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The Synthesis of 4‐Hydroxypipecolic Acids by Stereoselective Cycloaddition of Configurationally Stable Nitrones
Author(s) -
Cordero Franca M.,
Bonollo Simona,
Machetti Fabrizio,
Brandi Alberto
Publication year - 2006
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/ejoc.200600104
Subject(s) - nitrone , chemistry , enantiopure drug , cycloaddition , stereoselectivity , selectivity , stereochemistry , adduct , yield (engineering) , organic chemistry , enantioselective synthesis , catalysis , materials science , metallurgy
Abstract The diastereoselective synthesis of trans ‐ and cis ‐4‐hydroxypipecolic acids has been achieved with geometry‐controlled nitrone cycloaddition chemistry. The cycloaddition of 3‐butenol to enantiopure C ‐aminocarbonyl and C ‐alkoxycarbonyl nitrones having a definite ( Z ) and ( E ) configuration, respectively, occurs with complete regio‐ and exo selectivity. The acyclic ( Z )‐nitrone 12 affords two cycloadducts in a 1:1 ratio, which can be separated and converted into (2 R ,4 R )‐ and (2 S ,4 S )‐4‐hydroxypipecolic acids, respectively, in four steps. The cyclic ( E )‐nitrone 17 reacts with complete diastereofacial selectivity and the elaboration of its sole adduct gives the methyl ester of (2 R ,4 S )‐4‐hydroxypipecolic acid, albeit in low yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)