Synthesis of 2-Aryl-Substituted Chromans by Intramolecular C-O Bond Formation

Abstract

A synthetic route for the preparation of 2-aryl-substituted chromans from commercially available starting materials and utilizing either a palladium- or copper-catalyzed intramolecular cyclization of aryl bromides is described. Chromans with stereocontrol at C-2 can thus be obtained via a palladium-catalyzed asymmetric allylic etherification procedure utilizing a chiral indole-phosphine oxazoline (IndPHOX) ligand.

intramolecular cyclization - chromans - chalcones - palladium - copper

References and Notes

<A NAME="RD82011ST-1A">1a</A> Chemistry of Heterocyclic Compounds: Chromans and Tocopherols   Vol. 36:  Ellis GP. Lockhart IM. Wiley; New York: 1981. 

<A NAME="RD82011ST-1B">1b</A> Saengchantara ST. Wallace TW. Nat. Prod. Rep.  1986,  3:  465 

<A NAME="RD82011ST-2">2</A> Bauer DJ. Selway JWT. Batchelor JF. Tisdale M. Caldwell IC. Young DA. Nature (London)  1981,  292:  369 

<A NAME="RD82011ST-3">3</A> Efange SMN. Tu Z. von Hohenberg K. Francesconi L. Howell RC. Rampersad MV. Todaro LJ. Papke RL. Kung MP. J. Med. Chem.  2001,  44:  4704 

For some recent examples of the racemic synthesis of chromans, see:

<A NAME="RD82011ST-4A">4a</A> Sugimoto H. Nakamura S. Ohwada T. Adv. Synth. Catal.  2007,  349:  669 

<A NAME="RD82011ST-4B">4b</A> Yamamoto Y. Itonaga K. Org. Lett.  2009,  11:  717 

<A NAME="RD82011ST-4C">4c</A> Batsomboon P. Phakhodee W. Ruchirawat S. Ploypradith P. J. Org. Chem.  2009,  74:  4009 

<A NAME="RD82011ST-4D">4d</A> Radomkit S. Sarnpitak P. Tummatorn J. Batsomboon P. Ruchirawat S. Ploypradith P. Tetrahedron  2011,  67:  3904 

For some recent examples of the asymmetric synthesis of chromans, see:

<A NAME="RD82011ST-5A">5a</A> Hernandez-Torres G. Carreno MC. Urbano A. Colobert F. Eur. J. Org. Chem.  2011,  20-21:  3864 

<A NAME="RD82011ST-5B">5b</A> Valla C. Baeza A. Menges F. Pfaltz A. Synlett  2008,  3167 

<A NAME="RD82011ST-5C">5c</A> Chandrasekhar S. Reddy MV. Tetrahedron  2000,  56:  6339 

<A NAME="RD82011ST-5D">5d</A> Hodgetts KJ. Tetrahedron  2005,  61:  6860 

<A NAME="RD82011ST-6">6</A> For a recent review on the asymmetric synthesis of chromans, see: Shen HC. Tetrahedron  2009,  65:  3931 

For some selected examples, see:

<A NAME="RD82011ST-7A">7a</A> Neogi A. Majhi TP. Achari B. Chattopadhyay P. Eur. J. Org. Chem.  2008,  2:  330 

<A NAME="RD82011ST-7B">7b</A> Kuwabe S. Torraca KE. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  12202 

<A NAME="RD82011ST-7C">7c</A> Shelby Q. Kataoka N. Mann G. Hartwig J. J. Am. Chem. Soc.  2000,  122:  10718 

<A NAME="RD82011ST-7D">7d</A> Torraca KE. Kuwabe SI. Buchwald SL. J. Am. Chem. Soc.  2000,  122:  12907 

For some recent examples, see:

<A NAME="RD82011ST-8A">8a</A> Zhao J. Zhao YF. Fu H. Angew. Chem. Int. Ed.  2011,  50:  3769 

<A NAME="RD82011ST-8B">8b</A> Niu JJ. Guo PR. Kang JT. Li ZG. Xu JW. Hu SJ. J. Org. Chem.  2009,  74:  5075 

<A NAME="RD82011ST-8C">8c</A> Adams H. Gilmore NJ. Jones S. Muldowney MP. von Reuss SH. Vemula R. Org. Lett.  2008,  10:  1457 

<A NAME="RD82011ST-8D">8d</A> Fang Y. Li C. J. Org. Chem.  2006,  71:  6427 

<A NAME="RD82011ST-9A">9a</A> Xu B. Xue J. Zhu J. Li Y. Chem. Lett.  2008,  37:  202 

<A NAME="RD82011ST-9B">9b</A> Kataoka N. Shelby Q. Stambuli JP. Hartwig JF.
J. Org. Chem.  2002,  67:  5553 

<A NAME="RD82011ST-9C">9c</A> Palucki M. Wolfe JP. Buchwald SL. J. Am. Chem. Soc.  1996,  118:  10333 

<A NAME="RD82011ST-10">10</A> Gan Y. Spencer TA. J. Org. Chem.  2006,  71:  5870 

<A NAME="RD82011ST-11">11</A>

General Procedure for Palladium-Catalyzed Intramolecular Cyclization: To a mixture of Pd(OAc)₂ (2.4 mg, 0.0105 mmol), ligand 11 (3.1 mg, 0.0105 mmol) and Cs₂CO₃ (0.17 g, 0.525 mmol), compound 9 (0.35 mmol) in toluene (1.2 mL) was added. After stirring under 90 ˚C for reported time, the reaction mixture was cooled to r.t., diluted with Et₂O, and filtered through a pad of celite. The resulting solution was purified by silica gel chromatography (n-hexane-EtOAc, 30:1).

<A NAME="RD82011ST-12">12</A>

The by-product was 1-(furan-2-yl)-3-phenylpropan-1-one, isolated in 22% yield. For the reaction mechanism, see reference 7b.

<A NAME="RD82011ST-13">13</A> Fagan PJ. Hauptman E. Shapiro R. Casalnuvo A.
J. Am. Chem. Soc.  2000,  122:  5043 

<A NAME="RD82011ST-14">14</A>

General Procedure for Copper-Catalyzed Intramolecular Cyclization: To a mixture of CuI (2.8 mg, 0.015 mmol), 2-aminopyridine (2.8 mg, 0.03 mmol) and NaOMe (12 mg, 0.225 mmol), compound 9 (0.15 mmol) in diglyme (0.7 mL) was added. After stirring under 100 ˚C for reported time, the reaction mixture was cooled to r.t., quenched with H₂O, and extracted with Et₂O. The extracts were washed with brine and dried over MgSO₄. The solvent was removed in vacuo and the residue was purified by column chromatography (n-hexane-EtOAc, 30:1).

<A NAME="RD82011ST-15A">15a</A> Wang Y. Hämäläinen A. Tois J. Franzén R. Tetrahedron: Asymmetry  2010,  21:  2376 

<A NAME="RD82011ST-15B">15b</A> Wang Y. Vaismaa M. Hämäläinen A. Tois J. Franzén R. Tetrahedron: Asymmetry  2011,  22:  524 

<A NAME="RD82011ST-16">16</A> Miyabe H. Matsumura A. Moriyama K. Takemoto Y. Org. Lett.  2004,  6:  4631 

<A NAME="RD82011ST-17">17</A>

The reported ee is the average value of three entries.

<A NAME="RD82011ST-18">18</A>

2-(2-Bromophenyl)chroman (20): [α]_D ^²0 +71.2 (c = 0.95, CHCl₃, 89% ee). ^¹H NMR (300 MHz, CDCl₃): δ = 7.54-7.61 (m, 2 H), 7.36 (td, J = 7.7, 1.2 Hz, 1 H), 7.10-7.19 (m, 3 H), 6.86-6.93 (m, 2 H), 5.38 (td, J = 10.2, 2.2 Hz, 1 H), 3.00-3.10 (m, 1 H), 2.75-2.83 (m, 1 H), 2.31-2.39 (m, 1 H), 1.85-1.94 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 155.4, 141.3, 133.0, 130.0, 129.4, 128.1, 127.8, 127.7, 122.3, 121.8, 120.8, 117.2, 77.3, 29.1, 25.5. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₅H₁₃ONaBr: 311.0047; found: 311.0015.

<A NAME="RD82011ST-19">19</A>

[α]_D ^²0 +27.7 (c = 0.5, CH₂Cl₂, 87% ee).

<A NAME="RD82011ST-20">20</A> Yasunori Y. Tomohiko S. Momoko W. Kazunori K. Norio M. Molecules  2011,  16:  5020 

For some reviews of reactions for aromatic halides, see:

<A NAME="RD82011ST-21A">21a</A> Sadig JER. Willis MC. Synthesis  2011,  1 

<A NAME="RD82011ST-21B">21b</A> Surry DS. Buchwald SL. Angew. Chem. Int. Ed.  2008,  47:  6338 

<A NAME="RD82011ST-21C">21c</A> Bubnov YN. Heterocycles  2010,  80:  1 

<A NAME="RD82011ST-21D">21d</A> Alonso F. Beletskaya IP. Yus M. Tetrahedron  2008,  64:  3047 

<A NAME="RD82011ST-21E">21e</A> Martin R. Buchwald SL. Acc. Chem. Res.  2008,  41:  1461 

<A NAME="RD82011ST-21F">21f</A> Bras JL. Muzart J. Chem. Rev.  2011,  111:  1170 

<A NAME="RD82011ST-21G">21g</A> Felpin FX. Nassar-Hardy L. Callonnec FL. Fouquet E. Tetrahedron  2011,  67:  2815 

<A NAME="RD82011ST-22">22</A>

2-([1,1′-Biphenyl]-2-yl)chroman (22): [α]_D ^²0 -36.5 (c = 0.40, CHCl₃, 89% ee). ^¹H NMR (300 MHz, CDCl₃): δ = 7.64-7.67 (m, 1 H), 7.25-7.46 (m, 8 H), 7.00-7.11 (m, 2 H), 6.80-6.88 (m, 2 H), 5.05-5.10 (m, 1 H), 2.71-2.78 (m, 2 H), 2.01-2.09 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 155.8, 141.2, 141.0, 139.3, 130.4, 129.8, 129.6, 128.5, 128.2, 128.0, 127.5, 127.4, 126.7, 122.2, 120.5, 117.3, 75.2, 30.1, 25.9. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₂₁H₁₈ONa: 309.1255; found: 309.1263.