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Diastereoselective Alkylation of Tricyclic Lactim Ethers
Author(s) -
Hätzelt André,
Laschat Sabine,
Jones Peter G.,
Grunenberg Jörg
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200212)2002:23<3936::aid-ejoc3936>3.0.co;2-v
Subject(s) - chemistry , bromide , alkylation , benzyl bromide , iodide , diastereomer , allyl bromide , methyl iodide , electrophile , isopropyl , tricyclic , deprotonation , medicinal chemistry , stereochemistry , organic chemistry , catalysis , ion
Alkylations of tricyclic 1‐methoxy‐3,6,11,11a‐tetrahydro‐4 H ‐pyrazino[1,2‐ b ]isoquinolin‐4‐one ( 5 ) were studied under various conditions. The highest conversions were obtained when LDA or LHMDS were used for the deprotonation step. The diastereoselectivity turned out to be highly dependent on the electrophile. While methyl iodide, isobutyl bromide, 4‐methylpent‐3‐enyl bromide, and isopropyl bromide yielded mixtures of trans and cis diastereomers 10 and 11 , respectively, allyl bromide, 3‐methylbut‐2‐enyl bromide, and benzyl bromide yielded the trans ‐product 10 with high diastereoselectivity. X‐ray crystal structures of 5 and its synthetic precursor 9 were determined. The alkylated lactim ethers 10a , c , g and 11a − c were converted into the corresponding dioxopiperazines 12a , c , g and 13a − c in high yields. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)