Fe/CuBr₂-Catalyzed Benzylation of Arenes and Thiophenes with Benzyl Alcohols

Abstract

An inexpensive and relatively nontoxic Fe/CuBr₂-catalyzed benzylation of arenes and thiophenes with benzyl alcohols has been developed. The reaction can be carried out under mild conditions to afford diarylmethane derivatives in high yields and good ­selectivity.

benzylation - benzyl alcohols - iron - cupric bromide - ­diarylmethanes

Reference and Notes

<A NAME="RW13909ST-1">1</A> Kakiuchi F. Murai S. Acc. Chem. Res.  2002,  35:  826 

<A NAME="RW13909ST-2">2</A> Bandini M. Melloni A. Umani-Ronchi A. Angew. Chem. Int. Ed.  2004,  43:  550 

<A NAME="RW13909ST-3">3</A> Thalji RK. Ahrendt KA. Bergman RG. Ellman JA. J. Am. Chem. Soc.  2001,  123:  9692 

<A NAME="RW13909ST-4">4</A> Reetz MT. Sommer K. Eur. J. Org. Chem.  2003,  3485 

<A NAME="RW13909ST-5">5</A> Pastine SJ. Youn SW. Sames D. Org. Lett.  2003,  5:  1055 

<A NAME="RW13909ST-6">6</A> Nakanishi S. Oda T. Ueda T. Otsuji Y. Chem. Lett.  1978,  7:  1309 

<A NAME="RW13909ST-7">7</A> Cantor PA. J. Chem. Eng. Data  1963,  8:  459 

<A NAME="RW13909ST-8">8</A> Nordberg MG. Kolmodin K. Aquist J. Queener SF. Hallberg A. J. Med. Chem.  2001,  44:  2391 

<A NAME="RW13909ST-9">9</A> Sun HH. Paul VJ. Fenical W. Phytochemistry  1983,  22:  743 

<A NAME="RW13909ST-10">10</A> Hoshina H. Maekawa K. Taie K. Igarashi T. Sakurai T. Heterocycles  2003,  60:  1779 

<A NAME="RW13909ST-11">11</A> Manzoni C. Lovati MR. Bonelli A. Galli G. Sirtori CR. Eur. J. Pharmacol.  1990,  190:  39 

<A NAME="RW13909ST-12">12</A> Rose C. Vtoraya O. Pluzanska A. Davidson N. Gershanovich M. Thomas R. Johnson S. Caicedo JJ. Gervasio H. Manikhas G. Ayed FB. Radoux SB. Ross HAC. Lang R. Eur. J. Cancer  2003,  39:  2318 

<A NAME="RW13909ST-13">13</A> Gihani MTE. Heaney H. Shuhaibar KF. Synlett  1996,  871 

<A NAME="RW13909ST-14">14</A> Fukuzawa SI. Tsuchimoto T. Hiyama T. J. Org. Chem.  1997,  62:  151 

<A NAME="RW13909ST-15">15</A> Tsuchimoto T. Tobita K. Hiyama T. Fukuzawa SI.
J. Org. Chem.  1997,  62:  6997 

<A NAME="RW13909ST-16">16</A> Sharma GVM. Mahalingam AK. J. Org. Chem.  1999,  64:  8943 

<A NAME="RW13909ST-17">17</A> Shiina I. Suzuki M. Tetrahedron Lett.  2002,  43:  6391 

<A NAME="RW13909ST-18">18</A> Noji M. Ohno T. Fuji K. Futabe N. Tajima H. Ishii K. J. Org. Chem.  2003,  68:  9340 

<A NAME="RW13909ST-19">19</A> Mukaiyama T. Kamiyama H. Yamanaka H. Chem. Lett.  2003,  32:  814 

<A NAME="RW13909ST-20">20</A> Mertins K. Iovel I. Kischel J. Zapf A. Beller M. Angew. Chem. Int. Ed.  2005,  44:  238 

<A NAME="RW13909ST-21">21</A> Iovel I. Mertins K. Kischel J. Zapf A. Beller M. Angew. Chem. Int. Ed.  2005,  44:  3913 

<A NAME="RW13909ST-22">22</A> Mertins K. Iovel I. Kischel J. Zapf A. Beller M. Adv. Synth. Catal.  2006,  348:  691 

<A NAME="RW13909ST-23">23</A> Rueping M. Nachtsheim BJ. Ieawsuwana W. Adv. Synth. Catal.  2006,  348:  1033 

<A NAME="RW13909ST-24">24</A> Csendea F. Stájerb G. Curr. Org. Chem.  2005,  9:  1737 

<A NAME="RW13909ST-25">25</A> Tsukervanik IP. Dokl. Akad. Nauk UzSSR  1959,  36 

<A NAME="RW13909ST-26">26</A>

Typical Procedure for the Benzylation of Arenes
Benzyl alcohol (1 mmol), arene (1 mL), CuBr₂ (10 mol%,
0.1 mmol), reductive Fe powder (20 mol%, 0.2 mmol), and DCE (5 mL) were put into a flask fitted with a pressure-equalized addition funnel (containing a cotton plug and 1 g of CaH₂ and acting as a Soxhlet extractor) surmounted by a reflux condenser. After stirring for 20 h at 84 ˚C, the reaction was quenched with H₂O. The stirring bar was removed and washed with CH₂Cl₂. The aqueous phase was extracted three times with CH₂Cl₂. The combined organic layers were dried over MgSO₄, and the solvents were evaporated. The product was purified by silica gel column chromatography (200-300 mesh; n-hexane-EtOAc, 50:1).
2-Benzyl-3,4-dibromothiophene (3u) ^¹H NMR (400 MHz, CDCl₃, 25 ˚C): δ = 7.34-7.28 (m, 2 H, Ar), 7.25-7.21 (m, 3 H, Ar), 7.17 (s, 1 H, Ar), 4.16 (s, 2 H, ArCH₂). HRMS: m/z calcd for C₁₁H₈SBr₂: 329.8713; found: 329.8714.
General Procedure for the Benzylation of Thiophene Benzyl alcohol (1 mmol), thiophene (1 mL), CuBr₂ (10 mol%, 0.1 mmol), reductive Fe powder (20 mol%, 0.2 mmol), and DCE (5 mL) were put into a flask fitted with a pressure-equalized addition funnel (containing a cotton plug and 1 g of CaH₂ and acting as a Soxhlet extractor) sur-mounted by a reflux condenser. After stirring for 20 h at 84 ˚C, the reaction was quenched with H₂O. The stirring bar was removed and washed with CH₂Cl₂. The aqueous phase was extracted three times with CH₂Cl₂. The combined organic layers were dried over MgSO₄, and the solvents were evaporated. The product was purified by silica gel column chromatography (200-300 mesh; n-hexane-EtOAc, 50:1).
2-Furyl-2-thienylmethane (6g) ^¹H NMR (400 MHz, CDCl₃, 25 ˚C): δ = 7.33 (s 1 H, Ar), 7.15 (d J = 4.8 Hz, 1 H, Ar), 6.93 (dt J = 2.8, 5.2 Hz, 1 H, Ar), 6.86 (d, J = 2.8 Hz, 1 H, Ar), 6.29 (s, 1 H, Ar), 6.08 (d, J = 2.8 Hz, 1 H, Ar), 4.15 (s, 2 H, ArCH₂). MS (EI): m/z = 164 [M⁺].