Carboannulation Reactions of Cyclohexenone Derivatives: Synthesis of Functionalized α-Tetralones

Abstract

The base-mediated cyclocondensation reactions of 3-(ethoxycarbonylmethylene)- and 3-(cyanomethylene)cyclohexen­ones with ethoxymethylenemalonate derivatives lead to two functionalized α-tetralones with selectivities which depend on the stoichiometric ratio of the reactants. α-Tetralones are selectively obtained when excess Michael acceptor is used.

carboannulation - Michael additions - condensation - carbocycles - α-tetralones.

References and Notes

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<A NAME="RD40908ST-23">23</A>

Typical Experimental Procedure (Table 1, entry 5) - Synthesis of Diethyl 5,6,7,8-Tetrahydro-7,7-dimethyl-4-hydroxy-5-oxo-1,3-naphthalenedicarboxylate (8a) and Diethyl 5,6,7,8-Tetrahydro-7,7-dimethyl-5-oxo-1,3-naphthalenedicarboxylate (9a)
Sodium hydride (50% oil, 48 mg, 1 mmol) was added to a mixture of ester 7a (211 mg, 1 mmol), DMAP (12 mg, 0.1 mmol) and diethyl ethoxymethylenemalonate (433 mg, 2 mmol) stirred at 0 ˚C under nitrogen. The reaction mixture immediately became yellow with release of hydrogen. After stirring for 10 min at r.t., the mixture was heated at 180 ˚C for 1 h. After cooling at r.t., the mixture was diluted with CH₂Cl₂ and hydrolyzed with sat. aq NH₄Cl. Workup gave an oil which was purified by flash chromatography (SiO₂, PE-Et₂O, 80:20) to afford α-tetralone 8a (50 mg, 15%) and
α-tetralone 9a (170 mg, 53%).
Compound 8a: mp 62-64 ˚C. TLC (SiO₂, PE-Et₂O, 50:50): R _f  = 0.39. IR (KBr film): 2950, 1717, 1701, 1635, 1605, 1443, 1228, 1208, 1191, 1150, 867, 774, 683 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 14.18 (s, 1 H, OH), 8.62 (s, 1 H, H-2), 4.32 (q, ^³ J = 7.1 Hz, 4 H, 2 × OCH ₂CH₃), 3.25 (s, 2 H,
H-8), 2.55 (s, 2 H, H-6), 1.38 (t, ^³ J = 7.1 Hz, 6H, 2 × OCH₂CH ₃), 1.06 [s, 6 H, gem-(CH ₃)₂]. ^¹³C NMR (75.5 MHz, CDCl₃): δ = 206.1 (C=O), 166.1 (OC=O), 166.0 (OC=O), 165.0 (C-4), 151.9 (C-8a), 141.4 (C-2), 120.7 (C-1), 117.9 (C-4a), 117.6 (C-3), 61.7 (OCH₂CH₃), 61.6 (OCH₂CH₃), 52.0 (C-6), 42.2 (C-8), 33.1 (C-7), 28.5 [gem-(CH₃)₂], 14.7 (OCH₂ CH₃), 14.6 (OCH₂ CH₃). ESI-HRMS: m/z calcd for C₁₈H₂₂O₆ [MNa⁺]: 357.1314; found: 357.1320.
Compound 9a: mp 78 ˚C. TLC (SiO₂, PE-Et₂O, 50:50): R _f  = 0.56. IR (KBr film): 2977, 2958, 2870, 1715, 1691, 1605, 1466, 1449, 1418, 1389, 1225, 1195, 1148, 1022, 755 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.81 (d, ^³ J = 1.8 Hz, 1 H, H-4), 8.68 (d, ^³ J = 1.8 Hz, 1 H, H-2), 4.32 (q, ^³ J = 7.1 Hz, 4 H, 2 × OCH ₂CH₃), 3.24 (s, 2 H, H-8), 2.54 (s, 2 H, H-6), 1.42 (t, ^³ J = 7.1 Hz, 3 H, OCH₂CH ₃), 1.40 (t, ^³ J = 7.1 Hz, 3 H, OCH₂CH ₃), 1.07 [s, 6 H, gem-(CH ₃)₂]. ^¹³C NMR (75.5 MHz, CDCl₃): δ = 197.5 (C=O), 166.6 (OC=O), 166.5 (OC=O), 148.4 (C-8a), 136.3 (C-4a), 133.6 (C-2), 131.9
(C-4), 131.7 (C-1), 129.2 (C-3), 61.9 (2 × OCH₂CH₃), 52.0 (C-6), 42.0 (C-8), 33.3 (C-7), 29.0 [gem-(CH₃)₂], 14.7 (OCH₂ CH₃), 14.6 (OCH₂ CH₃). ESI-HRMS: m/z calcd for C₁₈H₂₂O₅ [MNa⁺]: 341.1359; found: 341.1357.