Synthesis of Spirocyclopropanated Analogues of Iprodione

Abstract

Methyl 1-(tert-butoxycarbonylamino)cyclopropanecarboxylate (9) was converted into the spirocyclopropanated fivemembered ring analogue 7a of Iprodione (1) in five steps with an overall yield of 28 %. The spirocyclopropanated fivemembered ring analogue 8a was prepared from tert-butyl N-[1-(hydroxymethyl)cyclopropyl]carbamate (10) in five steps

Copper-Mediated Coupling Reactions and Their Applications in Natural Products and Designed Biomolecules Synthesis

“…In the first case, a selective N -arylation of bulky cyclopropylamino alcohol 15 was achieved in reasonable yield using ethylene glycol as ligand. The yield went down upon scaling up of the reaction (65% on 2 mmol scale, 53% on 15−25 mmol scale) and, as is often the case with hindered amines, arylation of the ligand was observed as a side reaction (Scheme ) . The second case is quite typical of the relative reactivity of amines toward arylation: whereas the arylation of primary or cyclic secondary amines, respectively, afforded anilines 20 and 21 in moderate to good yields (the reaction conditions used for the synthesis of tariquidar analogues are quite standard ones), acyclic secondary amines usually do not perform well under all reaction conditions (Scheme ).…”

“…The yield went down upon scaling up of the reaction (65% on 2 mmol scale, 53% on 15-25 mmol scale) and, as is often the case with hindered amines, arylation of the ligand was observed as a side reaction (Scheme 32). 282 The second case is quite typical of the relative reactivity of amines toward arylation: whereas the arylation of primary or cyclic secondary amines, respectively, afforded anilines 20 and 21 in moderate to good yields (the reaction conditions used for the synthesis of tariquidar analogues are quite standard ones), 283 acyclic secondary amines usually do not perform well under all reaction conditions (Scheme 33). Even with this limitation, the use of copper catalysis still provides a more efficient access to arylated amines compared to palladium catalysis because these conditions give less than 10% of the desired products.…”

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

“…Remarkably, nature not only produces a large variety of biologically active and structurally interesting compounds with single cyclopropyl moieties, [1][2][3] but also brings forward products which contain fatty acid residues with four and even five consecutive cyclopropane rings. [4] One example is the antifungal nucleoside FR-900848 1, which was isolated as a natural product from Streptoverticillum fervens in 1990, [5] the other is U-106305 2, a cholesteryl ester transfer protein inhibitor from the fermentation broth of Streptomyces sp.…”

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 1. 1-Aminocyclopropanecarboxylic Acid and Other 2,3-Methanoamino Acids

“…167,168 With the same concept in mind, spirocyclopropanated analogues 80 (Scheme 9) of the fungicide Iprodione were prepared; however, their biological activity was minimal. 169 The cyclopropylketiminium ion rearrangement (Cloke rearrangement) has been applied in the synthesis of a number of pyrrolidine-containing alkaloids, requiring ready access to substituted 2,3-diaminodihydropyrroles 76. ACC can easily be converted into its thioamide 81, and this undergoes rearrangement to the corresponding 3-amino-2-methylthiodihydropyrrole 77, in which the methylthio group can subsequently be substituted with various amines to afford the desired 2,3-diaminohydropyrroles 76 (Scheme 9).…”

“…Imidacloprid and Thiacloprid are highly effective insecticides finding worldwide application in crop protection. In order to study the influence of spirocyclopropane-annelation upon the biological activity, spirocyclopropanated analogues 83 (Scheme ) were synthesized and turned out to be of comparable potency as the original compounds. , With the same concept in mind, spirocyclopropanated analogues 80 (Scheme ) of the fungicide Iprodione were prepared; however, their biological activity was minimal …”