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Synlett 2009(11): 1812-1816  
DOI: 10.1055/s-0029-1217354
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Single-Step Symmetrical Double Alkylation of β,γ-Unsaturated δ-Lactams via Magnesium ‘Ate’ Complexes

Jacek G. Sośnicki*, Łukasz Struk
Institute of Chemistry and Environmental Protection, West Pomeranian University of Technology Szczecin, Al. Piastów 42, 71065 Szczecin, Poland
Fax: +48(91)4494639; e-Mail: sosnicki@ps.pl;
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Publication History

Received 26 February 2009
Publication Date:
12 June 2009 (online)

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Abstract

An easy approach to symmetrically 3,3-dialkylated derivatives of 3,6-dihydro-1H-pyridin-2-one in a one-pot and a single-step procedure via magnesium ‘ate’ complex is described. [Bu3Mg]Li used as the base showed great basic potential as one equivalent of it allowed double proton abstraction from 3,6-dihydro-1H-pyridin-2-one. Deprotonation at noncryogenic conditions yielded stable magnesiates which on treatment with more than two equivalents of alkyl halides provided 3,3-dialkylated products in good yield. In some cases minor 3,5-dialkylated lactams were formed due to allylic conjugation.

Key words

lactams - magnesium ‘ate’ complex - alkylation - piperidines

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Typical Procedure for the Dialkylation of 3 Using [Bu 3 Mg]Li (1a)
To a cooled (0 ˚C) and stirred solution of BuMgCl (2.1 mmol, 1.05 mL, 2.0 M in THF) in dry THF (2 mL) in a Schlenk flask, n-BuLi (4.2 mmol, 1.68 mL, 2.5 M in hexane) was added via syringe over 1 min under argon. A yellow suspension formed was stirred for 5 min and was next transferred via syringe to a cooled (0 ˚C) solution of 6-allyl-1-methyl-3,6-dihydro-1H-pyridin-2-ones (3a, 0.3 g, 2.0 mmol) in THF (10 mL). The resulting yellow solution was stirred for 30 min at 0 ˚C, and then benzyl bromide (0.75 g, 4.4 mmol) was added and stirred for 30 min. After addition of aq sat. NH4Cl (5 mL), the aqueous layer was extracted with EtOAc (2 × 50 mL) and the combined organic layers were dried over MgSO4. Filtration, concentration in vacuo, and purification by flash column chromatography (silica gel, n-hexane-EtOAc = 8:2, next 7:3) yielded 9a.

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Selected Spectroscopic Data
6-Allyl-3,3-dibenzyl-1-methyl-3,6-dihydro-1 H -pyridin-2-one (9a)
Colorless solid (0.62 g, 94%), mp 61-63 ˚C (from n-hexane). IR (KBr pellet): ν = 3028 (w), 2912 (w), 1628 (s), 1496 (w), 1456 (w), 1398 (w), 1348 (w), 1230 (w), 916 (w), 756 (m), 744 (m), 702 (m), 696 (m) cm-¹. ¹H NMR (400.1 MHz, CDCl3): δ = 1.03 (1 H, dt, J = 14.0, 8.3 Hz, 6-CHH), 1.86 (1 H, dm, J = 14.0 Hz, 6-CHH), 2.65 (2 H, d, J = 12.6 Hz, 2 × 3-CHH), 2.69 (3 H, s, NCH3), 3.14-3.20 (1 H, m, CH-6), 3.44 (1 H, d, J = 12.6 Hz, 3-CHH), 3.47 (1 H, d, J = 12.6 Hz, 3-CHH), 4.70-4.80 (2 H, m, =CH2), 4.92-5.05 (1 H, m, =CH), 5.42 (1 H, dd, J = 10.3, 3.2 Hz, =CH-5), 5.54 (1 H, dd, J = 10.3, 1.6 Hz, =CH-4), 7.08-7.27 (10 H, m, 2 × C6H5). ¹³C NMR (100.6 MHz, CDCl3): δ = 32.46 (NCH3), 38.20 (6-CH2), 45.93, 46.58 (2 × 3-CH2), 50.54 (C-3), 59.03 (CH-6), 117.86 (=CH2), 125.33 (=CH-5), 128.80 (=CH-4), 126.20, 126.35, 127.54, 127.79, 130.30, 130.66, 137.61, 137.82 (2 × C6H5), 132.61 (=CH), 170.80 (C-2). GC-MS (EI, 70eV): m/z = 331 (<1) [M+ ], 290 (100), 198 (28), 122 (37), 91 (63). Anal. Calcd for C23H25NO: C, 83.34; H, 7.60; N, 4.23. Found: C, 83.25; H, 7.69; N, 4.13.

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PM3 calculations were performed using the HyperChem program (7.52 release).