Ruthenium-Catalyzed Functionalization of Pyrroles and Indoles
FULL PAPER
a FINNIGAN MAT 91. The intensity data of 1Ba were collected on
a STOE & CIE IPDS 2T diffractometer with MoKa radiation. The data
were collected with the STOE & CIE X-AREA[8a] program by using w-
scans. The space group was determined with the X-RED32[8a] program.
The structure was solved by direct methods (SHELXS-97)[8b] and refined
by full-matrix least-squares methods on F2 by using SHELXL-97.[8c] Cata-
lysts 1Aa and 1Ba (except for the crystal structure) have previously been
published.[4b] CCDC-853116 (1Ba)[6] contains the supplementary crystal-
lographic data for this paper. These data can be obtained free of charge
ac.uk/data_request/cif.
General catalytic procedure: Catalyst 1Ba (0.02 mmol) was dissolved in
toluene (1 mL) and TFA diluted in toluene (0.02 mmol, 1m), the proparg-
yl alcohol (1 mmol) and the pyrrole (1 mmol) or indole (1 mmol) were
subsequently added. The mixture was stirred at 1008C for 4 or 8 h under
argon. Evaporation of the solvent and flash column chromatography on
silica furnished the purified products.
Data of selected compounds
Compound 2c (C15H15NO): 1H NMR (400 MHz, CDCl3): d=3.03 (t, J=
7.0 Hz, 2H), 3.06 (t, J=7.0 Hz, 2H), 5.91 (brs, 1H), 6.32 (brs, 1H), 6.76
(brs, 1H), 6.80 (d, J=16.0 Hz, 1H), 7.27–7.59 (m, 5H), 7.64 (d, J=
16.0 Hz, 1H), 8.80 ppm (brs; N H); 13C NMR (100 MHz, DEPT,
À
CDCl3): d=21.7 (CH2), 40.9 (CH2), 104.7 (CH), 107.7 (CH), 117.5 (CH),
125.8 (CH), 128.1 (CH), 128.7 (CH), 130.2 (CH), 130.3 (C), 134.1 (C),
142.6 (CH), 200.1 ppm (C); IR: n˜ =3346 (m), 3057 (m), 3025 (m), 2922
(m), 2040 (w), 1965 (w), 1686 (s), 1655 (s), 1608 (s), 1575 (s), 1494 (s),
1449 (s), 1337 (s), 1178 (s), 1096 (s), 974 (s), 750 (s), 697 cmÀ1 (s); MS
(EI): m/z (%): 225 [M+] (22), 149 (39), 131 (100), 105 (57), 103 (80), 93
(30), 91 (31), 77 (80); HRMS: m/z calcd for C15H15NO: 225.1154 [M+];
found: 225.1151.
Scheme 16. Proposed mechanisms regarding the catalytic transformations
of 1-vinyl propargyl alcohols.
Compound 3c[9a] (C19H17NO): 1H NMR (400 MHz, CDCl3): d=3.13 (t,
J=6.8 Hz, 2H), 3.23 (t, J=6.8 Hz, 2H), 6.78 (d, J=16.4 Hz, 1H), 6.99
(brs, 1H), 7.19–7.51 (m, 8H), 7.57 (d, J=16.4 Hz, 1H), 7.70 (d, J=
hols catalyzed by ruthenium complex 1Ba. The reaction
pathway depends on the alcoholsꢀ substitution pattern.
Three fundamentally different modes of activation can be
distinguished. Secondary substrates form alkenyl complexes
by a 1,2-hydrogen shift, whereas the transformation of terti-
ary substrates involves allenylidene intermediates. The over-
all reactions lead to the formation of b-heteroarylated ke-
tones in the former and to propargylated heteroaromatics in
the latter case. 1-Vinyl propargyl alcohols are converted by
a cascade allylation/cyclization sequence to yield cycloaddi-
tion products in the presence of the binucleophilic pyrroles
or indoles. The stepwise combination of these transforma-
tions allows the selective synthesis of highly functionalized
pyrroles and indoles by using a single pre-catalyst and gen-
erating water as the only waste product. Further investiga-
tions regarding the reaction mechanisms, scope, and limita-
tions focused on sequential catalyzed processes and asym-
metric catalytic applications by the use of axial-chiral mem-
bers of the series of complexes 1B are currently under in-
vestigation.
7.6 Hz, 1H), 8.16 ppm (brs; N H); 13C NMR (100 MHz, DEPT, CDCl3):
À
d=19.8 (CH2), 41.2 (CH2), 111.2 (CH), 115.0 (C), 118.6 (CH), 119.1
(CH), 121.6 (CH), 121.8 (CH), 126.2 (CH), 127.1 (C), 128.2 (CH), 128.8
(CH), 130.4 (CH), 134.3 (C), 136.3 (C), 142.6 (CH), 200.3 ppm (C); IR:
n˜ =3400 (s), 3055 (m), 3024 (m), 2924 (m), 2070 (w), 2006 (w), 1958 (w),
1686 (s), 1655 (s), 1607 (s), 1576 (s), 1493 (m), 1457 (s), 1413 (m), 1338
(m), 1180 (s), 1095 (w), 977 (m), 742 (s), 700 (m), 690 cmÀ1 (m); MS (EI):
m/z (%): 275 [M+] (100), 257 (75), 144 (98), 130 (86), 105 (38), 103 (37),
77 (40), 61 (39), 60 (48); HRMS: m/z calcd for C19H17NO: 275.1310 [M+
]; found: 275.1310.
Compound 4a (C12H15N): 1H NMR (400 MHz, CDCl3): d=1.60 (s, 3H),
1.80–1.85 (m, 2H), 1.99–2.05 (m, 2H), 2.40 (s, 1H), 4.94 (dd, J=10.4,
1.2 Hz, 1H), 5.01 (dd, J=16.8, 1.2 Hz, 1H), 5.80 (ddt, J=16.8, 10.4,
6.4 Hz, 1H), 6.01 (brs, 1H), 6.19 (brs, 1H), 6.69 (brs, 1H), 8.46 ppm
(brs; N H); 13C NMR (100 MHz, DEPT, CDCl3): d=29.3 (CH3), 29.8
À
(CH2), 35.8 (C), 43.0 (CH2), 71.0 (CH), 87.9 (C), 102.9 (CH), 108.7 (CH),
114.4 (CH2), 115.8 (CH), 135.0 (C), 138.2 ppm (CH); IR: n˜ =3420 (m),
3304 (s), 2950 (s), 2868 (s), 2104 (w), 1694 (s), 1466 (s), 1098 (w), 1039
(m), 990 (m), 922 (m), 787 (m), 720 cmÀ1 (s); MS (EI): m/z (%): 173
[M+] (58), 158 (15), 130 (100), 117 (39); HRMS: m/z calcd for C12H15N:
173.1204 [M+]; found: 173.1204.
Compound 6a[9b] (C10H11N): 1H NMR (400 MHz, CDCl3): d=2.47 (s,
3H), 2.58 (s, 3H), 6.63 (brs, 1H), 7.11 (d, J=8.4 Hz, 1H), 7.16 (brs, 1H),
7.18 (d, J=8.4 Hz, 1H), 8.05 ppm (brs; N H); 13C NMR (100 MHz,
À
DEPT, CDCl3): d=15.4 (CH3), 19.2 (CH3), 100.7 (CH), 108.1 (CH),
123.7 (CH), 124.5 (CH), 125.3 (C), 127.4 (C), 128.4 (C), 134.1 ppm (C);
IR: n˜ =3392 (s), 2922 (s), 2856 (s), 2274 (w), 1991 (w), 1656 (s), 1485 (s),
1451 (s), 1328 (s), 1240 (s), 1153 (s), 1091 (s), 873 (w), 802 (m), 768 (s),
725 (s), 606 (w), 555 (w), 521 cmÀ1 (w); MS (EI): m/z (%): 145 [M+]
(100), 144 (78), 130 (95); HRMS: calcd for C10H11N: 145.0891 [M+];
found: 145.0891.
Compound 15c (C22H27N): 1H NMR (400 MHz, CDCl3): d =0.80–0.83
(m, 3H), 1.18–1.24 (m, 4H), 1.32–1.39 (m, 2H), 1.44–1.52 (m, 2H), 1.80
(s, 3H), 2.29 (t, J=7.0 Hz, 2H), 5.16 (d, J=9.8 Hz, 1H), 5.76 (brs, 1H),
5.88 (d, J=9.9 Hz, 1H), 6.05 (dd, J=5.7, 2.9 Hz, 1H), 6.61 (brs, 1H),
Experimental Section
General methods: All reactions were carried out in a dry atmosphere
under argon by using standard Schlenck techniques. The chemicals used
were dried and purified according to common procedures. Products were
identified by spectroscopic analysis (1H NMR, 13C NMR, IR, MS,
HRMS). IR spectra were obtained on a Perkin–Elmer FTIR 2000. NMR
spectra were recorded on
a BRUKER DPX 400 or a BRUKER
AVANCE 600 spectrometer. MS and HRMS data were obtained on
Chem. Eur. J. 2012, 18, 6302 – 6308
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6307