Cobalt-Mediated [2+2+2] Cycloaddition
of Alkynyl Boronates to Indole and Pyrrole Double Bonds

Sabine Amslinger; Corinne Aubert; Vincent Gandon; Max Malacria; Elisa Paredes; K. Peter C. Vollhardt

doi:10.1055/s-2008-1077950

LETTER

Cobalt-Mediated [2+2+2] Cycloaddition of Alkynyl Boronates to Indole and Pyrrole Double Bonds

Sabine Amslinger^a, Corinne Aubert^b, Vincent Gandon^b, Max Malacria^b, Elisa Paredes^a, K. Peter C. Vollhardt*^a
^a Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720-1460, USA
Fax: +1(510)6435208; e-Mail: kpcv@berkeley.edu;
^b Laboratoire de Chimie Organique (UMR CNRS 7611), Institut de Chimie Moléculaire (FR 2769), Université Pierre et Marie Curie-Paris 6, case 229, 4 place Jussieu, 75252 Paris cedex 05, France

Abstract

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Abstract

The complex [CpCo(C₂H₄)₂] facilitates the [2+2+2] cycloaddition of borylalkynes to N-(4-pentynoyl)indole and -pyrrole to furnish heterocyclofused borylcyclohexadienes regioselectively.

Keywords

alkynes - cycloadditions - heterocycles - polycycles - transition metals

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References

References and Notes

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Other complexes based on Ru, Rh, and Ni, reported to effect the cocycloaddition of two alkyne units to double bonds, failed for these substrates. For recent leading references to such complexes, see:

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Indoles:

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Pyridones:

<A NAME="RS04608ST-6L">6l</A> Aubert C. Betschmann P. Eichberg MJ. Gandon V. Geny A. Heckrodt TJ. Lehmann J. Malacria M. Masjost B. Paredes E. Vollhardt KPC. Whitener GD. Chem. Eur. J. 2007, 13: 7443

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Representative Cyclization Conditions; Synthesis of 5: To a degassed solution of N-(4-pentynoyl) indole (1;^6g,¹4 197 mg, 1 mmol) and 4,4,5,5-tetramethyl-2-(3-methylbut-1-ynyl)[1,3,2]dioxaborolane (2; 242 mg, 1.25 mmol) in anhyd THF (15 mL) at 0 ˚C under an atmosphere of argon was added η⁵-cyclopentadienylbis(ethene)cobalt (150 mg, 0.833 mmol) in anhyd, degassed THF (6 mL) over a period of 3 h via syringe pump. The ensuing dark-red solution was treated with bright yellow Fe(NO₃)₃˙9H₂O (337 mg, 0.834 mmol) in THF-H₂O (5 mL, 3:1). After stirring for 5 min at 0 ˚C, the brown mixture was poured into iced water (50 mL) and the solution was extracted with CH₂Cl₂ (3 × 100 mL), followed by sat. aq NaHCO₃ (3 × 150 mL). The extracts were dried (MgSO₄), filtered through a short silica gel column to give a red-orange foam, and then subjected to flash chromatography on silica gel (hexanes-acetone, 9:1) to yield 5 (189 mg, 58%) as a white solid; mp 91-92 ˚C.
All new compounds gave satisfactory elemental analytical and/or HRMS data. For selected spectra, see: 3: ^¹H NMR (500 MHz, CDCl₃): δ = 1.21 (d, J = 7.0 Hz, 3 H, (CH ₃)₂CH], 1.25 (s, 6 H, Me), 1.32 (s, 6 H, Me), 1.48 [d, J = 6.5 Hz, 3 H, (CH ₃)₂CH], 1.80-1.85 (m, 1 H, CH₂), 1.98-2.03 (m, 1 H, CH₂), 2.52-2.66 [m, 3 H, CH₂, (CH₃)₂CH], 2.55 (d, J = 8.0 Hz, 1 H, CH), 3.24 (d, J = 7.5 Hz, 1 H, CH), 4.52 (s, 5 H, Cp), 5.01 (s, 1 H, CH), 6.98 (t, J = 7.5 Hz, 1 H, CH_arom), 7.23 (t, J = 7.5 Hz, 1 H, CH_arom), 7.77 (d, J = 7.5 Hz, 1 H, CH_arom), 8.20 (d, J = 7.5 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃): δ = 20.5, 24.5, 26.0, 26.1, 30.4, 31.5, 32.5, 45.2, 63.4, 64.9, 72.1, 81.1, 83.4, 106.4, 116.1, 122.8, 126.4, 127.6, 135.2, 142.7, 169.8; C-B not detected. MS (FAB, NBA): m/z (%) = 515 (100) [M⁺].
4: ^¹H NMR (500 MHz, CDCl₃): δ = 0.62 [d, J = 6.5 Hz, 3 H, (CH ₃)₂CH], 1.29 [d, J = 7.0 Hz, 3 H, (CH ₃)₂CH], 1.33 (s, 6 H, Me), 1.35 (s, 6 H, Me), 1.75-1.81 (m, 1 H, CH₂), 2.28 (m, 1 H, CH₂), 2.43-2.48 (m, 1 H, CH₂), 2.69-2.76 (m, 1 H, CH₂), 3.08 [sep, J = 6.5 Hz, 1 H, (CH₃)₂CH], 3.83 (d, J = 11.0 Hz, 1 H, CH), 4.41 (d, J = 11.5 Hz, 1 H, CH), 4.67 (s, 1 H, CH), 4.68 (s, 5 H, Cp), 6.83 (t, J = 7.0 Hz, 1 H, CH_arom), 6.99-7.04 (m, 2 H, CH_arom), 7.68 (d, J = 7.5 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃): δ = 19.5, 24.8, 25.5, 25.8, 29.5, 31.3, 33.3, 44.4, 62.1, 67.1, 76.3, 81.1, 82.8, 109.7, 115.5, 123.2, 124.4, 127.0, 133.6, 140.8, 169.8; C-B not detected. MS (FAB, NBA): m/z (%) = 515 (100) [M⁺].
5: ^¹H NMR (400 MHz, CDCl₃): δ = 0.93 [d, J = 6.8 Hz, 3 H, (CH ₃)₂CH], 0.96 [d, J = 6.8 Hz, 3 H, (CH ₃)₂CH], 1.32 (s, 6 H, Me), 1.35 (s, 6 H, Me), 2.47-2.57 (m, 2 H, CH₂), 2.65-2.81 (m, 2 H, CH₂), 3.46 [sep, J = 6.9 Hz, 1 H, (CH₃)₂CH], 4.57 (d, J = 12.8 Hz, 1 H, CH), 5.01 (dd, J = 1.2, 13.6 Hz, 1 H, CH), 5.88 (br s, 1 H, CH), 6.98 (t, J = 7.2 Hz, 1 H, CH_arom), 7.16 (t, J = 7.8 Hz, 1 H, CH_arom), 7.31 (d, J = 7.6 Hz, 1 H, CH_arom), 8.12 (d, J = 7.6 Hz, 1 H, CH_arom). ^¹³C NMR (101 MHz, CDCl₃): δ = 21.0, 21.5, 24.8, 25.1, 26.0, 30.9, 32.8, 41.2, 58.6, 83.3, 115.9, 118.4, 123.6, 124.4, 127.5, 133.8, 136.0, 140.1, 152.1, 170.2; C-B not detected. MS (70 eV, EI): m/z (%) = 391 (100) [M⁺], 286 (35), 260 (30). IR (neat): 2977, 1673, 1594, 1480, 1461, 1390, 1317, 1289, 1269, 1143, 1017, 857, 752, 732, 672 cm^-¹.
7: ^¹H NMR (500 MHz, CDCl₃): δ = 0.85 (t, J = 6.8 Hz, 3 H, Me), 1.25 (m, 8 H, CH₂), 1.32 (s, 6 H, Me), 1.35 (s, 6 H, Me), 2.19-2.23 (m, 1 H, CH₂), 2.47-2.58 (m, 3 H, CH₂), 2.66-2.79 (m, 2 H, CH₂), 4.57 (d, J = 14.0 Hz, 1 H, CH), 5.01 (d, J = 13.5 Hz, 1 H, CH), 5.70 (s, 1 H, CH), 6.97 (t, J = 7.0 Hz, 1 H, CH_arom), 7.15 (t, J = 7.8 Hz, 1 H, CH_arom), 7.33 (d, J = 7.5 Hz, 1 H, CH_arom), 8.12 (d, J = 8.0 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃): δ = 14.1, 22.6, 25.0, 25.7 (2 × C), 29.1, 29.8, 31.7, 32.7, 35.4, 41.2, 58.6, 83.3, 115.9, 123.6, 123.7, 124.5, 127.5, 133.5, 136.0, 140.1, 148.2, 170.3; C-B not detected. MS (70 eV, EI): m/z (%) = 433 (20) [M⁺], 432 (40), 431 (100), 361 (45), 285 (95). IR (neat): 2976, 2926, 2855, 1673, 1594, 1479, 1459, 1396, 1379, 1328, 1317, 1268, 1143, 1020, 857, 752 cm^-¹.
9: Diastereomer 1: ^¹H NMR (500 MHz, CDCl₃): δ = 1.32 (s, 6 H, Me), 1.36 (s, 6 H, Me), 1.50 (m, 2 H, CH₂), 1.57 (m, 2 H, CH₂), 1.68 (m, 1 H, CH₂), 1.80 (m, 1 H, CH₂), 2.52-2.58 (m, 2 H, CH₂), 2.67-2.80 (m, 2 H, CH₂), 3.44-3.50 (m, 1 H, CH₂), 3.83-3.89 (m, 1 H, CH₂), 4.20 (d, J = 11.5 Hz, 1 H, CH₂), 4.58-4.67 (m, 3 H, CH, CHO, CH₂), 5.04 (br d, J = 13.5 Hz, 1 H, CH), 6.00 (s, 1 H, CH), 6.97 (t, J = 7.5 Hz, 1 H, CH_arom), 7.17 (t, J = 7.8 Hz, 1 H, CH_arom), 7.34 (d, J = 7.5 Hz, 1 H, CH_arom), 8.14 (d, J = 8.0 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃): δ = 19.5, 25.0 (2 × C), 25.4, 25.9, 30.7, 32.7, 41.3, 58.5, 62.2, 67.5, 83.8, 97.7, 110.1 (br, C-B), 116.1, 120.9, 123.6, 24.4, 127.7, 133.7, 135.1, 140.1, 143.0, 170.1. MS (70 eV, EI): m/z (%) = 463 (16) [M⁺], 462 (6), 461 (10), 363 (32), 361 (52). IR (neat): 3053, 2977, 2941, 2870, 1671, 1595, 1480, 1460, 1391, 1381, 1321, 1269, 1202, 1142, 1076, 1022, 869, 754, 736 cm^-¹. Diastereomer 2: ^¹H NMR (500 MHz, CDCl₃): δ = 1.32 (s, 6 H, Me), 1.36 (s, 6 H, Me), 1.48-1.59 (m, 4 H, CH₂), 1.66-1.83 (m, 2 H, CH₂), 2.52-2.58 (m, 2 H, CH₂), 2.67-2.80 (m, 2 H, CH₂), 3.44-3.50 (m, 1 H, CH₂), 3.83-3.89 (m, 1 H, CH₂), 4.17 (d, J = 12.0 Hz, 1 H, CH₂), 4.58-4.67 (m, 3 H, CH, CHO, CH₂), 5.03 (d, J = 13.5 Hz, 1 H, CH), 6.00 (s, 1 H, CH), 6.97 (t, J = 7.5 Hz, 1 H, CH_arom), 7.17 (t, J = 7.8 Hz, 1 H, CH_arom), 7.36 (d, J = 8.0 Hz, 1 H, CH_arom), 8.14 (d, J = 8.0 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃): δ = 19.4, 24.9, 25.0, 25.4, 25.9, 30.5, 32.7, 41.3, 58.5, 62.1, 68.0, 83.8, 98.6, 110.2 (br, C-B), 116.1, 120.9, 123.6, 124.5, 127.7, 133.7, 135.2, 140.1, 143.3, 170.1.
11/12 mixture, major regioisomer 11: ^¹H NMR (400 MHz, CDCl₃): δ = 0.18 (s, 9 H, SiMe₃), 1.33 (s, 6 H, Me), 1.37 (s, 6 H, Me), 2.45-3.03 (m, 4 H, CH₂), 4.60 (d, J = 14.0 Hz, 1 H, CH), 5.01 (br d, J = 14.0 Hz, 1 H, CH), 6.01 (br s, 1 H, CH), 6.98 (t, J = 7.4 Hz, 1 H, CH_arom), 7.17 (t, J = 7.8 Hz, 1 H, CH_arom), 7.38 (d, J = 7.6 Hz, 1 H, CH_arom), 8.14 (d, J = 7.6 Hz, 1 H, CH_arom). ^¹³C NMR (101 MHz, CDCl₃): δ = 0.75, 24.6, 25.6, 26.1, 32.8, 42.1, 58.4, 83.9, 116.0, 122.7, 123.6, 124.6, 127.5, 130.8, 135.7, 140.2, 147.6, 170.5; C-B not detected. Minor regioisomer 12: ^¹H NMR (400 MHz, CDCl₃): δ = 0.36 (s, 9 H, SiMe₃), 1.25 (s, 6 H, Me), 1.26 (s, 6 H, Me), 2.45-3.03 (m, 4 H, CH₂), 4.52 (d, J = 12.8 Hz, 1 H, CH), 5.01 (dd, J = 1.6, 14.0 Hz, 1 H, CH), 6.11 (s, 1 H, CH), 6.98 (dt, J = 1.2, 7.4 Hz, 1 H, CH_arom), 7.17 (t, J = 7.8 Hz, 1 H, CH_arom), 7.38 (d, J = 7.6 Hz, 1 H, CH_arom), 8.14 (d, J = 7.6 Hz, 1 H, CH_arom). ^¹³C NMR (101 MHz, CDCl₃): δ = 1.38, 24.8, 25.0, 25.1, 32.7, 43.3, 59.5, 83.8, 115.7, 122.5, 123.5, 124.3, 127.8, 129.1, 134.9, 140.2, 147.6, 170.5; C-B not detected. MS (70 eV, EI): m/z (%) = 421 (52) [M⁺], 420 (66), 404 (28), 348 (22), 347 (20), 322 (30), 278 (65), 83 (100). IR (neat): 2979, 1667, 1594, 1537, 1481, 1460, 1398, 1317, 1247, 1216, 1142, 1091, 1058, 1020, 983, 960, 844, 755, 701, 667 cm^-¹.
14/15 mixture, major regioisomer 14: ^¹H NMR (500 MHz, CDCl₃): δ = 1.07 (s, 6 H, Me), 1.13 (s, 6 H, Me), 2.60 (m, 2 H, CH₂), 2.79 (m, 2 H, CH₂), 4.70 (d, J = 13.5 Hz, 1 H, CH), 5.11 (d, J = 13.5 Hz, 1 H, CH), 6.07 (br s, 1 H, CH), 7.05 (t, J = 7.5 Hz, 1 H, CH_arom), 7.20-7.40 (m, 6 H, CH_arom), 7.52 (d, J = 7.5 Hz, 1 H, CH_arom), 8.21 (d, J = 8.0 Hz, 1 H, CH_arom). Minor regioisomer 15: ^¹H NMR (500 MHz, CDCl₃): δ = 1.16 (s, 6 H, Me), 1.20 (s, 6 H, Me), 2.60 (m, 2 H, CH₂), 2.79 (m, 2 H, CH₂), 4.81 (d, J = 14.0 Hz, 1 H, CH), 5.17 (d, J = 14.0 Hz, 1 H, CH), 5.95 (br s, 1 H, CH), 6.67 (t, J = 7.5 Hz, 1 H, CH_arom), 7.12 (t, J = 7.5 Hz, 1 H, CH_arom), 7.20-7.40 (m, 6 H, CH_arom), 8.17 (d, J = 8.0 Hz, 1 H, CH_arom). ^¹³C NMR (126 MHz, CDCl₃; 14/15 mixture): δ = 24.2, 24.6 (2 × C), 24.7, 26.0, 26.1, 30.9, 32.8, 33.1, 36.6, 41.9, 44.0, 58.1, 58.9, 83.5, 83.6, 116.0, 116.2, 120.8, 123.0, 123.1, 123.8, 124.7, 125.0, 127.1, 127.2, 127.7, 127.8, 127.9 (2 × C), 129.0, 132.2, 132.4, 134.9, 140.2, 140.3, 141.4, 142.8, 144.7, 144.9, 169.4, 169.9; C-B (2 × C) not detected. MS (70 eV, EI):
m/z (%) = 425 (18) [M⁺], 424 (33), 423 (86), 307 (52), 297 (60), 169 (41), 84 (100). IR (neat): 3015, 2979, 2930, 1705, 1655, 1594, 1482, 1408, 1367, 1317, 1141, 1066, 1023, 853, 755, 702, 667 cm^-¹.
17: ^¹H NMR (500 MHz, CDCl₃): δ = 0.88 [d, J = 7.0 Hz, 3 H, (CH ₃)₂CH], 0.91 [d, J = 7.0 Hz, 3 H, (CH ₃)₂CH], 1.15 (s, 6 H, Me), 1.20 (s, 6 H, Me), 2.47 (m, 2 H, CH₂), 2.57 (dd,
J = 6.4, 14.3 Hz, 1 H, CH₂), 2.66 (dd, J = 6.4, 13.0 Hz, 1 H, CH₂), 3.34 [sep, J = 7.0 Hz, 1 H, (CH₃)₂CH], 4.18 (br d, J = 14.6 Hz, 1 H, CH), 4.70 (d, J = 14.4 Hz, 1 H, CH), 5.36 (m, 1 H, CH), 5.83 (br s, 1 H, CH), 6.80 (m, 1 H, CH). ^¹³C NMR (126 MHz, CDCl₃): δ = 21.2, 24.4, 24.7, 24.9, 26.6, 30.9, 31.6, 45.4, 55.5, 82.9, 117.4, 117.9, 125.0, 132.5, 150.8, 167.1; C-B not detected. MS (70 eV, EI): m/z (%) = 341 (12) [M⁺], 340 (11), 339 (30), 326 (11), 298 (10), 224 (6), 198 (8), 185 (9), 129 (16), 83 (100). IR (neat): 2976, 2872, 1716, 1643, 1518, 1468, 1412, 1371, 1220, 1144, 1110, 1078, 1016, 983, 951, 924, 885, 858, 831, 787, 744, 674 cm^-¹.
19: ^¹H NMR (500 MHz, CDCl₃): δ = 1.04 [d, J = 6.9 Hz, 6 H, (CH ₃)₂CH], 1.21 (s, 12 H, Me), 1.95 (quint, J = 6.0 Hz, 2 H, CH₂), 2.50 (sep, J = 7.0 Hz, 1 H, CH), 2.54 (td, J = 2.0, 6.0 Hz, 2 H, CH₂), 3.95 (t, J = 6.0 Hz, 2 H, CH₂), 5.38 (s, 1 H, CH), 6.16 (m, 1 H, CH), 6.42 (m, 1 H, CH), 6.59 (m, 1 H, H-2), 6.61 (br s, 1 H, CH). ^¹³C NMR (126 MHz, CDCl₃): δ = 21.7, 23.9, 24.9, 25.6, 37.2, 45.5, 82.7, 103.1, 108.3, 119.9, 120.7, 129.6, 131.8, 165.0; C-B not detected. MS (70 eV, EI): m/z (%) = 327 (10) [M⁺], 312 (10), 284 (26), 184 (40), 59 (100). IR (neat): 3100, 2972, 2871, 1695, 1620, 1458, 1380, 1331, 1259, 1107, 1077, 970, 851, 756, 722, 667 cm^-¹.

<A NAME="RS04608ST-13A">13a</A> Grotjahn DB. Vollhardt KPC. J. Am. Chem. Soc. 1990, 112: 5653

<A NAME="RS04608ST-13B">13b</A> Grotjahn DB. Vollhardt KPC. Synthesis 1993, 579

Aechtner, T.; Barry, D. A.; Grotjahn, D. B.; Vollhardt, K. P. C. unpublished results.

<A NAME="RS04608ST-14">14</A> The acylation of indole was modified from that described in ref. 6b, according to: Teranishi K. Nakatsuka S. Goto T. Synthesis 1994, 1018