Eric S. Sherman and Sherry R. Chemler
UPDATE
Representative Method for Aminoacetoxylation
Reactions
1-Phenyl-1,2,3,4-tetrahydroquinolin-3-yl acetate (2a) and 1-
phenyl-2,3-dihydro-1H-indol-2-ylmethyl acetate (3a): N-
Phenyl-2-allylaniline (1a) (42.0 mg, 0.200 mmol, 1 equiv.)
was dissolved in 1.7 mL DMF in a pressure tube equipped
with a magnetic stir bar. CuACHTNUGRTENUNG(OAc)2 (109 mg, 0.600 mmol,
3 equiv.) and Cs2CO3 (65.2 mg, 0.200 mmol, 1 equiv.) were
added. The tube was sealed and heated to 1208C for 24 h.
After cooling, the mixture was diluted with Et2O and fil-
tered through a pad of silica gel with additional Et2O. The
filtrate was concentrated under vacuum to give the crude
oil. This oil was purified by flash chromatography on silica
gel (13% Et2O in hexanes) to provide the aminoacetoxyla-
tion products as a 4.5:1 mixture of regioisomers favoring the
6-member ring product; yield: 41.6 mg (0.156 mmol, 78%).
The regioisomers were separated by HPLC (5% EtOAc in
hexanes) to give the pure products with the major isomer
eluting first, both products as yellow oils.
Data for 1-phenyl-1,2,3,4-tetrahydroquinolin-3-yl acetate
(2a): 1H NMR (400 MHz, CDCl3): d=7.30–7.35 (m, 2H),
7.20 (d, J=7.6 Hz, 2H), 7.06–7.10 (m, 2H), 6.97 (m, 1H),
6.75–6.80 (m, 2H), 5.30 (m, 1H), 3.72–3.76 (m, 2H), 3.17
(dd, J=6.0, 21 Hz, 1H), 2.96 (dd, J=6.5, 22 Hz, 1H), 1.96
(s, 3H); 13C NMR (125 MHz, CDCl3): d=170.7, 147.9, 143.6,
129.9, 129.4, 126.7, 124.2, 123.7, 121.3, 119.2, 116.2, 67.1,
52.9, 32.8, 21.1; IR (neat, thin film): n=2924, 2856, 1738,
1652, 1565, 1481, 1455, 1375 cmÀ1; HR-MS: m/z=268.1339,
calcd. for C17H18NO2 [M+H]+: 268.1332.
per(II) acetate is also an effective catalyst for the car-
boamination reaction, we believed that it would be
possible to perform both the coupling and carboami-
nation in a single pot. Towards that end, 2-allylaniline
was treated with 20 mol% copper(II) acetate, 40
mol% myristic acid, 1.1 equiv. of phenylboronic acid,
and 1 equiv. of cesium carbonate at room temperature
for 24 h in toluene.[12] The toluene was then removed
under vacuum and replaced with a,a,a-trifluoroto-
luene. Manganese dioxide (3 equiv.) and cesium car-
bonate (1 equiv.) were added, and the mixture was
stirred at 1208C for 24 h, resulting in good overall
yield (55%) for the two-step process [Eq (7)]. The
solvent had to be changed because the carboamina-
tion reaction does not proceed efficiently in toluene,
while the coupling does not proceed efficiently in
Data for 1-phenyl-2,3-dihydro-1H-indol-2-ylmethyl ace-
1
tate (3a) from a 1.2:1 mixture of 3a:2a: H NMR (400 MHz,
C6D6): d=6.70–7.24 (m, 9H), 4.23 (dd, J=4.6, 11.2 Hz, 1H),
4.11 (m, 1H), 3.88 (dd, J=6.4, 11.6 Hz, 1H), 2.58–2.91 (m,
2H), 1.51 (s, 3H); 13C NMR (75 MHz, CDCl3): d=170.9,
148.3, 143.8, 129.9, 129.0, 127.3, 125.0, 123.2, 121.3, 119.3,
109.5, 65.2, 62.6, 32.6, 20.7; IR (neat, thin film): n=2921,
2851, 1736, 1676, 1513, 1456, 1247 cmÀ1.
a,a,a-trifluorotoluene.
In conclusion, we have developed methods for the
aminoacetoxylation, aminooxygenation and carboami-
nation of N-aryl-2-allylanilines. The aminoacetoxyla-
tion, promoted by stoichiometric copper(II) gives pre-
dominately tetrahydroquinoline products, whereas the
copper(II)-catalyzed aminooxygenation reaction with
TEMPO gives solely the dihydroindoline products. In
this study the scope of the copper(II)-catalyzed car-
boamination and aminooxygenation reactions have
been increased to include N-arylaniline substrates and
more mechanistic possibilities for this class of copper-
facilitated reactions have been observed.
Representative Method for Carboamination
10a,11-Dihydro-10H-indoloACTHNUGTRENNUG[1,2-a]indole (4a): CuACHTUNGTRENNUNG(OTf)2
(13.8 mg, 0.038 mmol, 0.20 equiv.) was added to 1 mL PhCF3
in a pressure tube equipped with a magnetic stirrer. To this
was added 2,2’-bipyridyl (7.4 mg, 0.049 mmol, 0.25 equiv.).
The resulting mixture was heated to 608C for 2 h. N-phenyl-
2-allylaniline (1a) (40.0 mg, 0.191 mmol, 1 equiv.) was dis-
solved in 0.9 mL PhCF3 and added. Cs2CO3 (62.2 mg,
0.191 mmol, 1 equiv.) and MnO2 (49.5 mg, 0.573 mmol,
3 equiv.) were added. The tube was sealed and the mixture
was heated to 1208C for 24 h. After cooling, the mixture
was diluted with Et2O and filtered through a pad of silica
gel. The filtrate was concentrated under vacuum to provide
the crude oil. Purification by flash chromatography on silica
gel (2% Et2O in hexanes) provided the product as a red oil;
yield: 34.4 mg (0.166 mmol, 87%).
Experimental Section
1
Data for (4a): H NMR (400 MHz, CDCl3): d=7.15–7.17
For experimental details and spectral data for all new com-
pounds, see the Supporting Information.
(m, 6H), 6.88–6.93 (m, 3H), 4.88 (m, 1H), 3.35 (dd, J=9.5,
16.0 Hz, 2H), 3.08 (dd, J=7.5, 16.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3): d=148.8, 132.3, 127.5, 125.0, 121.6, 112.9,
65.2, 36.6; IR (neat, thin film): n=3023, 2907, 1599, 1489,
1200, 1169, 1073, 810, 746 cmÀ1; HR-MS: m/z=207.1040,
calcd. for C15H13N [M]+: 207.1043.
470
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 467 – 471