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Synlett 2012(4): 565-568  
DOI: 10.1055/s-0031-1290335
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Au(I)-Catalysed Allenamide Cyclisation Giving Access to an α-Vinyl-Substituted Tetrahydroisoquinoline Building Block

Sanjitpal Singh, Mark R. J. Elsegood, Marc C. Kimber*
The Department of Chemistry, Loughborough University, Loughborough, Leicester, LE11 3TU, UK
Fax: +44(150)9223925; e-Mail: M.C.Kimber@lboro.ac.uk;
Further Information

Publication History

Received 29 November 2011
Publication Date:
06 February 2012 (online)

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Abstract

An Au(I)-catalysed intramolecular hydroarylation of an enantiopure allenamide has been achieved and has given access to a key α-vinyl-substititued tetrahydroisoquinoline. Additionally this has been accomplished in very high yield and high diastereoselectivity.

Key words

alkaloids - allenamide - tetrahydroisoquinoline - Au(I) catalysis - diastereoselective

13

( S )-4-(3,4-Dimethoxybenzyl)-3-(propa-1,2-dienyl) oxazolidin-2-one (22)
To a solution of 15 (0.58 g, 2.45 mmol) in THF (20 mL) at 0 ˚C under an N2 atmosphere was added NaH (0.12 g, 2.93 mmol), and the mixture stirred at r.t. for 2 h. After this period propargyl bromide (0.32 mL, 2.88 mmol) was added cautiously, and the reaction mixture was stirred for a further 24 h at r.t. After this period sat. NH4Cl was added, and the resultant aqueous layer was extracted with Et2O (2×). The combined organic layers were then washed with brine, dried (Na2SO4), filtered, and the solvent removed in vacuo. The crude product was then dissolved in THF (20 mL) and cooled to 0 ˚C followed by addition of KOt-Bu (0.08 g, 0.66 mmol). The reaction mixture was then stirred for 2 h at 0 ˚C after which all the starting material had been consumed. The reaction mixture was then diluted with Et2O and washed sequentially with H2O and brine. The combined organic layers were then dried (Na2SO4), filtered, and the solvent removed in vacuo. The crude product was then purified by column chromatography (R f  = 0.55, EtOAc-PE = 1:1) yielding the title compound as a colourless solid (0.40 g, 60%); mp 118-120 ˚C (from CH2Cl2-PE). IR (solution, CHCl3): νmax = 3021, 1752, 1516, 1461, 1409, 1262, 1226, 1028 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.84 (t, J = 6.8 Hz, 1 H), 6.76-6.73 (m, 1 H), 6.64-6.62 (m, 1 H), 6.58 (d, J = 1.6 Hz, 1 H), 5.51 (dd, J = 6.4, 10.0 Hz, 1 H), 5.44 (dd, J = 6.4, 10.0 Hz, 1 H), 4.20 (t, J = 8.4 Hz, 1 H), 4.08 (dd, J = 3.6, 8.8 Hz, 1 H), 4.05-4.00 (m, 1 H), 3.80 (s, 3 H), 3.79 (s, 3 H), 3.06 (dd, J = 3.2, 14.0 Hz, 1 H), 2.65 (dd, J = 8.8, 14.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 201.7 (C), 155.0 (C), 149.2 (C), 148.3 (C), 127.7 (C), 121.4 (CH), 112.4 (CH), 111.5 (CH), 111.5 (CH), 96.0 (CH), 87.9 (CH2), 66.6 (CH2), 56.0 (CH3), 55.7 (CH3), 36.6 (CH2). HRMS: m/z calcd for C15H17NO4 [MNa+]: 298.1055; found: 298.1045. [α]D ²¹ +20.3 (c 1.00, CHCl3).

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Crystal Data for 22
C15H17NO4, M = 275.30, orthorhombic, space group P212121, a = 7.2379 (10), b = 11.5884 (15), c = 16.677 (2) Å, V = 1398.8 (3) ų, T = 150 K, Z = 4, µ (Mo Kα) = 0.095 mm-¹, 14225 data measured using a Bruker APEX 2 CCD diffractometer with graphite-monochromated Mo Kα radiation (λ = 0.71073 Å); 2026 data were unique, R int = 0.0329; all unique data used in refinement against
F ² values to give final wR2 = 0.0885 (on F ² for all data), R = 0.0338 [for 1831 data with F ² > 2σ(F ²)], absolute structure could not be determined from the diffraction data; Friedel pairs were merged. H atoms on C(6) had coordinates freely refined; all other H atoms were constrained. Programs used were Bruker SMART,¹6 SAINT,¹6 SHELXTL,¹7,¹8 and local programs. CCDC 838703 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

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To a solution of 22 (100 mg, 0.36 mmol) in CH2Cl2 (2 mL) at r.t. was added a 5 mol% solution of AuPPh3OTf. [NB: The 5 mol% solution of AgPPh3OTf was prepared from the addition of AuClPPh3 (9 mg, 0.018 mmol) to AgOTf (4.7 mg, 0.018 mmol) in CH2Cl2 (1 mL), and the resultant suspension was stirred for 10 min at r.t.]. After 5 min the starting material was consumed after which the solvent was removed in vacuo. The crude product was then purified by column chromatography (R f  = 0.25, 1:1 EtOAc-PE) to yield 23 as a colourless oil (98 mg, quant.). IR (solution, CHCl3): νmax = 3020, 2936, 1749, 1613, 1518, 1420, 1226, 1115 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.62 (s, 1 H), 6.58 (s, 1 H), 5.98-5.90 (m, 1 H), 5.29-5.24 (m, 3 H), 4.57-4.52 (t, J = 8.4 Hz, 1 H), 4.15-4.12 (dd, J = 8.4, 8.8 Hz, 1 H), 4.05-3.99 (m, 1 H), 3.89 (s, 3 H), 3.84 (s, 3 H), 2.83 (d, J = 7.7 Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 156.7 (C), 148.3 (C), 148.0 (C), 136.4 (CH), 125.2 (C), 127.7 (C), 117.5 (CH2), 111.6 (CH), 110.4 (C), 68.5 (CH2), 56.0 (CH3), 55.9 (CH3), 54.7 (CH2), 48.6 (C), 33.8 (CH2). HRMS: m/z calcd for C15H17NO4 [MNa+]: 298.1055; found: 298.1044. [α]D ²¹
-160.8 (c 1.00, CHCl3).