Stereoselective Addition of Grignard Reagents and Lithium Alkyls onto 3,5-Disubstituted-1,3-oxazolidine-2,4-diones

Access to 6a-Alkyl Aporphines: Synthesis of (±)-N-Methylguattescidine

“…7 was prepared according to the previously reported method. 7 rel-(4R,5S)-5-(2-Bromophenyl)-3-(4-((tert-butyldimethylsilyl)oxy)-3-methoxyphenethyl)-4-hydroxy-4-methyloxazolidin-2-one (8). To a solution of MeMgCl (3.0 M in anhydrous THF, 2 mL, 5.9 mmol) was added a solution of 7 (1.5 g, 2.9 mmol) in anhydrous THF (5 mL) at −30 °C under argon, and the temperature was slowly allowed to rise from −30 to 0 °C over 1 h. The reaction was then quenched by the addition of saturated aqueous NH 4 Cl, evaporated in vacuo to remove THF, and partitioned between H rel-(3 1 S,12bS)-8-Hydroxy-7-methoxy-3 1 -methyl-3 1 ,4,5,12btetrahydro-2H-dibenzo[de,g]oxazolo [5,4,3-ij]quinolin-2-one (6).…”

“…7 In this reaction, the methyl group was selectively introduced to the more electron deficient amide at −30 °C. 8 Furthermore, addition occurred to the less sterically hindered face, furnishing diastereomer 8 in 80% yield as the only product. The relative configuration was confirmed based on strong correlations in the 2D-NOESY spectra between the proton on the carbon atom in the cyclic carbamate and the adjacent methyl group.…”

“…As illustrated in Scheme , the synthesis commenced with Grignard addition of methyl magnesium chloride to N -acylcarbamate 7 , which was prepared from 2-bromo­mandelic acid . In this reaction, the methyl group was selectively introduced to the more electron deficient amide at −30 °C . Furthermore, addition occurred to the less sterically hindered face, furnishing diastereomer 8 in 80% yield as the only product.…”