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)

Selective Carbon–Carbon Bond Cleavage of Cyclopropanols

“…This reaction is selective for ring opening at the exocyclic C–C bond. This process can also be catalyzed by Pd/C/HCl or PdCl 2 /AcOH, ,, as well as by a bimetallic Ni catalyst. , …”

Diastereoselective Diels−Alder Reactions of a Novel Cyclopropenyl-Containing Chiral Auxiliary

“…With 10 in hand, a variety of Lewis acids were screened by NMR spectroscopy to determine how many equiv are required to activate 10 , the compatibility of the Lewis acids with 10 , and under what reaction conditions 10 would react with cyclopentadiene. It is well-known that cyclopropenyl systems are very good Michael acceptors, and we wished to minimize potential side reactions …”

Unusual Nucleophilic Addition of Grignard Reagents in the Synthesis of 4-Amino-pyrimidines

“…Although the 4-amino-2-methyl pyrimidines have been investigated with many differing structural modifications, 17−19 there are very few examples for the synthesis of α-keto-4-amino-2-methyl pyrimidines and their analogues. 20 As the core pyrimidine ring is observed widely throughout nature, it was surprising to find such a lack of examples because these α-keto structural analogues could be good candidates for inhibitor mimics and for potential structural manipulations in structure–activity relationship studies. To address this issue, we have devised a new synthetic route, which uses cheap and readily available starting materials, to construct α-keto-4-amino-2-methyl pyrimidines.…”