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Synlett 2007(10): 1521-1524  
DOI: 10.1055/s-2007-982542
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Access to Kainic Acid via Intramolecular Palladium-Catalyzed Allylic Alkylation

Mathieu Bui The Thuonga, Silvia Sottocornolaa, Guillaume Prestata, Gianluigi Brogginib, David Madec*a, Giovanni Poli*a
a Université Pierre et Marie Curie-Paris 6, Laboratoire de Chimie Organique (UMR CNRS 7611), Institut de Chimie Moléculaire (FR 2769), case 183, 4 place Jussieu, 75252 Paris cedex 05, France
b Dipartimento di Scienze Chimiche e Ambientali, Università dell"Insubria, via Valleggio 11, 22100 Como, Italy
Fax: +33(1)44277567; e-Mail: giovanni.poli@upmc.fr; e-Mail: madec@ccr.jussieu.fr;
Further Information

Publication History

Received 22 March 2007
Publication Date:
06 June 2007 (online)

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Abstract

The formal synthesis of kainic acid was carried out in eleven steps. The key cyclization step was accomplished through an intramolecular palladium-catalyzed allylic alkylation of an allylic sulfone. Further functionalization of the resulting pyrrolidone ­featured, inter alia, a N-heterocyclic carbene-copper hydride (NHC-CuH)-mediated stereoconvergent conjugate reduction.

Key words

kainic acid - synthesis - palladium - allylic alkylation - ring closure

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Procedure for the Palladium-Catalyzed Cyclization Reaction: To a solution of tetrabutylammonium bromide (10 mol%) in CH2Cl2 (1 mL) were added in this order allylpalladium chloride dimer (5 mol%) and dppe (12.5 mol%). After 5 min stirring, to the thus formed catalytic system were added successively a CH2Cl2 (5 mL) solution of 6 (795 mg, 1.6 mmol), H2O (6.0 mL), and a 50% aq KOH solution (6.4 mmol). The resulting biphasic system was stirred vigorously at r.t. for 16 h. The aqueous phase was extracted with CH2Cl2 (3 ×). The collected organic phases were dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified by flash chromatography to afford 7 in quantitative yield as an oil. 1H NMR (400 MHz, CDCl3): δ = 7.19 (d, J = 8.6 Hz, 2 H), 6.86 (d, J = 8.6 Hz, 2 H), 4.78 (br s, 2 H), 4.46 (d, J = 14.6 Hz, 1 H), 4.40 (d, J = 14.6 Hz, 1 H), 3.87 (d, J = 10.8 Hz, 3 H), 3.81 (d, J = 10.8 Hz, 3 H), 3.80 (s, 3 H), 3.55 (dd, J = 8.3, 9.6 Hz, 1 H), 3.20-3.32 (m, 1 H), 2.98-3.07 (m, 1 H), 2.94 (dd, J = 4.5, 22.8 Hz, 1 H), 1.63 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 168.3, 159.2, 144.3, 129.6, 127.4, 114.1, 112.3, 55.3, 53.5 (J = 100 Hz), 50.1, 46.4, 46.0 (J = 140 Hz), 39.7, 19.2. IR: 2955, 2360, 1688, 1514, 1247, 1031 cm-1. MS (ESI+): m/z = 392 [M + K+], 376 [M + Na+], 354 [M + H+].

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Procedure for the Hydride Conjugate Addition: An oven-dried flask under an argon atmosphere was charged with IPr-CuCl (2 mol%), t-BuONa (10 mol%) and anhydrous toluene (1 mL). After 10 min stirring at r.t., PMHS (90 µL) was added and the resulting orange solution was stirred at r.t. for 5 min. Then toluene (1 mL), and further PMHS (270 µL) were added. A solution of 8 (1:1 E/Z mixture) (508 mg, 1.54 mmol) in toluene (8 mL) was added via cannula to the thus generated reducing system and the reaction mixture was stirred at r.t. for 16 h. H2O was added, the aqueous phase was extracted with EtOAc (3 ×). The collected organic phases were washed with brine, dried over MgSO4 and the solvents were removed in vacuo. The crude product was purified by flash chromatography to afford pure 9 as an oil (72%). 1H NMR (400 MHz, CDCl3): δ = 7.16 (d, J = 8.6 Hz, 2 H), 6.83 (d, J = 8.6 Hz, 2 H), 4.74 (br s, 1 H), 4.65 (br s, 1 H), 4.39 (d, J = 14.2 Hz, 1 H), 4.35 (d, J = 14.2 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.77 (s, 3 H), 3.36-3.42 (m, 1 H), 3.10-3.15 (m, 2 H), 3.03 (dd, J = 1.3, 10.1 Hz, 1 H), 2.83 (dd, J = 3.5, 17.2 Hz, 1 H), 2.21-2.32 (m, 1 H), 1.42 (s, 3 H), 1.23 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 174.1, 172.5, 159.2, 143.1, 130.0, 128.1, 114.9, 114.0, 60.6, 55.3, 49.0, 46.3, 42.0, 41.6, 31.0, 19.8, 14.3. IR: 2936, 1731, 1687, 1513, 1246, 1175, 1032 cm-1.