Cyclization Reactions of Vinyl Radicals via 1,6-H-Atom Transfer: Facile Access to 2,3-Disubstituted Dihydrobenzofurans

Abstract

A new method for the synthesis of 2,3-disubstituted dihydrobenzofurans is reported making use of radical formation via translocation by 1,6-hydrogen atom transfer and subsequent 5-exo-trig cyclization.

dihydrobenzofurans - radicals - hydrogen transfer - ring-closure - radical reactions

References

1a Heiba EI. Messau RM. J. Am. Chem. Soc.  1967,  89:  3772 

1b Freidlina RK. Terent’ev AB. Acc. Chem. Res.  1977,  10:  9 

2a Borthwick AD. Caddick S. Parsons PJ. Tetrahedron Lett.  1990,  31:  6911 

2b Lathbury DC. Parsons PJ. Pinto I. J. Chem. Soc., Chem. Commun.  1988,  81 

2c Kim S. Koh JS. J. Chem. Soc., Chem. Commun.  1992,  1377 

2d Weng W. Luh T. J. Org. Chem.  1993,  58:  5574 

2e Bogen S. Journet M. Malacria M. Synlett  1994,  958 

2f Gross A. Fensterbank L. Bogen S. Thouvenot R. Malacria M. Tetrahedron  1997,  53:  13797 

2g Bogen S. Fensterbank L. Malacria M. J. Am. Chem. Soc.  1997,  119:  5037 

2h Stien D. Samy R. Crich D. Bertrand MP. J. Org. Chem.  1997,  62:  275 

2i Devin P. Fensterbank L. Malacria M. J. Org. Chem.  1998,  63:  6764 

2j Gulea M. Lopez-Romero JM. Fensterbank L. Malacria M. Org. Lett.  2000,  2:  2591 

3 Snieckus V. Cuevas JC. Sloan CP. Liu H. Curran DP. J. Am. Chem. Soc.  1990,  112:  896 

4a Curran DP. Kim D. Liu HT. Shen W. J. Am. Chem. Soc.  1988,  110:  5900 

4b Curran DP. Abraham AC. Liu H. J. Org. Chem.  1991,  56:  4335 

4c Curran DP. Kim D. Ziegler C. Tetrahedron  1991,  47:  6186 

4d Curran DP. Somayajula KV. Yu H. Tetrahedron Lett.  1992,  33:  2295 

4e Curran DP. Shen W. J. Am. Chem. Soc.  1993,  115:  6051 

4f Curran DP. Xu J. Lazzarini E. J. Am. Chem. Soc.  1995,  117:  6603 

4g Curran DP. Xu J. J. Am. Chem. Soc.  1996,  118:  3142 

4h Curran DP. Fairweather N. J. Org. Chem.  2003,  68:  2972 

5a Curran DP. Yu H. Synthesis  1992,  125 

5b Imboden C. Villar F. Renaud P. Org. Lett.  1999,  1:  837 

6a Karady S. Abramson NL. Dolling U. Douglas AW. McManemin GJ. Marcune B. J. Am. Chem. Soc.  1995,  117:  5425 

6b Cummins JM. Dolling U. Douglas AW. Karady S. Leonard WR. Marcune BF. Tetrahedron Lett.  1999,  40:  6153 

6c Karady S. Cummins JM. Dannenberg JJ. Rio E. Dormer PG. Marcune BF. Reamer RA. Sordo TL. Org. Lett.  2003,  5:  1175 

7a Carvalho CF. Sargent MV. J. Chem. Soc., Perkin Trans. 1  1984,  1605 

7b Ganzalez AG. Barrera JB. Yanes AC. Diaz JG. Rodriguez EM. Phytochemistry  1989,  28:  2520 

7c Murray RDH. Nat. Prod. Rep.  1995,  12:  447 

7d Walker JA. Rossen K. Reamer RA. Volante RP. Reider PJ. Tetrahedron Lett.  1999,  40:  4917 

Lews acid promoted reactions:

8a Enger TA. Combrink KD. Letavic MA. Lynch KO. Ray JE. J. Org. Chem.  1994,  59:  6567 

8b Enger TA. Wei D. Letavic MA. Combrink KD. Reddy JP. J. Org. Chem.  1994,  59:  6588 

8c Enger TA. Gfesser GA. Braney BW. J. Org. Chem.  1995,  60:  3700 

8d Engler TA. Iyengar R. J. Org. Chem.  1998,  63:  1929 

8e Rupprecht KM. Boger J. Hoogsteen K. Nachbar RB. Springer JP. J. Org. Chem.  1991,  56:  6108 

Anionic cyclization:

9a Nakao J. Inoue R. Shinokubo H. Oshima K. J. Org. Chem.  1997,  62:  1910 

9b Plotkin M. Chen S. Spoors PG. Tetrahedron Lett.  2000,  41:  2269 

9c Kneisel FF. Monguchi Y. Knapp KM. Zipse H. Knochel P. Tetrahedron Lett.  2002,  43:  4875 

Radical reactions:

10a Sloan CP. Cuevas JC. Quesnelle C. Snieckus V. Tetrahedron Lett.  1988,  29:  4685 

10b Wolff S. Hoffmann HMR. Synthesis  1988,  760 

10c Boger DL. Palanki MSS. J. Am. Chem. Soc.  1992,  114:  9318 

10d Boger DL. Yun W. Teegarden BR. J. Org. Chem.  1992,  57:  2873 

10e Clive DLJ. Etkin N. Joseph T. Lown JW. J. Org. Chem.  1993,  58:  2442 

10f Boisvert G. Giasson R. Tetrahedron Lett.  1992,  33:  6587 

10g Rai R. Collum DB. Tetrahedron Lett.  1994,  35:  6221 

10h Itoh T. Ohara H. Emoto S. Tetrahedron Lett.  1995,  36:  3531 

Palladium chemistry:

11a Larock RC. Yang H. Pace P. Tetrahedron Lett.  1998,  39:  237 

11b Rozhkov RV. Larlock RC. J. Org. Chem.  2003,  68:  6314 

11c Zhang H. Ferreira EM. Stoltz BM. Angew. Chem. Int. Ed.  2004,  43:  6144 

Rhodium chemistry:

12a Saito H. Oishi H. Kitagaki S. Nakamura S. Anada M. Hashimoto S. Org. Lett.  2002,  4:  3887 

12b Davies HML. Grazini MVA. Aouad E. Org. Lett.  2001,  3:  1475 

13a Jezek E. Schall A. Kreitmeier P. Reiser O. Synlett  2005,  915 

13b Chhor RB. Nosse B. Sörgel S. Böhm C. Seitz M. Reiser O. Chem.-Eur. J.  2003,  9:  260 

13c Nosse B. Chhor RB. Jeong WB. Böhm C. Reiser O. Org. Lett.  2003,  5:  941 

13d Böhm C. Reiser O. Org. Lett.  2001,  3:  1315 

13e Seitz M. Reiser O. Curr. Opin. Chem. Biol.  2005,  9:  285 

14

General Procedure for the Radical Cyclizations of Vinyl Bromides. To a refluxing solution of vinyl bromide (0.5 mmol) and AIBN (11 mg, 0.065 mmol) in benzene (7 mL) was added Bu₃SnH (264 µL, 1.0 mmol) and AIBN (11 mg, 0.065 mmol) in 10 mL benzene via a syringe pump within 3 h (3.5 mL/h). After refluxing the reaction mixture for one additional hour, the solvent was removed, and to the residue was added DBU (1.5 mmol) in 10 mL of Et₂O to remove the tin halides, followed by titration with 0.1 M iodide solution and filtration of the solution through silica.¹⁸ The crude product was purified by column chromatography on silica (EtOAc-hexane in an appropriate ratio) to give the benzofurane product.

15

Representative Spectroscopic Data. Compound 5c: trans/cis 67:33 (GC); colorless oil. IR (NaCl): 1195, 1496, 1621, 1732, 2982 cm^-1. cis-Isomer: ¹H NMR (300 MHz, CDCl₃): δ = 1.26 (t, 3 H, J = 6.9 Hz, CH₃), 2.47-2.63 (m, 2 H, CH₂), 3.74 (s, 3 H, CH₃), 3.88-3.99 (m, 1 H, CH), 4.18 (q, 2 H, J = 7.2 Hz, CH₂), 5.18-5.33 (br, 3 H, CH, CH₂), 5.83-5.96 (m, 1 H, CH), 6.68-6.76 (br, 3 H, 3 CH). ¹³C NMR (300 MHz, CDCl₃): δ = 14.2 (CH₃), 35.5 (CH₂), 41.8 (CH), 55.7 (CH₃), 60.7 (CH₂), 86.4 (CH), 109.7 (CH), 110.7 (CH), 113.5 (CH), 119.0 (CH₂), 130.7 (C), 133.0 (CH), 152.9 (C), 154.3 (C), 172.0 (C). trans-Isomer: ¹H NMR (300 MHz, CDCl₃): δ = 1.28 (t, 3 H, J = 6.9 Hz, CH₃), 2.56-2.76 (m, 2 H, CH₂), 3.55-3.61 (m, 1 H, CH), 3.74 (s, 3 H, CH₃), 4.18 (q, 2 H, J = 7.2 Hz, CH₂), 4.76-4.84 (m, 1 H, CH), 5.30-5.48 (m, 2 H, CH₂), 5.91-6.07 (m, 1 H, CH), 6.68-6.76 (br, 3 H, 3 CH). ¹³C NMR (300 MHz, CDCl₃): δ = 14.2 (CH₃), 38.9 (CH₂), 44.8 (CH), 56.0 (CH₃), 60.8 (CH₂), 89.1 (CH), 109.7 (CH), 110.8 (CH), 113.7 (CH), 117.1 (CH₂), 129.8 (C), 136.5 (CH), 153.1 (C), 154.3 (C), 171.5 (C). MS (EI): m/z (relative intensity) = 262 (97) [M⁺], 187 (15), 174 (100), 157 (12), 147 (7), 115 (17), 91 (26), 77 (21). HRMS: m/z calcd for C₁₅H₁₈O₄ [M⁺]: 262.1205; found: 262.1207. Anal. Calcd for C₁₅H₁₈O₄: C, 68.68; H, 6.92. Found: C, 68.45; H, 6.41.
Compound cis-13: colorless oil. IR (NaCl): 1197, 1477, 1597, 1734, 2982 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.27 (t, 3 H, J = 7.2 Hz, CH₃), 1.30 (t, 3 H, J = 7.2 Hz, CH₃), 2.55-2.70 (m, 2 H, CH₂), 4.10-4.36 (br, 5 H, CH, 2 CH₂), 5.27 (d, 1 H, J = 9.0 Hz, CH), 6.84-6.94 (br, 2 H, 2 CH), 7.10-7.21 (br, 2 H, 2 CH). ¹³C NMR (300 MHz, CDCl₃): δ = 14.2 (2 CH₃), 35.8 (CH₂), 40.8 (CH), 60.9 (CH₂), 61.5 (CH₂), 82.5 (CH), 110.1 (CH), 121.4 (CH), 124.3 (CH), 128.0 (C), 129.1 (CH), 158.7 (C), 169.1 (C), 171.2 (C). MS (EI): m/z (relative intensity) = 278 (20) [M⁺], 232 (8), 204 (49), 191 (48), 131 (100), 118 (17), 91 (9), 77 (10). HRMS: m/z calcd for C₁₅H₁₈O₅ [M⁺]: 278.1154; found: 278.1156.
Compound trans-13: colorless oil. IR (NaCl): 1197, 1477, 1597, 1734, 2982 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.26 (t, 3 H, J = 7.2 Hz, CH₃), 1.30 (t, 3 H, J = 7.2 Hz, CH₃), 2.73-2.80 (m, 2 H, CH₂), 3.98-4.10 (m, 1 H, CH), 4.18 (t, 2 H, J = 7.2 Hz, CH₂), 4.27 (t, 2 H, J = 7.2 Hz, CH₂), 4.93 (d, 1 H, J = 5.7 Hz, CH), 6.86-6.95 (br, 2 H, 2 CH), 7.12-7.22 (br, 2 H, 2CH). ¹³C NMR (300 MHz, CDCl₃): δ = 14.2 (2 CH₃), 39.7 (CH₂), 42.9 (CH), 60.9 (CH₂), 61.7 (CH₂), 84.1 (CH), 110.1 (CH), 121.4 (CH), 124.3 (CH), 127.6 (C), 129.1 (CH), 158.8 (C), 170.5 (C), 171.0 (C). MS (EI): m/z (relative intensity) = 278 (7) [M⁺], 232 (10), 204 (23), 191 (98), 131 (100), 118 (19), 91 (12), 77 (12). HRMS: m/z calcd for C₁₅H₁₈O₅ [M⁺]: 278.1154; found: 278.1153.

Analysis by NOE and vicinal coupling constants ³ J _{( H-2, H-3)} in 2,3-dihydrobenzofurans: ³ J _cis may be expected to be larger than ³ J _trans , see:

16a Brust DP. Tarbell DS. Hecht SM. Hayward EC. Colebrook LD. J. Org. Chem.  1966,  31:  2191 

16b Annibali D. Ecker G. Fleischhacker W. Helml T. Hotzer W. Noe CR. Monatsh. Chem.  2000,  131 

17 For an excellent discussion see: Curran DP. Porter NA. Giese B. In Stereochemistry of Radical Reactions: Concepts, Guidelines, and Synthetic Applications   VCH; Weinheim Germany: 1995.  p.30-43  

18 Curran DP. Chang C.-T. J. Org. Chem.  1989,  54:  3140