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DOI: 10.1055/s-0029-1219561
An Aromatic Amination Approach towards Ancistrocladinium A/B
Publication History
Publication Date:
02 March 2010 (online)
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Abstract
We report a high yielding approach to N-aryl tetrahydroisoquinolines and tetrahydroquinolines in one step from readily available starting materials. We have used this methodology to prepare the full carbon skeleton of the ring system of ancistrocladinium A in one step.
Key words
amination - natural products - palladium - Buchwald-Hartwig - tetrahydroquinoline - tetrahydroisoquinoline
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References and Notes
General Procedure
A
50 mL round-bottomed flask was charged with Pd2(dba)3 (0.088
mmol), (±)-BINAP (0.18 mmol), and toluene (6 mL). The resulting
solution was degassed for 10 min before being heated to 110 ˚C
for 15 min. The reaction mixture was allowed to cool to r.t. before
NaOt-Bu (4.1 mmol), the aryl bromide
(2.2 mmol), and tetrahydroquinoline or tetrahydroisoquinoline (4.4
mmol) were added. The resulting mixture was heated under reflux
for 4-16 h, before being cooled to r.t. and filtered through
a pad of Celite®. Solvents were removed under
reduced pressure and the crude material purified by column chromatography
(silica gel, 99:1 light PE-EtOAc).
Data
for Compound 9
Colorless solid, 99% yield
(0.56 g). IR (thin film): νmax = 1627,
1265, 740 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 3.04 (2 H,
t, J = 11.6 Hz, CH2CH
2), 3.67 (2 H, t, J = 11.6 Hz, CH2CH
2), 4.51 (2 H, s, CH2),
7.17-7.21 (5 H, m, ArH), 7.26-7.28 (1 H, m, ArH),
7.33-7.36 (1 H, m, ArH), 7.39-7.41 (1 H, m, ArH),
7.76-7.68 (3 H, m, ArH). ¹³C
NMR (100 MHz, CDCl3): δ = 29.19 (CH2),
47.18 (CH2), 51.13 (CH2), 109.37 (ArCH), 118.73
(ArCH), 123.01 (ArCH), 126.10 (ArCH), 126.29 (ArCH), 126.42 (ArCH),
126.58 (ArCH), 126.60 (2 ArCH), 127.46 (ArCH), 128.07 (ArC), 128.64 (ArCH),
128.84 (ArCH), 134.36 (ArC), 134.76 (ArC), 148.39 (ArCN). MS (FAB+): m/z (%) = 259
(100) [M+], 258 (64). HRMS
(ES): m/z calcd for [C19H17N]:
259.1361; found [M+]: 259.1365.
We have found that isolation of isoquinolinium salts as crystalline solids can be easily achieved when counterion exchange with sodium tetraphenylborate is carried out. See, for example, ref. 7a.
14
Crystal Data for
18
C19H17N, M = 259.34, a = b = 7.0515
(8), c = 28.297
(3) Å, α = β = γ = 90˚, V = 1407.0(3) ų.
pale yellow crystal, 1.04 × 0.47 × 0.25
mm³, D
calc = 1.224
g cm-³, µ = 0.071 mm-¹;
13580 data, 1247 unique (R
int = 0.0757).
Data were measured on a Bruker APEX II diffractometer with MoKα radiation
at 150 K.
[¹5]
Data were corrected
for absorption. The structure was solved by direct methods and refined
on F
² values.
[¹6]
[¹7]
Half
the molecule is unique and the structure is 50/50 disordered
at C(2A)/C(2X) and at N(1)/C(10). R = 0.0489 [for
1134 observed data with F
² > 2σ(F
²)] and wR = 0.1278
(for all data). Crystal data have been deposited with the Cambridge
Crystallographic Data Centre. CCDC: 758059. Data can be retrieved
in CIF format by quoting the relevant deposition number in an e-mail
request to deposit@ccdc.cam.ac.uk.
SAINT and APEX 2 (2008) software for CCD diffractometers. Bruker AXS Inc., Madison, USA.