ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Diastereoselective Hydroxyalkylations in Position 1 of Tetrahydroisoquinolines and Synthesis of Aporphine, Protoberberine, and Pathalide AlkaloidsUnsubstituted and 6,7-dialkoxy-N-pivaloyl-tetrahydroisoquinolines 1-3 are converted to 1-bromomagnesium derivatives by sequential treatment with t-BuLi (-75°/THF) and MBr2.OEt2. Addition of the metalated tetrahydroisoquinolines to aliphatic or aromatic aldehydes occurs with relative topicity ul (Scheme 2). The 1-hydroxyalkylated 2-pivaloyl-tetrahydroisoquinolines a of u-configuration thus obtained (14 examples) can be converted to free aminoalcohols c of either l-or u-configuration (9 examples; Scheme 3). The depivaloylation with retention (→ u-c) is best achieved by heating in EtOH/KOH, the conversion to 1-aminoalcohols l-c by treatment with CF3COOH/(CF3CO)2O (→ l,-pivalates l-b), followed by alkaline saponification or by LiAlH4 reduction of the esters. The configuration of the products is assigned by 1H-NMR spectroscopy, by X-ray crystal structure analysis, by chemical correlation, and by comparison of the chemical properties of the l- and the u-isomers. The diastereoselective hydroxybenzylation of the tetrahydroisoquinoline is used for short syntheses of ushinsunine/oliveroline (Scheme 4), β-hydrastine, and ophiocarpine/epiopliocarpine (Scheme 6; aporphine, phthalide, and protoberberine alkaloids, respectively).
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19870700517
