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Ein effektiver Weg zu GABA‐analogen Aminosäuren: Cyclopropanierung von N ‐silylierten Allylaminen und Enaminen
Author(s) -
Paulini Klaus,
Reißig HansUlrich
Publication year - 1991
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199119910183
Subject(s) - chemistry , carbenoid , cyclopropanation , cyclopropane , catalysis , enamine , medicinal chemistry , yield (engineering) , stereochemistry , bicyclic molecule , organic chemistry , ring (chemistry) , rhodium , materials science , metallurgy
An Efficient Route to GABA‐Analogous Amino Acids: Cyclopropanation of N ‐Silylated Allylamines and Enamines N ‐Silylated allylamines 1 are effectively transformed into methyl cyclopropanecarboxylates 2 by methyl diazoacetate under Rh 2 (OAc) 4 catalysis. Derivatives 2a and 2b are smoothly converted into trans ‐substituted amino acids 6a and 6b , respectively, and to bicyclic γ‐lactams 5a and 5b . The pharmacologically interesting γ‐aminobutyric acid (GABA) analogue trans ‐ 6a is now available in few steps. Photochemical and thermal Fe(CO) 5 ‐induced hydrogen shift converts allylamine derivatives 1 into N ‐silylated enamines 7 . While enamine ( E )‐ 7a can be cyclopropanated with methyl diazoacetate under Cu(acac) 2 catalysis to afford the desired cyclopropane derivatives 8a in good yield, the other enamines are rather unreactive towards the carbenoid. Use of an optically active catalyst provides 8a with an ee of 56% ( cis ) and 20% ( trans ). Acid‐induced ring cleavage of 8a gives the β‐formyl ester 10a , and reduction of 8a followed by desilylation provides the aminocyclopropane 14 in good overall yield, thus demonstrating that cyclopropanes like 8a can serve as useful synthetic intermediates.