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Nitrone Ylides: Two Possible 1,3‐Dipolar Cycloadditions but Only One Stepwise Formation of all‐ cis ‐5‐Aryl‐2,3,5‐trisubstituted N ‐Hydroxypyrrolidines
Author(s) -
Merino Pedro,
Tejero Tomás,
DíezMartínez Alba,
Gültekin Zeynep
Publication year - 2011
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.201101035
Subject(s) - nitrone , chemistry , alkene , cycloaddition , intramolecular force , yield (engineering) , 1,3 dipolar cycloaddition , stereoselectivity , amine gas treating , medicinal chemistry , organic chemistry , stereochemistry , catalysis , materials science , metallurgy
Abstract An efficient methodology for the synthesis of all‐ cis ‐ N ‐hydroxypyrrolidines has been developed through the formal [3+2] dipolar cycloaddition of electron‐poor alkenes and nitrone ylides generated from N ‐(methoxycarbonylmethyl)nitrones. Treatment of the nitrone with a tertiary amine in the presence of either a lithium salt or butyllithium followed by addition of the alkene at low temperature provided the product in very good chemical yield and excellent diastereoselectivity. Isolation and characterization of a key intermediate demonstrated that the reaction is a stepwise process consisting of an initial Michael addition followed by an intramolecular Mannich‐type reaction.