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Synlett 2010(6): 939-943  
DOI: 10.1055/s-0029-1219561
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Aromatic Amination Approach towards Ancistrocladinium A/B

Benjamin R. Buckleya, Steven D. R. Christie*a, Mark R. J. Elsegooda, Claire M. Gillingsa, Philip C. Bulman Page*b, William J. M. Pardoea
a Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK
Fax: +44(1509)223925; e-Mail: s.d.christie@lboro.ac.uk;
b School of Chemistry, University of East Anglia, Norwich, Norfolk NR4 7TJ, UK
Fax: +44(1603)593008; e-Mail: p.page@uea.ac.uk;
Further Information

Publication History

Received 18 December 2009
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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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.

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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.

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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.

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SAINT and APEX 2 (2008) software for CCD diffractometers. Bruker AXS Inc., Madison, USA.