First Thermal and Transition Metal Catalysed Intramolecular [4+2] Cycloaddition Reactions with N-Tethered Ynamides

Abstract

Cationic rhodium(I)-complexes generated from [RhCl(PPh₃)₃] and AgSbF₆ catalyse at room temperature the first examples of intramolecular [4+2] cycloaddition reactions with N-tethered ynamides and provide an efficient access to synthetically versatile tetrahydroindoles.

ynamides - tetrahydroindoles - Diels-Alder reaction - catalysis - alkynyliodonium salts

References

1a Corey EJ. Angew. Chem. Int. Ed.  2002,  41:  1650 

1b Nicolaou KC. Snyder SA. Montagnon T. Vassilikogiannakis GE. Angew. Chem. Int. Ed.  2002,  41:  1701 

1c Fringuelli F. Taticchi A. The Diels-Alder Reaction   Wiley and Sons; Chichester: 2002. 

2a Fearnley SP. Market E. Chem. Commun.  2002,  438 

2b Padwa A. Bur SK. Danca DM. Ginn JD. Lynch SM. Synlett  2002,  851 

2c Oppolzer W. Flaskamp E. Bieber LW. Helv. Chim. Acta  2001,  84:  141 

2d Boger DL. Wolkenberg SE. J. Org. Chem.  2000,  65:  9120 

2e Magnus P. Cairns PM. J. Am. Chem. Soc.  1986,  108:  217 

2f Martin SF. Tu C. Kimura M. Simonsen SH. J. Org. Chem.  1982,  47:  3634 

2g Stork G. Morgans DJ. J. Am. Chem. Soc.  1979,  101:  7110 

3a Genet JP. Ficini J. Tetrahedron Lett.  1979,  1499 

3b Iwamoto K. Fukuta H. Suzuki S. Maruyama J. Oishi E. Miyashita A. Higashino T. Heterocycles  1996,  43:  2409 

3c Barluenga J. Ferrero M. Peláez-Arango E. López-Ortiz F. Palacios F. J. Chem. Soc., Chem. Commun.  1994,  865 

3d Padwa A. Gareau Y. Harrison B. Rodriguez A. J. Org. Chem.  1992,  57:  3540 

3e Boger DL. Dang Q. Tetrahedron  1988,  44:  3379 

3f Himbert G. Brunn W. Liebigs Ann. Chem.  1986,  1067 

3g For Hetero Diels-Alder reactions with ynamines, see: van Elburg PA. Honig GWN. Reinhout DN. Tetrahedron Lett.  1987,  28:  6397 

3h See also: Vilsmaier E. Baumheier R. Chem. Ber.  1989,  122:  1285 

4 Witulski B. Stengel T. Angew. Chem. Int. Ed.  1998,  37:  498 

5a Witulski B. Alayrac C. Angew. Chem. Int. Ed.  2002,  41:  3281 

5b Witulski B. Stengel T. Fernández-Hernández JM. Chem. Commun.  2000,  1965 

5c Witulski B. Buschmann N. Bergsträßer U. Tetrahedron  2000,  56:  8473 

5d Witulski B. Gößmann M. Synlett  2000,  1793 

5e Witulski B. Stengel T. Angew. Chem. Int. Ed.  1999,  38:  2426 

5f Witulski B. Gößmann M. Chem. Commun.  1999,  1879 

5g For other contributions to the chemistry of ynamides, see: Hoffmann RW. Brückner D. New J. Chem.  2001,  25:  369 

5h Rainier JD. Imbriglio JE. J. Org. Chem.  2000,  65:  7272 

5i Mulder JA. Hsung RP. Frederick MO. Tracey MR. Zificsak CA. Org. Lett.  2002,  4:  1383 

5j Wei L.-L. Mulder JA. Xiong H. Zificsak CA. Douglas CJ. Hsung RP. Tetrahedron  2001,  57:  459 

5k Saito N. Sato Y. Mori M. Org. Lett.  2002,  4:  809 

6a Kitamura T. Kotani M. Yokoyama T. Fujiwara Y. Hori K. J. Org. Chem.  1999,  64:  680 

6b Murch P. Arif AM. Stang PJ. J. Org. Chem.  1997,  62:  5959 

6c Zhdankin VV. Stang PJ. Chem. Rev.  2002,  102:  2523 

7 Feldman KS. Mareska DA. J. Am. Chem. Soc.  1998,  120:  4027 

8

Spectral data for dienyne 7: ¹H NMR (400 MHz, CDCl₃): δ = 7.80 (m, 2 H), 7.35 (m, 2 H), 6.23 (m, 1 H), 6.07 (m, 1 H), 5.55 (m, 1 H), 5.11 (d, J = 16.1 Hz, 1 H), 5.01 (d, J = 9.1 Hz, 1 H), 3.38 (m, 2 H), 2.78 (s, 1 H), 2.43 (s, 3 H), 2.39 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.7, 136.6, 133.8, 130.0, 129.8, 127.6, 134.6, 116.3, 75.8, 59.5, 50.6, 30.9, 21.6.

Nickel(0)-catalysed intramolecular [4+2] cycloaddition reactions:

9a Wender PA. Jenkins TE. J. Am. Chem. Soc.  1989,  111:  6432 

9b Wender PA. Smith TE. J. Org. Chem.  1996,  61:  824 

9c Wender PA. Smith TE. Tetrahedron  1998,  54:  1255 

9d DiMauro EF. Kozlowski MC. J. Chem. Soc., Perkin Trans. 1  2002,  439 

Rhodium(I)- and cationic rhodium(I)-catalysed intramolecular [4+2] cycloaddition reactions:

10a Jolly RS. Luedtke G. Sheehan D. Livinghouse T. J. Am. Chem. Soc.  1990,  112:  4965 

10b Wender PA. Jenkins TE. Suzuki S. J. Am. Chem. Soc.  1995,  117:  1843 

10c McKinstry L. Livinghouse T. Tetrahedron  1994,  50:  6145 

10d O’Mahony DJR. Belanger DB. Livinghouse T. Synlett  1998,  443 

10e Gilbertson SR. Hoge GS. Genov DG. J. Org. Chem.  1998,  63:  10077 

10f Paik S.-J. Son SU. Chung YK. Org. Lett.  1999,  1:  2045 

11

Experimental Procedure: [RhCl(PPh₃)₃] (9.3 mg, 0.01 mmol) was added to a solution of ynamide 4-8 (0.20 mmol) in dry toluene (10 mL) under argon. After stirring for 5 min at r.t., AgSbF₆ (0.01 mmol, 0.2 mL of a 0.05 M solution in 1,2-dichloroethane) was added and the reaction mixture was stirred at r.t. The reaction mixture was filtered through a small plug of celite, the solvent was evaporated and the resulting crude product was purified by column chromatography (Al₂O₃ III/N, hexanes-EtOAc = 8:2) to afford 9, 11-14.
Compound 9: Mp 87-88 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.72 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H), 5.76 (m, 2 H), 5.66 (m, 1 H), 3.76 (m, 1 H), 3.33 (m, 1 H), 2.77 (m, 2 H), 2.54 (m, 1 H), 2.41 (s, 3 H), 2.02 (m, 1 H), 1.49 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.6, 137.9, 134.8, 129.5, 127.2, 126.5, 125.3, 103.1, 48.9, 38.0, 28.7, 26.9, 21.5. MS (EI, 70 eV): m/z (%) = 275 (43) [M⁺], 91 (100). Anal. Calcd for C₁₅H₁₇NO₂S: C, 65.43; H, 6.22; N, 5.09. Found: C, 65.15; H, 6.06; N, 5.31. Compound 11: Mp 74-75 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.70 (d, J = 8.3 Hz, 2 H), 7.27 (d, J = 8.3 Hz, 2 H), 5.79 (m, 1 H), 5.64 (m, 1 H), 3.46 (m, 2 H), 2.96-2.81 (m, 2 H), 2.47 (s, 3 H), 1.89 (m, 2 H), 1.34 (m, 1 H), 0.35 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 145.2, 143.6, 134.8, 129.5, 128.1, 125.9, 125.8, 125.7, 47.2, 36.9, 29.8, 28.7, 21.5, 0.0. MS (EI, 70 eV): m/z (%) = 347 (3) [M⁺], 99 (100). Anal. Calcd for C₁₈H₂₅NO₂SSi: C, 62.21; H, 7.25; N, 4.03. Found: C, 61.98; H, 7.35; N, 3.93. Compound 13: Mp 121-122 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.52 (m, 2 H), 7.44 (m, 2 H), 7.32 (m, 2 H), 7.22 (m, 3 H), 5.77 (m, 1 H), 5.70 (m, 1 H), 3.54 (m, 2 H), 3.38 (m, 1 H), 2.78 (m, 1 H), 2.40 (s, 3 H), 2.23 (m, 1 H), 2.11 (m, 1 H), 1.55 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.4, 141.0, 134.1, 129.4, 128.0, 127.6, 125.4, 125.3, 124.8, 47.7, 38.0, 33.3, 29.3, 21.6. Compound 14: Oil. ¹H NMR (400 MHz, CDCl₃) δ = 7.67 (d, J = 8.2 Hz, 2 H), 7.27 (d, J = 8.2 Hz, 2 H), 5.67 (m, 1 H), 5.54 (m, 1 H), 3.42 (m, 2 H), 2.89 (m, 1 H), 2.60 (m, 2 H), 2.41 (s, 3 H), 2.34 (m, 1 H), 1.87 (m, 2 H), 1.52 (m, 1 H), 1.38 (m, 3 H), 1.28 (m, 1 H), 0.93 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃) δ = 143.5, 134.6, 131.8, 129.5, 128.5, 127.8, 125.7, 124.8, 47.9, 36.8, 32.0, 31.0, 29.6, 29.4, 22.9, 21.5, 14.0.

12

Crystal data for 12: C₁₃H₁₈NOF₃Si, triclinic, space group
P1 (No. 2), a = 8.896 (2), b = 9.643 (2), c = 9.830 (2) Å, α = 102.38 (3)°, β = 115.97 (3)°, γ = 92.73 (3)°, V = 730.8 (3) ų, Z = 2, D _c = 1.315 g cm^-3, F ₍₀₀₀₎ = 304,
µ (Mo-Kα) = 1.85 cm^-1. 6235 reflections collected, 2650 independent [R(int) = 0.0449], which were used in all calculations. 172 parameters, R ₁ = 0.0457, wR ₂ = 0.1129 for observed reflections [F²>2σ(F²)] and R ₁ = 0.0597, wR ₂ = 0.1217 for all reflections, GoF (on F²) = 0.871. Max. and min. residual electron densities: 0.285 and -0.231 eÅ^-3. Data were collected on a STOE-IPDS at r.t., the structure was solved by direct methods using SHELXS-97 and refined using SHELXL-97. CCDC: 194177.