anions, which were generated in situ by reacting diphenyl and dibutyl di­sulfide with NaBH₄ in ethanol, results in the regio-, stereo-, and chemoselective formation of (Z)-1-organylthio-4-organylbut-1-en-3-ynes and (Z)-1-organylthio-1,4-diorganylbut-1-en-3-ynes, respectively.

Key words

hydrothiolation - organylthiolate anion - vinyl sulfides - 1,3-diacetylenes - (Z)-1-organylthiobut-1-en-3-ynes

References and Notes

• For the synthesis of griseoviridin, see:
• 1a Marcantoni E. Massaccesi M. Petrini M. J. Org. Chem.  2000,  65:  4553 
• 1b Kuligowski C. Bezzenine-Lafollée S. Chaume G. Mahuteau J. Barrière J.-C. Bacqué E. Pancrazi A. Ardisson J. J. Org. Chem.  2002,  67:  4565 
• 1c For the synthesis of benzylthicrellidone, see, for example: Lan HW. Cooke PA. Pattenden G. Bandaranayake WM. Wickramasinghe WA. J. Chem Soc., Perkin Trans. 1  1999,  847 
• 2a Corey EJ. Shulman JI. J. Am. Chem. Soc.  1970,  92:  5522 
• 2b Oshima K. Shimoji K. Takahashi H. Yamamoto H. Nozaki H. J. Am. Chem. Soc.  1973,  95:  2694 
• 2c Mura AJ. Bennet DA. Cohen T. Tetrahedron Lett.  1975,  16:  4433 
• 2d Mura AJ. Majetich G. Grieco PA. Cohen T. Tetrahedron Lett.  1975,  16:  4437 
• 2e Mukayama T. Fukuyama S. Kumamoto T. Tetrahedron Lett.  1968,  3787 
• 2f Waters MS. Cowen JA. McWilliams JC. Maligres PE. Askin D. Tetrahedron Lett.  2000,  41:  141 
• 2g Sato T. Taguchi D. Suzuki C. Fujisawa S. Tetrahedron  2001,  57:  493 
• 2h Imanishi T. Ohara T. Sugiyama K. Ueda Y. Takemoto Y. J. Chem. Soc., Chem. Commun.  1992,  269 
• 2i Guerrero PG. Dabdoub MJ. Marques FA. Wosch C. Baroni ACM. Ferreira AG. Synth. Commun.  2008,  38:  4379 
• 3 Fortes CC. Fortes HC. Gonçalves DRG. J. Chem. Soc., Chem. Commun.  1982,  857 
• 4 Oshima K. Takahashi H. Yamamoto H. Nozaki H. J. Am. Chem. Soc.  1973,  95:  2693 
• 5a Cohen T. Weisenfeld RB. J. Org. Chem.  1979,  44:  3601 
• 5b Screttas CG. Micha-Screttas M. J. Org. Chem.  1978,  43:  1064 
• 5c Screttas CG. Micha-Screttas M. J. Org. Chem.  1979,  44:  713 
• 5d Foubelo F. Gutierrez A. Yus M. Tetrahedron Lett.  1999,  40:  8173 
• 6 Hojo M. Harada H. Yoshizawa J. Hosomi A. J. Org. Chem.  1993,  58:  6541 
• 7 Kanemasa S. Kobayashi H. Tanaka J. Tsuge O. Bull. Chem. Soc. Jpn.  1988,  61:  3957 
• 8a For a review, see: De Lucchi O. Pasquato L. Tetrahedron  1988,  44:  6755 
• 8b Dittami JP. Nie XY. Nie H. Ramanathan H. Buntel C. Rigatti S. Bordner J. Decosta DL. Williard P. J. Org. Chem.  1992,  57:  1151 
• 9 Harmata M. Jones D. Tetrahedron Lett.  1996,  37:  783 
• 10a See, for instance: Corey EJ. Seebach D. J. Org. Chem.  1966,  31:  4097 
• 10b For a review, see: Kolb M. Synthesis  1990,  171 
• 11a Trost BM. Lavoie AC. J. Am. Chem. Soc.  1983,  105:  5075 
• 11b Trost BM. Tanigawa Y. J. Am. Chem. Soc.  1979,  101:  4413 
• 12 Barton DHR. Boar RB. J. Chem. Soc., Perkin Trans. 1  1973,  654 
• 13a Okamura H. Miura M. Takei H. Tetrahedron Lett.  1979,  20:  43 
• 13b Trost BM. Ornstein PL. Tetrahedron Lett.  1981,  22:  3463 
• 13c Wenkert E. Ferreira TW.
  J. Chem. Soc., Chem. Commun.  1982,  840 
• 13d Truce WE. Goldhamer DL. Kruse RB. J. Am. Chem. Soc.  1959,  81:  4931 
• 13e Truce WE. Heine RF. J. Am. Chem. Soc.  1957,  79:  5311 
• 13f Freeman F. Lu H. Zeng Q. Rodriguez E. J. Org. Chem.  1994,  59:  4350 
• 13g Zschunke A. Muegge C. Hintzsche E. Schroth W. J. Prakt. Chem.  1992,  334:  141 
• 14 Levanova EP. Volkov AN. Volknova KA. Zh. Org. Khim.  1983,  19:  62 
• 15a Truce WE. Goldhamer DL. Kruse RB. J. Am. Chem. Soc.  1959,  81:  4931 
• 15b Truce WE. Heine RF. J. Am. Chem. Soc.  1957,  79:  5311 
• 16a Peach ME. In The Chemistry of the Thiol Group   Vol. 2:  Patai S. Wiley; London: 1974. 
• 16b Ichinose Y. Wakamatsu K. Nozaki K. Birbaum J.-L. Oshima K. Utimoto K. Chem. Lett.  1987,  1647 
• 16c Benati L. Capella L. Montevecchi PC. Spagnolo P. J. Chem. Soc., Perkin Trans. 1  1995,  1035 
• 16d Griesbaum K. Angew. Chem., Int. Ed. Engl.  1970,  9:  273 ; and references therein
• 17a Shostakovskii MF. Bogdanova AV. The Chemistry of Diacetylenes   Halsted Press; Jerusalem: 1974. 
• 17b Bohlmann F. Bornowski H. Kramer D. Chem. Ber.  1963,  96:  584 
• 18 Brandsma L. Preparative Acetylenic Chemistry   Elsevier; New York: 1971. 
• 22 Dabdoub MJ. Baroni ACM. Lenardão EJ. Gianeti TR. Hurtado GR. Tetrahedron  2001,  57:  4271 
• 23 Dabdoub MJ. Dabdoub VB. Tetrahedron  1995,  36:  9839 

19

Typical Procedure for the Synthesis of ( Z )-1-Phenylthio-1,4-diorganylbut-1-en-3-ynes To a solution of 1,4-diphenylbuta-1,3-diyne 1a ^¹7 (1.797 g, 5 mmol) and PhSSPh (1.845 g, 2.5 mmol) in 95% EtOH (20 mL) under a nitrogen atmosphere, NaBH₄ (0.57 g, 15 mmol) was added at r.t. and under vigorous stirring. Gas evolution was observed during addition. The reaction mixture was stirred under reflux for 3 h, allowed to reach r.t., diluted with EtOAc (3 × 20 mL), and washed with brine (3 × 30 mL) and H₂O (3 × 30 mL). After drying the organic phase over anhyd MgSO₄, the solvent was removed under reduced pressure and the residue purified by flash chromatography on SiO₂ using hexane as mobile phase, to give pure (Z)-1-phenylthio-1,4-diphenylbut-1-en-3-yne (2a) as a white solid; mp 92-95 ˚C; yield 72%. GC-MS: m/z (%) = 312 [M⁺], 202, 149, 105, 77, 28 (100). IR (KBr): 3072 (m), 2195 (m), 1680 (m), 1580 (s), 1481 (vs), 1440 (vs), 1071 (m), 1024 (m), 750 (vs), 740 (s), 687 (s) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 6.32 (s, 1 H), 7.03-7.7 (m, 15 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 87.60, 98.36, 112.27, 123.34, 126.39, 127.49, 127.88, 127.93, 128.27, 128.35, 128.64, 128.75, 129.25, 129.51, 131.60, 138.38, 147.20.

20

Typical Procedure for the Synthesis of ( Z )-1-Phenylthio-4-organylbut-1-en-3-ynes A solution of 1-phenylbuta-1,3-diyne (1c, 10 mmol) was obtained in situ by reaction of 2-hydroxy-2-methyl-6-phenylhexa-3,5-diyne (1e, 1.84 g, 10 mmol) with powered NaOH (25 mg) in dry xylene (11 mL) under reflux for 15 min.^²² The temperature was then allowed to reach r.t., and 95% EtOH (70 mL) and PhSSPh (1.845 g, 5.0 mmol) were added. The reaction was run under an atmosphere of N₂ and NaBH₄ (0.57 g, 15 mmol) was added. The resulting reaction mixture was refluxed for 3 h, diluted with EtOAc (70 mL), and washed with brine (4 × 30 mL). After drying the organic phase over anhyd MgSO₄, the solvent was removed under reduced pressure, and the residue purified by flash chromatography on SiO₂ using hexane as mobile phase, to give the pure phenylthio enyne 2c as a yellow oil; yield 75%. GC-MS: m/z = 236 [M⁺], 202, 149, 126, 115, 77, 51, 28 (100). IR (neat): 689 (vs), 742 (s), 756 (s), 816 (m), 1480 (m), 1488 (m), 1553 (w), 1585 (w), 2205 (w), 3055 (w) cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 5.83 (d, J = 10 Hz, 1 H), 6.75 (d, J = 10 Hz, 1 H), 7.22-7.54 (m, 10 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 85.62, 97.95, 106.36, 123.26, 127.45, 128.30, 129.18, 129.19, 129.23, 130.31, 130,33, 130.36, 130.39, 130.41, 131.45, 131.49, 134.73, 138.91.

21

1-Butylthio-4-cyclohexenylbut-1-en-3-yne (2j) The same procedure for obtaining 2c was performed,^²0 however, 6-cyclohexenyl-2-methylhexa-3,5-diyn-2-ol (1k) and BuSSBu were used as starting materials, affording the pure compound 2j as a yellow oil; yield 50%. ^¹H NMR (300 MHz, CDCl₃): δ = 0.74-1.72 (m, 11 H), 2.07 (m, 2 H), 2.15 (m, 2 H), 2.74 (t, J = 7.2 Hz, 2 H)), 5.56 (d, J = 9.6 Hz, 1 H), 6.11 (s, 1 H), 6.39 (d, J = 9.6 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 13.4, 21.4, 21.5, 22.2, 25.6, 29.1, 32.4, 33.3, 83.4, 99.1, 104.8, 120.8, 134.2, 138.7.