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A New and Productive Route to 1‐Heteroarylcyclopropanols
Author(s) -
Belov Vladimir N.,
Savchenko Andrei I.,
Sokolov Viktor V.,
Straub Alexander,
Meijere Armin de
Publication year - 2003
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.200390093
Subject(s) - chemistry , guanidine , protecting group , yield (engineering) , steric effects , amination , palladium , hydrazine (antidepressant) , ether , cleavage (geology) , medicinal chemistry , lithium (medication) , alcohol , catalysis , organic chemistry , medicine , alkyl , materials science , geotechnical engineering , chromatography , fracture (geology) , engineering , metallurgy , endocrinology
( E / Z )‐2‐(1‐Allyloxycyclopropyl)‐3‐methoxyacrylonitrile ( 4 ‐All) was designed and prepared in five steps (58% overall yield) from ethyl cyclopropylidenacetate as a valuable precursor to various 1‐heteroarylcyclopropanols. Its condensation with amidines, guanidine, hydrazine, and methyl thioglycolate and subsequent removal of the allyl protecting group yields 1‐heteroarylcyclopropanols such as 1 ‐OH (36% over 2 steps), a very potent NO‐independent stimulator of soluble guanylate cyclase. Direct cleavage of the allyl ether protecting group [by palladium‐catalyzed substitution with lithium p ‐toluenesulfinate in AcOH or treatment with c ‐HexMgBr/Ti(O i Pr) 4 ] gives highly functionalized, sterically congested 1‐heteroarylcyclopropanols 29 , 30 , and 34 with intact amino and ester groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)