Preparation of (Phenyldifluoromethyl)- and (Phenoxydifluoromethyl)-silanes by Magnesium-Promoted Carbon-Chlorine Bond Activation

Abstract

Treatment of α-chloro-α,α-difluorotoluene and α-chloro-α,α-difluoroanisole with chlorotrimethylsilane in the presence of magnesium in DMF led to their corresponding trimethylsilyl derivatives. These compounds are able to transfer their fluorinated group to various electrophilic substrates (carbonyl compounds, disulfides, phenyl isocyanate).

fluorine - alkyl halides - silicon - magnesium - nucleophilic additions

References

<A NAME="RG07904ST-1">1</A> Singh RP. Shreeve JM. Tetrahedron  2000,  56:  7613 ; and references cited therein

<A NAME="RG07904ST-2">2</A> Surya Prakash GK. Hu J. Olah GA. J. Org. Chem.  2003,  68:  4457 

<A NAME="RG07904ST-3">3</A> Gilman H. J. Organomet. Chem.  1975,  100:  83 

<A NAME="RG07904ST-4">4</A> Farnham WB. Synthetic Fluorine Chemistry   Olah GA. Chambers RD. Surya Prakash GK. Wiley and Sons Inc.; New York: 1992.  p.247 

<A NAME="RG07904ST-5">5</A> Yoshida M. Suzuki D. Iyoda M. Chem. Lett.  1994,  2357 

<A NAME="RG07904ST-6">6</A> Yoshida M. Suzuki D. Iyoda M. J. Chem. Soc., Perkin Trans. 1  1997,  643 

<A NAME="RG07904ST-7">7</A>

This method is reported to give an almost quantitative yield. In our hands, the yield was limited to 20%, even with carefully distilled solvents.

<A NAME="RG07904ST-8">8</A> Clavel P. Léger-Lambert M.-P. Biran C. Serein-Spirau F. Bordeau M. Roques N. Marzouk H. Synthesis  1999,  5:  829 

<A NAME="RG07904ST-9">9</A> Clavel P. Lessene G. Biran C. Bordeau M. Roques N. Trévin S. de Montauzon D. J. Fluorine Chem.  2001,  107:  301 

<A NAME="RG07904ST-10">10</A>

DMF has already been used for the formation of fluorinated organometallic intermediates. [12]

<A NAME="RG07904ST-11">11</A> Burton DJ. Yang Z.-Y. Tetrahedron  1992,  48:  189 ; and references cited therein

<A NAME="RG07904ST-12">12</A>

Transformation of 1,4-bis(trifluoromethyl)benzene into α-trimethylsilyl-α,α,α′,α′,α′-pentafluoroxylene by Gilman’s procedure in DMF has been reported.¹³ However, these conditions are not efficient when the aromatic ring is substituted by only one trifluoromethyl group.

<A NAME="RG07904ST-13">13</A> Amii H. Hatamoto Y. Seo M. Uneyama K. J. Org. Chem.  2001,  66:  7216 

<A NAME="RG07904ST-14">14</A>

Preparation of 2: To anhyd DMF (20 mL) were added magnesium powder (0.486 g, 20 mmol) and chlorotri-methylsilane (5.07 mL, 40 mmol) under argon. Then α-chloro-α,α-difluorotoluene(4) (1.625 g, 10 mmol) was added dropwise. The reaction was very exothermic and the mixture was stirred until it turned brown. After hydrolysis, the mixture was extracted with Et₂O and the organic layer washed with H₂O, dried over MgSO₄ and then purified by flash chromatography on silica gel using pentane as eluent to afford 1.96 g of a colourless liquid identified as 2 (98% from PhCF₂Cl). ¹³C NMR (50 MHz, CDCl₃): δ = -4.9, 124.6 (t, ³ J _CF = 7 Hz), 128.2, 128.8, 131.8 (t, ¹ J _CF = 265 Hz), 138.2 (t, ² J _CF = 20 Hz).

<A NAME="RG07904ST-15">15</A>

Preparation of 3: In the same way, (phenoxydifluoro-methyl)trimethylsilane was synthesised by reaction of α-chloro-α,α-difluoroanisole(5) (1.785 g, 10 mmol), magnesium powder (0.486 g, 20 mmol) and chlorotrimethyl-silane (12.67 mL, 100 mmol). The reaction mixture was stirred and heated (55 °C) until it turned brown. Treatment and purification are the same as for compound 2. Reagent 3 was isolated as a colourless liquid (60% from PhOCF₂Cl). ¹⁹F NMR (282 MHz, CDCl₃): δ = -75.2 (s); ¹H NMR (300 MHz, CDCl₃): δ = 0.33 (s, 9 H, CH₃), 7.18-7.39 (m, 5 H,
Ar-H). ¹³C NMR (50 MHz, CDCl₃): δ = -4.7, 122.1, 125.0, 129.1, 131.1 (t, ¹ J _CF = 268 Hz), 150.6 (t, ⁴ J _CF = 5 Hz). MS: m/z (%) = 216 (11)[M⁺ ] 197 (2) [M⁺ - F] 77 (100), [ Ph] 73 (43) [SiMe₃]. Degradation of 3 into olefins 6 and 7 sometimes occurs and does not allow an accurate elemental analysis.

<A NAME="RG07904ST-16">16</A>

Olefin 6: ¹⁹F NMR (188 MHz, CDCl₃): δ = -128.6 (s). ¹H NMR (200 MHz, CDCl₃): δ = 7.16-7.43 (m, 10 H, Ar-H). Olefin 7: ¹⁹F NMR (188 MHz, CDCl₃): δ = -122.5 (s). ¹H NMR (200 MHz, CDCl₃): δ = 7.12-7.39 (m, 5 H, Ar-H).

<A NAME="RG07904ST-17">17</A>

Dimerisation of the analogous chlorophenoxycarbene has been reported.¹³

<A NAME="RG07904ST-18">18</A> Brük W. Dürr H. Angew. Chem., Int. Ed. Engl.  1982,  21:  916 

<A NAME="RG07904ST-19">19</A>

Preparation of difluorinated compounds 8 and 9: Fluoride source [KF or (n-Bu₄N⁺, Ph₃SnF₂ ^-), 0.5 mmol), DMF (5 mL) and the electrophile (10 mmol) were introduced, in that order, into a round bottomed flask under argon. The difluoroalkyltrimethysilylated reagent was then added in one portion. The solution was stirred. Evolution of the mixture was followed by ¹⁹F NMR. After consumption of the silylated compound, the mixture was poured onto 20 mL of HCl (0.5 M) and stirred for 20 min. The aqueous layer was extracted with Et₂O and the resulting organic phase was washed with brine, an iced sat. NaHCO₃ aq solution and again with brine. The organic phases were dried over MgSO₄ and concentrated under vacuum. Alcohols were obtained in their O-silylated form; deprotection was achieved by an acidic treatment [HCl 35% (0.2 mL) in EtOH (10 mL)]. See Table [1] and Table [2] for ¹H NMR and ¹⁹F NMR data. Compound 8b: ¹³C NMR (75 MHz, CDCl₃): δ = 76.9 (t, ² J _CF = 31 Hz), 121.2 (t, ¹ J _CF = 248 Hz), 126.3 (t, ³ J _CF = 6 Hz), 127.8, 127.9, 128.0, 128.6, 130.0, 133.8 (t, ² J _CF = 26 Hz), 135.8. IR: 3431, 3057, 3032 cm^-1. MS: m/z (%) = 127 (26) [PhCF₂], 107 (88) [PhCHOH], 77 (51) [Ph]. Anal. Calcd for C₁₄H₁₂F₂O: C, 71.79%; H, 5.13%. Found: C, 71.69%; H, 5.03%. The spectral data agree with those reported in the literature.^8,9 Compound 8f: isolated as a white solid, mp 102 °C. ¹³C NMR (75 MHz, CDCl₃): δ = 114.8 (t, ¹ J _CF = 254 Hz), 120.3, 125.6 (t, ³ J _CF = 6 Hz), 125.7, 128.7, 129.2, 131.1, 132.6 (t, ² J _CF = 25 Hz), 135.8, 149.3, 161.9 (t, ² J _CF = 31 Hz). IR: 3334, 3057, 1685 cm^-1. MS: m/z (%) = 247 (78) [M⁺], 127 (76) [PhCF₂], 120 (67) [PhNHC(O)], 92 (79) [PhNH], 77 (41) [Ph]. Anal. Calcd for C₁₄H₁₁F₂ON: C, 68.00%; H, 4.45%. Found: C, 68.21%; H, 4.47%.

<A NAME="RG07904ST-20">20</A> Billard T. Langlois BR. Medebielle M. Tetrahedron Lett.  2001,  42:  3463 

<A NAME="RG07904ST-21">21</A> Middleton KJ. Bingham EM. J. Org. Chem.  1980,  45:  2883 

<A NAME="RG07904ST-22">22</A> Saint-Jalmes L. inventors; PCT Int. Appl. WO97  43,231.  ; Chem. Abstr. 1998, 128, 365773r

<A NAME="RG07904ST-23">23</A> Tozer MJ. Herpin TF. Tetrahedron  1996,  52:  8619 

<A NAME="RG07904ST-24">24</A> Yagupolskii LM. Korinko VA. J. Gen. Chem. USSR  1969,  39:  186 

<A NAME="RG07904ST-25">25</A> Yagupolskii LM. Belinskaya RV. J. Gen. Chem. USSR  1958,  28:  750