Enantioselective Synthesis of (+)‐(S)‐Laudanosine and (–)‐(S)‐Xylopinine

Abstract

The study presents a new pathway for the enantioselective synthesis of benzylisoquinoline alkaloids. The key steps of the synthesis of (+)‐(S)‐laudanosine (1) and (–)‐(S)‐xylopinine (2) are a Sonogashira coupling that builds up the C1–C8a bond of the benzylisoquinoline skeleton, an intramolecular Ti‐catalyzed hydroamination of an alkyne, and a subsequent enantioselective imine reduction according to Noyori’s protocol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…As broadly applicable hydroamination catalysts have remained elusive to date, hydroamination has been employed infrequently for the assembly of natural products and other complex target compounds. Several early examples have been summarized in previous reviews [10], including Trost's [368] synthesis of (+)-pseudodistomin D using Ag(I)-catalyzed hydroamination of an aminoalkyne, Yamamoto's [110] synthesis of an indolizidine using Pd(0)/benzoic acid-catalyzed alkyne/allene hydroamination, and Doye's [369] enantioselective synthesis of (S)-(+)-laudanosine and (S)-(−)-xylopinine with Ticatalyzed cyclohydroamination to give cyclic imines, which underwent further reactivity, including enantioselective reduction. When applied to complex target synthesis, hydroamination, hydroamidation, hydrocarbamation, hydrohydrazination, and hydroguanylation have all been used to advantage.…”

Synthesis of (–)‐(S)‐Norlaudanosine, (+)‐(R)‐O,O‐Dimethylcoclaurine, and (+)‐(R)‐Salsolidine by Alkylation of an α‐Aminonitrile

“…These data are in accordance with the values reported in the literature. [7] Determination of the enantiomeric excess was carried out by 1 H NMR spectroscopy after derivatization with (S)-(α)-methylbenzyl isocyanate (er Ͼ 99.5:0.5). Enantiomeric ratio: 26.7:1, ee = 93%.…”

“…[2] An example is the large group of tetrahydroisoquinoline alkaloids, several members of which have become classical targets for the development of new synthetic methodologies. [3][4][5][6][7] Here we report on a short asymmetric approach to α-branched secondary amines and its application to the synthesis of 1-substituted 1,2,3,4-tetrahydrosioquinoline alkaloids.…”

Avanços recentes na hidroaminação de compostos insaturados

“…22,23 A partir do composto 27 foi realizada uma hidroaminação intramolecular para gerar a imina 28, após tautomerização. Uma sequência de redução assimétrica de Noyori e ciclização de Pictet-Spengler foi utilizada para a conclusão da síntese da (−)-xilopinina (Esquema 5).…”