ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The 1,2,3,4-tetrahydro-N-pivaloyl-isoquinoline-3-carboxylic acids 1d, 2d, and 3d, derived from (R)- or (S)-phenylalanine, (S)-dopa, and (S)-α-methyldopa, respectively, are doubly deprotonated with (tert-butyl)lithium in THF and alkylated at the 1-position (products 5-10). The major diastereoisomers formed are the result of electrophilic attack from the face opposite to the carboxylate group (rel. topicity ul-1,3). Even the addition to benzaldehyd (→7,8) is highly stereoselective (one of four diastereoisomers is formed exclusively (300-MHz 1H-NMR analysis)), if MgBr2 etherate is added prior to the electrophile. Some of the obtained amino-acid derivatives are decarboxylated by anodic oxidation in MeOH (→11, 12, 17) and NaBH3CN reduction, and converted to the known 1-methyl- and 1-benzyltetrahydroisoquinolines (15, 16) of 〉 95% ee as well as to the phthalide isoquinoline alkaloid (+)-corlumine of ≥80% ee. The synthetic approach described here is compared with other methods of synthesizing enantiomerically pure 1-substituted tetrahydroisoquinolines (and thus an important group of alkaloids, Scheme 1).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19870700729
Permalink
