A New and Productive Route to 1‐Heteroarylcyclopropanols

Abstract (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(OiPr)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)