Ethyl 1 - butyl - 5 - formyl - 2 - methyl

Ethyl 2-methyl-4-(D-ara6mo-tetrahydroxybutyl)pyrrole-3-carbothiolate (18) yields a tetra-O-acetyl derivative, and, on oxidation with periodic acid, affords ethyl 4-formyl-2-methylpyrrole-3-carbothiolate (22). Lactone (27) gives a tri-O-acetyl derivative and, on alkaline hydrolysis, consumes one equivalent of base and furnishes 2-methyl-4-(D-arofemo-tetrahydroxy-butyl)pyrrole-3-carboxylic acid (19) in almost quantitative yield. This acid can, in turn, be transformed into a tetra-O-acetyl derivative, and, when oxidized with sodium metaperiodate, it gives 4-formyl-2-methyl-pyrrole-3-carboxylic acid (23). Attempts to determine the size of the lactone ring in compound (27) by oxidation with sodium metaperiodate were unsuccessful three moles of metaperiodate were consumed per mole, as if, during the oxidation, hydrolysis of the lactone had occurred. 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

Vilsmeier formylation of carbazole can be conducted to give good yields of 3-monoformylcarbazoles 9-methyl, 9-ethyl, 9-n-butyl, 9-isoamyl, and 9-isobutyl derivatives were made in this way. The C-form-ylation of various carbazoles required for alkaloid and alkaloid analog synthesis makes instructive reading 1,4-dimethyl-, - 1,4,6-trimethyl-, - 1,4,9-trimethyl-, 1,4-diraethyl-6,7-methylenedioxy-, l,4-dimethyl-6,7-dimethoxy-, l,4-dimethyl-8-methoxy- (some N-formylation also obser-... 

To demonstrate that optically active aldehydes from formylation of the methyl groups of optically active olefins can be obtained as main reaction products with good optical yields, we have studied the hydroformylation of ( + )(S)-2,2,5-trimethyl-3-heptene. None of the methyl groups of the tertiary butyl group were carbonylated. Primarily the reaction product was from carbonylation of the other two methyl groups present in the molecule (Table 1). (S)-3-Ethyl-6,6-dimethylheptanal... 

Lithium chloride (2.6 g) is dissolved in THF (170 mL). Dimethyl-(2-oxo-4-phenylbutyl)phosphonate (7.87 g) and triethylamine (4.3 mL) are added. The mixture is stirred and cooled to -10°C. A solution of the Corey aldehyde benzoate, (lS,5R,6R,7R)-6-formyl-7-(benzyloxy)-2-oxabicyclo[3.3.0]octan-3-one (8.42 g) in THF (75 mL) is added to the reaction mixture over three hours. The resulting mixture is stirred for 18 hours at -10°C. At the end of this time, methyl t-butyl ether (MTBE) (100 mL) is added and the mixture warmed to 0-20°C. Sodium bisulfite (38%, 100 mL) is added and the two-phase mixture was stirred for 10 min. The phases are separated and the organic phase is washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase is separated and concentrated under reduced pressure to a volume of <100 mL. Ethyl acetate (200 mL) is added and the... 

Pentane-washed NaH (4.1 g) was suspended in 70 ml DMSO and a solution of ethyl (E,E)-6-(diethoxyphosphinyl)-3-methyl-2,4-hexdienolate (24.5 g) dissolved in 70 ml DMSO added. The reaction was stirred for 30 minutes at ambient temperature and 2-formyl-3-hexyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene (11.3 g) dissolved in 70 ml DMSO and 35 ml THE added. The mixture was stirred 2 hours and the product precipitated in ice water acidified with 6M HCl. The mixture was extracted with EtOAc and purified by flash chromatography on silica gel with hexane/methyl t-butyl ether, 98 2, and the product isolated as a pale yellow oil. 

Typical procedure. tert-Butyl 2-isocyano-4-methyl pentanoate 1554 [1182] N-Formyl-leucine tert-butyl ester 1553 (5.00 g, 23.2 mmol) and triethylamine (7.13 g, 69.7 mmol) were dissolved in dichloromethane (36 mL) and the solution was cooled to 0 °C. At this temperature, a solution of triphosgene (2.30 g, 7.74 mmol) in dichloromethane (25 mL) was added dropwise. The mixture was stirred for 2 h at room temperature, water (5 mL) was then poured into it, and the phases were separated. The organic layer was washed with 5% aq. sodium hydrogen carbonate solution, dried over sodium sulfate, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate to furnish tert-butyl 2-isocyano-4-methyl pentanoate 1554 (4.29 g, 94%) as a colorless oil. 

Typical procedure. 4-Bromo-3-[2-isocyano-2-(methoxycarbonyl)ethyl]ir dole-l-carboxylic acid tert-butyl ester 1559 [1187] The N-formyl-N -Boc-4 -bromo-tryptophan methyl ester 1558 (0.05 g, 0.14 mmol) was suspended in dry dichloromethane (3 mL) under argon and the solution was cooled to below 0 °C using an ice/salt bath. Tri-ethylamine (0.09 g, 0.86 mmol) was added through a septum, and then a solution of triphosgene (0.014 g, 0.05 mmol) in dichloromethane (1 mL) was added dropwise. The solution was allowed to warm to room temperature and stirred for a further... 

Ethyl and t-butyl BCOD-fused pyrrolecarboxylates 8a and 8b reacted with paraformaldehyde under acidic conditions to give dipyrromethane diethyl and di-f-butyl diesters 36a and 36b, the former of which were transformed to a-free dipyrromethane 37 in good yield by treatment with NaOH at 170-180 °C in ethylene glycol [36]. Both a-free dipyrromethane 37 and dipyrromethane di-f-butyl diester 36b were successfully employed for formylation with methyl orthoformate in the presence of TFA [36]. The dipyrromethane dicarbaldehyde 38 was obtained in good yields. 

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