An asymmetric synthesis of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN)

Abstract

An asymmetric synthesis of 2-amino-6,7-dimethoxy -1,2,3,4-tetrahydronaphthalene, which can be converted to the title compound by a literature procedure, is described. The synthesis, starting from 2-amino-4,5-dimethoxybenzoic acid and the acrylate of S-methyl lactate, was accomplished in eight steps in 11% overall yield and >97% optical purity.Key words: o-quinodimethanes, Diels-Alder, asymmetric, cycloaddition, induction, diastereoselective, ADTN. Chem. 68, 2028Chem. 68, (1990. On dCcrit une synthkse asymktrique du 2-amino-6,7-dimCthoxy-1,2,3,4-tCtrahydronaphtalkne qui peut Ctre transforme dans le composC mentionnC dans le titre par une procedure dCcrite dans la 1ittCrature. La synthkse, i partir de I'acide 2-amino-4,5-dimCthoxybenzoique et de I'acrylate du lactate de S-mCthyle, a CtC rCalisCe en huit Ctapes, avec un rendement global de 11% et une pureti optique >97%.

The mechanism of stereoselectivity in the cycloaddition reactions of α-hydroxy-ortho-quinodimethanes with the fumarate of methyl lactate and mandelate

“…For all cycloadducts H1 appear between 4.6 and 5.2 ppm (in CDCl,) and endo (cis-1,2) coupling constants, J,,, are 2-5 Hz, while exo (trans-1,2) coupling constants are 7-12 Hz (for previous examples see refs. [2][3][4][5][6]17). The results of the product study are shown in Table 1.…”

“…The solution was dried (MgS04) and evaporated, giving a yellow oil (2.99 g, 42%) that crystallized on standing. Flash chromatography on silica (eluent 20% ethyl acetate/ hexanes) yielded a colourless solid (1.74 g, 24%) a sample of which was crystallized from ethyl acetate/hexanes; mp 62-63°C; ir (CH?C12): 1709 cm-l; 'H nrnr (60 MHz, CDCl,) 6 …”

“…While these reactions are proving useful in asymmetric synthesis (1,3,6 ) , a satisfactory explanation of the stereoselectivity observed has not yet been proposed. Such an explanation would have to account for both the absolute stereoselectivity and the unusual relative stereoselectivity observed.…”

An Alternative Synthesis of the Dopaminergic Drug 2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐5,6‐diol (5,6‐ADTN)

“…Since recrystallization and CC failed to give pure 15, the crude product was used without further purification in the next step. (17). In a 100-ml flask were placed Pd · C (80 mg) and 16 (1.00 g, 2.94 mmol) in MeOH (50 ml) and CHCl 3 (3 ml), and a balloon filled with H 2 gas (3 l) was fitted to the flask.…”

“…As expected, the reaction with Na in liquid NH 3 took place on the electron-deficient ring of 14, giving rise to the carboxylic acid 15 in high yield (90%; Scheme). Next, 15 was transformed into the carbamate 16 by applying a literature procedure described for the synthesis of 6,7-ADTN [13] [17]: reaction of 15 with diphenylphosphoryl azide in the presence of Et 3 N via Curtius rearrangement, followed by treatment with benzyl alcohol, afforded 16 in high yield (88%). Hydrogenolysis of 16 in MeOH in the presence of CHCl 3 then afforded pure 17, which was finally demethylated to the hydrobromide 18 with 48% HBr, as previously described for the synthesis of 5,6-ADTN [8].…”