RESUMO
The stereoselective amination of various chiral benzylic ethers using chlorosulfonyl isocyanate is developed, and the application of this method to the total synthesis of a potent antidepressant, (+)-sertraline, from readily available 1-naphthol is also described.
Assuntos
Antidepressivos/síntese química , Isocianatos/química , Naftóis/química , Sertralina/síntese química , Aminação , Benzeno/química , Éteres/química , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
This paper reports a novel synthetic method for the preparation of various urethanes and the application to the synthesis of carisbamate. The reaction of primary (2a, 2e and 2f) or secondary (2g-2i) trimethylsilyl ethers with chlorosulfonyl isocyanate afforded the corresponding urethanes in good yields without affecting the olefin moiety. However, in the case of secondary benzylic trimethylsilyl ether 2j, the corresponding urethane 3j was obtained in low yield. From the difference in reactivity between the primary and secondary benzylic trimethylsilyl ethers, the one-pot synthesis of carisbamate 1 from bis-trimethylsilyl ether 2l was achieved.
Assuntos
Carbamatos/química , Isocianatos/química , Compostos de Trimetilsilil/química , Uretana/análogos & derivados , Uretana/síntese química , Alcenos/química , Indicadores e ReagentesRESUMO
A stereoselective approach for synthesizing (2R,5S)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidine 1 (2,5-dideoxy-2,5-imino-d-glucitol, DGDP) was achieved using a seven-step approach starting from 2,3,4,6-tetra-O-benzyl-d-mannose (7). Key steps for the preparation of the title compound 1 involved the regioselective and diastereoselective amination of the cinnamyl anti-1,2-polybenzyl ethers 5 and 6 using chlorosulfonyl isocyanate (CSI) and ring cyclization to form the pyrrolidine ring. The reaction between anti-1,2-polybenzyl ether 5 and CSI in toluene at 0 degrees C afforded the corresponding anti-1,2-amino alcohol 4 as a major product with a diastereoselectivity of 16:1 in 76% yield. The mechanism underlying these reactions may be explained by the neighboring-group effect leading to the retention of stereochemistry.
