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Synlett 2003(12): 1778-1782  
DOI: 10.1055/s-2003-41471
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New and Practical Procedure for the Bruylants Reaction. Zinc-Mediated Synthesis of Tertiary Homoallylamines and β-Aminoesters

Luca Bernardi*, Bianca F. Bonini, Elena Capitò, Gabriella Dessole, Mariafrancesca Fochi, Mauro Comes-Franchini, Alfredo Ricci*
Dipartimento di Chimica Organica ‘A. Mangini’, Facoltà di Chimica Industriale, Università di Bologna, V. Risorgimento 4, 40136 Bologna, Italy
Fax: +39(51)2093654; e-Mail: nacca@ms.fci.unibo.it;
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Publication History

Received 23 June 2003
Publication Date:
19 September 2003 (online)

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Abstract

N,N-Disubstituted α-aminonitriles undergo Bruylants reaction under Barbier and Reformatsky conditions with activated halides, in the presence of zinc and 10 mol% HOAc. The high yields and the simple operational conditions make this reaction an appealing approach to N,N-disubstituted homoallylamines and β-aminoesters.

Key words

α-aminonitriles - Bruylants reaction - tertiary amines - zinc - metathesis

    References

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8

The cyanoboranes were obtained, according to ref. [3] , using a one pot procedure starting from the corresponding N-silylamines, BCl3 and TMSCN, and were directly used after evaporation of the solvent, without purification.

10

Zinc-Mediated Bruylants Reaction - General procedure: To a stirred solution of the α-aminonitrile 1 (0.5 mmol) in dry THF (1 mL) were sequentially added allyl bromide or ethyl bromoacetate (1 mmol), zinc dust (1 mmol), and HOAc (0.05 mmol in 0.05 mL of dry THF). A slightly exothermic reaction occurred. The mixture was stirred at r.t. for 2 h, quenched with sat. Na2CO3 and then extracted three times with Et2O. The organic extracts were dried (MgSO4), filtered, evaporated and the crude product purified by chromatography on silica gel or neutral Al2O3 (hexane/EtOAc mixtures). Selected data for representative examples: 1-(1-Phenyl-3-butenyl)-pyrrolidine ( 2a). Colourless oil. 1H NMR (300 MHz, CDCl3): δ = 7.22-7.05 (m, 5 H), 5.53-5.39 (m, 1 H), 4.90-4.72 (m, 2 H), 3.06 (dd. J = 4.2, 9.3 Hz, 1 H), 2.65-2.55 (m, 1 H), 2.52-2.40 (m, 3 H), 2.38-2.20 (m, 2 H), 1.79-1.60 (m, 4 H). 13C NMR (70 MHz, CDCl3): δ = 142.5, 135.4, 128.2, 128.0, 126.9, 116.4, 70.9, 52.7, 40.5, 23.2. HRMS: exact mass calcd for C14H19N [M + Na]+ 224.1415. Found: 224.1399. N -Allyl- N -benzyl-1-cyclohexyl-3-buten-1-amine ( 2h). Colourless oil. 1H NMR (300 MHz, CDCl3): δ = 7.30-7.08 (m, 5 H), 5.96-5.60 (m, 2 H), 5.17-4.80 (m, 4 H), 3.79 (d, J = 14.4 Hz, 1 H), 3.54 (d, J = 14.1 Hz, 1 H), 3.22 (ddt, J t = 1.7 Hz, J d = 4.9 Hz, J d = 14.2 Hz, 1 H), 3.08 (dd, J = 7.5 Hz, J = 14.4 Hz, 1 H), 2.42-2.22 (m, 2 H), 2.18-2.03 (m, 1 H), 2.00-1.90 (m, 1 H), 1.70-1.50 (m, 4 H), 1.45-1.30 (m, 3 H), 1.22-0.71 (m, 3 H). 13C NMR (70 MHz, CDCl3): δ = 141.0, 139.0, 138.0, 128.7, 128.0, 126.5, 116.1, 115.1, 62.9, 54.4, 53.6, 40.7, 32.1, 31.1, 31.0, 26.7, 26.6. HRMS: exact mass calcd for C20H29N [M + H]+ 284.2378. Found: 284.2388. Ethyl 3-Phenyl-(1-pyrrolidinyl)propanoate ( 3h). Colourless oil. 1H NMR (300 MHz, CDCl3): δ = 7.34-7.05 (m, 5 H), 3.88 (q, J = 7.2 Hz, 2 H), 3.63 (dd. J = 5.7, 9.0 Hz, 1 H), 2.90 (dd. J = 5.7, 14.7 Hz, 1 H), 2.63 (dd. J = 9.0, 14.7 Hz, 1 H), 0.99 (t, J = 7.2 Hz, 3 H). 13C NMR (70 MHz, CDCl3): δ = 171.5, 141.5, 128.1, 128.0, 127.4, 66.4, 60.2, 52.1, 41.6, 23.2, 13.9. IR (thin layer): ν = 1728 cm-1. HRMS: exact mass calcd for C15H21NO2 [M + H]+ 248.1651. Found: 248.1667. Ethyl 3-[Allyl(benzyl)amino]-3-cyclohexylpropanoate ( 3h). Colourless oil. 1H NMR (300 MHz, CDCl3): δ = 7.40-7.18 (m, 5 H), 5.89-5.86 (m, 1 H), 5.21-5.02 (m, 2 H), 4.14 (q, J = 7.2 Hz, 2 H), 3.75 (d, J = 14.1 Hz, 1 H), 3.43 (d, J = 14.1 Hz, 1 H), 3.18 (m, 1 H), 3.01-2.86 (m, 2 H), 2.58 (dd, J = 5.1 Hz, J = 15.0 Hz, 1 H), 2.26 (dd, J = 7.2 Hz, J = 15.0 Hz, 1 H), 2.18-2.14 (m, 1 H), 1.80-1.58 (m, 4 H), 1.40-1.05 (m, 3 H), 1.25 (t, J = 7.2 Hz, 3 H), 0.98-0.80 (m, 2 H). 13C NMR (70 MHz, CDCl3): δ = 173.8, 140.3, 137.3, 128.8, 128.0, 126.6, 116.6, 61.0, 60.3, 54.1, 53.1, 41.1, 33.3, 31.0, 30.3, 26.5, 26.4, 26.3, 14.2. IR (thin layer): ν = 1734 cm-1. HRMS: exact mass calcd for C21H31NO2 [M + Na]+ 352.2252. Found: 352.2237.

16

To a solution of homoallylamine 2 (0.11 mmol) in dry, degassed toluene (3.5 mL) was added ruthenium alkylidene 5 (4 mol%). The solution was stirred at 85 °C for 4 h 30 min, then pentane was added, followed by celite and charcoal. The mixture was stirred at r.t. overnight, then filtered and concentrated. Chromatography on silica gel (hexane/EtOAc) afforded tetrahydropyridines 6.