Synthesis of 2-octalones from quinaldine

Abstract

General. Reactions were carried out in an inert atmosphere using predried (sodium benzophenone ketyl) and distilled THF. Haloalkanes were obtained commercially. Product mixtures were separated to obtain analytical data by medium-pressure chromatography using an EM Lobar Si 60 column with 10% diethyl ether-gO% ligroin (60-80 "C) as eluent. Quantitative analysis of the reaction mixtures was accomplished on a Waters 6000 HPLC using an IBM silica column with 15% diethyl ether-85% ligroin (60-80 "C). The UV detector was calibrated on known product mixtures. NMR spectra were obtained using a Varian EM-390 spectrometer.General Alkylation Procedure. One millimole each of the sulfone and base were added to 7-15 mL of T H F and allowed to stir for 1 h at 0 "C. One millimole of the alkylating agent was added a t that same temperature, and the mixture was allowed to stir a t room temperature for 5 h. Addition of 5 mL of water, ether extraction, drying with MgS04, and removal of the solvent via a rotary evaporator provided the product mixture.Kinetic Reactions. Six millimoles of the appropriate sulfone in T H F and of butyllithium were mixed a t 0 "C. After 1 h the slurry was brought to room temperature, and then 6 mmol of bromoalkane was added. Alliquots (1 mL) were removed and quenched with water a t specific times. The samples were recovered as above and analyzed by HPLC.Equilibration-Deuterium Quench. An equimolar mixture of butyllithium, sulfone 1, and sulfone 4a were stirred for 1 h at 0 "C in 7 mL of THF. Deuterium oxide was added to the mixture, and the products were recovered as above, separated by medium-pressure chromatography, and analyzed for deuterium content by NMR spectroscopy.Deuterium Quench. An equimolar mixture of 1 and butyllithium were stirred in 7 mL of T H F a t 0 "C for 1 h. Deuteriosulfuric acid (1 M) was added, and the product was recovered as above and analyzed for deuterium content by NMR spectroscopy.Methyl phenyl sulfone (1): via oxidation of methyl phenyl sulfide with 30% hydrogen peroxide in acetic acid;18 91%; mp 87.4-89.6 "C (lit.IEb mp 86-88 "C); 'H NMR (CDCl,) 6 3.0 (9, 3), 7.5-7.8 (m, 5).Butyl phenyl sulfone (4a): 'H NMR (CC14) 6 0.9 (t, 3, J = 6 Hz), 1.1-1.9 (m, 41, 3.0 (t, 2, J = 6 Hz), 7.3-7.9 (m, 5 ) . Anal. Calcd for CI0Hl4O2S: C, 60.58; H, 7.12. Found C, 60.71; H, 7.20. 4-Heptyl phenyl sulfone (5a): 'H NMR (CC14) 6 0.9 (t, 6, J = 6 Hz), 1.1-1.9 (m, a), 2.6-2.9 (m, l), 7.2-7.9 (m, 5). Anal. Calcd for C13H,o0,S: C, 64.96; H, 8.39. Found: C, 64.79; H, 8.07. 4-(4-Propylheptyl) phenyl sulfone (6a): 'H NMR (CDCl,) 6 0.8 (t, 9, J = 6 Hz), 1.2-1.8 (m, 12), 7.3-7.8 (m, 5 ) .

Lateral Deprotometallation‐Trapping Reactions on Methylated Pyridines, Quinolines and Quinoxalines Using Lithium Diethylamide

“…Like pyridines, methylquinolines have already been α-functionalized by deprotometallation-trapping using different bases [13,39] (Figure 4). [15,41] As for 2-methylquinoline, n-butyllithium, for example, has been used successfully whether in diethylether [48] or THF. [49] Since the α-deprotometallated product is stabilized in its metal enamide form, weaker bases such as potassium amide in ammonia, [50] potassium bis(trimethylsilyl)amide in toluene, [51] and LiDA in THF [52] have also been employed.…”

Iridium-Catalyzed C-Alkylation of Methyl Group on N-Heteroaromatic Compounds using Alcohols

“…This method is useful because the synthetic process is simple, and analogues of the N -heteroaromatic compound can be systematically synthesized. C-Alkylation is typically achieved using a compound, such as a halogenated alkyl in the presence of a strong base (Scheme a) . However, this method is neither environmentally friendly nor atom-efficient because a halogen salt is produced as a byproduct.…”

Enantioselective Synthesis of Quinolizidines and Indolizidines via a Catalytic Asymmetric Hydrogenation Cascade

“…Initial studies with the easily accessible 5-(2-quinolinyl)-2-pentanone (1), 12 Hantzsch dihydropyridine 2 as hydride donor, and catalytic amounts of an achiral diaryl phosphate 3 revealed that the reaction can well be performed. However, beside the desired tertiary amine 4 small amount of the tetrahydroquinoline 5 was obtained.…”