Methylsulfonyl and Hydroxyl Substituents Induce Z-Stereocontrol in the McMurry Olefination Reaction

Abstract

Aryl ketones possessing methylsulfonyl and hydroxyl substituents, that induce stereocontrol, selectively afford Z-olefins using a Zn-TiCl₄ catalyzed McMurry reaction.

McMurry olefination - stereocontrol - Z-olefins - acetylation

References

1 McMurry JE. Chem. Rev.  1989,  89:  1513 

2 Corey EJ. Danheiser RL. Chandrasekaran S. J. Org. Chem.  1976,  41:  260 

3 McMurry JE. Krepski LR. J. Org. Chem.  1976,  41:  3929 

4 McMurry JE. Fleming MP. Kees KL. Krepski LR. J. Org. Chem.  1978,  43:  3255 

5 Dams R. Malinowski M. Westdrop I. Geise HY. J. Org. Chem.  1982,  47:  248 

6 Coe PL. Scriven CE. J. Chem. Soc., Perkin Trans. 1  1986,  475 

7a Gauthier S. Sancéau J.-Y. Mailhot J. Caron B. Cloutier J. Tetrahedron  2000,  56:  703 

7b Detsi A. Koufaki M. Calogeropoulou T. J. Org. Chem.  2002,  67:  4608 

8 Habeeb AG. Rao PNP. Knaus EE. J. Med. Chem.  2001,  44:  3039 

9 Rahim MA. Rao PNP. Knaus EE. Bioorg. Med. Chem. Lett.  2002,  12:  2753 

10 Rao PNP. Amini M. Li H. Habbeb AG. Knaus EE. J. Med. Chem.  2003,  46:  4872 

11 Uddin MJ. Rao PNP. Knaus EE. Bioorg. Med. Chem. Lett.  2004,  14:  1953 

12 Huang H.-C. Li JJ. Garland DJ. Chamberlain TS. Reinhard EJ. Manning RE. Seibert K. Koboldt CM. Gregory SA. Anderson GD. Veenhuizen AW. Zhang Y. Perkins WE. Burton EG. Cogburn JN. Isakson PC. Reitz DB. J. Med. Chem.  1996,  39:  253 

13 Buu-Hoi NP. Hoan N. J. Org. Chem.  1952,  17:  350 

14a Fringuelli F. Pellegrino R. Piermatti O. Pizzo F. Synth. Commun.  1994,  18:  2665 

14b Habeeb AG. Rao PNP. Knaus EE. J. Med. Chem.  2001,  44:  2921 

14c

General Procedure for the Synthesis of Compounds 1. Synthesis of 4-(Methylsulfonyl)butyrophenone (1, R ^¹ = SO ₂ Me, R ^² = n -Pr): A solution of Oxone^® (potassium peroxymonosulfate) (4.06 g, 6.6 mmol) in H₂O (20 mL) was added to a stirred solution of 4-(methylthio)butyrophenone [13] (0.64 g, 3.3 mmol) in 50% THF-MeOH (1:1, v/v; 10 mL) at 0 °C, and the reaction mixture was stirred for 15 h at 25 °C. The solvent was removed in vacuo, H₂O (20 mL) was added to the residue, and the mixture was extracted with EtOAc (3 × 30 mL). The combined EtOAc extracts were washed with H₂O, the EtOAc fraction was dried (Na₂SO₄), and the solvent was removed in vacuo to afford a white solid which was purified by recrystallization from CH₂Cl₂ n-hexane (1:9, v/v) to afford 1 (R¹ = SO₂Me, R² = n-Pr) in 89% yield as white needles; mp 86-88 °C. IR (film): 1148, 1313 (SO₂), 1698 (C=O) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.02 (t, 3 H, J = 7.3 Hz, CH ₃), 1.73-1.85 (m, 2 H, CH ₂), 2.90 (t, 2 H, J = 7.0 Hz, COCH ₂), 3.09 (s, 3 H, SO₂CH ₃), 8.04 (d, 2 H, J = 8.5 Hz, 4-methylsulfonylphenyl H-2, H-6), 8.13 (d, 2 H, J = 8.5 Hz, 4-methylsulfonylphenyl H-3, H-5). Anal. Calcd for C₁₁H₁₄O₃S·1/6H₂O: C, 57.61; H, 6.25. Found: C, 57.89; H, 6.25.

15 Rubin VN. Ruenitz PC. Boudinot FD. Boyd JL. Bioorg. Med. Chem.  2001,  9:  1579 

16 Strazzolini P. Verardo G. Giumanini AG. J. Org. Chem.  1988,  53:  3321 

17

General Procedure for Synthesis of Compounds 4. Synthesis of (Z)-1-(4-acetoxyphenyl)-1-phenyl-2-(4-methylsulfonylphenyl)pent-1-ene [(Z)-4l]: TiCl₄ (1.83 mL, 13 mmol) was added drop wise to a stirred suspension of Zn powder (1.7 g, 26.5 mmol) in dry THF (30 mL) under argon at -10 °C, and this mixture was refluxed for 2 h. A solution of 4-(methylsulfonyl)butyrophenone (1, R¹ = SO₂Me, R² = n-Pr) (0.75 g, 3.3 mmol) and 4-hydroxybenzophenone (2, R³ = 4-hydroxyphenyl, R⁴ = Ph) (0.66 g, 3.3 mmol) in THF (65 mL) was added to the cooled suspension of the titanium reagent at 0 °C, and the reaction mixture was refluxed for 2.5 h. After cooling to 25 °C, the reaction mixture was poured into a 10% aq K₂CO₃ solution (100 mL), vigorous stirring was maintained for 5 min, and the dispersed insoluble material was removed by vacuum filtration using Celite 545. The organic layer was separated and the aqueous layer was extracted with EtOAc (3 × 50 mL). The combined EtOAc extracts were dried (Na₂SO₄), the solvent was removed in vacuo to afford the olefinic intermediate 3 (R¹ = SO₂Me, R² = n-Pr, R³ = 4-hydroxy-phenyl, R⁴ = Ph), which was dissolved in Et₂O (10 mL), and Et₃N (0.5 g, 5.0 mmol) was added. Acetyl chloride (0.39 g, 5.0 mmol) was added drop wise at 0 °C, and the reaction was allowed to proceed for 1.5 h at 25 °C with stirring prior to quenching with H₂O (20 mL). The organic layer was separated, the aqueous layer was extracted with EtOAc (3 × 30 mL), the combined organic fractions were washed with H₂O, and the organic fraction was dried (Na₂SO₄). Removal of the solvent in vacuo gave a solid that was purified by flash silica gel column chromatography using n-hexaneEtOAc (3:1, v/v) as eluant to afford (Z)-4l (R = n-Pr) as colorless crystals (0.97 g, 68%); mp 132-134 °C. IR (film): 1142, 1322 (SO₂), 1585 (C=C), 1757 (C=O of OAc) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.82 (t, 3 H, J = 7.3 Hz, CH₂CH ₃), 1.25-1.40 (m, 2 H, CH ₂CH₃), 2.23 (s, 3 H, OCOCH ₃), 2.44 (t, 2 H, J = 7.9 Hz, C=C-CH ₂), 3.04 (s, 3 H, SO₂CH ₃), 6.76 (d, 2 H, J = 8.5 Hz, 4-acetoxyphenyl H-3,
H-5), 6.85 (d, 2 H, J = 8.5 Hz, 4-acetoxyphenyl H-2, H-6), 7.20-7.40 (m, 7 H, phenyl hydrogens, and 4-methylsulfonyl-phenyl H-2, H-6), 7.74 (d, 2 H, J = 8.5 Hz, 4-methyl-sulfonylphenyl H-3, H-5). ¹³C NMR (75 MHz, CDCl₃):
δ = 14.10 (CH₂CH₂ CH₃), 17.77 (CH₃C=O), 21.16 (CH₂ CH₂CH₃), 37.64 (CH₂CH₂CH₃), 44.53 (SO₂ CH₃), 120.69, 126.99, 127.11, 128.26, 129.23, 130.44, 131.46 (C_arom-H), 138.03, 139.44, 139.53, 140.53, 142.22, 148.64, 148.96 (C_arom-C, C_olefin-C, C_arom-O, C_arom-S), 169.00 (CH₃ C=O). Anal. Calcd for C₂₆H₂₆O₄S: C, 71.86; H, 6.03; S, 7.38. Found: C, 71.74; H, 5.96; S, 7.27.

18

Crystal data for (Z)-4l: Molecular formula: C₂₆H₂₆O₄S, formula weight: 434.53, crystal system: monoclinic, space group: P2₁/c(14) with unit cell dimensions a = 8.0403 (6) Å, b = 14.5485 (12) Å, c = 19.9285 (16) Å, β = 101.4182 (15)º, V = 2285.0 (3) ų, Z = 4, = 1.263 gcm^-3, µ = 0.171 mm^-1. A crystal fragment of approximate dimensions(mm³) 0.73 × 0.40 × 0.04 was mounted in a nonspecific orientation on Bruker PLATFORM/SMART 1000 CCD diffractometer. All intensity measurements were performed using Mo Kα radiation (λ = 0.71073 Å) with a graphite crystal incident beam monochromator. The intensity data were collected at -80 °C using an ω scan (0.3º) (10 s exposures). A total 4675 independent reflections were collected to a maximum 2θ limit at 52.9°. The structure was solved by direct methods. Refinement of atomic parameters was carried out by using full-matrix least-squares on F² (SHELXL-93), giving final agreement factor (R indices) of R1 = 0.0484 and wR2 = 0.1116. Crystallographic data (excluding structure factors) have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 228635. Copies of the data can be obtained free of charge by application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: [phone] or e-mail: [e-mail]).